WHO continues to monitor the situation closely for any changes that may affect this interim guidance. Should any factors change, WHO will issue a further update. Otherwise, this interim guidance document will expire 2 years after the date of publication.# 1) supress transmission;
2) provide optimized care for all patients; and save lives 3) minimize the impact of the epidemic on health systems, social services and economic activity.
To achieve these objectives, the WHO Operational considerations for case management of COVID-19 in health facility and community (1) describes key actions that should be taken in different scenarios: no cases; sporadic cases; clusters of cases; and community transmission, in order to enable delivery of clinical and public health services in a timely fashion.
This guideline is based on the above strategic priorities, and is intended for clinicians involved in the care of patients with suspected or confirmed COVID-19. It is not meant to replace clinical judgment or specialist consultation but rather to strengthen frontline clinical management and the public health response. Considerations for special and vulnerable populations, such as paediatric patients, older people and pregnant women, are highlighted throughout the text.
In this document we refer to the COVID-19 care pathway (Annex 1). This describes a coordinated and multidisciplinary care pathway that a patient enters after s/he is screened for COVID-19 and becomes a suspect COVID-19 case, and follows the continuum of their care until release from the pathway. The objective is to ensure delivery of safe and quality care while stopping onwards viral transmission. All others enter the health system in the non-COVID-19 pathway. For the most up-to-date technical guidance related to the COVID-19 response, visit WHO Country & Technical Guidance (2).
Basic psychosocial support skills are at the core of any clinical intervention for COVID-19. Such skills are indispensable for all involved in the COVID-19 clinical response, whether they identify as mental health and psychosocial providers or not. Basic psychosocial skills are essential for supporting the emotional well-being of people who have COVID-19, those who have lost someone to COVID-19, or are family members and carers who are caring for someone with COVID-19 or have recovered from COVID-19.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
The Strategic preparedness and response plan outlines the World Health Organization (WHO) strategic objectives to end the COVID-19 pandemic and assists national stakeholders with developing a structured approach to their response. The WHO's main objectives for COVID- 19
As of 29 October 2021, over 249 million people worldwide have been diagnosed with COVID-19, according to the WHO dashboard (6).
The pandemic has thus far claimed more than 4.9 million lives (6). Vaccination is having a substantial impact on case numbers and hospitalizations in a number of high-income countries, but limitations in global access to vaccines mean that many populations remain vulnerable (7) (8). Even in vaccinated individuals, uncertainties remain about duration of protection and efficacy of current vaccines against emerging SARS-CoV-2 variants. Taken together, there remains a need for more effective treatments for COVID-19. The COVID-19 pandemic -and the explosion of both research and misinformation -has highlighted the need for trustworthy, accessible and regularly updated living guidelines to place emerging findings into context and provide clear recommendations for clinical practice (9).
been reported (37) (38), described as multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) in children and adolescents. Underlying conditions with severe illness in children appear to be similar to adults. Among 655 children with laboratory-confirmed severe/critical COVID-19 and complete information about underlying conditions, 23% had an underlying condition, with obesity, chronic lung disease (including asthma), cardiovascular disease and immunosuppression most commonly reported (38).

# Clinical characterization in pregnant women:
The results of a living systematic review (as of 6 October 2020) show that pregnant and recently pregnant women with COVID-19 appear to be less likely to be symptomatic (0.28, 95% CI 0.13-0.62; 4 studies; 462 051 women), or manifest common symptoms such as fever, dyspnoea and myalgia, compared with non-pregnant women of reproductive age (39). These findings are largely influenced by studies of pregnant women who were managed in hospitals for any reason, with limited data on women during early pregnancy or postpartum. Pregnant or recently pregnant women with severe COVID-19 are at higher risk of requiring admission to an ICU (OR=2.13, 95% CI 1.53-2.95; 7 studies, 601 108 women), invasive ventilation (OR=2.59, 95% CI 2.28-2.94; 6 studies, 601 044 women) or extra corporeal membrane oxygenation (ECMO) (OR=2.02, 95% CI 1.22-3.34; 2 studies, 461 936 women). Older maternal age, high body mass index (BMI), non-white ethnicity (this is uncertain and may be a associated with sample bias), pre-existing comorbidities, chronic hypertension, pre-existing diabetes, are risk factors for developing severe COVID-19. Complications related to COVID-19 did not seem to be increased in women presenting in the third trimester compared with earlier trimester of pregnancy or in multiparous compared with primiparous women, but the existing sample sizes for these comparisons are not large.
Post COVID-19 condition: WHO has recently released A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021 (40). To harmonize coding, the Classification and Terminologies unit at the WHO created ICD-10 and ICD-11 codes for "post COVID-19 condition" (41). Evidence on this condition is emerging. A recent meta-analysis suggests the following factors may be associated with post COVID-19 condition: older age, female sex, poor pre-pandemic mental or general health, asthma, smoking, vaping, hospitalization, or being overweight or obese (42). Three meta-analysis suggest the following symptoms to be more common: fatigue, dyspnea, cough, sleep disturbances, anxiety, depression, cognitive impairment, and difficulty concentrating (43)(44) (45). Of these, fatigue and concentration problems were noted to last beyond 12 weeks (46).
Variants of concern and severity of disease: At present, there are four variants of concern (VoC) recognized by WHO: Alpha, Beta, Gamma and Delta (Coronavirus disease -Answers) (47). VoCs seem to be more transmissible with Delta currently outcompeting the other variants (219)(48)(49)(50) (51). However, it is complex to determine whether a VoC causes more severe disease or higher mortality, as many other factors may also impact mortality. Such factors include, but are not restricted to, the proportion of the population that is at risk, vaccination rates within the at risk population, stress on the health care system, and medical countermeasures administered to patients (i.e., therapeutics). There have been some recent publications showing association of Delta virus and hospitalization, but more data is needed (52)(53)(54)(55)(56) (57).

# Guideline development and implementation
What triggered this version of the guideline?
The current version of the WHO living guideline addresses the use of corticosteroids in children with MIS-C. It follows the availability of two observational studies published on 1 July 2021 (3) (5).

# Who made this guideline?
For these new recommendations, the WHO selected additional Guideline development group (GDG) members with expertise on the subject matter. The GDG was made up of 25 individuals, of whom 23 were content experts (clinicians, methodologists, scientists) and 2 were parents of patients who previously had COVID-19. The methods chair (methodological expertise) and a clinical chair (content expertise) guided the GDG discussions. See link here for short bios of GDG members.
WHO selected GDG members to ensure global geographical representation, gender balance, and appropriate technical and clinical expertise, thus not all of the standing GDG members participated in this current update. The technical unit collected and managed declarations of interests (DOIs) and found no GDG member to have a conflict of interest. In addition to distribution of a DOI form, during the meeting, the WHO Secretariat described the DOI process and an opportunity was given to GDG members to declare any interests not provided in written form. Web searches also did not identify any conflicts.
methodological aspects of the living guideline process.
The guideline is available via:
- WHO website in PDF format - MAGICapp in online, multilayered format
The purpose of the online formats and additional tools, is to make it easier to navigate and make use of the guideline in busy clinical practice. The online multilayered formats are designed to allow end-users to find recommendations first and then drill down to find supporting evidence and other information pertinent to applying the recommendations in practice, including tools for shared decision-making (clinical encounter decision aids) (58).
Additional educational modules and implementation tools for health workers can be found via:
- WHO COVID-19 essential supplies forecasting tool (COVID-ESFT)
- WHO Clinical care for severe acute respiratory infection toolkit: COVID- 19  The fourth (v1.4) and current version (v1.5) of the guideline, new recommendations have been developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for guideline development (60).

# Related guidelines
This living WHO guideline for the clinical management of COVID-19 is related to the Living Guideline for therapeutics and COVID- 19 (61), also published in the BMJ (62) and available in MAGICapp.
This guideline aims to be trustworthy and living; dynamically updated and globally disseminated once new evidence warrants a change in recommendations for COVID-19. The aim is to produce at least two updates per year, maintaining standards for trustworthy guidelines.
Stepwise approach Here we outline the stepwise approach we take to improve efficiency and timeliness of the living, trustworthy guideline, in the development and dissemination of the recommendations. To do so, various processes occurred simultaneously.
Step 1: Evidence monitoring and mapping and triggering of evidence synthesis Regular monitoring of evidence around key topics occurs with support from the WHO rapid review team and their network of collaborators. In February 2021, the WHO Steering Committee triggered this guideline update process, including PICO development.
The trigger for producing or updating specific recommendations is based on the following:
- likelihood to change practice;
- relevance to a global audience.
Step 2: Convening the GDG A series of meetings were held with a smaller subset of the WHO Steering committee, entitled the WHO Maternal and Child Health Guidance Coordination Group (see Acknowledgement) to prepare for the GDG. A survey was conducted to refine the prioritization of outcomes specifically for the MIS-C population and inform the values and preferences. The GDG meeting was held on 10 June 2021 to
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
Earlier versions (v1.1, v1.2) of this document were developed in consultation with the International Forum for Acute Care Trialists (InFACT), the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) and the Surviving Sepsis Campaign 2019) and were adapted from previously published Clinical management of severe acute respiratory infection when Middle East respiratory syndrome coronavirus (MERS-CoV) infection is suspected: interim guidance (59).
For the third version (v1.3) of the COVID-19 clinical guideline the WHO steering committee expanded the scope of the from the previous versions to include recommendations on the full spectrum of disease (mild, moderate in addition to severe) and the full patient care pathway from screening to rehabilitation. A guideline Development Group (GDG) comprising individuals with broad expertise spanning multiple specialties and all regions was convened. Because of the accelerated timeline and very broad scope of the third version of the guideline, it was not feasible to undertake a formal GRADE process (PICO questions; systematic reviews; formal documentation of values and preferences and incorporation of considerations of costs, resources, and feasibility) for each recommendation. Instead, PICOs were drafted and published evidence was synthesized under the coordination of the Science Division in rapid systematic reviews. The WHO Steering Committee drafted the recommendations about interventions based on these reviews. These draft recommendations and evidence summaries were pre-circulated to the GDG. The GDG was convened over multiple meetings, and consensus was achieved for all recommendations. The direction and strength of recommendations were presented using symbols rather than formal GRADE terminology (strong and conditional recommendations with grading of certainty of evidence, or best practice statements).
- To advise on the priority questions and scope of guideline.
- To advise on the choice of important outcomes for decision-making.
- To comment on the evidence used to inform the guideline.
- To advise on the interpretation of the evidence, with explicit consideration of overall balance or risks and benefits.
- To formulate recommendations, taking into account diverse values and preferences according to GRADE.
The GRADE approach provided the framework for establishing evidence certainty and generating both the direction and strength of recommendations (63) (64). Good practice statements can be made in addition to, or instead of a recommendation when a large body of indirect evidence, made up of linked evidence including several indirect comparisons, strongly supports the net benefit of the recommended action, if deemed that it will be an onerous and unproductive exercise to collect the indirect linked evidence supporting the recommendations. However, it still requires transparency and explicitness, with a clear rationale for the approach. Although a priori voting procedures were established at the outset, in case consensus was not reached, these procedures were not necessary for this recommendation which reached consensus amongst the panel.
The following key factors were used to formulate transparent and trustworthy recommendations:
- absolute benefits and harms for all patient-important outcomes through structured evidence summaries (e.g. GRADE summary of findings tables); - quality/certainty of the evidence (63) (65); - values and preferences of patients (66); - resources and other considerations (including considerations of feasibility, applicability, equity) (66);
- each outcome will have an effect estimate and confidence interval, with a measure of certainty in the evidence, as presented in summary of findings tables. If such data are not available narrative summaries will be provided; - recommendations will be rated as either conditional or strong, as defined by GRADE. If the panel members disagree regarding the evidence assessment or strength of recommendations, WHO will apply voting according to established methods.
Step 5: External and internal review The WHO guideline was then reviewed by pre-specified external reviewers (see Acknowledgements) and then approved by the WHO Publication and Guideline Review Committees. The members of the External Review Group reviewed the final guideline document to identify any factual errors, and to comment on clarity of the language, contextual issues and implications for implementation.

# Benefits and harms
For the previous recommendations, the GDG members prioritized outcomes (rating from 9  to 1  with severe and critical COVID-19, taking a patient perspective (Tables 2.1). For these new recommendations on MIS-C, the GDG concluded that the values and preferences for children and adolescence with MIS-C may differ from that used in previous recommendations. A new targeted outcomes prioritization exercise was conducted (Table 14.1). These new prioritized outcomes were used to update the metaanalysis.

# Baseline risk estimates
The evidence summaries that informed the guideline recommendations report the anticipated absolute effects of corticosteroids compared with usual care across all patient-important outcomes. The absolute effects of treatment are informed by the prognosis (i.e. baseline risk estimates) combined with the relative estimates of effects (e.g., RR, OR) obtained from the meta-analysis.

# Values and preferences
There were insufficient published data to provide the GDG with an informative systematic review of studies describing patients' experiences or values and preferences on treatment decisions for COVID-19 drug treatments. The GDG therefore relied on their own judgments of what well-informed patients would value after carefully balancing the benefits, harms and burdens of treatment and their review the survey results and PICO, and this was followed up with another GDG meeting to agree the recommendations on the 24 June 2021.
Step 3: Evidence synthesis The WHO Maternal and Child Health Guidance Coordination Group with support of the Quality Assurance of Norms and Standards (QNS) unit, commissioned an independent systematic review to examine the benefits and harms of the intervention. The systematic review team included librarian, methodologists, and clinicians and had experience in GRADE methodology and rating certainty of evidence (see Acknowledgements).
Step 4: Development of recommendations The GDG panel members are responsible for the following critical activities:
- Mortality would be the outcome most important to patients, followed by need and duration of mechanical ventilation, time to clinical improvement, and serious intervention-related adverse events. - Most patients would be reluctant to use a medication for which the evidence left high uncertainty regarding effects on the outcomes listed above. This was particularly so when evidence suggested treatment effects, if they do exist, are small, and the possibility of important harm remains. - In an alternative situation with larger benefits and less uncertainty regarding both benefits and harms, more patients would be inclined to choose the intervention.
The GDG acknowledged, however, that values and preferences are likely to vary. There will be patients inclined to use a treatment in which evidence has not excluded important benefit, particularly when the underlying condition is potentially fatal. On the other hand, there will be those who have a high threshold of likely benefit before they will choose the intervention. Although the GDG focused on an individual patient perspective, they also considered a population perspective in which feasibility, acceptability, equity and cost are important considerations.
For these new recommendations (see Chapter 15) the majority of GDG members inferred that most well-informed patients, and their families, would, despite the high uncertainty of important benefit want to receive some therapeutic agent in addition to supportive care for MIS-C, compared with no specific therapeutic agent. In doing so, patients would be placing a high value on uncertain benefit and a low value on avoiding any mild adverse effects associated with treatment.

# Selecting and rating the importance of outcomes
GDG members prioritized outcomes from the perspective of patients with severe/critical COVID-19. subsequent treatment preferences. The GDG included four patient-representatives who had lived experience with COVID-19. The WHO is currently conducting a survey of patients to expand the values and preferences statements for the next version update of the guideline.
In previous recommendations, the GDG agreed that the following values and preferences would be representative of those of typical well-informed patients:

# Who the recommendations apply to

# Info Box
The GDG elected to use the WHO severity definitions based on clinical indicators, adapted from WHO COVID-19 disease severity categorization. These definitions avoid reliance on access to health care to define patient subgroups.

# WHO severity definitions
- Critical COVID-19 -Defined by the criteria for acute respiratory distress syndrome (ARDS), sepsis, septic shock, or other conditions that would normally require the provision of life-sustaining therapies such as mechanical ventilation (invasive or non-invasive) or vasopressor therapy.
- Severe COVID-19 -Defined by any of:
- Oxygen saturation < 90% on room air;
- in adults, signs of severe respiratory distress (accessory muscle use, inability to complete full sentences, respiratory rate > 30 breaths per minute), and, in children, very severe chest wall indrawing, grunting, central cyanosis, or presence of any other general danger signs (inability to breastfeed or drink, lethargy or reduced level of consciousness, convulsions) in addition to the signs of pneumonia.
- Non-severe COVID-19 -Defined as absence of any criteria for severe or critical COVID-19.
The GDG noted that the oxygen saturation threshold of 90% to define severe COVID-19 was arbitrary and should be interpreted cautiously when used to define disease severity. For example, clinicians must use their judgment to determine whether a low oxygen saturation is a sign of severity or is normal for a given patient with chronic lung disease. Similarly, a saturation 90-94% on room air is abnormal (in the patient with normal lungs) and can be an early sign of severe disease, if the patient is on a downward trend. Generally, if there is any doubt, the GDG suggested erring on the side of considering the illness as severe.
The infographic illustrates these three disease severity groups and key characteristics to apply in practice. We recommend that COVID-19 care pathways be established at local, regional and national levels. COVID-19 care pathways are for persons with suspected or confirmed COVID-19.
- A person enters the COVID-19 care pathway after s/he is screened, based on a standardized case definition, including assessment of symptoms, and meets criteria for a suspect case.
-Suspect cases may be referred to as "persons or patients under investigation" (PUIs) in some contexts.

# Immediate implementation of appropriate infection prevention and control measures
Infection prevention and control (IPC) is a critical and integral part of clinical management of patients, health workers' safety and hospital-acquired infections. In addition to screening, triage, and rapid source control, WHO guidance emphasizes the importance of administrative, environmental and engineering controls in health care settings (68). Universal masking in health facilities (wearing a mask at all times except when eating or drinking) is required for all persons (staff, patients, visitors, service providers and others) in areas of known or suspected community or cluster SARS-CoV-2 transmission (69), as well as rational and appropriate use of all personal protective equipment (PPE) (70).
For the most up-to-date, comprehensive WHO guidance see Infection prevention and control during health care when coronavirus disease (COVID-19) is suspected or confirmed (68) and Transmission of SARS-CoV-2: implications for infection prevention precautions, 9 July 2020 (71).

# How to implement IPC measures for patients with suspected or confirmed (68)
Screening and triage for early recognition of suspected COVID-19 patients and rapid implementation of source control measures. Screen all persons at first point of contact in health facility to allow for early recognition followed by their immediate isolation/ separation.
Ask the suspected or confirmed COVID-19 patient to wear a medical mask and direct the patient to a separate, well-ventilated area, ideally an isolation room/area if available. Keep at least 1 m distance between patients. Instruct all patients to cover nose and mouth during coughing or sneezing with tissue or flexed elbow, dispose of tissues safely immediately after use in a closed bin and perform hand hygiene after contact with respiratory secretions. In areas with COVID-19 community transmission, restrict visitors to those that are essential such as the parents of paediatric patients and caregivers and ask them to wear a mask.
Apply standard precautions for all patients.
Apply standard precautions according to risk assessment for all patients, at all times, when providing any diagnostic and care services. Standard precautions include but are not limited to, hand and respiratory hygiene and the appropriate use of PPE; universal masking is required for all persons in areas of known or suspected community or cluster SARS-CoV-2 transmission (69). Standard precautions also include appropriate patient placement; environmental cleaning; prevention of needle-stick or sharps injury and safe waste management.
Carefully practise hand hygiene using an alcohol-based hand rub if hands are not visibly dirty or soap and water and disposable towels, before PPE use and after PPE removal, and when indicated while providing care, according to the WHO Five Moments for hand hygiene (72).
If possible, use either disposable or dedicated equipment (e.g. stethoscopes, blood pressure cuffs, pulse oximeters and thermometers). If equipment needs to be shared among patients, clean and disinfect between each patient use. Ensure that health care workers avoid contaminating environmental surfaces that are not directly related to patient care (e.g. door handles and light switches) and refrain from touching their eyes, nose and mouth with potentially contaminated gloved or ungloved hands. All surfaces should be routinely cleaned and disinfected, especially high touch surfaces, those surfaces touched by patients and whenever visibly soiled or if contaminated with blood and body fluids.
Best practices for safely managing health care waste, including waste related to surgeries and obstetric care, should be followed.

# Apply contact and droplet precautions for suspected or confirmed COVID-19 patients.
For suspected and confirmed COVID-19 patients, contact and droplet or airborne precautions should be applied depending on activity to be undertaken. Where possible, designate a team of health workers to care for patients with suspected or confirmed COVID-19 and restrict their contact with COVID-19 patients. Place all cases in well ventilated single rooms if feasible. When single rooms are not available or bed occupancy rate is anticipated to be 100% or more, suspected, probable or confirmed COVID-19 patients should be grouped together (cohorted) in adequately ventilated areas with bed space at least 1 m apart.
Limit patient movement within the institution and ensure that patients wear medical masks when outside of their care area (e.g. when being transported).
Health workers should use gloves, a clean, long sleeved gown, medical mask and eye protection (goggles or face shield). Remove PPE when leaving the patient care area, following instructions how to remove PPE safely (73).
Apply airborne precautions when performing aerosol-generating procedures.
Perform procedure in adequately ventilated rooms.
When performing aerosol-generating procedures (tracheal intubation, non-invasive ventilation tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, bronchoscopy and sputum induction induced by using nebulized hypertonic saline) or in settings where aerosol-generating procedures are performed, airborne in combination with contact precautions should be used. Use the appropriate PPE, including fit-tested particulate respirators (N95 or equivalent, or higher level of protection), gloves, long-sleeved gowns, eye protection (goggles or face shield). In areas of community transmission, in ICUs where aerosol-generating procedures are frequently performed, the health worker may choose to wear a particulate respirator throughout their shift. There is insufficient evidence to classify high-flow nasal oxygen (HFNO) and nebulizer therapy as an aerosol-generating procedure that is associated with transmission of COVID-19; thus airborne in combination with contact precautions should be used.
In situations where TB may co-exist, specific measures may be necessary in addition to the above (74).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO) Please find new recommendation on methods for clinical decision-making in COVID-19 as the third recommendation.
We recommend screening all persons at the first point of contact with the health system in order to identify individuals that have suspected or confirmed COVID-19.
- Screening can be performed in areas such as the emergency unit, outpatient department/primary care clinic, in the community by a community health worker or by telemedicine. In the context of this outbreak, this should be done at a distance (> 1 m). Use a simple set of questions based on the WHO case definition (see Table 6.1). This is best done by establishing screening protocols at all health access points and during contact tracing activities. Older people and those immunosuppressed may present with atypical symptoms such as fatigue, reduced alertness, reduced mobility, diarrhoea, loss of appetite, delirium and absence of fever (75)(76) (77). Thus, screening questions may need to be adjusted for certain settings and guided by epidemiologic considerations. 2. Persons with symptoms (see Table 6.1) that meet the case definition for suspected COVID-19 enter into the COVID-19 care pathway and should immediately be given a medical mask and directed to a single room. If a single room is not possible, then group patients with similar clinical diagnosis and based on epidemiological risk factors, with a spatial separation (at least 1 m between patients). Suspected cases should not be cohorted together with confirmed cases (see Chapter 7 on infection prevention and control. 3. In areas with other endemic infections that cause fever, such as malaria, dengue, tuberculosis (TB) etc., as part of screening, febrile patients should be tested as per routine protocols (74)(78)(79)(80)(81), irrespective of the presence of respiratory signs and symptoms. Coinfection with COVID-19 may coexist. 4. When influenza virus is known or suspected to be circulating, ensure that is also considered as part of screening of patients with fever and influenza-like-illness; and that testing is per local routine protocols. Coinfection with COVID-19 may exist. 5. Large outbreaks have been observed in long-term care facilities (LTCFs) (76). The COVID-19 care pathway should be activated for all residents of LTCFs who are contacts of a confirmed case in that LTCF, including immediate isolation, testing and treatment as needed. The priority focus in these settings should be to ensure the well-being of residents and protect health workers, and implementation of clinical management and IPC that considers the individual's condition and prognosis (such as screening visitors for COVID-19) (82).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Screening, triage and clinical assessment: early recognition of patients with COVID-19
The primary objective of the COVID-19 global response is to slow and stop transmission, find, isolate and test every suspect case, and provide timely appropriate care of patients with COVID-19. The recommended location of care will depend on the epidemiologic scenario and be either at a designated COVID-19 health facility, community facility or, where not possible, at home. Refer to the WHO Operational considerations for case management of COVID-19 in health facility and community (1).

# Practical Info
Existing prognostic models are reviewed in a living systematic review, available at /.
Available prognostic models need to be validated in other populations.

# Evidence To Decision
In community settings, community health workers should continue to follow usual protocols for recognition and treatment of other common illnesses and danger signs while activating the COVID-19 care pathway (including for referral as needed) for suspect cases. Refer to WHO/IFRC/UNICEF guidance on community-based health care, including outreach and campaigns, in the context of the COVID-19 pandemic (83).
At a health facility, after screening and isolation, triage patients with suspected COVID-19 using a standardized triage tool (such as the WHO/IFRC Interagency Integrated Triage Tool); and evaluate the patient to determine disease severity (see Table 6.3).
- Initiate timely care for the acutely ill using a systematic approach, as described in WHO/ICRC Basic emergency care (84)

# Conditional recommendation
For patients COVID-19 of any severity assessed in a clinic or hospital, we suggest clinical judgment, including consideration of patients' values and preferences and local and national policy if available, to guide management decisions including admission to hospital and to the ICU, rather than currently available prediction models for prognosis (conditional recommendation, very low certainty).
Clinical judgment and policy developed locally or nationally are typically used to make decisions regarding admission of patients Important harms

# Benefits and harms
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
The GDG emphasized the very low certainty evidence supporting the use of prognostic models to enhance clinical-decision making and patient outcomes, and recognized the lack of studies and uncertain feasibility in resource-constrained settings and potential negative impact on health equity, depending on how prognostic models are used to inform clinical decisions. Accordingly, the GDG made a conditional recommendation in favour of usual practice to guide decision-making, consisting of clinical judgement, patients' values and preferences, and local and national policy, if available.

# Subgroup analyses
The GDG did not find any evidence bearing on subgroup effects across patients with different levels of COVID-19 disease severity or between children and adults. In other words, the conditional recommendation is applicable across all these subgroups.

# Special populations
There is insufficient information on the performance and impact of prognostic models in pregnant women. Therefore, the GDG concluded that the recommendation applies to pregnant women.
with COVID-19 to hospital and to the ICU. Judgment and policy may include ethical considerations regarding allocation of resources. Over the course of the pandemic, many models have been developed for patients with COVID-19 to predict hospital admission, ICU admission, need for mechanical ventilation, mortality, or other outcomes. All existing models are at unclear or high risk of bias using the multiple domain PROBAST assessment tool (89), and there are as yet no studies of whether the use and implementation of these models improves (shared) decision-making and subsequent patient outcomes. With respect to their effects on patient outcomes, the certainty of evidence for any of these prognostic models is very low.
The GDG considered the evidence in favour of prognostic models in patients with COVID-19 to be of very low certainty, due to risk of bias, insufficient predictive accuracy with many models (range of C-statistics for prognosis models 0.54 to 0.99), lack of validation studies, and lack of evidence of the impact of using models on decision-making and patient outcomes. A review and assessment of existing models on their applicability and risks of bias is available (/). These prediction models for patient prognosis are distinct from triage models that have been developed to decide which patients are offered admission (typically to an ICU); triage models were not reviewed.
The GDG acknowledged that ongoing model development and validation, along with studies of predictive accuracy and impact on decision-making and patient outcomes of those selected models with sufficient predictive accuracy, may change the certainty of evidence in the future.

# Very low

# Certainty of the Evidence
Applying the agreed values and preferences, the GDG inferred that the majority of well-informed physicians and patients would not want care decisions to be based on existing prognostic models, due to the very low certainty of evidence for benefit on patient outcomes. Given the lack of evidence of harm, some patients may choose to have their care informed by the use of such models.

# Substantial variability is expected or uncertain

# Preference and values

# Important considerations
Commonly included predictors in these prognostic models include age, sex, comorbidities, vital signs (e.g. temperature, heart rate, respiratory rate, oxygen saturation, blood pressure), imaging features, lymphocyte count, and C reactive protein (/). Some laboratory tests and imaging modalities may not be available in resourceconstrained settings, and existing models have not been validated such settings.

# Resources and other considerations
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)  (92). Loss of smell (anosmia) or loss of taste (ageusia) preceding the onset of respiratory symptoms has also been reported (17)(93) (94).
Additional neurological manifestations reported include dizziness, agitation, weakness, seizures, or findings suggestive of stroke including trouble with speech or vision, sensory loss, or problems with balance in standing or walking (18) (19).
Older people and immunosuppressed patients in particular may present with atypical symptoms such as fatigue, reduced alertness, reduced mobility, diarrhoea, loss of appetite, confusion, and absence of fever (75)(76) (77).
Symptoms such as dyspnoea, fever, gastrointestinal (GI) symptoms or fatigue due to physiologic adaptations in pregnant women, adverse pregnancy events, or other diseases such as malaria, may overlap with symptoms of COVID-19 (95).
Children might not have reported fever or cough as frequently as adults (96).
Info Box  (99).
Other risk factors associated with higher risk include: smoking (100)(101) and higher sequential organ failure assessment (SOFA) score and D-dimer >1 g/L on admission were associated with higher mortality (86)(?)
In pregnancy, increasing maternal age, high BMI, non-white ethnicity, chronic conditions and pregnancy specific conditions such as gestational diabetes and pre-eclampsia (39).
Info Box We recommend, for all suspect COVID-19 cases, at minimum the collection of respiratory specimens for nucleic acid amplification testing (NAAT) for example reverse transcription polymerase chain reaction (RT-PCR). Repetitive testing of upper respiratory tract (URT) and/or lower respiratory tract (LRT) might be needed to establish a diagnosis (113). Additional samples that might aid the diagnosis of COVID-19 can be faecal specimens (if appropriately validated by the receiving laboratory). If deceased consider the collection of postmortem specimens (112). In addition, testing for other respiratory viruses and bacteria should be considered when clinically indicated according to local guidelines.

# SARS-CoV-2 antibody tests are not recommended for diagnosis of current infection with COVID-19.
- Use appropriate PPE for specimen collection (droplet and contact precautions for URT specimens; airborne precautions for LRT specimens). See IPC guidelines for the most up-to-date guidance (70) (71). 2. In the first week of symptom onset relatively high viral loads are generally observed in the upper respiratory tract (URT) specimens. For the collection of URT samples, we recommend the collection of nasopharyngeal and oropharyngeal specimens. When collecting URT samples, use viral swabs (sterile Dacron or rayon, not cotton), for nasopharyngeal swabbing use a swab with a long flexible shaft designed for nasopharyngeal sampling. For instructions on appropriate URT sampling see Clinical care for severe acute respiratory infection toolkit: COVID-19 adaptation (85). Unless specified differently by the receiving laboratory, transport sample in viral transport media. 3. LRT (vs URT) samples are more likely to be positive after the first week of illness. Thus if URT are negative and clinical suspicion remains, also collect specimens from the LRT when readily available (expectorated sputum, or endotracheal aspirate/bronchoalveolar lavage in ventilated patient). Clinicians may elect to collect only LRT samples when these are readily available (for example, in mechanically ventilated patients). Sputum induction should be avoided owing to increased risk of aerosol transmission. In a patient with suspected COVID-19, especially with pneumonia or severe illness, a single negative URT sample does not exclude the diagnosis, and additional URT and LRT samples are recommended (112). In hospitalized patients with confirmed COVID-19, repeated URT and LRT samples can be collected, as clinically indicated, but are no longer indicated for release from COVID-19 precautions (67). 4. NAAT testing is the recommended for the diagnosis of COVID-19. However in cases where NAAT is unavailable or where prolonged turnaround times preclude clinical utility, antigen testing can be included in the diagnostic algorithm under the right circumstances. For details on appropriate utilization of antigen testing see interim guidance Antigen-detection in the diagnosis of SARS-CoV-2 infection using rapid immunoassays (114). If antigen testing is used, assure that sample collection and testing is performed according to the instructions for use of the antigen tests, staff are appropriately trained and testing quality is embedded in a diagnostic quality system and assessed regularly. 5. If repetitive negative NAAT/RT-PCR results are obtained from a patient in whom COVID-19 is strongly suspected, a paired serum specimen could be collected. One specimen taken in the acute phase and one in the convalescent phase 2-4 weeks later. This is only useful if validated (semi) quantitative serology assays and trained staff for the interpretations are available in the receiving laboratory. With these paired samples it can be retrospectively evaluated whether there is seroconversion or a rise in antibody titres, further supporting the suspicion that this individual indeed had recent COVID-19 despite negative NAATs.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Laboratory diagnosis
For more details, we refer to published WHO guidance Diagnostic testing for SARS-CoV-2 regarding specimen collection, processing and laboratory testing and the diagnostic algorithm (112).
Depending on the local epidemiology and clinical symptoms, test for other potential etiologies (e.g. influenza, malaria, dengue fever, typhoid fever) as appropriate.
- Patients should also be tested for other respiratory pathogens, as recommended in local clinical management guidelines (Examples, but not excluding others as this depends on epidemiological or clinical parameters, are the viral respiratory pathogens influenza A and B (including zoonotic influenza A), respiratory syncytial virus, parainfluenza viruses, rhinoviruses, adenoviruses, enteroviruses (e.g. EVD68), human metapneumovirus and endemic human coronaviruses (i.e. HKU1, OC43, NL63, and 229E). Examples of bacterial pathogens include Streptococcus pneumoniae, Haemophilus influenzae, atypical respiratory pathogens (e.g. Legionella pneumophila, Coxiella burnetii, Chlamydia psittaci or pneumoniae, Mycoplasma pneumoniae). URT and LRT specimens are generally suitable for viral respiratory pathogens. For bacterial culture sputum or other LRT specimens are required.

# Dual infections with other respiratory infections (viral, bacterial and fungal) have been found in COVID-19 patients (115). As a result, a positive test for a non-COVID-19 pathogen does not rule out COVID-19, or vice versa. Some microbes found in respiratory culture can be either be a pathogen or be part of normal mouth/respiratory flora, thus evaluation on whether a found micro-organism is a coinfection or part of the normal flora needs to be weighted for each individual patient. 3. In malaria-endemic areas, patients with fever should be tested for the presence of malaria or other co-infections with validated rapid diagnostic tests (RDTs) or thick and thin blood films and treated as appropriate (116). In endemic settings, arbovirus infection (dengue/ chikungunya) should also be considered in the differential diagnosis of undifferentiated febrile illness, particularly when thrombocytopenia is present (79). Coinfection with COVID-19 virus may also occur and a positive diagnostic test for dengue (e.g. dengue RDTs) does not exclude the testing for COVID-19 (117). If TB is also suspected, collect sputum with specific instructions (e.g. to be done in open area outside the home and away from others) or in an open, well-ventilated space -preferably outside of the health facility (74). Staff should not stand near the patient during sample collection. 4. When influenza virus is known or suspected to be circulating, test patients with severe or complicated disease and those with risk factors for severe influenza (note, this includes younger children and pregnant women up to two weeks postpartum) for influenza virus with a rapid molecular testing when results can be made available within 24 hours preferably. The longer the time lag between sampling and test results, the less the test will benefit clinical management (see policy brief) (118). Empiric treatment, when indicated, should not be delayed while waiting for results (see Chapter 16. Treatment of other acute and chronic infections in patients with COVID-19).
For COVID-19 patients with severe or critical disease, also collect blood cultures, ideally prior to initiation of antimicrobial therapy (109).
If blood cultures cannot be taken timely before the administration of antimicrobial therapies, indicate the details of administered antibiotics on the laboratory request.

# Info Box
Please find new recommendation on the use of pulse oximetry at home in Chapter 10 (Management of moderate COVID-19: pneumonia treatment).

# We recommend that patients with suspected or confirmed mild COVID-19 be isolated to contain virus transmission according to the established COVID-19 care pathway. This can be done at a designated COVID-19 health facility, community facility or at home (self-isolation).
- In areas with other endemic infections that cause fever (such as malaria, dengue, etc.), febrile patients should be tested and treated for those endemic infections per routine protocols (79)(78)(81) irrespective of the presence of respiratory signs and symptoms. Coinfection with COVID-19 may occur.

# The decision to monitor a suspect case with mild COVID-19 in a health facility, community facility or home should be made on a caseby-case basis based on the local COVID-19 care pathway. Additionally, this decision may depend on the clinical presentation, requirement
for supportive care, potential risk factors for severe disease, and conditions at home, including the presence of vulnerable persons in the household.

# If managed at home in self-isolation, refer to WHO guidance on home care for patients with COVID-19 presenting with mild symptoms and management of their contacts (119).
We recommend patients with mild COVID-19 be given symptomatic treatment such as antipyretics for fever and pain, adequate nutrition and appropriate rehydration.
At present, there is no evidence to indicate that there are severe adverse events in patients with COVID-19 as a result of the use of nonsteroidal anti-inflammatory drugs (120).

# Counsel patients with mild COVID-19 about signs and symptoms of complications that should prompt urgent care.
Patients with risk factors for severe illness should be monitored closely, given the possible risk of deterioration. If they develop any worsening symptoms (such as light headedness, difficulty breathing, chest pain, dehydration, etc.), they should seek urgent care through the established COVID-19 care pathway. Caregivers of children with mild COVID-19 should monitor for signs and symptoms of clinical deterioration requiring urgent re-evaluation. These include difficulty breathing/fast or shallow breathing (for infants: grunting, inability to breastfeed), blue lips or face, chest pain or pressure, new confusion, inability to awaken/not interacting when awake, inability to drink or keep down any liquids. Consider alternative delivery platforms such as home-based, phone, telemedicine or community outreach teams to assist with monitoring (121). See new recommendation in Chapter 10 on use of home pulse oximetry.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Management of mild COVID-19: symptomatic treatment
Patients with mild disease may present to an emergency unit, primary care/outpatient department, or be encountered during community outreach activities, such as home visits or by telemedicine.
We recommend that antibiotic therapy or prophylaxis should not be used in patients with mild COVID-19.
Widespread use of antibiotics should be discouraged, as their use may lead to higher bacterial resistance rates, which will impact the burden of disease and deaths in a population during the COVID-19 pandemic and beyond (122)
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Practical Info
The GDG made a conditional recommendation for the use of home pulse oximetry monitoring. This recommendation is predicated on the availability and accessibility of high-quality and reliable pulse oximeters for home use; the integration of home pulse oximetry into a health system, from a training and human resources perspective; and targeting the intervention to patients who would likely get the most benefit, namely those at high-risk and those who are symptomatic. Also, no recommendation was made on the frequency or duration of pulse oximetry monitoring. Note: training on appropriate IPC (cleaning and disinfection) should be included.
The panel encourage further research to clarify uncertainties, especially in low-resource settings. Research gaps remain as to ensuring standards of quality across pulse oximeter devices.

# Evidence To Decision

# Info Box
Please find new recommendation on the use of pulse oximetry at home in this chapter as the second recommendation.
We recommend that patients with suspected or confirmed moderate COVID-19 (pneumonia) be isolated to contain virus transmission. Patients with moderate illness may not require emergency interventions or hospitalization; however, isolation is necessary for all suspect or confirmed cases.
- The location of isolation will depend on the established COVID-19 care pathway and can be done at a health facility, community facility or at home.

# - The decision on location should be made on a case-by-case basis and will depend on the clinical presentation, requirement
for supportive care, potential risk factors for severe disease, and conditions at home, including the presence of vulnerable persons in the household.
- For patients at high risk for deterioration (see Table 6.2), isolation in hospital is preferred.
In areas with other endemic infections that cause fever (such as malaria, dengue, etc.), febrile patients should be tested and treated for those endemic infections per routine protocols (79)(78)(116), irrespective of the presence of respiratory signs and symptoms. Coinfection with COVID-19 may occur.

# Conditional recommendation
For symptomatic patients with COVID-19 and risk factors for progression to severe disease who are not hospitalized, we suggest the use of pulse oximetry monitoring at home as part of a package of care, including patient and provider education and appropriate follow-up (conditional recommendation, very low certainty evidence).

# Uncertain benefits or harms
Possible theoretical benefits of home oximetry monitoring include earlier detection of and intervention for severe disease (such as more intense monitoring for deterioration or starting corticosteroid therapy), patient reassurance in case of normal values, limiting hospital strain due to prevented admission of patients who may not need acute care, and increased opportunities for patient-provider educational conversations (very low certainty).
Possible harms of home oximetry monitoring include the possibility of increased patient anxiety and stress, the possibility of increased hospital visits for patients who would otherwise not seek out hospital care, and the possibility of false reassurance

# Benefits and harms
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Management of moderate COVID-19: pneumonia treatment
Patients with moderate disease may present to an emergency unit or primary care/outpatient department, or be encountered during community outreach activities, such as home visits or by telemedicine. See Table 6.3 for definition of non-severe pneumonia.
When moving from evidence to the conditional recommendation for the use of home pulse oximetry monitoring for patients with COVID-19, the panel emphasized the lack of evidence in either direction and the need for high-quality clinical trials examining both patient symptoms of stress, as well as other clinical outcomes listed above. The panel also emphasized contextual factors, such as resource-considerations, accessibility, feasibility, and impact on health equity as important considerations. Ultimately, the panel thought that the theoretical benefit targeted to symptomatic and high-risk populations was notable only as part of a larger package of care including education and follow-up. Important caveats raised by the panel included the importance of integrating any intervention with education between providers and patients about the meaning of relevant output from the pulse oximeter and ability to act on results.

# Subgroup analyses
There were insufficient data based on the presented data to perform any subgroup analyses.

# Special populations
There is no evidence for home pulse oximetry monitoring for patients with COVID-19 in special populations. Considerations for implementation and applicability centred around focusing on higher-risk populations, where benefits would be most notable. Please see Table 7.2 for information on definitions of who would be considered high-risk for this implementation.
with misinterpretation of the data. Low quality or inaccurate pulse oximeters, particularly with pulse oximeters not validated in different skin colours, may provide false reassurance or false alarms (very low certainty). The GDG suggested that the possible benefits would outweigh the possible harms, and this may be most likely in specific subgroups of patients, i.e. those with symptoms and those with risk factors for severe disease. The GDG also suggested that the intervention would only have benefit in symptomatic patients with COVID-19, and that asymptomatic patients would have no benefit.
For key outcomes of hospitalization, mortality, mechanical ventilation, and ICU admission the panel considered the evidence to be of very low certainty.

# Very low

# Certainty of the Evidence
Applying the agreed values and preferences, the GDG inferred that well-informed patients would consider the minimal possible harms associated with home oximetry monitoring to not outweigh the possible, theoretical benefits on the outcomes of hospitalization and patient satisfaction. Patient members of the panel agreed with this standard.

# No substantial variability expected

# Preference and values

# Important considerations
Home oximetry monitoring is not accessible to many patients, due to lack of available equipment, lack of relevant personnel to monitor it, lack of ability to interpret the results at home, or lack of knowledge about implementation. Home pulse oximetry may be useful in certain settings, including low resource settings, particularly when hospitals are strained and where it may be necessary to effectively monitor patients in a home-based setting. However home oximetry monitoring will only be of value if the users are adequately informed on how to interpret the readings and have ready access to providers who can advise on the response to readings. Considerations for education and training of patients and providers, as well as adequate staffing, to implement care pathways with available access to acute care will need to be integrated.

# Resources and other considerations
Clinical Question/ PICO Population:
Patients treated at home with confirmed or suspected COVID-19 disease

# Very low
Due to serious risk of bias, Due to serious imprecision 5 No data re whether home SpO2 monitoring vs no monitoring affects hospitalization rates
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
We recommend for patients with suspected or confirmed moderate COVID-19, that antibiotics should not be prescribed unless there is clinical suspicion of a bacterial infection.
- Few patients with COVID-19 experience a secondary bacterial infection. A recent systematic review of patients hospitalized with COVID-19 reported only 8% were reported as experiencing bacterial/fungal co-infection during hospital admission (115). 2. Consider in older people, particularly those in LTCFs, and children < 5 years of age, to provide empiric antibiotic treatment for possible pneumonia (122) (123). As these patients are not hospitalized, treatment with Access antibiotics (such as co-amoxicillin) is adequate, instead of broad-spectrum antibiotics (Watch and Reserve antibiotics) (124).

# We recommend close monitoring of patients with moderate COVID-19 for signs or symptoms of disease progression. Provision of mechanisms for close follow up in case of need of escalation of medical care should be available.
- For patients being treated at home, counselling regarding signs and symptoms of complications (such as difficulty breathing, chest pain, etc.) should be provided to patients and their caregivers. If they develop any of these symptoms, they should seek urgent care through the established COVID-19 care pathway. Consider alternative delivery platforms such as home-based, phone, telemedicine or community outreach teams to assist with monitoring. 2. For hospitalized patients, regularly monitor vital signs (including pulse oximetry) and, where possible, utilize medical early warning scores (e.g. NEWS2, PEWS) that facilitate early recognition and escalation of treatment of the deteriorating patient (125).

# Management of severe COVID-19: severe pneumonia treatment

# Info Box

# Please find new recommendation on awake prone positioning in this chapter as the fourth recommendation.
All areas where severe patients may be cared for should be equipped with pulse oximeters, functioning oxygen systems and disposable, single-use, oxygen-delivering interfaces (nasal cannula, Venturi mask and mask with reservoir bag).
This includes areas in any part of health facilities, including emergency units, critical care units, primary care/outpatient clinics, as well as pre-hospital settings and ad hoc community facilities that may receive patients with severe COVID-19. See WHO Oxygen sources and distribution for COVID-19 treatment centres (126).
We recommend immediate administration of supplemental oxygen therapy to any patient with emergency signs during resuscitation to target SpO2  94% and to any patient without emergency signs and hypoxaemia (i.e. stable hypoxaemic patient) to target SpO2 > 90% or  92-95% in pregnant women.

# Remarks for adults:
- Adults with emergency signs (obstructed or absent breathing, severe respiratory distress, central cyanosis, shock, coma and/or convulsions) should receive emergency airway management and oxygen therapy during resuscitation to target SpO2  94% (84)(127). 2. Once the patient is stable, target > 90% SpO2 in non-pregnant adults and  92-95% in pregnant women. 3. Deliver oxygen flow rates using appropriate delivery devices (e.g. use nasal cannula for rates up to 5 L/min; Venturi mask for flow rates 6-10 L/min; and face mask with reservoir bag for flow rates 10-15 L/min). For more details about oxygen titration, refer to the WHO Clinical care for severe acute respiratory infection toolkit: COVID-19 adaptation (85). 4. In adults, techniques such as positioning, e.g. high supported sitting, may help to optimize oxygenation, ease breathlessness and reduce energy expenditure (279). 5. In adult patients with evidence of increased secretion production, secretion retention, and/or weak cough, airway clearance management may assist with secretion clearance. Techniques include gravity-assisted drainage and active cycle of breathing technique. Devices including mechanical insufflation-exsufflation and inspiratory positive pressure breathing should be avoided where possible. Implementation of techniques should be tailored to the individual patient and follow available guidelines (279).

# Remarks for children

# Practical Info
The GDG made a conditional recommendation for awake prone positioning in severely ill patients with COVID-19 requiring supplemental oxygen (including HFNO) or non-invasive ventilation.
In light of the uncertain benefits of awake prone positioning, a high level of vigilance should be maintained, and patients should be monitored closely for signs of clinical deterioration.
Monitoring of patients and training of providers in caring for patients who are awake and prone is an important part of implementation, as part of multi-faceted training for acute care management, which includes medical device training.
As for duration, some suggest regimens that target being in awake prone position for 8-12 hours/day, broken into shorter periods over the day.
Further RCTs are recommended to better define benefits and harms, as well as specific populations of interest.

# Evidence To Decision

# Conditional recommendation

# We suggest awake prone positioning of severely ill patients hospitalized with COVID-19 requiring supplemental oxygen (includes high flow nasal oxygen) or non-invasive ventilation (conditional, low certainty evidence).

# Uncertain benefits or harms
There have been no randomized controlled trials (RCTs) completed for awake prone positioning for patients with COVID-19 requiring supplemental oxygen or non-invasive ventilation. Observational studies of awake prone position in patients with COVID-19 suggest benefits on patient-important outcomes of mortality and the need for intubation COVID-19 (very low certainty). Evidence from RCTs of prone positioning for intubated, critically ill patients with ARDS (non-COVID-19) have demonstrated benefits in mortality. The effect on less important outcomes is uncertain. The harms of awake prone positioning are possibly patient discomfort and pain (very low certainty). The indirect evidence on harms of prone positioning from the randomized evidence on sedated, intubated patients are pressure sores, nerve injury, and haemodynamic instability, which were not considered relevant for this less severely ill population.

# Benefits and harms
For patient-important outcomes of mortality and the need for mechanical ventilation, the panel considered the direct evidence to be of very low certainty. For the patient-important outcomes of mortality, indirect evidence from intubated, sedated patients with ARDS was downgraded for indirectness, from high to low, with key considerations including the different physiology of critical disease, data from a non-COVID-19 period, and the different sedation strategies employed.

# Certainty of the Evidence
Applying the agreed values and preferences, the GDG inferred that almost all well-informed patients would want to undergo prone positioning if awake, requiring oxygen or non-invasive respiratory support, given the lack of harm from the observational studies and panel experience. The panel did not expect there would be much variation in values and preferences between patients when it came to this intervention. Patient discomfort for prone position could limit time spent in individual circumstances.

# No substantial variability expected

# Preference and values

# Important considerations

# Resources and other considerations
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
When moving from evidence to the conditional recommendation for the use of awake prone positioning in severely ill hospitalized patients with COVID-19, the panel emphasized the low certainty evidence of reduction in mortality, downgraded from higher certainty evidence in critically ill patients with ARDS. It also noted the limited harm with the experience thus far with awake prone positioning across different resource settings.

# Subgroup analyses
The panel commented on the need for data in specific populations, namely paediatrics, older people, and pregnant women in the first two trimesters.
Patients who are able to follow instructions can self-prone, without assistance from health care workers. Proning patients who require assistance is associated with human resource requirements regarding training, particularly with monitoring of respiratory status. The panel felt that that this intervention should be feasible in all settings, but implementation requires dedicated training and monitoring.

# Very low
Due to serious risk of bias, Due to very serious imprecision 2 There are no comparative data assessing the effect of awake proning in COVID-19 patients with regards to intubation rates.

# Adverse effect (pain or discomfort)

# Very low
Due to serious risk of bias, Due to very serious imprecision 3 There are no comparative data assessing the effect of awake proning in COVID-19 patients with regards to adverse events.  (134).
We recommend prompt recognition of progressive acute hypoxaemic respiratory failure when a patient with respiratory distress is failing to respond to standard oxygen therapy and adequate preparation to provide advanced oxygen/ventilatory support.

# Remark: Patients may continue to have increased work of breathing or hypoxaemia even when oxygen is delivered via a face mask with reservoir bag (flow rates of 10-15 L/min, which is typically the minimum flow required to maintain bag inflation; FiO2 0.60-0.95). Hypoxaemic respiratory failure in ARDS commonly results from intrapulmonary ventilation-perfusion mismatch or shunt and usually requires mechanical ventilation (109).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Management of critical COVID-19: acute respiratory distress syndrome (ARDS)
The mortality in hospitalized and critically ill patients has varied substantially in different case series throughout the pandemic. The following recommendations are aligned with current international standards for management of all cause ARDS (109).
We recommend that endotracheal intubation be performed by a trained and experienced provider using airborne precautions.
Remark: Patients with ARDS, especially young children or those who are obese or pregnant, may desaturate quickly during intubation. Preoxygenation with 100% FiO2 for 5 minutes, and use of a face mask with reservoir bag is preferred. When possible, avoid bag-valve mask ventilation to reduce exposure to aerosols. Rapid-sequence intubation is appropriate after an airway assessment that identifies no signs of difficult intubation (135) (136) (137).

# We recommend implementation of mechanical ventilation using lower tidal volumes (4-8 mL/kg predicted body weight and lower inspiratory pressures (plateau pressure < 30 cmH2O).

# Remark for adults:
The implementation of mechanical ventilation using lower tidal volumes and lower inspiratory pressures is a strong recommendation from a clinical guideline for patients with ARDS (109), and is also suggested for patients with sepsis-induced respiratory failure who do not meet ARDS criteria (109). The initial target tidal volume is 6 mL/kg PBW; tidal volume up to 8 mL/kg PBW is allowed if undesirable side-effects occur (e.g. dyssynchrony, pH < 7.15). Permissive hypercapnia is permitted. Ventilator protocols are available (138). The use of deep sedation may be required to control respiratory drive and achieve tidal volume targets.

# Remarks for children:
In children, a lower level of plateau pressure (< 28 cmH2O) is targeted, and a lower target of pH is permitted (7.15-7.30). Tidal volumes should be adapted to disease severity: 3-6 mL/kg PBW in the case of poor respiratory system compliance, and 5-8 mL/kg PBW with better preserved compliance (139).
In adult patients with severe ARDS (PaO2/FiO2 < 150) prone ventilation for 12-16 hours per day is recommended.
- Application of prone ventilation is recommended for adult patients, preferably for 16 hours per day, and may be considered for paediatric patients with severe ARDS but requires sufficient human resources and expertise to be performed safely; protocols (including videos) are available (140)(141). 2. There is little evidence on prone positioning in pregnant women with ARDS; this could be considered in early pregnancy. Pregnant women in the third trimester may benefit from being placed in the lateral decubitus position.

# Use a conservative fluid management strategy for ARDS patients without tissue hypoperfusion and fluid responsiveness.

# Remarks for adults and children: This has also been recommended in another international guideline (109). The main effect is to shorten the duration of ventilation. A sample protocol for implementation of this recommendation is available (142).
In patients with moderate or severe ARDS, a trial of higher positive end-expiratory pressure (PEEP) instead of lower PEEP is suggested and requires consideration of benefits versus risks. In COVID-19, we suggest the individualization of PEEP where during titration the patient is monitored for effects (beneficial or harmful) and driving pressure.
- PEEP titration requires consideration of benefits (reducing atelectrauma and improving alveolar recruitment) vs risks (end-inspiratory overdistension leading to lung injury and higher pulmonary vascular resistance). Tables are available to guide PEEP titration based on the FiO2 required to maintain SpO2 (143). In younger children, maximal PEEP pressures are 15 cmH2O. Although high driving pressure (plateau pressure  PEEP) may more accurately predict increased mortality in ARDS compared with high tidal volume or plateau pressure (144); data from RCTs of ventilation strategies that target driving pressure are not currently available. 2. A related intervention of recruitment manoeuvres (RMs) is delivered as episodic periods of high CPAP (30-40 cmH2O), progressive incremental increases in PEEP with constant driving pressure, or high driving pressure; considerations of benefits vs risks are similar. Higher PEEP and RMs were both conditionally recommended in a clinical practice guideline. For PEEP, the guideline considered an individual patient data meta-analysis ( 145) of three RCTs. However, a subsequent RCT of high PEEP and prolonged high-pressure RMs showed harm, suggesting that the protocol in this RCT should be avoided (146). Monitoring of patients to identify those who respond to the initial application of higher PEEP or a different RM protocol and stopping these interventions in non-responders are suggested (147).
In patients with moderate-severe ARDS (PaO2/FiO2 < 150), neuromuscular blockade by continuous infusion should not be routinely used.
A trial found that this strategy improved survival in adult patients with moderate-severe ARDS (PaO2/FiO2 < 150) without causing significant weakness (148), but results of a recent larger trial found that use of neuromuscular blockade with high PEEP strategy was not associated with a survival benefit when compared with a light sedation strategy without neuromuscular blockade (149). Intermittent or continuous neuromuscular blockade may still be considered in patients with ARDS, both adults and children, in certain situations: ventilator dyssynchrony despite sedation, such that tidal volume limitation cannot be reliably achieved; or refractory hypoxaemia or hypercapnia.
Avoid disconnecting the patient from the ventilator, which results in loss of PEEP, atelectasis and increased risk of infection of health care workers.
- Use in-line catheters for airway suctioning and clamp endotracheal tube when disconnection is required (for example, transfer to a transport ventilator).

# Manual hyperinflation should be avoided and ventilator hyperinflation used instead, if indicated (279).
In patients with excessive secretions, or difficulty clearing secretions, consider application of airway clearance techniques. These should be performed only if deemed medically appropriate (279) and appropriate IPC measures are in place.
- Active cycle of breathing techniques and positioning techniques can be used to optimize oxygenation (150) (151). Techniques for airway clearance and secretion management include positioning with gravity-assisted drainage, active cycle of breathing techniques, positive expiratory pressure therapy, and assisted or stimulated cough manoeuvres (151). These techniques are only indicated for patients with mucous hypersecretion and difficulties clearing secretions, and for patients with co-existing respiratory or neuromuscular comorbidities (151) (151). 4. Especially for critically ill patients, the early involvement of the multidisciplinary rehabilitation team is paramount to improve short-and long-term outcomes. This may include physiotherapists, occupational therapists, speech and language therapists, mental health and psychosocial providers, dieticians and in complex cases, physical and rehabilitation medicine doctors. However, rehabilitation workforce composition may vary by context and availability in different parts of the world.

# Remarks for adults:
An RCT of ECMO for adult patients with ARDS was stopped early and found no statistically significant difference in the primary outcome of 60-day mortality between ECMO and standard medical management (including prone positioning and neuromuscular blockade) (152). However, ECMO was associated with a reduced risk of the composite outcome that consisted of mortality and crossover to ECMO treatment (152), and a post-hoc Bayesian analysis of this RCT showed that ECMO is very likely to reduce mortality across a range of prior assumptions (153). In patients with MERS, ECMO vs conventional treatment was associated with reduced mortality in a cohort study (133). ECMO is a resource-intensive therapy and should be offered only in expert centres with a sufficient case volume to maintain expertise and staff volume and capacity to apply the IPC measures required (154) (155). In children, ECMO can also be considered in those with severe ARDS, although high-quality evidence for benefit is lacking (139). Recognize septic shock in adults when infection is suspected or confirmed AND vasopressors are needed to maintain mean arterial pressure (MAP)  65 mmHg AND lactate is  2 mmol/L, in the absence of hypovolaemia (see Table 6.
Recognize septic shock in children with any hypotension (SBP  2 SD below normal for age) or two or more of the following: altered mental status; bradycardia or tachycardia (HR  160 bpm in infants and HR  150 bpm in children); prolonged capillary refill (> 2 sec) or feeble pulses; tachypnoea; mottled or cold skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia (see Table 6.3).
- In the absence of a lactate measurement, use blood pressure (i.e. MAP) and clinical signs of perfusion to define shock. (109). The use of central venous and arterial catheters should be based on resource availability and individual patient needs. Detailed guidelines from the Surviving Sepsis Campaign and WHO are available for the management of septic shock in adults (109) and children (104) (110). Alternate fluid regimens are suggested when caring for adults and children in resource-limited settings (156) (157).

# Standard care includes early recognition and the following treatments to be done immediately, within 1 hour of recognition: antimicrobial therapy, and initiation of fluid bolus and vasopressors for hypotension
In resuscitation for septic shock in adults, give 250-500 mL crystalloid fluid as rapid bolus in first 15-30 minutes.
In resuscitation for septic shock in children, give 10-20 mL/kg crystalloid fluid as a bolus in the first 30-60 minutes.
Fluid resuscitation may lead to volume overload, including respiratory failure, particularly with ARDS. If there is no response to fluid loading or signs of volume overload appear (e.g. jugular venous distension, crackles on lung auscultation, pulmonary oedema on imaging, or hepatomegaly), then reduce or discontinue fluid administration. This step is particularly important in patients with hypoxaemic respiratory failure.
- Crystalloids include normal saline and Ringer's lactate. 2. Determine the need for additional fluid boluses (250-500 mL in adults; 10-20 mL/kg in children) based on clinical response and improvement of perfusion targets and reassess for signs of fluid overload after each bolus. Perfusion targets include MAP (> 65 mmHg or age-appropriate targets in children), urine output (> 0.5 mL/kg/hr in adults; 1 mL/kg/hr in children), and improvement of skin mottling and extremity perfusion, capillary refill, heart rate, level of consciousness, and lactate. (109). These indices include passive leg raises, fluid challenges with serial stroke volume measurements, or variations in systolic pressure, pulse pressure, inferior vena cava size, or stroke volume in response to changes in intrathoracic pressure during mechanical ventilation. 4. In pregnant women, compression of the inferior vena cava can cause a decrease in venous return and cardiac preload and may result in hypotension. For this reason, pregnant women with sepsis and or septic shock may need to be placed in the lateral decubitus position to offload the inferior vena cava (158). 5. Clinical trials conducted in resource-limited settings comparing aggressive versus conservative fluid regimens suggest higher mortality in patients treated with aggressive fluid regimens (156) (157). Refer to the WHO-ICRC Basic emergency care (Shock module) for an initial approach and management of shock in resource-limited settings (84).

# Consider dynamic indices of volume responsiveness to guide volume administration beyond initial resuscitation based on local resources and experience
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Management of critical COVID-19: septic shock
The mortality in hospitalized and critically ill patients has varied substantially in different case series throughout the pandemic. The following recommendations are aligned with current international standards for management of all-cause sepsis (109).

# Do not use hypotonic crystalloids, starches or gelatins for resuscitation.
Remark: Starches are associated with an increased risk of death and acute kidney injury compared with crystalloids. The effects of gelatins are less clear, but they are more expensive than crystalloids (109) (159). Hypotonic (vs isotonic) solutions are less effective at increasing intravascular volume. Surviving Sepsis guidelines also suggest albumin for resuscitation when patients require substantial amounts of crystalloids, but this conditional recommendation is based on low-quality evidence (109).
In adults, administer vasopressors when shock persists during or after fluid resuscitation. The initial blood pressure target is MAP  65 mmHg in adults and improvement of markers of perfusion.
In children, administer vasopressors if signs of fluid overload are apparent or the following persist after two fluid bolus:
- signs of shock such as altered mental state;
- bradycardia or tachycardia (HR  160 bpm in infants and HR  150 bpm in children); - prolonged capillary refill (> 2 seconds) or feeble pulses;
- tachypnoea; mottled or cool skin or petechial or purpuric rash; increased lactate; oliguria persists after two repeat boluses;
- or age-appropriate blood pressure targets are not achieved (110).
- Vasopressors (i.e. norepinephrine, epinephrine, vasopressin and dopamine) are most safely given through a central venous catheter at a strictly controlled rate, but it is also possible to safely administer them via peripheral vein (160) and intraosseous needle. Monitor blood pressure frequently and titrate the vasopressor to the minimum dose necessary to maintain perfusion and prevent side-effects. A recent study suggests that in adults 65 years or older a MAP 60-65 mmHg target is equivalent to  65 mmHg (161). 2. Norepinephrine is considered the first-line treatment in adult patients; epinephrine or vasopressin can be added to achieve the MAP target. Because of the risk of tachyarrhythmia, reserve dopamine for selected patients with low risk of tachyarrhythmia or those with bradycardia. 3. In children, epinephrine is considered the first-line treatment, while norepinephrine can be added if shock persists despite optimal dose of epinephrine (110).

# If central venous catheters are not available, vasopressors can be given through a peripheral IV, but use a large vein and closely monitor for signs of extravasation and local tissue necrosis. If extravasation occurs, stop infusion. Vasopressors can also be administered through intraosseous needles.
If signs of poor perfusion and cardiac dysfunction persist despite achieving MAP target with fluids and vasopressors, consider an inotrope such as dobutamine.
No RCTs have compared dobutamine with placebo for clinical outcomes.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Prevention of complications in hospitalized and critically ill patients with COVID-19 Practical Info
The GDG made a conditional recommendation in favour of care bundles for critically ill patients with COVID-19. Existing care bundles for critically ill patients include those for reducing delirium and improving cognition and sleep (reviewed in (162); other information available at ), preventing VAP (163), treating sepsis (reviewed in ), preventing central venous catheter infection (164), and preventing pressure ulcers (). For some bundles, observational data have shown variable association between the bundle components and patient important outcomes (165). Even in currently accepted care bundles, the components may change as the evidence base evolves. Hospitals and ICUs should choose bundles for which adherence is likely to be high.
Monitor multiple RCTs in process in patients with COVID-19.

# Evidence To Decision

# Info Box
Please find new recommendation on the use of existing care bundles in this chapter as the first recommendation, and new recommendation on anticoagulation for thromboprophylaxis in this chapter as the third recommendation.

# Conditional recommendation
For patients with COVID-19 who are critically ill, with or without invasive mechanical ventilation, we suggest the use of existing care bundles (defined as three or more evidence informed practices delivered together and consistently to improve care; (see Evidence to decision for examples), chosen locally by the hospital or ICU and adapted as necessary for local circumstances (conditional recommendation, very low certainty).

# Some benefits
Indirect evidence in patients without COVID-19 suggest that some care bundles may improve patient-important outcomes, such as mortality, but the effects vary depending on the specific bundle, and the population targeted. The certainty of evidence is generally low to very low. Examples of care bundles in the critically ill can be found in the practical info tab and in the Cochrane Collaboration review of the literature published in the Web Annex. The effect on other outcomes is uncertain.
Potential harms of bundles include the administrative burden of initial implementation, ongoing training, and monitoring of performance (very low certainty).

# Benefits and harms
The evidence review consisted of a rapid review by the Cochrane Collaboration, supplemented by references provided by GDG members. The Cochrane review found very low certainty evidence in support of a mortality reduction with implementation of care bundles in critically ill patients. Supplementary references provided low to very low certainty evidence for important effects on mortality with bundles to reduce delirium (162), prevent VAP (163), treat sepsis (), and prevent central venous catheter infection (164) and pressure ulcers (). All evidence reviewed was indirect, from non-COVID-19 populations.

# Very low

# Certainty of the Evidence
Applying the agreed values and preferences, the GDG inferred that the majority of well-informed patients would want to receive care bundles, locally adapted as necessary and applicable to their situation, given the low to very low certainty evidence

# No substantial variability expected

# Preference and values
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
When moving from evidence to the conditional recommendation in favour of care bundles for critically ill patients with COVID-19, the panel emphasized the low to very low certainty evidence of reduction in mortality and possible administrative burdens for implementation. The GDG recognized that hospital or ICUs may select among existing care bundles and adapt them to local circumstances as required, based on contextual factors of resource considerations and feasibility. The GDG judged that considerations of accessibility and impact on health equity would not alter the recommendation. The GDG was not aware of ongoing studies of care bundles in the critically ill COVID-19 population.

# Subgroup analyses
The panel did not find any evidence bearing on the question of subgroup effects across patients with different levels of disease severity or between children and adults. In other words, the conditional recommendation is applicable across all these subgroups.

# Special populations
None of the reviewed studies of care bundles enrolled children, and therefore the applicability of this recommendation to children is uncertain. However, the panel thought that the implementation of relevant care bundles for children with COVID-19 would have similar effects to care bundles in adults. Similarly, the panel concluded that the recommendation applies to pregnant women. suggesting a reduction in mortality and very low certainty of harm.

# Important considerations
Care bundles may contain practices that require adaptation to implement in all settings, depending on their contents. For example, early mobilization and rehabilitation as part of a care bundle to reduce delirium may require additional training, and central line insertion may require multiple sterile towels or a sterile gown placed on the patient, if large sterile drapes are not available.

# Resources and other considerations

# Clinical Question/ PICO Population:
Patients with COVID-19 and ARDS or viral pneumonia who are critically ill in ICU, with or without invasive ventilation. Populations of children (defined <18 years) and adult patients (18 years)
Existing validated care bundles, chosen locally by the hospital or ICU, adapted to local circumstances, and felt to be appropriate for patients with COVID-19 as specified above. A care bundle is defined as three or more evidence informed practices delivered together and consistently to improve care.
Not using existing care bundles

# Administrative burden
Based on data from: 0 patients in 0 studies.

# Very low
Care bundles may be associated with an appreciable administrative burden.

# Impingement on physician autonomy
Based on data from: 0 patients in 0 studies.

# Very low
Care bundles may be associated with an impingement of physician autonomy.
Coagulopathy is common in patients with severe COVID-19, and both venous and arterial thromboembolism have been reported (27)(28)(166)(167) (168).
Monitor patients with COVID-19, for signs or symptoms suggestive of thromboembolism, such as stroke, deep venous thrombosis, pulmonary embolism or acute coronary syndrome. If these are clinically suspected, proceed immediately with appropriate diagnostic and management pathways.

# Conditional recommendation
In hospitalized patients with COVID-19, without an established indication for higher dose anticoagulation, we suggest administering standard thromboprophylaxis dosing of anticoagulation rather than therapeutic or intermediate dosing (conditional recommendation, very low certainty).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO) Suggested dosing of standard thromboprophylaxis is as follows:
Enoxaparin 40 mg by subcutaneous injection every 24h: -Prophylactic dosages (non-weight adjusted) in low body weight (women < 45 kg, men < 57 kg) may lead to a higher risk of bleeding. Careful clinical observation is advised.
-If BMI > 40 kg/m 2 or weight > 120 kg: enoxaparin 40 mg by subcutaneous injection every 12h. Unfractionated heparin (UFH) 5000 units by subcutaneous injection every 8 or 12h:
-If BMI> 40 kg/m 2 or weight > 120 kg: 7500 units q12h or 5000 units every 8h. Tinzaparin 4500 units/day if BMI  40 kg/m 2 or weight > 120 kg.
Dalteparin 5000 units/day BMI  40 kg/m 2 or weight > 120 kg. Fondaparinux 2.5 mg by subcutaneous injection every 24h.
Exoxaparin and unfractionated heparin are both on the WHO Model List of Essential Medicines; enoxaparin has the advantage of daily dosing. The suggested duration of standard thromboprophylaxis is until hospital discharge.
If therapeutic dosing is prescribed, clinicians should be aware of the increased risk of bleeding, including major bleeding requiring transfusion (e.g., gastrointestinal) or clinically significant bleeding even if transfusion is not required (e.g., intracranial). These increased risks may also occur with intermediate dosing of anticoagulants, especially in the presence of other risk factors for bleeding. Heparin-induced thrombocytopenia associated with thrombosis is also a risk of unfractionated heparin and, less commonly, low molecular weight heparin.
Potential agents for therapeutic and intermediate intensity anticoagulation include low molecular weight heparin, unfractionated heparin, direct oral anticoagulants, or fondaparinux. Factors influencing the choice of agent include availability of laboratory monitoring (needed for unfractionated heparin), requirement for rapid reversibility (favours unfractionated heparin), presence of severe renal dysfunction (favours unfractionated heparin), interaction with other drugs used to treat COVID-19 (especially direct oral anticoagulants), convenience (least with unfractionated heparin, most with direct oral anticoagulants), and suspicion of heparininduced thrombocytopenia (favours fondaparinux or direct oral anticoagulants).

# Evidence To Decision
Therapeutic or intermediate dosing of anticoagulation, compared with prophylactic dosing of anticoagulation, possibly reduces mortality (very low certainty) and pulmonary embolism and probably increases the risk of major bleeding (moderate certainty for therapeutic anticoagulation; low certainty for intermediate dosing of anticoagulation). The effects on other outcomes are uncertain. The absolute reductions in risks of mortality and pulmonary embolism, and the absolute increase in risk of major bleeding, are likely to be higher in patients with severe or critical illness due to COVID-19, who may have a higher baseline risk of these outcomes compared with patients with mild or moderate illness.

# Important harms

# Benefits and harms
For reduction in mortality and pulmonary embolism, the panel considered the evidence in favour of therapeutic or intermediate dosing of anticoagulation to be of very low certainty, due to serious imprecision (confidence intervals included both important benefit and important harm) and risk of bias (confounding in observational studies; no randomized trials). For avoidance of major bleeding, the panel considered the evidence in favour of standard thromboprohylaxis dosing, compared with therapeutic anticoagulation, to be of moderate certainty. This judgment was based on low-certainty evidence in observational studies in COVID-19 that was upgraded to moderate certainty based on a large body of supportive indirect evidence at low risk of bias (randomized trials of therapeutic anticoagulation for other indications). For the comparison of standard thromboprophylaxis dosing compared with intermediate dosing of anticoagulation, the evidence for avoidance of major bleeding was rated as low certainty.

# Very low

# Certainty of the Evidence
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
When moving from evidence to the conditional recommendation in favour of standard thromboprophylaxis anticoagulation for patients with moderate, severe, and critical COVID-19, the panel emphasized the very low certainty evidence of reduction in mortality or pulmonary embolism with higher anticoagulant dosing. The panel recognized that the evidence supporting an increased risk of major bleeding was dominated by studies of therapeutic anticoagulation rather than intermediate dosing. The GDG panellists anticipated variability in patient values and preferences, and judged that other contextual factors, such as resource considerations, accessibility, feasibility and impact on health equity would not alter the recommendation. The panel acknowledged that ongoing randomized trials are expected to add substantially to the evidence base over the next several months.

# Subgroup analyses
The panel did not find any evidence bearing on the question of subgroup effects across patients with different levels of disease severity, between children and adults, by different anticoagulant regimens (including agent, dose and duration), and therefore did not make any subgroup recommendations. In other words, the conditional recommendation is applicable across all these subgroups.

# Special populations
None of the studies enrolled children, and therefore the applicability of this recommendation to children is uncertain. However, the panel did not think that children with COVID-19 would respond any differently to therapeutic or intermediate intensity anticoagulation. One observational study enrolled pregnant women, with very low certainty evidence in this population for a possible reduction in mortality. The panel thought that pregnant women would have a similar risk of increased bleeding as nonpregnant individuals. Therefore, the panel concluded that the recommendation applies to pregnant women. Safe anticoagulants for the fetus in pregnancy include unfractionated heparin and low molecular weight heparin, which do not cross the placental barrier.
The panel acknowledged that reporting of ongoing randomized trials of therapeutic and intermediate dosing of anticoagulation, compared with standard thromboprophylaxis dosing, over the next several months were highly likely to upgrade the certainty of evidence and may lead to changes in recommendations.
The majority of GDG members inferred that most well-informed patients would not want to receive therapeutic or intermediate dosing of anticoagulation given the very low certainty evidence suggesting a possible reduction in mortality and pulmonary embolism and the low certainty (for intermediate dosing of anticoagulation) or moderate certainty (for therapeutic anticoagulation) of increased risk of major bleeding. A minority of GDG members believed that some well-informed patients would choose to receive intermediate dosing of anticoagulation, given the very low certainty evidence suggesting a possible reduction in mortality and pulmonary embolism and the low certainty of increased risk of major bleeding.

# Substantial variability is expected or uncertain

# Preference and values

# Important considerations
Unfractionated heparin sodium and low molecular weight heparins such as enoxaparin are relatively inexpensive and are listed on the WHO Model List of Essential Medicines; but availability is variable. Shortages may reduce the availability of low molecular weight heparins in some settings. In low-resource settings, management of bleeding complications in patients receiving anticoagulant dosing higher than that used for standard thromboprophylaxis may be challenging due to limited coagulation testing and transfusion capacity.

# Resources and other considerations

# Clinical Question/ PICO Population:
Hospitalized patients without an indication for therapeutic anticoagulation
Anticoagulation at therapeutic or intermediate intensity
Anticoagulation at prophylactic intensity   (171), and are generally limited to feasible recommendations based on high-quality evidence. Recent publications have encouraged best practices to continue during the COVID-19 outbreak (172). See the WHO Clinical care for severe acute respiratory infection toolkit: COVID-19 adaptation for practical tools to assist implementation (85). - Do not prescribe antibiotics to suspected or confirmed COVID-19 patients with low suspicion of a bacterial infection, to avoid more short-term side-effects of antibiotics in patients and negative long-term consequences of increased antimicrobial resistance

# Careful consideration should be given to the numerous, clinically significant side-effects of medications that may be used in the context of COVID-19, as well as drug-drug interactions between medications, both of which may affect COVID-19 symptomatology (including effects on respiratory, cardiac, immune and mental and neurological function). Both pharmacokinetic and pharmacodynamic effects should be considered.
- The risk of relevant side-effects and drug-drug interactions relating to COVID-19 symptomatology include sedation, cardiotoxicity via QTc-prolongation and respiratory suppression, and these may be dose-dependent (i.e. increase with escalating doses). For this reason, care should be taken that minimum effective doses of medications with dose-dependent negative effects are used and for the shortest durations possible.

# Use medications that carry the least risk possible for drug-drug interactions with other medications the person may be receiving. Psychotropic medications with sedative proprieties, such as benzodiazepines, can worsen respiratory function. Some, psychotropic medications have QTc-prolonging activity (such as some antipsychotics and some antidepressants). Use medications that carry the least risk possible for side-effects that may worsen COVID-19 symptomatology, including sedation, respiratory or cardiac function, risk of fever or other immunological abnormalities, or coagulation abnormalities.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO) Adverse effects of medications and critical COVID-19, taking a patient perspective (Table 2.1). For these new recommendations on MIS-C, the GDG concluded that the values and preferences of children and adolescents with MIS-C may differ from those used in previous recommendations. A new targeted outcomes prioritization exercise was conducted (Table 14.1). These new prioritized outcomes were used to update the metaanalysis.

# Values and preferences
For these new recommendations for MIS-C, the majority of GDG members inferred that most well-informed patients, and their families, would, despite the high uncertainty of important benefit, want to receive some therapeutic agent in addition to supportive care for MIS-C, compared with no specific therapeutic agent. In doing so, patients would be placing a high value on uncertain benefit and a low value on avoiding any mild adverse effects associated with treatment.

# Evidence summary
The GDG's recommendations for corticosteroid use in hospitalized children who meet the standard clinical definition for MIS-C were informed by the results of systematic review and meta-analysis of the literature that pooled data from 3 studies, n = 885 (3)(4) (5). In Annexes 3 and 4, the systematic search criteria and table of trial characteristics can be found, respectively. From these studies, for the three comparisons: a) adding corticosteroids to IVIG compared to IVIG alone; b) corticosteroids compared to IVIG; and c) adding corticosteroids to IVIG compared to corticosteroids alone and for all prioritized outcomes including death, need for invasive mechanical ventilation two days after initiation of treatment, need for hemodynamic support two days after initiation of treatment, coronary artery dilation, acute left ventricular dysfunction 2 days after initiation of treatment, and reduction in fever 2 days after initiation of treatment, the evidence was of very low certainty.
The evidence was summarized in the summary of findings tables and presented to the GDG addressing the pre-specified PICOs and prioritized outcomes: corticosteroids + IVIG vs IVIG alone; corticosteroids alone vs IVIG alone; and corticosteroids + IVIG vs corticosteroids alone (see Research Evidence tab) below). For all three PICOs, very low certainty evidence was ascertained for all outcomes.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Multisystem inflammatory syndrome in children (MIS-C) with C OVID-19
This section outlines what information the GDG requested and used in making their recommendations for corticosteroids in hospitalized children with COVID-19 aged 0 to 18 years, who meet standardized clinical definition for MIS-C (see Annex 5 for standardized definitions).

# Prioritized outcomes
For the previous recommendations, the GDG members prioritized outcomes (rating from 9  to 1  with severe

# Practical Info

# Practical info
There are slightly different case definitions for MIS-C (Annex 5). This guideline is applicable for any standard case definition of MIS-C. Case definitions will continue to be updated as new data emerge. Based on accessibility to corticosteroids being much wider than accessibility to IVIG, the panel suggested that most patients will receive corticosteroids before they receive IVIG, even in patients where both are prescribed.
Route: Systemic corticosteroids can be given orally or intravenously. All studies examined intravenous administration.

# Dose and duration:
In the three studies included in the meta-analysis, intravenous methylprednisilone was used at varying doses; one study did not report a dose. The other two reported ranges between 0.8-2.0 mg/kg/day for 5 days; or higher bolus doses of 10-30 mg/kg/day for 3 days. Both lower and higher dose options can be considered. See Annex 4 for study details.
Monitoring: It would be prudent to monitor for known complications associated with corticosteroid use, such as hyperglycemia and behavioural changes.
Supportive care: Most emphatically, the GDG emphasized the importance of high-quality supportive care to improve the outcomes of these children, apart from specific therapies. Please see the WHO Pocket Book of Hospital Care for Children for syndromic management guidance of severely ill children, including the importance of recognizing other conditions such leading to shock, sepsis and severe infections; as well as guidance from other organizations on supportive management of Kawasaki disease (104).
The GDG emphasized the need for further randomized clinical trials in this population with these agents. The panel acknowledged that results of ongoing randomized trials of therapeutic interventions for MIS-C over the next several months were highly likely to upgrade the certainty of evidence and may lead to changes in recommendations. Enrolment of patients into randomized trials should be prioritized.

# Evidence To Decision

# Conditional recommendation
- In hospitalized children aged 0-18 who meet a standard case definition for MIS-C, we suggest using corticosteroids in addition to supportive care (rather than either IVIG plus supportive care, or supportive care alone) (conditional recommendation, very low certainty). - In hospitalized children aged 0-18 who meet both a standard case definition for MIS-C and diagnostic criteria for Kawasaki disease, we suggest using corticosteroids in addition to standard of care for Kawasaki disease (conditional recommendation, very low certainty).
New Supportive care/standard of care: The GDG emphasized the importance of optimized supportive care for children meeting the standardized case definition of MIS-C. Thus, the interpretation of these results, should consider that supportive care is the current standard of care on which these interventions are additive. See WHO Pocket Book of Hospital Care for Children (104), and the WHO Paediatric emergency triage, assessment and treatment: care of critically ill children (127).
- The effects of corticosteroids in addition to IVIG, compared with IVIG alone plus supportive care, or supportive care alone, all prioritized outcomes, including death during hospitalization, need for mechanical ventilation, coronary artery abnormalities, and cardiac dysfunction are very uncertain (very low certainty, direct evidence). - The effects of corticosteroids alone, compared with IVIG plus supportive care, or supportive care alone on all prioritized outcomes, including death during hospitalization, need for mechanical ventilation, coronary artery abnormalities,

# Benefits and harms
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Subgroup analysis
Subgroup analyses were not conducted.
When moving from evidence to the conditional recommendations for children hospitalized with MIS-C, the panel emphasized the very low certainty evidence of reduction in mortality and the need for haemodynamic support and mechanical ventilation with the use of corticosteroids. The panel also acknowledged that some children will simultaneously meet diagnostic criteria for Kawasaki disease, and the standard of care in many parts of the world is to use IVIG, where available, in that population. The panel emphasized the practical difficulty in differentiating the two populations, leading to the emphasis on IVIG in care pathways, despite the lack of supporting direct evidence. In the absence of randomized evidence showing IVIG to be harmful, the panel expressed concern about not providing IVIG, where available, to children who meet diagnostic criteria of both Kawasaki disease and MIS-C. The panel acknowledged that ongoing randomized trials are expected to add substantially to the evidence base over the next several months.

# Subgroup analyses
Given the available evidence, the panel did not find any evidence bearing on the question of subgroup effects across patients with different levels of disease severity, and therefore did not make any subgroup recommendations. In other words, the conditional recommendations are applicable across all patient subgroups. In particular, there are insufficient data to support different recommendations in the younger age ranges (given the predilection for younger age ranges in Kawasaki disease). Analyses based on dose of corticosteroid or IVIG administered were unable to be performed, given the limitations of the studies.
and cardiac dysfunction are very uncertain (very low certainty, direct evidence). - The effects of corticosteroids in addition to IVIG compared to corticosteroids alone on all prioritized outcomes including death during hospitalization, need for mechanical ventilation, and other prioritized outcomes are very uncertain (very low certainty, direct evidence).
Based on the clinical experience of the GDG of other conditions, the possible harms of steroids were deemed to be of lesser importance than the possible benefits. However, the GDG did emphasize that for appropriate evaluation and management for undifferentiated children presenting with shock, consider other serious infections based on epidemiologic considerations (i.e., malaria, HIV, etc). Possible harms of IVIG, based on the clinical experience of the panel of other conditions, include fluid overload due to the volume of IVIG preparations. The GDG acknowledged the care of Kawasaki disease, a clinically similar condition which can be difficult to distinguish from MIS-C, includes IVIG (104).
For all outcomes in the three pre-specified PICOs, the GDG considered the evidence to be of very low certainty, due to risk of bias from observational designs and due to serious imprecision (confidence intervals included both important benefit and important harm). The evidence for corticosteroids and IVIG is from observational studies that compare the combination of these agents against them individually.

# Very low

# Certainty of the Evidence

# Variability expected
The majority of GDG members inferred that most well-informed patients, and their families, would, despite the high uncertainty of important benefit, want to receive some therapeutic agent in addition to supportive care for MIS-C, compared with no specific therapeutic agent. In doing so, patients would be placing a high value on uncertain benefit and a low value on avoiding any mild adverse effects associated with treatment.

# Preference and values

# Important considerations
Corticosteroids are widely available in all regions of the world and methylprednisolone is on the WHO Model List of Essential Medicines. IVIG has important resource considerations, including higher cost, and is not readily available across all care settings and regions.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Special populations
There was no special population where the panel inferred different applicability of these recommendations.

# Clinical Question/ PICO Population:
Children aged 0-19 years meeting any standard case definition of MIS-C in hospitals in high-income countries (HIC) and low-and middle-income countries (LMIC)
IVIG plus steroids as the initial treatment
IVIG alone as the initial treatment

# Very low
Due to very serious risk of bias and serious imprecision 2 The evidence is very uncertain about the effect of adding steroids to IVIG on death during hospitalization

# Ventilation support 2 days after initiation of treatment

# Very low
Due to very serious risk of bias, serious inconsistency, and serious imprecision 4 The evidence is very uncertain about the effect of adding steroids to IVIG on the need for ventilation support 2 days after initiation of treatment

# Haemodynamic support 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 8 The evidence is very uncertain about the effect of adding steroids to IVIG on coronary artery dilatation at discharge

# Acute left ventricular dysfunction 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 10 The evidence is very uncertain about the effect of adding steroids to IVIG on acute left ventricular dysfunction 2 days after initiation of treatment 1. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention.
- Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 3. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 4. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Inconsistency: serious. Downgraded for inconsistency as I squared > 50% or p value represented presence of statistical heterogeneity. Random effects model for pooling ORs was used. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 5. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 6. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. 7. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 8. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 9. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 10. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 11. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 12. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 13. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 14. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect..

# Clinical improvement 2 days after initiation of treatment
Odds Ratio 1.09 (CI 95% 0.53 -2.23) Based on data from 304 patients in 1 studies. 11 (Observational (nonrandomized))

# Very low
Due to very serious risk of bias and serious imprecision 12 The evidence is very uncertain about the effect of adding steroids to IVIG on clinical improvement 2 days after initiation of treatment

# Fever persisting 2 days after initiation of treatment
Odds Ratio 0.69 (CI 95% 0.5 -0.95) Based on data from 661 patients in 3 studies. 13 (Observational (nonrandomized)) Comparator:

# Steroids alone as the initial treatment

# Study results and measurements

# Steroids alone as the initial treatment

# IVIG plus steroids as the initial treatment
Certainty of the Evidence (Quality of evidence)

# Plain language summary

# Death during hospitalization
Based on data from 233 patients in 1 studies. 1 (Observational (nonrandomized)) 0 per 1000

# Very low
Due to very serious risk of bias and serious imprecision 2 The evidence is very uncertain about the effect of adding IVIG to steroids on death during hospitalization

# Ventilation support 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 4 The evidence is very uncertain about the effect of adding IVIG to steroids on the need for haemodynamic support 2 days after initiation of treatment

# Haemodynamic support 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 6 The evidence is very uncertain about the effect of adding IVIG to steroids on the need for ventilation support 2 days after initiation of treatment

# Coronary artery dilatation at discharge
Odds Ratio 0.61 (CI 95% 0.06 -5.88) Based on data from 159 patients in 1 studies. 7 (Observational (nonrandomized))

# Very low
Due to very serious risk of bias and serious imprecision 8 The evidence is very uncertain about the effect of adding IVIG to steroids on coronary artery dilatation at discharge

# Acute left ventricular dysfunction 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 10 The evidence is very uncertain about the effect of adding IVIG to steroids on acute left ventricular dysfunction 2 days after initiation of treatment

# Clinical improvement 2 days after initiation of treatment
Odds Ratio 0.56 (CI 95% 0.24 -1.32) Based on data from 212 patients in 1 studies. 11 (Observational (nonrandomized))

# Very low
Due to very serious risk of bias and serious imprecision 12 The evidence is very uncertain about the effect of adding IVIG to steroids on clinical improvement 2 days after initiation of treatment

# Study results and measurements

# Steroids alone as the initial treatment

# IVIG plus steroids as the initial treatment
Certainty of the Evidence (Quality of evidence)
Plain language summary 1. Systematic reviewwith included studies:. Adjusted relative risk not available.. Baseline/comparator: Control arm of reference used for intervention.
- Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 3. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 4. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 5. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 6. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 7. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 8. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 9. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 10. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 11. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 12. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 13. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 14. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect..

# Fever persisting 2 days after initiation of treatment
Odds Ratio 1.3 (CI 95% 0.55 -3.23) Based on data from 195 patients in 1 studies. 13 (Observational (nonrandomized))

# Very low
Due to very serious risk of bias and serious imprecision 14 The evidence is very uncertain about the effect of adding IVIG to steroids on fever persisting two days after initiation of treatment

# Clinical Question/ PICO Population:
Children aged 0-19 years meeting any standard case definition of MIS-C in hospitals in high-income countries (HIC) and low-and middle-income countries (LMIC)
Steroids alone as the initial treatment

# Comparator: IVIG alone as the initial treatment
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Outcome Timeframe

# Study results and measurements

# IVIG alone as the initial treatment

# Steroids alone as the initial treatment
Certainty of the Evidence (Quality of evidence)

# Plain language summary

# Death during hospitalization
Based on data from 239 patients in 1 studies. 1 (Observational (nonrandomized))
per 1000 0 per 1000

# Very low
Due to very serious risk of bias and serious imprecision 2 The evidence is very uncertain about the effect of steroids alone compared with IVIG alone on death during hospitalization

# Ventilation support 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 4 The evidence is very uncertain about the effect of steroids alone compared with IVIG alone on the need for ventilation support 2 days after initiation of treatment

# Haemodynamic support 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 6 The evidence is very uncertain about the effect of steroids alone compared with IVIG alone on the need for haemodynamic support 2 days after initiation of treatment

# Coronary artery dilatation at discharge
Odds Ratio 0.75 (CI 95% 0.18 -3.22) Based on data from 171 patients in 1 studies. 7 (Observational (nonrandomized))
1 fewer per 1000 ( CI 95% 4 fewer -11 more

# Very low
Due to very serious risk of bias and serious imprecision 8 The evidence is very uncertain about the effect of steroids alone compared with IVIG alone on coronary artery dilatation at discharge

# Acute left ventricular dysfunction 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious imprecision 10 The evidence is very uncertain about the effect of steroids alone compared with IVIG alone on acute left ventricular dysfunction 2 days after initiation of treatment

# Clinical improvement 2 days after initiation of treatment
Odds Ratio 1.95 (CI 95% 0.83 -4.6) Based on data from 212 patients in 1 studies. 11 (Observational (nonrandomized))

# Very low
Due to very serious risk of bias and serious imprecision 12 The evidence is very uncertain about the effect of steroids alone compared with IVIG alone on clinical improvement 2 days after initiation of treatment

# Fever persisting 2 days after initiation of treatment

# Very low
Due to very serious risk of bias and serious
The evidence is very uncertain about the effect of steroids alone compared with IVIG alone Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Outcome Timeframe

# Study results and measurements

# IVIG alone as the initial treatment

# Steroids alone as the initial treatment
Certainty of the Evidence (Quality of evidence)
Plain language summary 1. Systematic reviewwith included studies:. Adjusted relative risk not available.. Baseline/comparator: Control arm of reference used for intervention.
- Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 3. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 4. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 5. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 6. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 7. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 8. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 9. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 10. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 11. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 12. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect.. 13. Systematic reviewwith included studies:. Baseline/comparator: Control arm of reference used for intervention. 14. Risk of Bias: very serious. Downgraded two levels for serious risk of confounding and selection bias in all studies which substantially lowered confidence in the certainty of the estimate of effect.. Imprecision: serious. Downgraded for imprecision due to wide confidence intervals around the absolute effects which also crossed the line of no effect..

# Therapeutics and COVID-19

# Info Box
For the most up to date clinical practice guideline on therapeutics and COVID-19 see WHO website and BMJ website and MAGICapp.
We recommend that the use of unproven drugs not be administered as treatment or prophylaxis for COVID-19, outside of the context of clinical trials.
Outside of clinical trials, the following criteria should be met for access to investigational therapeutics: 1) no proven effective treatment exists; 2) it is not possible to initiate clinical studies immediately; 3) data providing preliminary support of the intervention's efficacy and safety are available, at least from laboratory or animal studies, and use of the intervention outside clinical trials has been suggested by an appropriately qualified scientific advisory committee on the basis of a favourable risk-benefit analysis; 4) the relevant country authorities, as well as an appropriately qualified ethics committee, have approved such use; 5) adequate resources are available to ensure that risks can be minimized; 6) the patient's informed consent is obtained; and 7) the emergency use of the intervention is monitored and the results are documented and shared in a timely manner with the wider medical and scientific community (174).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
We recommend for patients with suspected or confirmed mild COVID-19, against the use of antibiotic therapy or prophylaxis.
We recommend for patients with suspected or confirmed moderate COVID-19, that antibiotics should not be prescribed unless there is clinical suspicion of a bacterial infection.
We recommend for patients with suspected or confirmed severe COVID-19, the use of empiric antimicrobials to treat all likely pathogens, based on clinical judgment, patient host factors and local epidemiology, and this should be done as soon as possible (within 1 hour of initial assessment if possible), ideally with blood cultures obtained first. Antimicrobial therapy should be assessed daily for de-escalation.
- For patients with severe disease, early and appropriate empiric antimicrobial therapy (109) can be administered in the emergency unit and/or pre-hospital setting. Empiric antibiotic treatment should be based on the clinical diagnosis (community-acquired pneumonia, health care-associated pneumonia  or sepsis), local epidemiology and susceptibility data, and national treatment guidelines. Choose antibiotics with the least ecologic impact based on data and guidance from your own institution, region or country (e.g. of the Access group of the AWaRe classification) (124). The AWaRe classification categorizes antibiotics into three different groups (Access, Watch and Reserve) based on their indication for common infectious syndromes, their spectrum of activity, and their potential for increasing antibiotic resistance. The AWaRe classification is a tool for antibiotic stewardship at local, national and global levels with the aim of optimizing antibiotic use and reducing antibiotic resistance. 2. Empiric antibiotic therapy should be de-escalated on the basis of microbiology results and clinical judgment. Regularly review the possibility of switching of intravenous to oral route of administration and provide targeted treatment based on microbiologic results. 3. Duration of empiric antibiotic treatment should be as short as possible; generally 5-7 days.
- An increase in antibiotic use during the pandemic may cause adverse reactions such as Clostridioides difficile infections, with clinical disease ranging from diarrhoea and fever to colitis (175). Antibiotic stewardship programmes should be put into place or continue among COVID-19 patients.

# Treatment of other coinfections may be based on a laboratory-confirmed diagnosis or epidemiological and clinical criteria.
- In malaria endemic areas, when a malaria RDT is also positive, antimalarials should be initiated as soon as possible as per local protocol (78). 2. When there is ongoing suspected or confirmed local circulation of seasonal influenza, empiric therapy with a neuraminidase inhibitor (i.e. oseltamivir) should be considered for patients with severe disease or at risk for severe influenza, and given as soon as possible.

# If TB coinfection is suspected or confirmed, then follow local TB treatment protocols (81).
It is currently unknown whether immunosuppression caused by chronic coinfections such as human immunodeficiency virus (HIV) puts persons at greater risk for severe COVID-19. However, people living with HIV with advanced disease have an increased risk of opportunistic infections (notably TB) (176) and related complications in general. Facility-based HIV testing services should continue and those newly diagnosed should start antiretroviral therapy as soon as possible. For people living with HIV already on treatment, continuity of antiretroviral therapy and prophylaxis for coinfections is essential, with multi-month prescribing.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Treatment of other acute and chronic infections in patients with COVID-19
The prevalence of acute coinfections or secondary infections coinciding with COVID-19 has not been adequately described but appears to be low (115), and will be based on local factors and endemic or other emerging infections (90)(122)(123) (173). Antibiotic overuse increases the risk of emergence and transmission of multidrug-resistant bacteria. Infections with multidrug-resistant bacteria are more difficult to treat, and associated with increased morbidity and mortality.
We recommend, in patients with COVID-19, that measures to prevent delirium, an acute neuropsychiatric emergency, be implemented; and patients be evaluated using standardized protocols, for the development of delirium. If detected, then immediate evaluation by a clinician is recommended to address any underlying cause of delirium and treat appropriately.
- Manage any underlying cause of delirium by monitoring oxygenation and fluid status, correcting metabolic or endocrine abnormalities, addressing coinfections, minimizing the use of medications that may cause or worsen delirium, treating withdrawal from substances, understanding and minimizing the effects of any harmful drug-drug interactions and maintaining normal sleep cycles as much as possible (183).

# In patients receiving invasive ventilation, minimize continuous or intermittent sedation, targeting specific titration endpoints (light sedation unless contraindicated) or with daily interruption of continuous sedative infusions, to reduce delirium (183).
- In patients experiencing agitation (defined as marked restlessness or excessive motor activity, often accompanied by anxiety), use calming communication strategies and attempt to reorient the person. Acute pain due to physical illness or air hunger should be considered as triggers for agitation and need to be addressed immediately. If the person continues to be agitated despite the strategies described above and is experiencing severe distress, it may be necessary to use psychotropic medications (184). 4. When using antipsychotic medications for agitation, consider side-effects that may worsen symptomatology, including sedation, respiratory or cardiac function, risk of fever or other immunological abnormalities, or coagulation abnormalities and any potential drug-drug interactions between these and other medications. Use minimum effective doses of antipsychotic medications at the lowest frequency and for the shortest duration possible, with doses adjusted according to age, medical co-morbidities and degree of distress (184). For severe agitation, low doses of haloperidol (administered orally or by intramuscular injection) can be considered, while carefully monitoring for adverse effects such as QT prolongation and extrapyramidal symptoms (184). 5. If haloperidol is contraindicated due to the patient's clinical condition (e.g. prolonged QT interval, recent myocardial infarction, Parkinson's Disease, Lewy-Body dementia, etc.), other antipsychotic medications with safer cardiovascular profiles may be used after careful consideration of other risks (such as respiratory suppression or sedation) and drug-drug interactions (185). 6. If the patient remains severely agitated despite the strategies described above, benzodiazepines can be added, with preference given to those with shorter half-lives and lower risk of drug-drug interactions (such as lorazepam); lowest doses should be used and for the shortest duration possible. The intravenous route should be avoided (185).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Management of neurological and mental manifestations associated with COVID-19
People with COVID-19 are at increased risk for neurological, neuropsychiatric, and mental manifestations (see Chapter 1. Background). Neuropsychiatric manifestations such as delirium/encephalopathy and neurological manifestations such as stroke may be presenting features without respiratory symptoms (see Table 6.1). In addition to acute neurological manifestations, Guillain-Barre syndrome, acute disseminated encephalomyelitis, and acute haemorrhagic leukoencephalitis-like presentations may occur weeks after the acute stage of infection (32). Moreover, there may be potential for longer term neurological consequences such as cognitive impairment (177) and/or post-intensive care syndrome (PICS). Further research is needed in order to fully characterize these complications.
Anxiety and depressive symptoms constitute common reactions for people in the context of COVID-19 diagnosis, especially for those who may be hospitalized, due to concerns for one's own health or the health of others, the need for physical isolation (which can lead to social isolation), potential risk of death, concerns over the risk of infecting others, and concerns over leaving family members alone who may need care. Stressors particular to COVID-19 include: fear of falling ill and dying, fear of being socially excluded/placed in quarantine, loss of livelihood and loss of loved ones, and feelings of helplessness, boredom and loneliness due to being isolated. These stressors may trigger new symptoms or exacerbate underlying mental or neurological conditions. Pre-existing mental, neurological or substance use disorders increase the risk of becoming severely ill or of death, or of having long-term complications due to COVID-19 (98)(99)(178)(179)(180) (181). People with COVID-19 are also at higher risk for sleep problems owing to acute stress responses, as well as additional reasons for those who are hospitalized such as environmental factors, invasive medical procedures (e.g. mechanical ventilation) and the frequent combination of multiple medications possibly disrupting sleep patterns (182).
Patients presenting with rapidly developing neurological symptoms suggestive of stroke should be evaluated as soon as possible and standard stroke protocols should be followed including systemic thrombolysis and/or intra-arterial thrombectomy, if indicated. Signs and symptoms of stroke can include weakness of limbs or face, sensory loss, speech difficulties, impairment of vision, ataxia, confusion, or decreased consciousness. Standard IPC measures must be followed during the clinical evaluation, neuroimaging or procedures for patients with stroke.
Remark: Strokes can be missed in severely sick or unresponsive ICU patients and a low threshold for further evaluation (including neuroimaging) is recommended for acute neurological worsening.
We recommend providing basic mental health and psychosocial support (MHPSS) for all persons with suspected or confirmed COVID-19 by asking them about their needs and concerns, and addressing them (186).
- Basic psychosocial support skills are essential for management of all patients and they represent an integral part of the care to be provided for different groups, including children, older adults, pregnant women and others affected by COVID-19 (187). 2. This recommendation is consistent with the Inter-Agency Standing Committee briefing note about mental health and psychosocial aspects of COVID-19 (186), and guidance on basic psychosocial skills for COVID-19 responders (187), and WHO recommendations on providing access to support based on psychological first aid principles to people in acute distress exposed recently to a traumatic event (188). 3. Ask people about their needs and concerns around diagnosis, prognosis, and other social, family or work-related issues. Listen carefully, try to understand what is most important to the person at this moment, and help them work out what their priorities are and link them with relevant resources and services. 4. Give accurate information on the person's condition and treatment plans in easily understood and non-technical language, as lack of information can be a major source of stress. Help people address urgent needs and concerns, and help with decision-making, as necessary. Help connect people with loved ones and social support, including through phone or internet as appropriate. 5. MHPSS and follow up should continue after the person is discharged from hospital to ensure their symptoms are not worsening and they are continuing to do well. This can be provided through telehealth, where available and appropriate. 6. Given the stress that COVID-19 may create at individual and family levels, the high prevalence of common mental health conditions among women in the antenatal and postpartum period, and the acceptability of programmes aimed at them, interventions for MHPSS targeted to mothers need to be more widely implemented. Prevention services should be available in addition to services that treat mental health conditions. 7. Parents and caregivers who may need to be separated from their children, and children who may need to be separated from their primary caregivers, should have access to appropriately trained health or non-health workers for MHPSS. MHPSS should be appropriately adapted for the needs of children, taking into consideration their social and emotional development, learning and behaviour (186).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
We recommend prompt identification and assessment for anxiety and depressive symptoms in the context of COVID-19 and to initiate psychosocial support strategies and first-line interventions, for the management of new anxiety and depressive symptoms.
- For people who are experiencing symptoms of anxiety, basic psychological skills such as psychological first aid stress management, and brief psychological interventions based on the principles of cognitive behavioural therapy should be considered (188) (189). 2. For relieving anxiety causing severe distress that is not responsive to psychosocial support strategies, benzodiazepines can be considered, specifically in the hospital setting. Benzodiazepines should only be used with extreme caution with preference for those with shorter half-lives and lower risk of drug-drug interactions (such as lorazepam). Lowest doses should be used and for the shortest duration possible; high doses and longer term use should be avoided. Benzodiazepines carry the risks of confusion and respiratory suppression, may worsen traumatic stress reactions, can produce tolerance and dependence, and are known to be prescribed indiscriminately in many emergencies (184). (190). Consider using remote mental health support (i.e. telephone therapy) when access to regular services is disrupted. 4. If a person's anxiety or depressive symptoms persist beyond recovery from COVID-19 and/or discharge from the hospital, then an underlying anxiety or depressive disorder may be suspected, and a mental health professional should be consulted and these conditions should be managed appropriately. Refer to the mhGAP Intervention Guide for mental, neurological and substance use disorders in nonspecialized health settings (191). 5. It is important to ask about thoughts or acts of self-harm, particularly during COVID-19, due to risk factors for self-harm and suicide such as sense of isolation, loss of a loved one, job, or financial loss and hopelessness. Remove possible means of self-harm, activate psychosocial support, follow up with the person, and consult a mental health professional as necessary. Refer to the mhGAP Intervention Guide for mental, neurological and substance use disorders in non-specialized health settings (191). 6. To ensure comprehensive care and based on the initial assessment, following discharge, link the person to employment, education, social services (including housing) and other relevant sectors (191). 7. Cognitive-behavioural therapy with a trauma focus, eye movement desensitization and reprocessing or stress management should be considered for adults with post-traumatic stress disorder (PTSD) (192).

# For people who are experiencing symptoms of depression, brief psychological interventions based on the principles of cognitive behavioural therapy, problem-solving treatment and relaxation training can be considered
We recommend psychosocial support strategies as the first-line interventions for management of sleep problems in the context of acute stress.
- Sleep hygiene advice (including avoiding the use of psychostimulants such as caffeine, nicotine or alcohol), and stress management (including relaxation techniques and mindfulness practices) are effective in reducing sleep problems and may be offered. Psychological interventions based on the principles of cognitive behavioural therapy may also be considered. 2. For people who are hospitalized for COVID-19, additional causes of insomnia may include environmental factors (e.g. excessive light and noise at night), anxiety, persistent cough, delirium, agitation, pain or air hunger. Identifying and promptly addressing underlying causes should be prioritized before using any pharmacological sleep aids.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)
We recommend when caring for patients with suspected and confirmed COVID-19 that have underlying NCDs to continue or modify previous medical therapy according to the patient's clinical condition. Antihypertensive drugs should not routinely be stopped in patients with COVID-19, but therapy may need to be adjusted based on general considerations for patients with acute illness, with particular reference to maintaining normal blood pressure and renal function.
Remark: SARS-CoV-2 uses the ACE 2 receptor for entry into cells. It has been suggested that antihypertensive drugs that exert their effect by inhibiting ACE or blocking the ACE 2 receptor may either aggravate or ameliorate the clinical course of patients with COVID-19 (193). To date, there are no studies that can substantiate this, and it is generally advised to continue these medications unless there are other reasons to stop these (e.g. hyperkalaemia, hypotension or acute deterioration in renal function) (194).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Noncommunicable diseases and COVID-19
Pre-existing NCDs, including cardiovascular disease, diabetes, chronic respiratory disease, hypertension, obesity and cancer, have been identified as independent risk factors for death (see Table 6.1).

# Rehabilitation for patients with COVID-19
At the outset of the pandemic, the rehabilitation needs for patients recovering from COVID-19 were based on evidence from the critical care population and long-term sequelae in SARS-CoV-1 survivors (195) (196) (197) (198) (199) (200) (201) (202) (203) (204) (205) (206). Postintensive care syndrome (PICS) refers to a range of impairments including physical deconditioning, and cognitive and mental health impairments. The COVID-19 patients who are at higher risk of ICU admission are also those at higher risk to develop PICS, i.e. older persons with underlying diseases such as diabetes, hypertension, increased frailty and other chronic disorders (207). Intensive care unitacquired weakness is ubiquitous in ARDS survivors, as it is in critically ill COVID-19 patients who required prolonged sedation (208), and recovery may be incomplete at 5 years after ICU discharge (209). Some studies suggest that cognitive impairment ranges from 70-100% at hospital discharge, 46-80% at 1 year, and 20% at 5 years. Mood disorders including depression and PTSD are also sustained and prevalent (209). For ARDS survivors, a reduced exercise capacity persists in the context of relatively preserved pulmonary function at 1 year (210). In SARS-CoV-1 survivors, pulmonary function at 1-year is reported to be normal in 63%, mildly reduced in 32% and moderately impaired in 5%, with abnormalities characterized by restrictive patterns and reduced carbon monoxide diffusing capacity (211).
The following symptoms have been reported 4-8 weeks after discharge from the hospital in both ICU admitted COVID-19 patients and non-ICU admitted COVID-19 patients: new illness-related fatigue, breathlessness, PTSD symptoms, pain, voice change, cough, dysphagia, anxiety, depression, and problems with concentration, memory and continence. Patients admitted to ICU had greater prevalence of symptoms in almost all reported symptom domains than COVID-19 patients not admitted to ICU (212). More than half of all COVID-19 patients who had been hospitalized, regardless of their clinical management, reported persistence of fatigue at 60 days since the onset of symptoms (212) (213).
With progression of the pandemic and the follow up of patients who have not been critically ill, new evidence is emerging about COVID-19 related persistent symptoms, which have parallels with other coronavirus diseases. Some patients with SARS-CoV-1 infection went on to develop a long-term illness with widespread pain, fatigue, depression and sleep disturbance (214) (205). PTSD has also been described after SARS-CoV-1 infection (205) (205).
Early findings report, most commonly reported ongoing symptoms (regardless of hospitalization status) are fatigue, muscle ache, shortness of breath and headache at a follow up of 4 months (215). Not returning to usual health within 2-3 weeks of testing was reported by approximately one third of symptomatic adults in an outpatient setting (216). A study reported that at 3 months after the onset of symptoms, one third of non-hospitalized patients were to some degree dependent on others for personal care (217).
In addition, several complications from COVID-19 have been reported in different clinical domains, resulting from a thrombotic event (such as ischaemic stroke and ischaemic heart disease), direct invasion (such as myocarditis, myositis, and meningitis) or an immunemediated reaction (such as Guillain-Barre syndrome). While many of these complications are amenable for rehabilitation, they are not addressed in this chapter. Clinicians and rehabilitation professionals can refer to existing clinical practice guidelines for the appropriate management of these sequelae.
In hospitalized patients, during the acute phase of illness, rehabilitation professionals may provide interventions that relieve respiratory distress, prevent complications and support communication.
- Decision on when to start rehabilitation should be determined by a multidisciplinary team taking into account the patient's medical status (220). Ensure that appropriate IPC is available at designated rehabilitation areas caring for patients with COVID-19 that remain infectious. Make optimal use of digital and/or written information for the instruction of patients (151). Telehealth may play a role in the acute and subacute phases, in which face-to-face rehabilitation is costly, risky, and impractical (221). Consider strategies for communication with and engagement of families during physical distancing (222). 2. Early mobilization is recommended for all patients with severe risk of functional limitations, resulting from frailty or ICU-acquired weakness (279). In ICU, early mobilization should be part of a bundle of care (See Chapter 12 and 13 on management of critical COVID-19 for new recommendation on bundles), and appropriate levels of activity would be based on the Richmond Agitation-Sedation Scale (151). Monitor oxygen saturation levels closely as desaturation may occur. To identify every next level of mobility the ICU mobility scale can be used.

# See Chapter 12 (Management of critical COVID-19: ARDS) for examples of respiratory interventions that may be considered. 4. Communication challenges may result from voice and speech disorders that are often linked with intubation or a cognitive impairment.
Augmented communication strategies may assist, and where available, refer for speech and language therapy. 5. COVID-19 patients with dysphagia are at risk of aspiration. Dysphagia is common post-extubation and the presumed aspiration prevalence for the general critical care population is 10-25% at ICU discharge (195). Referral to an appropriately trained health professional such as a speech and language therapist, for additional breathing exercises, vocal exercises, and eating and drinking exercises where available (223). 6. Patients with COVID-19 have demonstrated improved mobility at hospital discharge and higher probability of discharging home with increased frequency and longer mean duration of physical therapy visits (224). Some reports have found that early aerobic exercises may not be well tolerated and result in rapid desaturation in COVID-19 inpatients. Exercise training may have to start with gradual functional exercises, using no or minimal equipment (151) including an active range of motion exercises, balance exercises, and walking with or without a walking aid. When (assisted) exercises are well tolerated while lying supine, the rehabilitation professional may proceed with exercises while sitting, and then standing (151).
Prior to hospital discharge, COVID-19 patients should be screened for rehabilitation needs in order to facilitate onward referral.
- Hospitalized COVID-19 patients may have ongoing rehabilitation needs which prevent safe discharge or require continued rehabilitation services. These needs can be based on physical deconditioning, and respiratory, swallow, cognitive and mental health impairments. Consider the context of the person's individual situation, including social support and home environment when making decisions about a course of intervention or support needs. 2. When indicated from screening, further assessment of rehabilitation needs can be based on a basic set of measures that cover potentially affected functioning domains. This includes, but is not limited to: respiratory function (such as respiratory rate and SpO2), mobility (such as ICU mobility scale), muscle strength (such as Medical Research Council sumscore), balance (such as Berg balance scale), dysphagia (such as fluid and food trials), and activities of daily living (ADL) (such as Barthel index). Additional tests might be helpful based on a first screening for mental and cognitive impairment (such as Montreal Cognitive Assessment, Hospital Anxiety and Depression Scale, PTSD Checklist-5). 3. When the patient is ready for discharge, evaluate the need of an assistive device (such as a mobility aid) and oxygen requirements at rest and during exertion. Oxygen desaturation on exertion may happen during the recovery phase, even during physical exercise of moderate activity, and is unrelated to the oxygen saturation at rest and the degree of dyspnoea (225). An example of a rapid exercise test to assess desaturation on exertion is the 1-minute sit-to-stand test (226). 4. Where continued rehabilitation needs are identified, refer for inpatient, outpatient or community-based follow up as indicated and according to the type and severity of rehabilitation needs. When a patient does not require inpatient rehabilitation but would benefit from rehabilitation follow up post-discharge, refer to outpatient or community-based services according to local service availability. Consider which options have the least barriers to attendance/service utilization and, where available and appropriate, refer to services delivered through telehealth (221) particularly where IPC measures prevent in-person consultations. 5. Information, including documentation, should be communicated between hospitals and to other hospital-based or community rehabilitation services and primary care services (220). 6. Ensure patients are provided with education and information resources for self-management management of COVID-19 symptoms, especially when barriers to accessing rehabilitation follow up are anticipated (patient leaflet / support-for-rehabilitation-self-management-after-covid-19-related-illness).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO) Provide individualized rehabilitation programmes from subacute to long term according to patient needs. The prescription and provision of rehabilitation programmes should be guided by persistent symptoms and functional limitations.
- COVID-19 related impairments, such as fatigue, muscle weakness and cognitive impairment, might impact the performance of ADLs. As patients regain strength and fitness, autonomy in ADLs will improve, but some will need to accept additional support from a caregiver for a time. Provide ADL training and consider home modifications (such as grab bars in the shower and toilet, handrails along stairs) and the provision of an assistive product (such as a mobility aid, shower chair, over-toilet frame), as needed. We recommend all pregnant women with history of contact with a person with confirmed COVID-19 be carefully monitored considering asymptomatic transmission of COVID-19.
Pregnant or recently pregnant women with suspected or confirmed mild COVID-19 may not require acute care in hospital, unless there is concern for rapid deterioration or an inability to promptly return to hospital; but isolation to contain virus transmission is recommended, and can be done at a health facility, community facility or at home, according to established COVID-19 care pathways.
Pregnant or recently pregnant women with moderate or severe COVID-19 require acute care in the hospital, as there is concern for rapid deterioration that may warrant supportive care for severe respiratory morbidity; and/or interventions to improve maternal and fetal survival.
- Counsel pregnant and recently pregnant women about maternal and newborn signs, including COVID-19 danger signs and maternal perception of decreased fetal movements, and advise them to seek urgent care if they develop any worsening of illness or other danger signs, such as danger signs of pregnancy (including: bleeding or leaking fluid from the vagina, blurry vision, severe headaches, weakness or dizziness, severe abdominal pain, swelling of face, fingers, feet, inability to tolerate foods or liquids, convulsions, difficulty in breathing, decrease in fetal movements). Update birth preparedness and complication readiness plans so they know when and where to seek care. 2. In pregnant and postnatal women that are being cared for at home in self-isolation, self-care interventions should be encouraged. Routine antenatal or postnatal health visits in health facilities should be postponed, and delivery of antenatal and postnatal counselling and care, should instead be conducted via alternative platforms such as home-based, phone or telemedicine (234) (235). If postponed, health visits should be rescheduled until after the period of self-isolation following national guidelines and advice, and in consultation with the health care provider. For women requiring abortion services, consider alternative modes of service delivery, including self-management of medical abortion up to 12 weeks' gestation, where women have access to accurate information and to a health care provider at any stage of the process. Postponing abortion care may lead to increased morbidity and mortality where individuals resort to unsafe abortion practices as abortion service delivery is time-bound by gestational limits prescribed by the law (236)

# Caring for women with COVID-19 during and after pregnancy
The results of a living systematic review (as of 6 October 2020) show that pregnant and recently pregnant women with COVID-19 appear to be less likely to be symptomatic (0.28, 95% CI 0.13-0.62; 4 studies; 462 051 women), or manifest common symptoms such as fever, dyspnoea and myalgia, compared with non-pregnant women of reproductive age (39). These findings are largely influenced by studies of pregnant women who were managed in hospitals for any reason, with limited data on women during early pregnancy or postpartum.
Pregnant women with COVID-19 are more likely to experience any type of preterm birth (OR=1.47, 95% CI 1.14-1.9; 18 studies; 8549 women) compared with pregnant women without the disease. Overall rates of spontaneous preterm birth in pregnant women with COVID-19 is broadly similar to those observed during the pre-pandemic period. A third of all neonates born to mothers with COVID-19 were admitted to the neonatal intensive care unit (NICU) (33%) and were at increased risk of NICU admission for any indication (OR=4.89, 95% CI 1.87-12.81; 10 studies, 5873 neonates) compared with those born to mothers without COVID-19.
Transmission of SARS-CoV-2 may be possible in utero or intrapartum, but most neonatal infections reported so far seem to have occurred in the postnatal period (39). However, available studies varied in the rigor of ascertaining mother-to-child transmission of SARS-CoV-2, limiting interpretation of these results. This section builds on existing recommendations from WHO on pregnancy and infectious diseases and provides additional remarks for the management of pregnant and recently pregnant women.
We recommend that mothers with suspected or confirmed COVID-19 should be encouraged to initiate and continue breastfeeding. From the available evidence, mothers should be counselled that the benefits of breastfeeding substantially outweigh the potential risks of transmission.
- WHO recognizes that the recommendation for an infected mother to be in close contact with her baby may appear to contradict other IPC measures that include isolation of persons infected with COVID-19 virus (39). However, the balance of risks is significantly different for infants than for adults. In infants, the risk of COVID-19 infection is low, the infection is typically mild or asymptomatic, and the consequences of not breastfeeding or separation of mother and child can be significant. At this point it appears that COVID-19 in infants and children represents a much lower risk to survival and health than the other infections and conditions that breastfeeding is protective against. This protection is especially important when health and other community services are themselves under pressure. In contrast, the risks associated with COVID-19 in adults are much higher and more severe. Improved communication is needed to address the uncertainties and confusion among programme managers, health workers and communities on this issue.

# See Table 21.1 below for recommendations when mother with COVID-19 is caring for infant.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Feeding and caring for infants and young children of mothers with COVID-19
Relatively few cases have been reported of infants confirmed with COVID-19; those that have been reported experienced mild illness. Of 115 mother-child pairs from 17 articles where the mother is confirmed to be infected with COVID-19, 13 children had COVID-19 (4 breastfed, 5 formula-fed, 2 mix-fed, 2 unreported feeding practice). Twenty mothers had breastmilk samples tested for the presence of SARS-CoV-2 RNA particles by RT-PCR; 7 of them had children with COVID-19 (2 breastfed,1 formula fed, 2 mix-fed, 2 unreported). Of the 20 with breastmilk tested, 18 had negative results and 2 had positive results. One of the two mothers whose breastmilk sample was positive for SARS-CoV-2, had a mix-fed child who was not infected with COVID-19; the other one had a child with COVID-19 (feeding practice was not reported) (242)( 243 Breastfeeding protects against morbidity and death in the post-neonatal period and throughout infancy and childhood. The protective effect is particularly strong against infectious diseases that are prevented through both direct transfer of antibodies and other antiinfective factors and long-lasting transfer of immunological competence and memory. See WHO Essential newborn care and breastfeeding (252). Therefore, standard infant feeding guidelines should be followed with appropriate precautions for IPC. Recommendations on the care and feeding of infants whose mothers have suspected or confirmed COVID-19 promote the health and well-being of the mother and infant. Such recommendations must consider not only the risks of infection of the infant with the COVID-19 virus, but also the risks of serious morbidity and mortality associated with not breastfeeding or the inappropriate use of breastmilk substitutes as well as the protective effects of skin-to-skin contact and kangaroo mother care. In light of the current evidence, WHO has concluded that mothers with suspected or confirmed COVID-19 should not be separated from their infants. Mother-infant contact and holding enhances thermoregulation and other physiological outcomes, significantly reduces mortality and morbidity, and improves child and parental attachment. Overall, the recommendation to keep mothers and their children together is based on several important benefits that outweigh the potential (and likely mild) harms of COVID-19 transmission to the child.

# Table 21.1. Summary of recommendations when mother with COVID-19 is caring for infant

# Mother infant contact at birth
Mothers should not be separated from their infants unless the mother is too sick to care for her baby. If the mother is unable to care for the infant another competent family caregiver should be identified.
Mother and infant should be enabled to remain together while rooming-in throughout the day and night and practise skin-to-skin contact, including kangaroo mother care, especially immediately after birth and during establishment of breastfeeding, whether they or their infants have suspected or confirmed COVID-19 virus infection.
Neonates born to mothers with suspected or confirmed COVID-19 should be breastfed within 1 hour of birth. Mothers should apply appropriate IPC.
Early and uninterrupted skin-to-skin contact between mothers and infants should be facilitated and encouraged as soon as possible after birth, while applying necessary measures for IPC. This applies also to infants who are born preterm or low birth weight. If the newborn or infant is ill and requires specialist care (such as neonatal unit), arrangements should be made to allow the mother free access to the unit, with appropriate IPC measures.
Earlier initiation of breastfeeding results in greater benefits. This may be relevant to mothers who give birth by caesarean section, after an anaesthetic, or those who have medical instability that precludes initiation of breastfeeding within the first hour after birth.

# During early childhood
Infants should be breastfed exclusively during the first 6 months after birth, as breastmilk provides all the nutrients and fluids they need.
From 6 months of age, breastmilk should be complemented with a variety of adequate, safe and nutrient-dense foods. Breastfeeding should continue up to 2 years of age or beyond.
Breastfeeding counselling, basic psychosocial support and practical feeding support should be provided to all pregnant women and mothers with infants and young children if they or their infants and young children have suspected or confirmed COVID-19 infection.

# If feeding is interrupted
In situations when severe illness in a mother prevents her from caring for her infant or prevents her from continuing direct breastfeeding, mothers should be encouraged and supported to express milk, and the breastmilk provided safely to the infant, while applying appropriate IPC measures.
In the event that the mother is too unwell to breastfeed or express breastmilk, explore the viability of feeding with donor human milk. If this is not possible, consider wet nursing (defined as another woman breastfeeds the child) or appropriate breastmilk substitutes, informed by feasibility, safety, sustainability, cultural context, acceptability to mother and service availability.
Mothers who are not able to initiate breastfeeding during the first hour after delivery should still be supported to breastfeed as soon as they are able. Assistance should be provided after recovery for relactation to re-establish a milk supply and continue breastfeeding.

# Practices the mother should perform during all infant and childcare
Perform frequent hand hygiene with soap and water or alcohol-based hand rub, especially before contact with her child.
Perform respiratory hygiene: sneeze or cough into a tissue and immediately dispose of the tissue. Hands should immediately be washed with soap and water or alcohol-based hand rub.
Clean and disinfect surfaces with which the mother has been in contact. Wear a medical mask until symptom resolution and criteria for release from isolation have been met. Additionally, breastfeeding mothers should be helped to clean her chest with soap and water if she has been coughing on it before breastfeeding. She does not need to wash her breasts prior to every breastfeed.
While mothers are recommended to wear medical masks, if the mother does not have a medical mask, she should still be encouraged to continue breastfeeding as the benefits of breastfeeding outweigh the potential risks of transmission of the virus when breastfeeding while applying other IPC measures.

# Best practices for breast-feeding
Health facilities providing maternity and newborn services should enable a mother to breastfeed for as often and for as long as she wishes. Minimizing disruption to breastfeeding will require health care practices that enable a mother to breastfeed.
All mothers should receive practical support to enable them to initiate and establish breastfeeding and manage common breastfeeding difficulties. This support should be provided by appropriately trained health care professionals and community-based lay and peer breastfeeding counsellors.
There should be no promotion of breastmilk substitutes, feeding bottles and teats, pacifiers or dummies in any part of facilities providing maternity and newborn services, or by any of the staff. Health facilities and their staff should not give feeding bottles and teats or other products that are within the scope of the International Code of Marketing of Breast-milk Substitutes and its subsequent related WHA resolutions, to infants.
If the mother is too unwell to breastfeed or express breastmilk, explore the best alternatives to breastfeeding a newborn or young infant, in priority order, as follows: 1) donor human milk should be fed if available from a human milk bank; 2) if supplies are limited, prioritize donor human milk for preterm and low birthweight newborns; 3) wet nursing may be an option depending on acceptability to mothers and families, availability of wet nurses and services to support mothers and wet nurses. COVID-19 testing of a woman who is a potential wet nurse is not required. Prioritize wet nurses for the youngest infants. In settings where HIV is prevalent, prospective wet nurses should undergo HIV counselling and rapid testing where available. In the absence of testing, if feasible, undertake HIV risk assessment. If HIV risk assessment or counselling is not possible, facilitate and support wet nursing; 4) breastmilk substitutes may be used as a last resort. We recommend that older people be screened for COVID-19 at the first point of access to the health system, be recognized promptly if they are suspected to have COVID-19 and treated appropriately according to established COVID-19 care pathways. This should occur in all settings where older people may seek care; included but not limited to facility-based emergency units, primary care, prehospital care settings and LTCFs.
- Older patients may present with atypical symptoms (including delirium) of COVID-19, especially those with cognitive decline and dementia (258)(259) (see Table 6.1); health workers should take this into account during the screening process. 2. Provide accessible information to older people and their caregivers on clinical manifestation of COVID-19 including atypical symptoms, how to monitor symptoms, as well as when and how to seek care.
Identify if there is an advance care plan for patients with COVID-19 (such as desires for intensive care support) and respect their priorities and preferences. Tailor the care plan to be in line with patients' expressed wishes and provide the best care irrespective of treatment choice.
We recommend a review of medication prescriptions to reduce polypharmacy and prevent medicine interactions and adverse events for those being treated with COVID-19.
- Older people are at greater risk of polypharmacy, as a result of newly prescribed medications, inadequate medication reconciliation, and a lack of coordination of care, all of which increases the risk of negative health consequences. If medications are prescribed for mental and neurological manifestations of COVID-19 in older people, this should be done with extreme caution given the increased susceptibility to drug side-effects and drug interactions with other prescribed medications. 2. Over 20% of adults over 60 years have pre-existing mental or neurological conditions for which they may already be taking medications before infection (260). If a person has a previously diagnosed mental or neurological condition and is already on medications, consider how these medications (or withdrawal from them) may affect their COVID-19 symptoms. Stopping or adjusting the dosage of medications in people with COVID-19 are decisions that require careful risk-benefit analyses and when possible, consultation with a specialist is advised.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Caring for older people with COVID-19
Older age has been reported as a risk factor for increased mortality in those affected by COVID-19. Other risk factors that have been reported are: smoking, diabetes, hypertension, cardiovascular, cancer, chronic lung disease, and functional decline (253)(254) (255). Since older people are often affected by these conditions, they are potentially at the highest risk for fatality. Furthermore, the majority of long-term care service users are older people with multiple underlying conditions and weak immune systems, which make them more susceptible to severe COVID-19 and poor outcomes (256). Refer to the WHO policy brief Preventing and managing COVID-19 across long-term care services (256) and WHO guidance Integrated care for older people (ICOPE) (257) for person-centred and coordinated model of care.
We recommend to identify, in all patients with COVID-19, if they have an advance care plan for COVID-19 (such as desires for intensive care support) and respect their priorities and preferences to tailor the care plan and provide the best care irrespective of treatment choice.
Palliative care interventions should be made accessible at each institution that provides care for persons with COVID-19.  4. Consider non-pharmacologic and pharmacologic interventions (such as opioids) for relief of dyspnoea that is refractory to treatment of the underlying cause (i.e. oxygen therapy, escalation of respiratory support, corticosteroids) and/or as part of end-of-life care (268). The narrow therapeutic margin of opioids in the management of dyspnoea requires that opioids are prescribed in accordance with evidencebased treatment protocols and that patients are closely monitored to prevent negative unintended effects due to inappropriate use of opioids. Where opioids are used, preference should be given for compounds less likely to cause delirium in medically ill patients. Providers should reference their institutional standards regarding the potential use of opioids for dyspnoea in patients with COVID-19. 5. Relieving spiritual and psychological suffering is an important aspect of palliative care. Visits from relatives and spiritual counsellors should be facilitated, especially for patients near to the end of life. This may include employing a range of techniques such as voice/video calls. 6. Palliative care is a person-centred approach, therefore all patients and families should be actively included in the decision-making processes about escalation of care. Medical decisions, where possible, should respect the priorities and preferences of patients, and should always be clearly explained to patients and relatives.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Palliative care and COVID-19
Palliative care is a multifaceted, integrated approach to improving the quality of life of adults and paediatric patients and their families facing the problems associated with life-threatening illness such as COVID-19. Palliative care focuses on prevention and relief of suffering by means of early identification, assessment and treatment of physical, psychosocial and spiritual stressors. Palliative care includes but is not limited to end-of-life care (266). Palliative interventions should be integrated with curative treatment (266). Basic palliative care, including relief of dyspnoea or other symptoms and social support, should be practised by all doctors, nurses, social workers and others caring for persons affected by COVID-19, adult or child (266) (267). Refer to the WHO guide Integrating palliative care and symptom relief into responses to humanitarian emergencies and crises (266).
Equal moral respect: Every person is equally valuable. Treatment and care decisions should be based on medical need and not on irrelevant or discriminatory features such as ethnicity, religion, sex, age, disability or political affiliation. Patients with similar health problems or symptoms must receive equal treatment and care. Showing moral respect means involving patients and their caregivers in decision-making to the greatest extent possible, explaining options and limitations in treatment.
Duty of care: Every patient is owed the best possible care and treatment available in the circumstances. Even when resources need to be rationed during a crisis, health care professionals and frontline workers have a duty of care to promote their patients' welfare within available resources. Health care professionals and frontline workers are also owed a duty of care. In this regard, appropriate PPE for health care professionals and frontline workers should be provided to promote their safety and well-being. This is a benefit to them but also to the whole of society by ensuring that they are available to support the clinical response for as long as possible.
Non-abandonment: It follows from consideration of equal moral respect and duty of care, that no person in need of medical care should ever be neglected or abandoned. Care will extend to families and friends of patients and options to maintain communication with them should be explored. Palliative care must be accessible for all patients with respiratory failure for whom ventilatory support will be withheld or withdrawn.

# Protection of the community:
Appropriate IPC should be in place, respected and enforced. Such actions protect patients, health care professionals and the community. During a pandemic the focus should be on both clinical care for patients and the promotion of public health.
Confidentiality: All communications between patient and clinician must remain confidential except in the case of compelling public health concerns (e.g. contact tracing and surveillance etc.) or other accepted justifications for breach of confidentiality. Private individual information must be kept secure unless it is a justified breach.
We recommend that hospitals and health systems at local, regional, national and global level plan prepare and be ready to surge clinical care capacity (staff, structure, supplies and systems) in order to be able to provide appropriate care of all COVID-19 patients and maintain essential health services (1)(272).

# Allocation of scarce resources:
We recommend that each institution should establish a plan for what to do in situations of resource scarcity to cover the allocation or access to critical medical interventions (such as oxygen, intensive care beds and/or ventilators). Such a plan should establish a clear overall aim. Decision-making regarding allocation: Part of planning for scarcity is ensuring that a fair system of decision-making for allocation is in place.
- Personnel familiar with the medical triage criteria and allocation protocols, who are distinct from the clinical treating team are one option. Allocation decisions should be done according to the established plan and regularly reviewed. If necessary, there should be a reallocation of a resource that was previously allocated where it is not proving beneficial. 2. For example, the aim might be to ensure the best possible use of limited resources based upon chosen medical criteria. Triage criteria should seek to balance medical utility and equity, and ease of implementation. The same criteria should be applied for all patients with similar levels of need, regardless of COVID-19 status.
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Ethical principles for optimum care during the COVID-19 pandemic
Ethics are central to the clinical care of COVID-19 patients in the same way that ethics pertain to all patients. Clinical care involves using clinical expertise to do what is best for patients within a relationship of care. This section provides a brief introduction to some of the ethical considerations that are important to remember in the context of COVID-19 (270) (271).

# Description of codes ICD -10
- An emergency ICD-10 code of "U07.1 COVID-19, virus identified" is assigned to a disease diagnosis of COVID-19 confirmed by laboratory testing. - An emergency ICD-10 code of "U07.2 COVID-19, virus not identified" is assigned to a clinical or epidemiological diagnosis of COVID-19 where laboratory confirmation is inconclusive or not available. - Both U07.1 and U07.2 may be used for mortality coding and tabulation as cause of death.
- The code for the confirmed diagnosis of COVID-19 is RA01.0. - The code for the clinical diagnosis (suspected or probable) of COVID-19 is RA01.1.
A set of additional categories has been agreed to be able to document or flag conditions that occur in the context of COVID-19. Both, 3-character and 4-character codes have been defined to respond to the different levels of coding depth that is in place in different countries. The categories below will not be seen in primary tabulation of the single underlying cause of death. They may be used in multiple cause of death analysis and reporting. 1. U08 Personal history of COVID-19 U08.9 Personal history of COVID-19, unspecified Note: This optional code is used to record an earlier episode of COVID-19, confirmed or probable that influences the person's health status, and the person no longer suffers of COVID-19. This code should not be used for primary mortality tabulation.
- U09 Post COVID-19 condition U09.9 Post COVID-19 condition, unspecified Note: This optional code serves to allow the establishment of a link with COVID-19. This code is not to be used in cases that still are presenting COVID-19.

# Reporting and coding during the COVID-19 pandemic (mortality and morbidity)
All coding advice is available in the official WHO languages and can be found together with more detail for classification purposes at . See

# Clinical characterization research protocols are also available (277).
The WHO Solidarity trial is a randomized clinical trial that is a currently enrolling. For more information see the WHO website (278).
Older age is reported to be a predictor of mortality in patients with COVID-19. The systematic exclusion of older adults from research activities or from accessing investigational therapeutic agents is not justified (271).
Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 -World Health Organization (WHO)

# Clinical research during the COVID-19 pandemic
A living mapping and systematic review of COVID-19 studies are available (275). For more information about the WHO research roadmap see .
Professor, University of British Columbia, Vancouver, Canada).
We would like to acknowledge the Guidance Support Collaboration Committee which provided the coordination to allow the rapid development of the WHO guidance and its dissemination: Neill Adhikari (Sunnybrook Health Sciences Centre and University of Toronto); Lisa Askie (WHO); Rajiv Bahl (WHO); Janet V Diaz (WHO); Karen Edmond (WHO); Gordon Guyatt (McMaster University, Canada); Marta Lado (WHO); Srinivas Murthy (University of British Columbia, Canada); Jacobus Preller (WHO); Archana Seahwag (WHO); Joan B Soriano (WHO); Wilson Were (WHO) and to the MAGIC Evidence Ecosystem Foundation for their support in the publication process through MAGICapp: Per Olav Vandvik, Arnav Agarwal, Lyubov Lytvyn, Stijn Rita Patrick van de Velde, Ying Wang, Linan Zeng, Dena Zeraatkar. protocols for the management of common and serious or potentially life-threatening conditions at district hospitals. The target audience includes doctors, clinical officers, health officers and senior nurse practitioners. It has been designed to be applicable in both high and low HIV prevalence settings. /

# Oxygen therapy for children (2016)
A bedside manual for health workers to guide the provision of oxygen therapy for children. The manual focuses on the availability and clinical use of oxygen therapy in children in health facilities to guide health workers, biomedical engineers and administrators. It addresses detection of hypoxaemia, use of pulse oximetry, clinical use of oxygen, delivery systems, and monitoring of patients on oxygen therapy. The manual also addresses the practical use of pulse oximetry, and oxygen concentrators and cylinders. /

# Technical specifications for oxygen concentrators (2015)
Provides an overview of oxygen concentrators and technical specifications to aid in selection, procurement, and quality assurance. It highlights the minimum performance requirements and technical characteristics for oxygen concentrators and related equipment that are suitable for the use in health facilities. / For use by doctors, nurses, and other health workers caring for children at first-level referral hospitals with basic laboratory facilities and essential medicines. These guidelines focus on the management of the major causes of childhood mortality in most developing countries, including pneumonia, and also cover common procedures, patient monitoring, and supportive care on the wards. /

# WHO-UNICEF technical specifications and guidance for oxygen therapy devices (2019)
The purpose of this document is to increase access to quality products to ensure the supply of oxygen, especially in low-and middleincome countries and low-resource settings within countries from all income groups. It aims to support ministries of health to ensure that oxygen supply is available, as well as to raise awareness of the importance of appropriate selection, procurement, maintenance, and use of medical devices, both capital equipment and single-use devices. We undertook a rapid evidence retrieval for relevant data, using the following criteria: