ESCMID rapid guidelines for assessment and management of long COVID

a b s t r a c tScope: The aim of these guidelines is to provide evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and to provide a definition for this entity, termed 'long COVID'. Methods: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design. Recommendations: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high-quality prospective clinical studies/trials, including a control group, to further evaluate the assessment and management of individuals with persistent symptoms of COVID-19. Dana Yelin, Clin Microbiol Infect 2022;28:955 Scope Long COVID is an umbrella term referring to signs and symptoms that persist after acute SARS-CoV-2 infection. The prevalence
of long COVID is highly heterogeneous among studies, probably reflecting the variability of definitions of this entity, the populations surveyed, and follow-up durations. According to the literature, 22% to 40% of convalescent patients are expected to experience one or more symptoms of long COVID [bib_ref] Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients, Peghin [/bib_ref]. The most common symptoms include fatigue, dyspnoea, cognitive impairment, and various pain symptoms (e.g. chest pain, headache, myalgia). Despite the mounting evidence, there are still significant gaps in our knowledge regarding pathogenesis, actual incidence, The search hierarchy was to first identify systematic reviews and meta-analyses, followed by randomized controlled trials and observational comparative studies. Prospective cohort, retrospective cohort, and case-control studies, as well as case series were included. Case reports and case series including less than 20 participants were excluded, unless they provided an innovative finding. If a methodologically appropriate meta-analysis was identified to answer a specific question, we planned to end the search for additional studies.
Key questions were formulated in a PICO format (population/ participant, intervention, comparator/control, outcome) when appropriate. Population/participant was defined as any adult patient (!18 years) after the acute phase of COVID-19 (see definitions given in the following). Intervention was defined as any intervention for the assessment and management (pharmacological or other) of participants, and comparison/control as patients receiving a comparator intervention (studies comparing two interventions) or no intervention. Outcomes for management was defined as any outcome addressing improvement in physical, cognitive, or mental function, including quality-of-life measures. We did not attempt to contact the study authors for primary data.
Two independent panel members performed the search and screened for relevant studies. Any discrepancies were resolved through discussion with a third panel member. The process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement [bib_ref] Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement, Moher [/bib_ref].

# Search results
The PubMed search yielded 13 881 titles (13 066 after exclusion of 815 duplicates). After inspection of titles and abstracts, 12 390 articles were excluded due to irrelevant study design, irrelevant population, or irrelevant topic. Subsequently, 676 articles were further inspected in full text, and 529 were excluded for similar reasons. Overall, we present data on 147 studies. Due to the paucity of comparative and/or randomized data, no recommendation could be based on evidence, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was not used.

## Quality of evidence scoring
Quality assessment of included studies was performed by two panel members independently, and discrepancies were resolved through discussion with a third member. For systematic reviews and meta-analysis, we used the AMSTAR tool for quality assessment [bib_ref] AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised..., Shea [/bib_ref]. Studies were graded as having high, moderate, low, and critically low quality of evidence according to the AMSTAR critical appraisal tool [bib_ref] AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised..., Shea [/bib_ref]. For randomized controlled trials (RCTs), risk of bias was assessed using the domains recommended by the Cochrane handbook. Studies were graded as having low, high, or unknown risk of bias per the Cochrane handbook criteria [bib_ref] Updated guidance for trusted systematic reviews: a new edition of the Cochrane..., Cumpston [/bib_ref]. For nonrandomized studies, the Newcastle Ottawa tool was used. We planned to classify evidence certainty per question as high, moderate, low, or very low and recommendation strength as strong or conditional according to the GRADE system [bib_ref] The GRADE system for rating clinical guidelines, Kavanagh [/bib_ref]. The panel also provided recommendations for research.

## Definitions of long covid
The WHO defines post-COVID-19 condition as persistent symptoms and/or signs, developing during or after an acute COVID-19 illness and lasting for at least 2 months and persisting beyond 12 weeks from the acute disease, that cannot be explained by an alternative diagnosis [bib_ref] WHO clinical case definition working group on post-COVID-19 condition. A clinical case..., Soriano [/bib_ref]. The CDC provides a similar definition, with a different timeframe of beyond 4 weeks after the acute disease. The Royal Society defines the same condition; however, no time frame is provided [bib_ref] WHO clinical case definition working group on post-COVID-19 condition. A clinical case..., Soriano [/bib_ref]. A similar term called post-acute sequelae of SARS-CoV-2 infection has been termed by the National Institutes of Health. A repository of published/available definitions of posteCOVID-19 condition is maintained by the WHO [bib_ref] WHO clinical case definition working group on post-COVID-19 condition. A clinical case..., Soriano [/bib_ref].
Although no consensus regarding a single term for long COVID/ posteCOVID-19 condition has been obtained by a WHO Delphi process [bib_ref] WHO clinical case definition working group on post-COVID-19 condition. A clinical case..., Soriano [/bib_ref] , we used the term long COVID in the current guidelines. [fig_ref] Table 1: Summary of definitions for long COVID/post-acute COVID according to level of certainty... [/fig_ref] provides the definitions used for long COVID for the purposes of this document.
Long COVID is defined herein as one or more symptoms and/or signs (detailed in the following) persisting or relapsing/remitting for more than 12 weeks since an acute COVID-19 diagnosis, without an alternative explanation. This condition can affect all individuals who encountered COVID-19, regardless of the severity of the acute disease. The syndrome can be definite, probable, or possible, according to the level of certainty of the original acute COVID-19 infection [fig_ref] Table 1: Summary of definitions for long COVID/post-acute COVID according to level of certainty... [/fig_ref]. We define post-acute COVID as one or more symptoms and/or signs persisting or relapsing/remitting from 4 to 12 weeks since a confirmed acute COVID-19 diagnosis, without an alternative diagnosis. This definition also includes several specific entities (thyroiditis, myocarditis, venous thromboembolism) that may appear during this period.

## Symptoms and risk factors of long covid
Across systematic reviews/meta-analyses, the most commonly observed symptoms among patients with long COVID are fatigue (31%e58%), dyspnoea (24%e40%), musculoskeletal pain (9%e19%), anosmia/dysgeusia (10%e22%), cognitive impairment (or brain fog; 12%e35%), sleep disturbances (11%e44%), cough (7%e29%), and chest pain (6%e17%) . provides a summary of reported symptoms and their respective prevalence ranges. [fig_ref] Table 4: Prevalence of long COVID symptoms in studies investigating patients regardless of disease... [/fig_ref] provide symptom prevalence according to time intervals from the acute illness (1e3 months, 3e6 months, >6 months) and hospitalization status, respectively. Persisting symptoms seem to considerably affect patients' quality of life and return to daily activities and work. A systematic review of 39 studies found that decreased quality of life was reported among 57% of patients with symptoms persisting beyond 12 weeks [bib_ref] A systematic review of persistent symptoms and residual abnormal functioning following acute..., Jennings [/bib_ref]. Follow-up studies report persistence of long-COVID symptoms up to 12 months after the acute disease [bib_ref] Sequelae in adults at 12 months after mild-to-moderate coronavirus disease 2019 (COVID-19), Boscolo-Rizzo [/bib_ref] [bib_ref] 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, Huang [/bib_ref].
The pathophysiologic mechanisms that underlie this disorder remain largely unknown, but available data implicate the multisystemic nature of COVID-19, immune dysregulation, autoimmunity, and the neurotropism of SARS-CoV-2 [bib_ref] Long COVID has exposed medicine's blind-spot, Burke [/bib_ref] [bib_ref] Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation,..., Song [/bib_ref] [bib_ref] Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments, Yong [/bib_ref]. Posteintensive care syndrome may provide an explanation for prolonged symptoms after critical COVID-19. This syndrome encompasses new or worsening abnormalities in physical, cognitive, and psychiatric domains after critical illness [bib_ref] Post-acute COVID-19 syndrome, Nalbandian [/bib_ref]. For patients who have long-COVID symptoms after critical care, it is difficult to distinguish whether persisting symptoms are caused by SARS-CoV-2 infection or posteintensive care syndrome.
Data on potential factors associated with an increased risk of developing specific long-COVID symptoms are accumulating in the literature, although the evidence is inconsistent. The two consistent risk factors for any long-COVID symptom are acute COVID-19 severity and sex [fig_ref] Table 1: Summary of definitions for long COVID/post-acute COVID according to level of certainty... [/fig_ref] [32e34]. Women have been shown to have an estimated two-fold risk of having long-COVID symptoms (OR: 1.3e5). Similarly, severe acute disease has been associated with an increased risk for long-COVID symptoms, with the strongest association with fatigue. Other risk factors, such as age, obesity, and the presence of comorbidities, have shown mixed results [fig_ref] Table 1: Summary of definitions for long COVID/post-acute COVID according to level of certainty... [/fig_ref].

## Recommendations
We aimed to answer the following PICO questions: (a) Who should be assessed; (b) what assessment is needed for individuals with long COVID (subdivided according to systems and further subdivided by specific tests); and (c) how should individuals with long COVID be managed (also subdivided according to systems). Each section reports the main summary of evidence for each topic. Tables 5e8 provide details of the studies included.

## Who should be assessed for long covid?
In symptomatic patients, other serious/life-threatening conditions should be ruled out prior to considering long COVID. These include prior overlooked conditions (e.g. malignancy) or complications of acute COVID-19 (e.g. thromboembolic events, myopericarditis, encephalitis). The investigation for other conditions should be guided by symptoms, signs, and other tests, performed according to the physician's discretion. Long COVID is a diagnosis of exclusion.

## Recommendation
As a first step, collecting specific clinical history is recommended to rule out previous underlying conditions, as well as iatrogenic causes or complications related to the acute episode. Hence, any patient with persisting or new symptoms that last more than 12 weeks after acute COVID-19 should be referred to medical care. For patients with symptoms 4 to 12 weeks after acute infection, assessment should be considered on a case-by-case basis, according to the severity and course of symptoms.

## General blood tests
Few studies have assessed the use of routine blood tests in patients with long COVID. Huang et al., at a follow-up of 12 months after patients with COVID-19 were hospitalized, demonstrated low rates of laboratory abnormalities and no significant difference in rates of lymphocyte count <0.8 A 109 per L or serum creatinine abnormality between recovering participants and controls. Nevertheless, as suggested, blood tests according to symptoms should be performed as part of an investigation to rule out other conditions. Some blood tests may be considered to identify possible complications after acute infection. These, however, should be interpreted with caution due to possible persistent abnormalities after COVID-19. In one study evaluating 734 patients with severe disease 28 days after recovery, an increase in insulin dependency from 18% to 63% was noted, and 1.4% of new-onset diabetes cases were identified [bib_ref] Clinical characteristics and short term outcomes after recovery from COVID-19 in patients..., Akter [/bib_ref]. Two additional studies found an increase in new-onset diabetes in the months after recovery from COVID-19 [bib_ref] Consortium for Characterization of COVID-19 by EHR (4CE), Patel CJ et al...., Estiri [/bib_ref] [bib_ref] Clinical characteristics and the long-term post-recovery manifestations of the COVID-19 patientseA prospective..., Chowdhury [/bib_ref] This might be a result of surveillance bias in previously unknown diabetics or a real shift from prediabetes to diabetes caused by the acute disease or its treatment, although there is no evidence for the latter. Elevated D-dimer can be observed at a median of >2 months after resolution of acute COVID-19, despite normalization of inflammatory markers and other coagulation parameters [bib_ref] Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of..., Townsend [/bib_ref]. Similarly, detectable levels of high-sensitivity troponin T (>3 pg/ mL) were reported in 71 of 100 patients evaluated at a median of 71 days (interquartile range (IQR), 64e92 days) after diagnosis of COVID-19, with 5 of 100 patients having significantly elevated high-sensitivity troponin T levels (>13.9 pg/mL) [bib_ref] Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus..., Puntmann [/bib_ref]. Increased NT-pro-BNP levels at a median follow-up of 71 days (IQR, 14e124 days) were reported from a systematic review in 10% of individuals tested (57 of 571) [bib_ref] Durante-mangoni E, monaldi hospital cardiovascular infection study group. Cardiac sequelae after coronavirus..., Ramadan [/bib_ref]. A systematic review accumulated data on 27 patients presenting with subacute thyroiditis after COVID-19 infection. Patients presented with typical features, including elevated fT4 and fT3, low thyroid stimulating hormone, and raised inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) [bib_ref] COVID-19-associated subacute thyroiditis: evidence-based data from a systematic review, Trimboli [/bib_ref].

## Recommendation
As recommended by other guidelines [5e7], the following may be considered for symptomatic patients according to symptoms: C-reactive protein, blood count, kidney function, and liver function tests. Consider troponin, CPK-MB, and B-type natriuretic peptide for cardiac symptoms and complete thyroid function tests to rule out thyroiditis, if clinically suspected. For patients with decreased oxygen saturation, blood gases are recommended by some guidelines, although the benefit of this test is limited. Ddimer should not be used in patients without respiratory symptoms. Patients at increased risk for diabetes or impaired fasting glucose should be monitored for fasting glucose and glycated haemoglobin levels.

## What assessment is needed for individuals with long covid?
After ruling out other conditions, the following evaluations are suggested for individuals with suspected long COVID. First, the evaluation should include an interview with the patient to identify symptom severity and their impact on quality of life. Physicians should consider whether further assessment is needed for symptoms that are self-limited and without an effective and safe therapy. Options for therapy that can be considered in the context of clinical trials are discussed later in this article.

## Investigating individuals with dyspnoea
In previous guidelines/recommendations [5e7], a diagnostic pathway is suggested for patients with dyspnoea persisting more than 4 to 12 weeks after acute COVID-19. Several studies used the modified Medical Research Council dyspnoea scale to assess severity of dyspnoea but did not provide a cut-off, thus necessitating further investigation [bib_ref] Postdischarge critical COVID-19 lung function related to severity of radiologic lung involvement..., Truffaut [/bib_ref] [bib_ref] A follow-up study of lung function and chest computed tomography at 6..., Wu [/bib_ref].

## Pulmonary function testing
Various rates of abnormal pulmonary function testing (PFT) have been reported in recovering patients, depending on definitions of abnormality, duration of follow-up, baseline (pre-COVID) pulmonary function, and mainly acute COVID-19 severity and the need for ventilatory support [bib_ref] Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month..., Qin [/bib_ref]. The most frequently impaired Prevalence of most common long-COVID/post-COVID-19 condition symptoms according to systematic reviews/meta-analyses pulmonary function test is diffusion capacity for carbon monoxide (DLCO), and the most frequent pattern observed is restrictive. DLCO impairment (<80% of predicted) has been found in varying proportions of patients, in correlation to disease severity. After critical disease and intensive care unit (ICU) admission, patients had up to 80% abnormal DLCO at discharge and 50% to 70% impairment at 3month follow-up. After severe disease, patients had 30% to 68% impairment at 3 months [bib_ref] Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month..., Qin [/bib_ref] [bib_ref] Radiological and functional lung sequelae of COVID-19: a systematic review and meta-analysis, So [/bib_ref]. At 3 months, higher computed tomography (CT) severity score and acute respiratory distress syndrome at acute disease were associated with impaired DLCO in one study including hospitalized patients [bib_ref] Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month..., Qin [/bib_ref]. Surprisingly, even among patients after mild-to-moderate disease, abnormal DLCO was demonstrated in approximately 10% [bib_ref] Radiological and functional lung sequelae of COVID-19: a systematic review and meta-analysis, So [/bib_ref]. Future progression to pulmonary fibrosis has been raised as a concern [bib_ref] Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy, George [/bib_ref] When tested at 6 months, patients exhibited somewhat lower rates of abnormalities than at 3 months, although the rates were still high (DLCO reduced in 29% for severe, 58% for critical) [bib_ref] 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Huang [/bib_ref]. This correlates with the finding that, on serial testing of patients with a restrictive pattern, tested individuals demonstrated an overall improvement at 6 months compared with 10 weeks, but not complete resolution [bib_ref] Clinical status and lung function 10 weeks after severe SARS-CoV-2 infection, Smet [/bib_ref] [bib_ref] Evolution of lung function and chest CT 6 months after COVID-19 pneumonia:..., Stylemans [/bib_ref]. At a longer follow-up of 1 year, Huang et al. reported DLCO <80% in 23% to 54% of 243 patients with severecritical acute COVID-19. Total lung capacity less than 80% of predicted decreased among critically ill patients from 39% at 6 months, but was still considerable at 29% at 12 months [bib_ref] 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, Huang [/bib_ref].
There is a paucity of data for patients with mild-to-moderate disease. Several studies included some patients after mild-tomoderate disease, mostly as a control group for the patients with severe disease [bib_ref] 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Huang [/bib_ref] [bib_ref] Pulmonary function and radiological features 4 months after COVID-19: first results from..., Guler [/bib_ref] [bib_ref] Comprehensive health assessment three months after recovery from acute COVID-19, Van Den Borst [/bib_ref]. These studies reported normal median PFTs and DLCO, but a considerable percentage of patients (10%e 22%) still had abnormal results.

## Recommendation
Evidence is insufficient to provide a recommendation for or against PFT. Considering that the test is simple and noninvasive and that future studies may suggest beneficial treatment for patients with abnormal PFT, the panel recommends considering routine PFT, including diffusion capacity, in all patients with severe and critical COVID-19 at 3 months from diagnosis, regardless of symptoms, as well as considering completing PFT with diffusion for patients Prevalence of symptoms by time from acute diseases Symptom 4e12 wk (%), range [bib_ref] A systematic review of persistent symptoms and residual abnormal functioning following acute..., Jennings [/bib_ref] 3 e6 mo (meta-analysis), % (95% CI) [bib_ref] Characterising long COVID: a living systematic review, Michelen [/bib_ref] 6e12 mo (%), range reporting persistent dyspnoea 3 months after acute disease and those with known prior lung disease.
Chest imaging Chest X-ray. Two observational studies investigating follow-up chest x-ray in patients with COVID-19 at 6 to 8 weeks concluded that it is a poor marker for recovery, demonstrating correlation to severity of initial disease but not to ongoing symptoms [bib_ref] Symptomatic, biochemical and radiographic recovery in patients with COVID-19, Mallia [/bib_ref] [bib_ref] Chest radiography is a poor predictor of respiratory symptoms and functional impairment..., D&apos;cruz [/bib_ref]. Three additional small observational studies reported conflicting findings. One study found reticular opacities/peripheral atelectasis in 88% and ground-glass opacities in 61% of x-rays performed at 8 to 12 weeks, and the other two studies found only 12% and 7% abnormalities, respectively (Tables 5e7) [bib_ref] Comprehensive health assessment three months after recovery from acute COVID-19, Van Den Borst [/bib_ref] [bib_ref] Radiological management and follow-up of post-COVID-19 patients, Alarc On-Rodriguez [/bib_ref] [bib_ref] Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from..., Arnold [/bib_ref]. Long-term followup data are lacking. Among survivors of SARS and Middle East respiratory syndrome severe illness, chest x-ray was found to have residual abnormalities in approximately a third of patients at 3 and even 6 months [bib_ref] Followup chest radiographic findings in patients with MERS-CoV after recovery, Das [/bib_ref] [bib_ref] Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity..., Hui [/bib_ref]. No studies had correlated abnormal chest xray with clinical outcomes.
Recommendation. Evidence is insufficient to provide a recommendation for or against chest x-ray. Chest x-ray may be considered in patients with long COVID and persistent respiratory symptoms at 3 months to rule out other diagnoses and for a possible early diagnosis of pulmonary fibrosis.
Chest computed tomography/magnetic resonance imaging. Chest CT in patients after severe and critical disease frequently shows abnormalities, mainly ground glass opacities (GGOs), consolidations, and fibrotic changes. These changes are reported in approximately 60% to 75% of patients at 3 months .
A systematic review summarizing chest CT findings at 3 to 6 months after COVID-19 of any severity, rates of polled CT abnormalities were 59% (IQR, 44%e73%), with GGO being the most prevalent pattern (39%; IQR, 26%e52%), followed by fibrosis and reticulation (each approximately 30%) [bib_ref] Long-term impact of COVID-19: a systematic review of the literature and meta-analysis, Sanchez-Ramirez [/bib_ref]. According to two studies including around 500 patients, approximately 60% still had parenchymal findings at 6 months [bib_ref] Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase, Huang [/bib_ref] [bib_ref] Six-month follow-up chest CT findings after severe COVID-19 pneumonia, Han [/bib_ref]. In one of these studies, fibrotic-like changes were reported in 35% of patients (40 of 114) [bib_ref] Six-month follow-up chest CT findings after severe COVID-19 pneumonia, Han [/bib_ref]. These findings correlated with older age and severity of acute disease and were reported regardless of ongoing symptoms. It is still unknown whether these findings predict future lung impairment. Later chest CT follow-up results were reported by Huang et al. for hospitalized patients 12 months after acute COVID. This study reported abnormal CT findings at 1 year for 55% of patients , with GGOs in 46%, mainly derived from critically ill patients, who had abnormalities in 87% of examinations [bib_ref] 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, Huang [/bib_ref]. Chest magnetic resonance imaging (MRI) was performed on 53 recovering patients at 2 to 3 months, showing parenchymal abnormalities in 60% (n 14 32), without clear clinical correlation [bib_ref] Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition,..., Raman [/bib_ref].
Limited data are available to report the long-term chest CT findings in mild-to-moderate patients, with some data showing similar rates of abnormalities as for severe patients and some showing lower rates. In the Huang et al. cohort, at 6 months, hospitalized patients with mild-to-moderate disease had CT abnormalities in approximately 50% of patients, which was similar to patients with more severe disease; however, at 1 year, rates were significantly lower among patients with mild-to-moderate disease (39%) [bib_ref] 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, Huang [/bib_ref] [bib_ref] 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Huang [/bib_ref] Another study reported similar rates of chest CT abnormalities among 51 patients recovering from moderate COVID-19 compared with those with severe disease. Signs of fibrosis specifically were significantly less common among patients with moderate disease [bib_ref] Comprehensive health assessment three months after recovery from acute COVID-19, Van Den Borst [/bib_ref]. In another study, CT abnormalities at 6 months were significantly less common among patients with moderate (~3%) compared with severe (53%) disease [bib_ref] A follow-up study of lung function and chest computed tomography at 6..., Wu [/bib_ref].
Recommendation. Evidence is insufficient to provide a recommendation for or against chest imaging. Chest CT should be considered at 3 to 6 months in patients with dyspnoea or abnormal PFTs, regardless of symptoms, to rule out other causes and identify fibrotic changes.
Investigating patients with dyspnoea, cardiac complaints, and fatigue Cardiac imaging. Reports on severe cardiac complications (pericarditis, myocarditis, heart failure, and cardiac arrhythmias) after COVID-19 have been published, although causality is not always evident. One observational study showed that 27.5% of patients (14 of 51) admitted for evaluation of cardiac symptoms (chest pain, palpitations, effort dyspnoea, oedema) 2 months after acute COVID-19 were diagnosed with severe cardiovascular complications [bib_ref] COVID-19 and cardiovascular complicationsePreliminary results of the LATE-COVID study, Lewek [/bib_ref]. However, this reflects the most severe end of the spectrum, due to selection bias. Another study assessed patients referred to outpatient cardiology evaluation in the first 3 months after mild-tomoderate disease and reported transthoracic echocardiographic (TTE) abnormalities in 25% of patients (38 of 150), mostly reduced ejection fraction (EF), elevated pulmonary artery pressure, diastolic dysfunction, and thickened pericardium [bib_ref] Associations between the severity of the post-acute COVID-19 syndrome and echocardiographic abnormalities..., Tudoran [/bib_ref]. Additional studies demonstrated considerable rates of TTE findings in asymptomatic people 30 to 100 days after COVID-19, including a reduction in the left ventricular global longitudinal strain, diastolic dysfunction, and pulmonary hypertension [bib_ref] Elevated highsensitivity troponin is associated with subclinical cardiac dysfunction in patients recovered..., Hayama [/bib_ref] [bib_ref] Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial, Sonnweber [/bib_ref]. At a similar follow-up duration, a systematic review reported echocardiographic findings for symptomatic patients with variable severity, including diastolic dysfunction in up to 55% of individuals tested, reduced left ventricular EF in up to 16%, and pulmonary hypertension in up to 10% [bib_ref] Durante-mangoni E, monaldi hospital cardiovascular infection study group. Cardiac sequelae after coronavirus..., Ramadan [/bib_ref].
Cardiac MRI studies have shown common abnormalities ranging from 19% to 71% in recovering patients at 1 to 4 months . These findings usually did not correlate with symptoms and were temporary, as suggested by Joy at el., and demonstrated resolution of findings at 6 months after diagnosis [bib_ref] Prospective case-control study of cardiovascular abnormalities 6 months following mild COVID-19 in..., Joy [/bib_ref]. In data from systematic reviews, including variable severity of an acute COVID-19 population at a follow-up of 14 to 180 days, cardiac MRI abnormalities were reported with wide variability, and in up to 60% of 73% of tested patients. In four studies reporting formal diagnoses using cardiac MRI, myocarditis was reported in 0% to 37%, myopericarditis in 0% to 11%, pericarditis in 0% to 3%, and myocardial infarction in 0% to 2% of patients [bib_ref] Durante-mangoni E, monaldi hospital cardiovascular infection study group. Cardiac sequelae after coronavirus..., Ramadan [/bib_ref] [bib_ref] Cardiac magnetic resonance imaging findings in 2954 COVID-19 adult survivors: a comprehensive..., Hassani [/bib_ref].
Recommendation. Evidence is insufficient to provide recommendations for or against any of the aforementioned cardiac tests. Considering TTE is noninvasive, it may be offered for patients presenting with persistent symptoms suggestive of perimyocardial injury (chest pain, palpitations, signs and symptoms of heart failure). It is reasonable that for patients who had cardiac abnormalities during acute disease (myocarditis, pericarditis, heart failure), a repeat TTE would be performed at 2 to 3 months. Further investigation for cardiac abnormalities should be performed according to symptoms in patients presenting with cardiac symptoms. Cardiac MRI should only be performed on a case-by-case basis with a specific clinical question in mind (e.g. athletes returning to physical activity).
Functional testing. There are several functional tests aimed at evaluating physical performance in frail and post-illness patients. The 6-minute-walk test (6MWT) includes measurement of distance walked during 6 minutes and SpO2 before and after. The sit-tostand test measures the number of repeats during a certain time period (15e30 seconds, usually). The Short Physical Performance Battery includes balance assessment in a standing position, walking speed for 4 minutes, and standing up from a chair with five repetitions. Several studies assessed discharged patients with acute or long COVID using these methods and mostly found moderate-to-severe impairment that correlated with acute disease severity .
Specifically, for the 6MWT, individuals recovering from COVID-19 exhibited inconsistent results in this test, depending on disease severity. In general, a mild-to-moderate limitation that was evident during the first few months after acute illness abated with time. A small comparative study found pulmonary rehabilitation to be effective in improving the physical capacity of recoverees, as reflected by the 6MWT [bib_ref] Six-month outcomes and effect of pulmonary rehabilitation among patients hospitalized with COVID-19:..., Dun [/bib_ref]. For the 6MWT according to disease severity in individual studies, refer to . Cardiopulmonary stress testing (CPET) can potentially reveal the mechanisms leading to subjective symptoms in individuals with long COVID. This has the potential to guide rehabilitation efforts. Although most studies assessed previously hospitalized individuals and found at least mild impairment months later, data gathered thus far have yielded conflicting results with respect to the pathophysiological mechanism contributing to dyspnoea and effort intolerance (see [fig_ref] Table 5: Studies addressing assessment of long COVIDdPulmonary function tests AMSTAR, A MeaSurement Tool... [/fig_ref]. Further research with appropriate control arms is warranted.
Recommendation. Evidence is insufficient to provide recommendations for or against any of the aforementioned functional tests. Consider performing them at the beginning of an interventional/rehabilitation program to assess progress.
Investigating patients with neurocognitive complaints Brain imaging. Few small studies have assessed brain imaging in patients with long COVID (Tables 5e7). Guedj et al. [bib_ref] 18F-FDG brain PET hypometabolism in patients with long COVID, Guedj [/bib_ref] conducted positron emission tomography/CT in 35 patients at a mean of 95.5  30 days after acute COVID-19 and compared the findings with age-and sex-matched historical uninfected controls. They found specific areas of hypometabolism that were associated with symptoms of hyposmia/anosmia, memory/cognitive impairment, pain, and insomnia and that were significantly distinguished from the control group [bib_ref] 18F-FDG brain PET hypometabolism in patients with long COVID, Guedj [/bib_ref]. These findings were also demonstrated in smaller studies [bib_ref] 18F-FDG-PET imaging for post-COVID-19 brain and skeletal muscle alterations, Rudroff [/bib_ref]. Raman et al. conducted a prospective study including 58 participants 2 to 3 months after acute moderate-tosevere COVID-19 compared with matched controls. Of the study cohort, 53 underwent brain MRI, with 32 showing abnormalities and higher rates of pathology in the thalamus and sagittal stratum compared with controls. Periventricular white matter hyperintensities in the study group did not correlate with cognitive impairment [bib_ref] Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition,..., Raman [/bib_ref].
Recommendation. Limited evidence does not support the use of brain imaging to investigate long-COVID complaints, other than to rule out other causes or for research purposes.
Psychological/psychiatric evaluation. Anxiety, depression, and posttraumatic stress disorder were reported in 16% to 47% of patients hospitalized for COVID-19 within 2 to 3 months of discharge, with no comparison to a control group [bib_ref] Psychological outcomes after hospitalization for COVID-19: data from a multidisciplinary follow-up screening..., Bonazza [/bib_ref] [bib_ref] A living systematic review of the psychological problems in people suffering from..., Dong [/bib_ref]. In a large retrospective cohort of 236 379 patients followed for 6 months after COVID-19, the estimated incidences of mood, anxiety, or psychotic disorders were higher compared with patients after other respiratory infections. Substance use disorders and insomnia were more common as well. Incidences of anxiety and psychotic disorder were 17% and 1.2%, respectively, for the entire cohort, but were higher in hospitalized patients and specifically those admitted to the ICU [bib_ref] 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a..., Taquet [/bib_ref].
Recommendations regarding psychological/psychiatric assessment are beyond the scope of these guidelines. Nevertheless, health care practitioners should be aware of the substantial incidence of psychological sequelae of COVID-19 of any severity, and, whenever relevant, refer patients for assessment and therapy.

## Management of patients with long covid
The studies included are summarized in [fig_ref] Table 8: Summary of studies addressing management of long-COVID/postCOVID-19 condition [/fig_ref].
Should post-discharge (extended) thromboprophylaxis be administered to patients with COVID-19?
Recommendations from several societies do not support routine use of post-discharge (extended) thromboprophylaxis based on low rates of post discharge venous thromboembolism (VTE) among patients with COVID-19 and studies addressing other hospitalized populations. All recommend individualized risk assessment and decisions. Extended prophylaxis refers to up to 45 days. The types of anticoagulation recommended include low-molecular-weight heparin or direct oral anticoagulants [84e87]. One randomized controlled trial suggested a benefit of rivaroxaban 10 mg daily compared with no anticoagulant after discharge in high-risk individuals [bib_ref] Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE):..., Ramacciotti [/bib_ref]. Other than this study, the recommendations are not based on comparative studies, but on considerations of risk and benefit.

## Recommendation
Evidence is insufficient to provide a recommendation for or against the intervention. It is advisable to perform individualized risk stratification of the risk for thrombotic events vs. haemorrhagic events. Consider extended anticoagulation prophylaxis for patients with a low risk of bleeding and elevated risk for VTE (active malignancy, immobility, history of VTE, recent major surgery, thrombophilia).

## Should physical or pulmonary rehabilitation be offered to patients, and when?
A meta-analysis and systematic review of RCTs was conducted to evaluate the effectiveness of pulmonary rehabilitation in interstitial lung disease in general, including COVID-19. This metaanalysis demonstrated improved walking distance in the 6MWT with the intervention (pooled effect size estimate for pulmonary rehabilitation: 44.55; 95% CI, 32.46e56.64), improved quality of life (effect size: 0.52; 95% CI, 0.22e0.82), improved dyspnoea (effect estimate: 0.39; 95% CI, e0.08 to 0.87), and significant improvement in lung function as evaluated by forced vital capacity (effect size: 0.37; 95% CI, 0.02e0.71) [bib_ref] Effectiveness of pulmonary rehabilitation in interstitial lung disease including coronavirus diseases: a..., Reina-Guti Errez [/bib_ref]. One small RCT included in the metaanalysis evaluated elderly patients discharged from the hospital after COVID-19 and demonstrated significant improvement in PFT, 6MWT, quality of life scale, and anxiety score with the intervention [fig_ref] Table 8: Summary of studies addressing management of long-COVID/postCOVID-19 condition [/fig_ref] [bib_ref] Respiratory rehabilitation in elderly patients with COVID-19: a randomized controlled study, Liu [/bib_ref].
A living systematic review evaluated rehabilitation specifically in COVID-19, both acute and post-acute phases, with one of the addressed questions being "what is the evidence for effect of intervention for limitation(s) of functioning?" [bib_ref] Rehabilitation and COVID-19: the Cochrane Rehabilitation 2020 rapid living systematic review, Ceravolo [/bib_ref] [bib_ref] Rehabilitation and COVID-19: a rapid living systematic review by Cochrane Rehabilitation Field..., De Sire [/bib_ref]. Only three comparative studies were available for this question, addressing different patients and comparisons [fig_ref] Table 8: Summary of studies addressing management of long-COVID/postCOVID-19 condition [/fig_ref]. One of these studies is the RCT by Liu et al. described earlier [bib_ref] Respiratory rehabilitation in elderly patients with COVID-19: a randomized controlled study, Liu [/bib_ref] [bib_ref] Effectiveness of pulmonary rehabilitation in COVID-19 respiratory failure patients post-ICU, Chikhanie [/bib_ref] [bib_ref] Outcomes of a COVID-19 recovery program for patients hospitalized with SARS-CoV-2 infection..., Hameed [/bib_ref]. Additional studies presented in this systematic review included noncomparative studies, all reporting significant improvement in symptoms and respiratory and general function in response to the intervention [fig_ref] Table 8: Summary of studies addressing management of long-COVID/postCOVID-19 condition [/fig_ref].
Explicit timing of starting rehabilitation was not provided in the literature. The British Society of Rehabilitation Medicine recommends that rehabilitation start on patient admission and be continued throughout hospitalization and then after discharge. Other guidelines for rehabilitation after critical illness in general recommend initiating rehabilitation programs within the first 30 days (at the post-acute phase). Rehabilitation programs should include (according to the individual patient) exercise, pulmonary, cardiac, musculoskeletal, neurological, and psychological rehabilitation [bib_ref] The Stanford Hall consensus statement for post-COVID-19 rehabilitation, Barker-Davies [/bib_ref].

## Recommendation
Evidence is insufficient to provide a recommendation for or against the intervention specifically for COVID-19. No data regarding persistent long COVID were identified. Until further evidence accumulates, it is reasonable that clinicians follow available consensus statements regarding multidisciplinary rehabilitation in the post-acute stage [bib_ref] The Stanford Hall consensus statement for post-COVID-19 rehabilitation, Barker-Davies [/bib_ref].
How should persistent pulmonary symptoms/signs be managed?
In one small, noncomparative, prospective study, 30 patients diagnosed with interstitial lung disease consistent with organizing pneumonia 6 weeks after discharge (persistent symptoms, functional or physiological abnormalities, and parenchymal abnormality on CT) were treated with corticosteroids (maximum initial dose of 0.5mg/kg prednisolone) for 3 weeks. All patients demonstrated significant symptomatic improvement, significant increase in gas transfer and forced vital capacity, and radiologic improvement [bib_ref] Persistent post-COVID-19 interstitial lung disease. An observational study of corticosteroid treatment, Myall [/bib_ref]. In another small study, the authors retrospectively reviewed the routine management of patients with abnormal CT findings over 4 weeks after COVID-19 and desaturation, treated with corticosteroids. At a follow-up at 12 to 14 weeks, 24 patients demonstrated improved fatigue, breathlessness, and cough, as well as improved modified Medical Research Council score, saturation at rest, 6MWT results, and imaging findings. However, others reported significant spontaneous recovery within 12 weeks for similar patients, raising the question of whether steroids are beneficial. Continuing steroids for patients with persistent hypoxemia and abnormal CT at discharge and/or follow-up has been suggested based on clinical experience but not tested in comparative clinical studies [bib_ref] Care of the postcoronavirus disease 2019 patient, Lafond [/bib_ref] [bib_ref] Post-COVID lung fibrosis: the tsunami that will follow the earthquake, Udwadia [/bib_ref].
Few cases of treatment of long-COVID lung fibrosis with antifibrotic agents have been reported [bib_ref] Usefulness of pirfenidone in COVID lung: a case series, Momen [/bib_ref]. This therapeutic option is currently being tested in clinical trials. Trials are ongoing to evaluate the use of the antifibrotic nintedanib and pirfenidone, as well as other drugs [104e106].

## Recommendation
Evidence is insufficient to provide a recommendation for or against any intervention.
How should persistent cough be managed?
There are no clinical studies evaluating the management of persistent cough after acute COVID-19. In a review discussing the possible pathophysiology and management of cough in patients with COVID-19, further investigation into the role of gabapentin and pregabalin, antimuscarinic drugs, and other novel drugs that interfere with the neuroinflammatory pathways has been suggested [bib_ref] Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation,..., Song [/bib_ref].

## Recommendation
Evidence is insufficient to provide a recommendation for or against any intervention.
How should smell and taste disturbances be managed?
A Cochrane systematic review aimed to assess interventions to treat persistent COVID-19erelated olfactory dysfunction. The search for RCTs for inclusion resulted in only one small trial comparing prednisone plus nasal irrigation (intranasal steroids with mucolytic and decongestant agents) for 15 days versus no treatment. The study included nine patients in each arm but was graded as high risk of bias, and the results were reported only up until 40 days, limiting the ability to draw conclusions [bib_ref] Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction, O&apos;byrne [/bib_ref].
Addison et al. conducted a systematic review evaluating the management of any postinfectious olfactory dysfunction. In total, 15 studies addressing this entity directly were included, but none specifically evaluated patients with COVID-19. The interventions tested included olfactory training and various topical and systemic treatments. All 11 studies evaluating olfactory training (not all comparative) showed a benefit of the intervention [bib_ref] Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory..., Addison [/bib_ref]. The manuscript included a consensus statement by the clinical olfactory working group, which recommended routine use of olfactory training, but was controversial regarding pharmacologic therapy with a recommendation to consider steroids (nasal or systemic), theophylline, and sodium citrate.
A role of smoking and olfactory dysfunction in general has been discussed. The consensus document states that the benefit of smoking cessation in patients with long-COVID anosmia/ageusia is not clear, but an overall benefit justifies the recommendation. Other therapies described that need further study include oral and intranasal corticosteroids, theophylline, sodium citrate, N-methyl D-aspartate antagonist (caroverine), traditional Chinese acupuncture, a-lipoic acid, vitamin A, minocycline, and zinc sulphate [bib_ref] Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory..., Addison [/bib_ref].
One low-quality RCT including 100 patients recovering from COVID-19 evaluated topical corticosteroid nasal spray (mometasone furoate) for 3 weeks combined with olfactory training versus olfactory training alone. In this study, no difference between groups was demonstrated in rates or patients with olfactory recovery or duration of anosmia/hyposmia [bib_ref] Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: a..., Abdelalim [/bib_ref]. An additional small, lowquality RCT evaluated insulin fast-dissolving film for intranasal delivery versus placebo in 40 post-COVID patients with olfactory loss. In this study, significantly higher olfactory detection scores were demonstrated with intervention (p 14 0.0163) [bib_ref] Insulin fast-dissolving film for intranasal delivery via olfactory region, a promising approach..., Mohamad [/bib_ref].

## Recommendation
Evidence is insufficient to provide a recommendation for or against any intervention. Due to its simplicity and safety, olfactory training should probably be suggested for all patients. Physicians should discuss the likelihood for spontaneous recovery with patients, and other interventions should be suggested only in clinical trials. Smoking cessation should be recommended.

## How should fatigue be managed?
Clinical overlap has been suggested between long COVID and postviral fatigue syndromes/postinfectious myalgia encephalomyelitis/chronic fatigue syndrome. For the latter, various interventions have been suggested [bib_ref] NICE guideline on long COVID, Sivan [/bib_ref] [bib_ref] Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)eA systemic review and comparison..., Wong [/bib_ref]. Systematic reviews of such interventions included various medications, complementary and alternative medicine, cognitive behavioural therapy, and exercise. The included studies were heterogeneous and data were limited, although the drug rintatolimod, counselling therapies, and graded exercise therapy suggested a benefit [bib_ref] Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review for a National..., Smith [/bib_ref] [bib_ref] A mixedmethods systematic review of post-viral fatigue interventions: are there lessons for..., Fowler-Davis [/bib_ref]. No evidence is available to support interventions for the management of fatigue in patients with long COVID. Graded exercise and cognitive behavioural therapy are controversial for the management of myalgia encephalomyelitis/chronic fatigue syndrome and should be further investigated for patients with long COVID prior to any recommendation [bib_ref] A mixedmethods systematic review of post-viral fatigue interventions: are there lessons for..., Fowler-Davis [/bib_ref].

## Recommendation
Evidence is insufficient to provide a recommendation for or against any intervention.
How should neurological/cognitive long-COVID sequelae be managed?
There are no clinical studies evaluating any pharmacological treatment for neurological sequelae of long COVID. The flavonoid luteolin has been suggested as a potential treatment, by inhibiting a proinflammatory cascade of mast cells and microglia activation in the hypothalamus. However, no studies have evaluated this intervention [bib_ref] Long-COVID syndromeassociated brain fog and chemofog: luteolin to the rescue, Theoharides [/bib_ref]. The cannabis derivatives cannabidiol and cannabivarin have been suggested to have the potential to bind to and downregulate central nervous system proteins related to long-COVID symptoms. These compounds have not been tested in clinical studies [bib_ref] Insilico inquest reveals the efficacy of cannabis in the treatment of post-COVID-19..., Sarkar [/bib_ref]. Methylene blue has been suggested as a possible therapy for neurocognitive impairment in long COVID due to its mitochondrial protective effects [bib_ref] Methylene blue: subduing the post-COVID-19 blues, Magoon [/bib_ref]. The therapeutic potential is theoretical, however, and without clinical evidence.

## Recommendation
Evidence is insufficient to provide a recommendation for or against any intervention.
How should emotional/psychiatric long COVID sequelae be managed?
Clomipramine, a tricyclic antidepressant with antiinflammatory action and penetrance to the central nervous system, has been suggested as a potential drug to prevent postinfectious mental complications. Further studies are needed [bib_ref] The antiinflammatory effect of the tricyclic antidepressant clomipramine and its high penetration..., Nobile [/bib_ref].

## Recommendation
Evidence is insufficient to provide a recommendation for or against any intervention.
Recommendations for future studies on long COVID As reflected in these guidelines, studies on long COVID are limited by the lack of a consistent definition of long COVID in terms of symptoms and timeframes, the absence of typical laboratory findings/diagnostic tests, and the absence of a comparison group in most studies. Selection bias might be pronounced due to the considerable portion of online recruitment studies [bib_ref] Causation or confounding: why controls are critical for characterizing long COVID, Amin-Chowdhury [/bib_ref]. In addition, the study design is usually retrospective, including symptomatic patients (rather than all recovering patients), thus limiting the ability to measure the scope of the problem and evaluate risk factors.
Additional studies are needed, including studies following consecutive patients recovering from COVID-19, with various severities of the acute disease. Such studies should be designed to evaluate the incidence of long COVID and to identify risk factors for its development. The first priority should be to evaluate healthy, community-treated persons and to evaluate the scope of the problem in this population and the need for follow up. Considering the toll of a stressful pandemic, quarantine, and unemployment, Amin-Chowdhury et al. suggested prospective longitudinal cohort studies using a noninfected control group [bib_ref] Causation or confounding: why controls are critical for characterizing long COVID, Amin-Chowdhury [/bib_ref].
Clustering of symptoms may assist in evaluating the scope of illness compared with noninfected people, as well as risk factors. Amin-Chowdhury et al. described the following clusters in a large prospective cohort: sensory (ageusia, anosmia, loss of appetite, and blurred vision), neurological (forgetfulness, short-term memory loss, and confusion/brain fog), and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/ at rest, and palpitations). Patients after ICU hospitalization should be addressed separately in studies, including studies assessing rehabilitation starting in the hospital and different interventions to prevent and treat lung injury. Patients with less severe disease should be investigated for interventions to resolve their leading symptom/cluster of symptoms (as described). Outcomes addressed should include return to work and return to previous activity level, including sports. Further research is also needed to elucidate the pathophysiology of various long-COVID symptoms. Additional studies should assess long-COVID prevalence and symptoms after different SARS-CoV-2 variants and vaccination.
Long-term follow-up studies of symptomatic patients are needed to evaluate the assessment and management of interventions, using predefined patient-related outcomes, including quality of life, time to return to work and baseline physical activity, and cognitive and functional assessments. These studies should be in the form of RCTs.

# Author contributions
These guidelines were developed by a group of infectious diseases specialists who care for patients recovering from acute COVID-19. All members formulated the questions and aims of these guidelines. DYa, DYe, and IM performed the literature search, and all members were involved in the data extraction and writing of the manuscript. All panel members reviewed the last version of the manuscript. The guidelines were written under the guidance and support of LS (ESCMID Guidelines Director).

# Transparency declaration
All authors declare no conflicts of interest. No funding sources.

## Updating
These are rapid guidelines aimed to capture current evidence on the topic. However, due to the rapid evolvement of the literature, the authors plan to conduct these as living guidelines to be modified with upcoming new evidence. The panel will meet monthly regarding the need for updates. The panel members will perform an updated search every 3 months and will update the guidelines once substantial evidence for changing any recommendation is observed.
[table] Table 1: Summary of definitions for long COVID/post-acute COVID according to level of certainty of COVID-19 diagnosis Acute COVID-19 diagnosis a /time from acute COVID-19 diagnosis For asymptomatic patients: Confirmed acute COVID-19 diagnosis is considered a positive PCR test in a relevant epidemiological setting. [/table]
[table] Table 4: Prevalence of long COVID symptoms in studies investigating patients regardless of disease severity and in studies in hospitalized patients [/table]
[table] Table 5: Studies addressing assessment of long COVIDdPulmonary function tests AMSTAR, A MeaSurement Tool to Assess systematic Reviews; DLCO, carbon monoxide diffusing capacity; FEV; forced expiratory volume; FVC, forced vital capacity; TLC, total lung capacity. a Pooled prevalence (standard deviation). b Pooled prevalence (95% CI). [/table]
[table] Table 6: Studies addressing assessment of long COVIDdChest imaging AMSTAR, A MeaSurement Tool to Assess systematic Reviews; CT, computed tomography; MRI, magnetic resonance imaging. a CT, high-resolution CT, chest radiography, and/or MRI. [/table]
[table] Table 7: Studies addressing assessment of long COVIDdOthers Evidence is variable. Different rates of abnormal findings (diastolic dysfunction, systolic dysfunction, elevated pulmonary artery pressure with or without pericardial disease). Rates are higher in patients hospitalized for analysis or referred to cardiology for ongoing cardiac symptoms (25%e27.5% overall abnormal findings). In one study, EF was normal in a cohort of 215 patients, but left ventricular global longitudinal strain was reduced in 29%.Systematic review reporting reduced left ventricular EF in 0%e16%; left ventricular hypertrophy in 0%e0.5%; diastolic dysfunction in 0%e55%; pulmonary hypertension in 0%e10%; and pericardial effusion in 0%e6%. Abnormal MRI myocardial findings are common in the postacute period. A study of athletes showed abnormalities in 5 of 26 asymptomatic patients after mild disease (20%). In severe cases, abnormalities may be found in up to 70% of patients. No correlation was shown with ongoing symptoms.Systematic review reporting increased T1 in 0%e73%; increased T2 in 0% e60%; late gadolinium enhancement (myocardial or pericardial) in 0% e46% and up to 100%. In four studies reporting formal diagnoses, myocarditis was reported in 0%e37%, myopericarditis in 0%e11%, pericarditis in 0%e3%, and myocardial infarction in 0%e2%. SPPB were moderately/severely impaired in comparison with expected ranges for age and sex. Impairment is mostly dependent on disease severity, and patients after severe disease had lower SPO2 after testing. [/table]
[table] Table 8: Summary of studies addressing management of long-COVID/postCOVID-19 condition [/table]