The COVID- 19 Therapeutics Working Group (WG) has updated the evolving evidence base for this document as best as possible but recognizes that future updates will be required based on ongoing therapeutic trials and emerging evidence. Supportive care remains an important component of therapy for individuals infected with SARS-CoV-2. Updated COVID-19 management guidelines from the Public Health Agency of Canada (PHAC), Association of Medical Microbiology and Infectious Diseases (AMMI), Canada/Canadian Critical Care Society (August 21, 2020) 1 , the Infectious Diseases Society of America (IDSA) (March 23, 2022) 2 and the Alberta Health Services COVID-19 Scientific Advisory Group 3 have been reviewed in preparing this update. Full details are available in the hyperlinks above and the referenced documents below.
Consultation with other specialties (e.g. Infectious Diseases, Respiratory Medicine, Critical Care, General Internal Medicine) who are most likely to be familiar with the rapidly evolving literature can be considered to help assess the risks and benefits for an individual patient. As recommended by AHS Ethics, any off-label use of medication requires the prescriber's careful consideration of risk/benefit, consultation between experts and attending physician as needed, and documenting consent from the patient or alternate decision-maker after discussion of the current state of evidence of benefit and harms. Adverse events with respect to offlabel use of medications for inpatient treatment should be documented and reported by clinicians through the AHS Reporting and Learning System for Patient Safety.
The guidance provided in this document does not replace best clinical judgment and/or expert consultation but rather is meant to inform clinicians of the most current management guidelines to facilitate best use of therapeutic options for patients with COVID-19.
Current Guidance for the Management of Adult Hospitalized Patients with COVID-19 Document Owner: COVID-19 Therapeutics Working Group Current Practice Guidance

# General Considerations
- Patients with mild suspected or confirmed COVID-19 should not require hospitalization, unless there is a clinical concern for rapid deterioration, significant underlying co-morbidities, extenuating sociodemographic circumstances, or an inability to return promptly to hospital. Patients with mild COVID-19 and their caregivers should be provided with information on symptom management and informed of the signs and symptoms of complications that should prompt medical re-evaluation.
- Patients with moderate suspected or confirmed COVID-19 (i.e. with clinical signs of pneumonia, SpO2  90% on room air, but no signs of severe pneumonia) who are not determined to be at high risk of deterioration may not require hospitalization, but they should self-monitor and be counseled along with their caregivers about the signs and symptoms of complications that should prompt medical reevaluation.
- Patients with severe suspected or confirmed COVID-19 and respiratory distress, hypoxemia, or shock should receive supplemental oxygen therapy immediately with target saturations of > 94% SpO2 during resuscitation. Patients with severe illness should be closely monitored for signs of clinical deterioration, specifically rapidly progressive respiratory failure, or shock.

# Guiding Principles
1) The use of antiviral or other immunomodulatory treatments, other than those recommended below, for patients with COVID-19 should occur within the context of controlled clinical trials wherever possible, given the currently available limited therapeutic options for which evidence-based data are available.
2) If the use of antiviral or immunomodulatory agents for COVID-19 outside of clinical trials is being considered, the potential risks (adverse reactions, drug interactions (see COVID drug interactions or Lexicomp) versus unverified benefits must be considered and discussed with the patient or caregiver, and consent documented on the chart.
3) Bacterial co-infection in patients with early COVID-19 is uncommon. Do NOT routinely add antibacterials unless bacterial infection is strongly suspected. If indicated, antibacterials should be reassessed within the first 3 days after initiation to determine if continuation is necessary, or to deescalate and/or optimize therapy in accordance with the principles of stewardship to avoid short-term adverse-effects and negative long-term consequences of increased microbial resistance.
- In hospitalized adult patients who meet criteria for severe disease (defined by the IDSA as SpO2 <94% on room air), and requiring supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation, clinicians should prescribe dexamethasone 6 mg IV/PO daily for 10 days (or equivalent glucocorticoid dose) 4 , or until off oxygen or discharged, whichever is earlier. Glucocorticoids are not recommended in patients who do not have hypoxemia requiring supplemental oxygen.

# Antibacterials
- For those patients with suspected or confirmed mild to moderate COVID-19, antibiotics should not be routinely prescribed unless there is clinical suspicion of a bacterial infection.
- For patients with severe COVID-19 but not critically ill, do NOT routinely add antibacterials unless bacterial infection is strongly suspected.
- For critically ill patients with suspected or confirmed severe COVID-19, empiric antibacterial agents to treat all likely pathogens causing severe acute respiratory bacterial infection and sepsis as soon as possible are reasonable, and optimally should be initiated within 1 hour of initial patient assessment for patients with sepsis.
- If indicated, empiric antibiotic treatment should be based on the working clinical diagnosis (e.g., community-acquired pneumonia, health care-associated pneumonia or sepsis), local epidemiology, and susceptibility data. See references such as Bugs & Drugs for empiric antibacterials.
- Use of antibacterial therapy should be judicious with reassessment after 3 days for de-escalation and/or optimization of therapy, in accordance with the principles of stewardship, after review of the clinical status, laboratory and imaging findings, and microbiology results.

# Antivirals/Immunomodulators
- Remdesivir has two approved formulary indications in AHS. Hospitalized patients with COVID-19 pneumonia, defined as having oxygen requirements above pre-hospitalization baseline (SpO2 less than 94% on room air, or requiring O2 supplementation to maintain SpO2 greater than 94%) and/or new infiltrates on chest X-ray not caused by other health conditions, who are not invasively mechanically ventilated, are eligible for a 5-day course of remdesivir (200 mg IV on day 1, followed by 100 mg IV daily on days 2-5) 5,6 . High risk inpatients admitted for non-COVID reasons with incidental or hospitalacquired COVID-19 are eligible for a 3-day course of remdesivir (200 mg IV on day 1, followed by 100 mg IV daily on days 2 and 3) 7 . See the AHS formulary for full eligibility criteria. In select clinical circumstances where multi-agent therapy including remdesivir, or extended duration remdesivir is being considered for highly immunocompromised people, Infectious Diseases consultation is required (in person or phone).
- Tocilizumab is approved for use in patients with severe COVID-19 pneumonia 8 . To be eligible, patients must have been admitted to hospital for COVID-19 pneumonia 7 or fewer days ago, or have developed symptoms from hospital-acquired COVID-19 pneumonia 7 or fewer days ago. They must also be experiencing significant progressive respiratory failure due to COVID-19 pneumonia that requires they receive ventilation (invasive or non-invasive) or supplemental oxygen to achieve a minimum SpO2 of 90%. Supplemental oxygen is defined as heated high flow oxygen with FiO2 > 0.5, nasal prong delivered oxygen at a rate of 6 L/minute, or mask delivered oxygen with FiO2 > 0.5. Furthermore, tocilizumab must be initiated within 24 hours of initiation of mechanical ventilation or, if not mechanically ventilated, as soon as possible. Tocilizumab is restricted for this indication to one dose per patient per hospitalization, dosed as follows:  40 kg: 400 mg Tocilizumab should not be used in patients who have received baricitinib for the treatment of COVID-19 during their current hospitalization. They each work on the same inflammatory pathway, so added benefit is unlikely. Due to their immunosuppressant effects, combination therapy may have adverse effects. 9
- Sarilumab is approved as an alternative to tocilizumab when tocilizumab is not available, using the same eligibility criteria as tocilizumab. It is available in Canada in a subcutaneous formulation, but is administered intravenously as a single 400mg dose for the treatment of COVID-19. It has the same mechanism of action as tocilizumab but has not been studied as widely. It was directly compared to tocilizumab in the REMAP-CAP trial 10 , and was found to lead to a similar reduction in mortality, albeit with less precision due to the much smaller number of patients given sarilumab. A network metaanalysis 11 done in support of the World Health Organization (WHO) living guidelines for COVID-19 therapeutics 12 concluded that sarilumab likely has similar effectiveness to tocilizumab, although their recommendation to use sarilumab has less certainty due to the smaller number of subjects and studies included in the meta-analysis. Approval of sarilumab was based on the similar mechanisms of action, direct trial evidence, and indirect network meta-analysis evidence. Sarilumab should not be used in patients who have received tocilizumab or baricitinib for the treatment of COVID-19 during their current hospitalization. They each work on the same inflammatory pathway, so added benefit is unlikely. Due to their immunosuppressant effects, combination therapy may have adverse effects. 9
- Baricitinib is approved for use in patients with severe COVID-19 pneumonia. To be eligible patients must be experiencing significant progressive respiratory failure due to COVID-19 pneumonia that requires they receive ventilation (invasive or non-invasive) or supplemental oxygen to achieve a minimum SpO2 of 90%. Supplemental oxygen is defined as heated high flow oxygen with FiO2 > 0.5, nasal prong delivered oxygen at a rate of 6 L/minute, or mask delivered oxygen with FiO2 > 0.5.
Baricitinib is an oral tablet given by mouth or enteral tube 4 mg once daily for 14 days or until discharge, whichever is sooner. The main trial 13 upon which approval of use was based excluded patients with eGFR < 30 mL/min/1.73m 2 . It was dosed at 2 mg daily for those with eGFR 30 to < 60 mL/min/1.73m 2 . However, the US Food and Drug Administration Emergency Use Authorization (FDA Current Guidance for the Management of Adult Hospitalized Patients with COVID-19 Document Owner: COVID-19 Therapeutics Working Group EUA) 14 also lists dosing of 1 mg for patients with eGFR 15 to < 30 mL/min/1.73m 2 . Baricitinib 1 mg tablets are not available in Canada, so for patients with eGFR in this range, the recommended dose is 2 mg every other day. Baricitinib should not be used in patients who have received tocilizumab or sarilumab for the treatment of COVID-19 during their current hospitalization. They each work on the same inflammatory pathway, so added benefit is unlikely and due to their immunosuppressant effects, combination therapy may have adverse effects. 9
- Casirivimab/imdevimab is no longer approved for use in hospitalized patients. Unfortunately, it fails to neutralize the Omicron variant in in vitro assays 15,16 . As Omicron constitutes nearly all cases of COVID in Alberta, and results from both COVID serology and variant of concern testing are required to determine the appropriateness of casirivimab/imdevimab, it is no longer appropriate as a treatment option. Variant of concern results take long enough to return that serology results may no longer be valid once variant status is known, as patients may have seroconverted in the meantime. Serology testing should no longer be ordered to help direct treatment for COVID-19 patients.
- Sotrovimab should only be used in patients who are confirmed to have the Omicron BA.1 variant, or any variants that emerged prior to Omicron (Alpha, Beta, Gamma, or Delta). As of May 13, 2022, the vast majority of new COVID cases in Alberta are from the Omicron BA.2 sub-variant, against which sotrovimab is unlikely to be effective. If a patient is confirmed to have one of the aforementioned approved variants, it can be used for outpatients, inpatients admitted for non-COVID reasons, and inpatients with hospital-acquired COVID-19, who are at high risk of progression to severe disease. See the AHS formulary for full eligibility criteria.
There is currently no clinical evidence to support the use of sotrovimab in patients hospitalized due to COVID-19. The ACTIV-3-TICO trial randomized 344 inpatients to receive either sotrovimab (n=169) or placebo (n=175). The trial was stopped early due to futility, meaning the evidence to date suggested it was of no benefit. Among sotrovimab recipients, there was one case of anaphylaxis and one case of cytokine release syndrome 17 .
- Nirmatrelvir-ritonavir (Paxlovid) is an oral COVID-specific antiviral approved for use in for high risk outpatients, as well as inpatients admitted for non-COVID reasons with incidental or hospital-acquired COVID-19, if therapy can be initiated within 5 days of symptom onset. See the AHS formulary for full eligibility criteria. Published data suggests it significantly reduces risk of hospitalization or death in outpatients at high risk for progression to severe disease 18 . Paxlovid has numerous significant drug interactions that may make patients ineligible for treatment. Outpatients who think they may be eligible for treatment with Paxlovid are advised to call the dedicated Alberta HealthLink phone line at 1-844-343-0971. Centralized assessing and prescribing physicians will determine eligibility and arrange for treatment in the community, if appropriate.
- Bamlanivimab is no longer available within AHS. All available stock expired. No future purchases will be made due to greater than 10-fold reduction in neutralizing activity against variants of concern 19 .
- Consideration of all other investigational antivirals or immunomodulators (e.g. lopinavir/ritonavir, famotidine, and colchicine) should be only under ethics approved, controlled trials.
- There is currently insufficient evidence to recommend routine use of fluvoxamine in outpatients 2,20 . It is not recommended for inpatient use.
- The use of hydroxychloroquine, or any hydroxychloroquine combinations (e.g. hydroxychloroquine plus azithromycin), is not recommended as a treatment in patients with COVID-19.
- Ivermectin should not be used for the prevention or treatment of COVID-19. 21 Its use is not supported by evidence 22 .
- Convalescent plasma is not recommended as a treatment in patients with COVID-19. Evidence suggests it has no benefit 23 .

# General Investigations
Please note the listed investigations below are for clinical consideration and not required tests. Please use the laboratory tests and Investigations incorporated into care pathways and order sets if there are differences between those and the list below.

# General Laboratory tests:
Laboratory tests may not be required in otherwise ambulatory patients who are clinically stable, and not felt to be at elevated risk of decompensation. In the presence of higher clinical severity and/or comorbidities, the following laboratory tests may be considered: 
- CBC & differential -