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COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")

COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")
Authors:
Mark E Mikkelsen, MD, MSCE
Benjamin Abramoff, MD, MS
Section Editors:
Scott Manaker, MD, PhD
Joann G Elmore, MD, MPH
Deputy Editors:
Geraldine Finlay, MD
Lisa Kunins, MD
Literature review current through: Jul 2022. | This topic last updated: Aug 10, 2022.

INTRODUCTION — The coronavirus disease 2019 (COVID-19) pandemic has resulted in a growing population of individuals recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accumulating observational data suggest that these patients may experience a wide range of symptoms after recovery from acute illness, referred to by several terms including "long COVID," "post-COVID conditions," and "postacute sequelae of SARS-CoV-2 infection (PASC)." Some aspects of this recovery may be unique to COVID-19, but many appear to be similar to recovery from other viral illnesses, critical illness, and/or sepsis [1-6].

In this topic we will discuss the evaluation and management of adults during the postacute and chronic recovery phase from COVID-19, which is based upon evolving evidence. The management of adults with acute COVID-19 is reviewed elsewhere:

(See "COVID-19: Clinical features".)

(See "COVID-19: Management in hospitalized adults".)

(See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

COVID-19 infection control issues, including management in hospitals, skilled nursing, and other rehabilitation facilities are reviewed elsewhere:

(See "COVID-19: Management in nursing homes".)

(See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

Rehabilitation issues for general patient populations, including patients with chronic pulmonary or cardiac conditions are discussed separately:

(See "Pulmonary rehabilitation".)

(See "Cardiac rehabilitation programs".)

(See "Overview of geriatric rehabilitation: Patient assessment and common indications for rehabilitation".)

(See "Geriatric rehabilitation interventions".)

TERMINOLOGY AND STAGES OF RECOVERY — The recovery process from COVID-19 exists on a continuum; early in the course of acute COVID-19, management is focused on detecting and treating acute COVID-19-related complications, while after recovery from the acute phase, some patients require evaluation and management for persistent or new symptoms.

Although there are no widely accepted definitions of the stages of COVID-19 recovery, we generally agree with the following categories as proposed by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) [7,8]:

Acute COVID-19 – Symptoms of COVID-19, up to four weeks following the onset of illness.

Post-COVID condition – Broad range of symptoms (physical and mental) and symptom clusters that develop during or after COVID-19, continue for ≥2 months (ie, three months from the onset of illness), have an impact on the patient's life, and are not explained by an alternative diagnosis.

These stages reflect symptomatic recovery and are not related to active viral infection and infectivity. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Viral shedding and period of infectiousness'.)

Several other terms have been used to describe prolonged symptoms following COVID-19 illness, such as "long COVID," "postacute sequelae of SARS-CoV-2 infection (PASC)," "postacute COVID-19," "chronic COVID-19," and "post-COVID syndrome" [9-13]. Despite the creation of case definitions, there are no widely accepted clinical diagnostic criteria for "long COVID" [14]. However, as of October 1, 2021, there is a new International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) for unspecified post-COVID conditions, which is U09.9, which was approved by the CDC.

The World Health Organization has also created a global COVID-19 clinical platform case report form for clinicians and patients to collect and report information, to allow for better understanding of the spectrum of post-COVID-19 conditions and recovery [15].

The United States Department of Health and Human Services and the Department of Justice released a guidance statement on "long COVID" as a disability under the Americans with Disabilities Act, the Rehabilitation Act of 1973, and the Patient Protection and Affordable Care Act. These acts provide protections for individuals with disabilities to allow for full and equal access to civic and commercial life. This statement classifies "long COVID" as a disability if it substantially limits, either physically or mentally, one or more major life activities. An individualized assessment is needed to determine whether a person's symptoms fit these criteria [16].

Challenges with defining and evaluating post-COVID conditions — Whether the constellation of symptoms and persistent issues experienced by patients represents a new syndrome unique to COVID-19 or if there is overlap with the recovery from other infectious and critical illnesses has not been determined. In addition, it is important to note that many studies evaluating the prevalence and severity of persistent post-COVID-19 symptoms have significant methodologic limitations, such as lack of a control population, selection and reporting bias, and lack of standardized assessment protocols.

PREVENTION OF POST-COVID CONDITIONS — The most effective means by which to prevent post-COVID conditions also is to prevent COVID-19 (eg, vaccination, masking, social distancing, hand hygiene). It is likely that any measure that decreases the incidence or severity of acute COVID-19 infection will in turn decrease the incidence and severity of post-COVID conditions.

Several studies report lower rates of post-COVID-19 symptoms in patients who are vaccinated [17-19]. A case-control study found that both symptom intensity in the first week of illness and persistent symptoms, defined as symptoms at 28 days or more, were significantly less common among those who developed postvaccination SARS-CoV-2 infection compared with unvaccinated cases [17]. In addition, those who were vaccinated were more likely to be asymptomatic. Another large observational cohort study from nine Italian centers totaling 2560 patients with mild COVID-19 reported that compared with unvaccinated individuals, the prevalence of postacute sequelae of SARS-CoV-2 infection (PASC) decreased in vaccinated individuals in a dose-dependent fashion: 42 percent in unvaccinated patients versus 30 percent in patients with one vaccine dose, 17 percent in patients with two vaccine doses (odds ratio [OR] 0.25; 95% CI, 0.07-0.87), and 16 percent in patients with three doses (OR, 0.16; 95% CI, 0.03-0.84 ) [18]. Older age, higher body mass index, and comorbidities such as allergies and obstructive lung disease were associated with increased risk of PASC.

COVID-19 RECOVERY

Persistent symptoms — Persistent physical symptoms following acute COVID-19 are common and typically include fatigue, dyspnea, chest pain, and cough. Patients recovering from COVID-19 may also have additional psychological (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) and cognitive (eg, poor memory and concentration) symptoms, similar to the syndrome experienced by patients recovering from other critical illnesses known as post-intensive care syndrome (PICS). This syndrome is discussed in detail separately. (See "Post-intensive care syndrome (PICS)".)

Prolonged symptoms can follow mild to severe illness and include:

Physical symptoms – Several observational series describe persistent symptoms in patients following acute COVID-19 with one-third or more experiencing more than one symptom (table 1) [1,4,5,20-55]. Common persistent physical symptoms include:

Fatigue (13 to 87 percent)

Dyspnea (10 to 71 percent)

Chest pain or tightness (12 to 44 percent)

Cough (17 to 34 percent)

Less common persistent physical symptoms include anosmia, joint pain, headache, sicca syndrome, rhinitis, dysgeusia, poor appetite, dizziness (from orthostasis, postural tachycardia, or vertigo), myalgias, insomnia, hoarseness, alopecia, sweating, and diarrhea.

Psychological or cognitive – Psychological and cognitive complaints are also common during recovery from acute COVID-19 and may be seen more commonly than in those recovering from similar illnesses [1,4,24,28,29,34,36,45,46,48,50,51,56-59]. In one study of 100 patients with acute COVID-19 who were discharged from the hospital, 24 percent reported PTSD, 18 percent had new or worsened problems with memory, and 16 percent had new or worsened problems with concentration; numbers were higher among patients admitted to the intensive care unit (ICU) [24]. In other studies, almost one-half of COVID-19 survivors reported a worsened quality of life [1,25], 22 percent had anxiety/depression [25], and 23 percent of patients were found to have persistent psychological symptoms at three months [4]. Among ICU survivors, another study reported anxiety in 23 percent, depression in 18 percent, and posttraumatic symptoms in 7 percent [34]. In a prospective cohort study of nonhospitalized Ecuadorian patients with COVID-19, most of whom had mild disease, 21 percent had memory impairment as evidenced by a four-point decrease in their Montreal Cognitive Assessment (MoCA) scores [57].

Psychological complaints may be seen more commonly than in those recovering from similar illnesses. As an example, a retrospective examination of electronic health records in the United States reported that the risk of developing a new psychiatric illness following COVID-19 was higher compared with those recovering from other medical illnesses such as influenza [56].

PICS – Among ICU survivors, at least three-quarters of individuals with COVID-19 report at least one component of PICS [50,60-63]. In a study of 301 ICU survivors, 74 percent of patients had at least one component of PICS at one year; the most common symptoms were physical weakness (39 percent), joint stiffness/pain (26 percent), mental/cognitive dysfunction (26 percent), and myalgias (21 percent) [50]. Of importance, survival and the frequency and severity of disability that COVID-19 ICU survivors experience at six months appears to be similar to that experienced by non-COVID-19 ICU survivors [63,64]. Details regarding the identification and management of PICS and weakness related to critical illness are discussed separately. (See "Post-intensive care syndrome (PICS)".)

Functional disability – Persistent symptoms can affect functional ability [28,34,36,43,65-67]. As examples:

In one retrospective study of approximately 1300 hospitalized COVID-19 patients discharged to home, despite home health services, only 40 percent of patients were independent in all activities of daily living (ADLs) at 30 days [65].

In another study, almost 40 percent of patients were unable to return to normal activities at 60 days following hospital discharge [66].

In another study of 219 patients who were hospitalized with COVID-19, 53 percent had limited functional impairment (as measured by the Short Physical Performance Battery [SPPB] score and two-minute walking test) at four months [28].

Among critically ill patients with COVID-19, the rate of disability at six months does not appear to be different to that in patients with non-COVID-19-related critical illness, despite a longer duration of mechanical ventilation [64].

Whether symptoms can develop after initial asymptomatic infection is unknown. Limited data from self-reporting questionnaires, subgroup analyses of larger observational studies, and health care claim databases (some of which are not peer-reviewed), suggest that a small proportion of patients with asymptomatic COVID-19 subsequently report post-COVID symptoms (eg, fatigue) [68-70]. Further data are needed to clarify the scope of post-COVID symptoms in this population.

Limited data suggest a lower prevalence of persistent symptoms in children, although data are sparse. One retrospective study of children and adolescents (median age 11 years) described at least one symptom lasting beyond 12 weeks in 4 percent of the study cohort [44]. The most frequently reported symptoms were tiredness (3 percent) and poor concentration (2 percent). (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Post-COVID-19 conditions'.)

Observational data suggest that persistent symptoms are unlikely to worsen and may stay the same or even improve following the administration of the SARS-CoV-2 vaccine [52,71-73]. This was illustrated in one study of 163 patients who had a heavy burden of post-COVID symptoms at eight months and who subsequently received the Pfizer-BioNTech (BNT162b2) or Oxford-AstraZeneca (ChAdOx1nCoV-19) vaccine [71]. One month after vaccination, symptoms that existed prior to vaccination in the majority of patients had either improved or remained unchanged, while only 5 percent had worsened.

The prevalence of persistent symptoms may also vary depending on the COVID-19 variant. As an example, among over 97,000 vaccinated individuals in the United Kingdom, subsequent infection with the Omicron variant was associated with a lower risk of developing persistent symptoms compared with the Delta variant (4.5 versus 10.8 percent) [74]. Data were consistent regardless of the interval between vaccination and infection. However, methodologic issues, including self-reporting through an electronic application and a shorter duration of follow-up for Omicron- versus Delta-infected patients, limit the interpretation of these findings, and further research is needed. Similarly, another observational study of nonhospitalized health care workers with COVID-19 reported that the prevalence of persistent symptoms waned with each successive COVID-19 wave (48 percent in wave 1 [wild-type variant], 36 percent in wave 2 [alpha variant], and 17 percent in wave 3 [Delta and Omicron]) [18]. However, the impact of vaccination status may have influenced the results.

The risk of cardiovascular events (eg, myocardial infarction, stroke, dysrhythmias, pericarditis, myocarditis, heart failure, and thromboembolic disease) may be increased after COVID-19 infection [75]. Cardiovascular complications of COVID-19 are discussed separately. (See "COVID-19: Arrhythmias and conduction system disease" and "COVID-19: Myocardial infarction and other coronary artery disease issues".)

Expected recovery time course — The time to symptom resolution appears to depend upon premorbid risk factors as well as the severity of the acute illness and spectrum of symptoms experienced by the patient [1,2,76-79]. However, despite early data suggesting a shorter recovery (eg, two weeks) for those with mild disease and a longer recovery (eg, two to three months or longer) for those with more severe disease [80,81], there is wide variability in time to symptom resolution.

A longer recovery course is expected in patients requiring hospitalization, older patients with preexisting comorbidities, patients who experienced medical complications (eg, secondary bacterial pneumonia, venous thromboembolism), and patients who had a prolonged stay in the hospital or ICU [1,2,20,24,46,50,82]. However, data suggest that even patients with less severe disease who were never hospitalized, including those with self-reported COVID-19, have often reported prolonged and persistent symptoms [4,5,20,77,83,84].

As examples:

Hospitalized patients (moderate to severe COVID-19) – Data suggest that a significant proportion of patients who are admitted with acute COVID-19 experience symptoms for at least two months and even longer (eg, up to 12 months) following discharge (52 to 87 percent) [1,24,27,46,50,66,85].

In an observational study of 1600 patients in United States hospitals with acute COVID-19, at 60 days after discharge, 33 percent reported persistent symptoms and 19 percent reported new or worsening symptoms [66]. The most common symptoms included dyspnea with stair climbing (24 percent), shortness of breath/chest tightness (17 percent), cough (15 percent), and loss of taste or smell (13 percent).

In a study including approximately 1700 patients previously hospitalized with COVID-19 in Wuhan, China, at six months, 74 percent continued to experience one or more symptoms. Fatigue or muscle weakness (63 percent), sleep difficulties (26 percent), dyspnea (26 percent), and anxiety or depression (23 percent) were among the most commonly reported persistent symptoms [27]. In a follow-up study of the same cohort, although the proportion of patients with at least one symptom had improved at 12 months, 49 percent of patients remained symptomatic [46]. Fatigue or muscle weakness remained the most common symptom (20 percent), but the proportion of patients with dyspnea (30 percent) and anxiety (26 percent) increased slightly. Similar results have been seen at one year among survivors of COVID-19 who were admitted to the ICU [50].

Outpatients (mild COVID-19) – Data also suggest that a significant proportion of patients with mild disease may experience symptoms for up to several months, if not longer, following acute illness [5,36,51,83-86].

In the only comprehensive study to date that enrolled 189 patients with mostly mild COVID-19 (88 percent), the presence of persistent symptoms at five months was compared with a group of 120 patients who did not have COVID-19 [51]. A higher proportion of patients with COVID-19 had a median of two symptoms consistent with postacute sequelae of SARS-CoV-2 infection (PASC; 55 versus 13 percent). The most frequent symptoms were fatigue, dyspnea, parosmia, concentration impairment, headache, memory impairment, insomnia, chest discomfort, and anxiety. Patients with COVID-19 also had more musculoskeletal findings (eg, tendinitis). Patients with COVID-19 had a shorter six-minute walk distance (560 versus 590 meters) and reported a poorer quality of life. Patients underwent an extensive evaluation, but no differences were found in routine laboratory and rheumatologic tests, serologic tests for SARS-CoV-2, inflammatory or immunologic markers, pulmonary function tests, echocardiography, or neurocognitive testing. Among candidate risk factors, only female sex and self-reported history of anxiety were associated with the development of PASC.

In a telephone survey of 292 outpatients with COVID-19, one-third had not returned to baseline health by three weeks [83]. Younger patients were less likely to have residual symptoms compared with older patients (26 percent among those 18 to 34 years versus 47 percent of those >50 years). In addition, an increasing number of medical comorbidities was associated with prolonged illness among all age groups. Young and healthy patients with mild disease typically recovered sooner, while patients with multiple comorbidities had a more prolonged recovery.

In a study of 410 Swiss outpatients with mild illness, 39 percent reported persistent symptoms seven to nine months following initial infection. The most common symptoms included fatigue (21 percent), loss of taste or smell (17 percent), dyspnea (12 percent), and headache (10 percent) [84].

In a prospective study, 177 patients recovering from acute COVID-19 (16 inpatients and 161 outpatients, 11 of whom had asymptomatic infection) were followed for an average of six months after acute illness [85]. Of the outpatients with symptomatic infection, 19 percent had one to two persistent symptoms at six months, 14 percent had ≥3 persistent symptoms, and 29 percent reported a decreased quality of life. The most common reported persistent symptoms were fatigue, loss of sense of taste or smell, and dyspnea.

In a Swedish survey of over 300 health care workers with mild disease, 26 percent had at least one moderate or severe symptom lasting more than two months, compared with 9 percent of seronegative control patients [36]. A higher proportion also had symptoms lasting longer than eight months (15 versus 3 percent). Approximately 8 to 15 percent reported that their symptoms interfered with their work, social, or home life compared with 4 percent of seronegative control patients.

Some symptoms resolve more quickly than others. For example, fevers, chills, and olfactory/gustatory symptoms typically resolve within two to four weeks, while fatigue, dyspnea, chest tightness, musculoskeletal pain, cognitive deficits, and psychological effects may last for months (eg, 2 to 12 months) [1,4,5,21-24,26,46,50,83,87,88]. Data regarding individual symptoms are included below:

Fatigue, weakness, and poor endurance – Fatigue is by far the most common symptom experienced by patients regardless of the need for hospitalization. Although the fatigue resolves in most patients, it can be profound and may last for three months or longer, particularly among ICU survivors [1,4,24,50,89].

Dyspnea – In patients with COVID-19 and dyspnea, the shortness of breath may persist, resolving slowly in most patients over two to three months, sometimes longer (eg, up to 12 months) [4,24,46,90-92].

Chronic cough – In several studies, many patients experienced persistent cough at two to three weeks following initial symptoms [83]. Cough resolved in the majority of patients by 3 months [4] and rarely persisted by 12 months [46].

Chest discomfort – Among patients with COVID-19, chest discomfort is common and may resolve slowly. Chest discomfort persists in 12 to 22 percent of patients approximately two to three months after acute COVID-19 infection, rarely longer [1,4,46].

Altered taste and smell – Several studies have examined the recovery of olfactory and gustatory symptoms in COVID-19 patients [21-23,66,87,93-95]. The majority have complete or near-complete recovery at one to 3 months month following acute illness, although in a small proportion (< 5 percent) these symptoms persisted longer [46,72,95,96]. Patients with hyposmia and male patients may recover more rapidly compared with those who have anosmia or are female [21,23,95].

Musculoskeletal pain – Musculoskeletal pain symptoms are common during and following COVID-19. In a meta-analysis of observational studies including over 25,000 patients (outpatients and previously hospitalized patients) at four weeks, persistent musculoskeletal symptoms were present, including myalgia in 5.7 percent, arthralgia in 4.6 percent, and chest pain in 7.9 percent of patients [88]. The prevalence of post-COVID musculoskeletal pain increased at 60 days but decreased after 180 days.

Neurocognitive symptoms – Data suggest that concentration and memory problems persist for six weeks or more in COVID-19 patients after discharge from the hospital [24].

Psychological – Observational studies report that psychological symptoms (eg, anxiety, depression, PTSD) are common after acute COVID-19 infection, with anxiety being the most common. In general, psychological symptoms improve over time but may persist for more than six months for a subset of survivors. Those hospitalized are likely at greater risk for persistent psychological symptoms [4,24,46,56,65,97]. (See "COVID-19: Psychiatric illness", section on 'Patients critically ill with COVID-19'.)

Risk of rehospitalization — Most patients hospitalized with COVID-19 are successfully discharged, although approximately 10 to 20 percent require rehospitalization within 30 and 60 days, respectively [35,65,66,98,99]. As examples:

In a retrospective study of over 100,000 patients admitted to United States hospitals with COVID-19, among those who were discharged, 9 percent were rehospitalized within two months to the same hospital [98]. Among those readmitted, 1.6 percent had multiple hospital readmissions. The median time for first readmission was eight days. Risk factors for rehospitalization included age ≥65 years, discharge to skilled nursing facility (SNF) or with home health services, or the presence of one or more comorbidities (ie, chronic obstructive pulmonary disease, heart failure, diabetes mellitus with complications, chronic kidney disease, and/or a body mass index [BMI] ≥30 kg/m²).

In another retrospective cohort of 1409 patients admitted with COVID-19, 10 percent were rehospitalized. Risk of rehospitalization or death was higher among male patients, White patients, and those with heart failure, diabetes, frequent emergency department visits within the previous six months, daily pain, cognitive impairment, or functional dependency [65].

In another study of 1775 patients discharged following COVID-19, 20 percent were readmitted within 60 days [100]; readmissions were associated with older age. Common readmission diagnoses were COVID-19 (30 percent), sepsis (8.5 percent), pneumonia (3.1 percent), and heart failure (3.1 percent). Over 20 percent required ICU admission, and the mortality was 9 percent. Rates of readmission or death were highest during the first 10 days following discharge.

In a United Kingdom study of nearly 50,000 patients who were discharged following an admission with COVID-19, 30 percent were readmitted and 10 percent died after discharge [35]. There were higher rates of respiratory disease, diabetes, and cardiovascular disease in patients discharged following COVID-19 compared with patients discharged with non-COVID diagnoses.

GENERAL EVALUATION — Patients recovering from COVID-19 range from those with mild illness not requiring medical attention to those with severe illness requiring prolonged critical care support. (See 'Additional considerations for the inpatient rehabilitation patient' below.)

Several organizations have developed guidelines to address the evaluation and management of patients recovering from COVID-19, and many institutions have established dedicated, interdisciplinary outpatient COVID-19 recovery clinics to address the long-term needs of patients after recovery from acute illness [6,10,101-112]. Given the unknown long-term sequelae of those with persistent symptoms following COVID-19, clinic protocols generally include a comprehensive physical, cognitive, and psychological assessment. High quality data on the outcomes of these evaluation and management strategies are lacking. Care should not be delayed if patients experience a long wait time for evaluation in a dedicated COVID-19 recovery clinic; referral to pulmonary, neurology, and/or physical medicine and rehabilitation specialists may be appropriate if referral to a COVID-19 recovery clinic is unavailable.

Our approach is based upon our clinical experience with patients who have recovered from acute COVID-19, accumulating data on patients with persistent symptoms following acute COVID-19, and data extrapolated from patients recovering from similar illnesses (eg, sepsis) and is consistent with expert advice from international societies and guideline groups [102-108,112-114].

Timing and location of follow-up evaluation — The optimal timing and location of follow-up evaluation for patients who have recovered from acute COVID-19 are unknown and depend upon several factors, including the severity of acute illness, current symptomatology, and resource availability.

The timing and location of follow-up for outpatients during the acute illness (eg, up to two to three weeks following illness onset) is reviewed in detail elsewhere. (See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and "COVID-19: Evaluation of adults with acute illness in the outpatient setting", section on 'Home management without in-person evaluation for others'.)

Our approach to the follow-up of patients after the acute illness has "resolved" (eg, after approximately three to four weeks) is discussed in this section. The recovery process exists on a continuum; follow-up early in the course of acute COVID-19 is focused on detecting and managing acute COVID-19-related complications, while later follow-up focuses on the evaluation and management of persistent symptoms after recovery from the acute phase (see 'Terminology and stages of recovery' above). While there is no guidance on timing or location for COVID-19 follow-up after the acute illness, we suggest the following:

In patients with mild to moderate disease not requiring hospitalization and who are improving, we do not routinely schedule a COVID-19 follow-up visit (telemedicine or in-person), unless the patient requests it or has persistent, progressive, or new symptoms. (See "COVID-19: Evaluation of adults with acute illness in the outpatient setting", section on 'Home management without in-person evaluation for others'.)

For patients with more severe acute COVID-19 disease requiring hospitalization (with or without the need for subsequent postacute care such as inpatient rehabilitation), we ideally follow-up within one week but no later than two to three weeks after discharge from the hospital or rehabilitation facility. We typically use telemedicine visits to facilitate early follow-up given that hospital readmissions may be reduced with early postdischarge follow-up based upon data reported for patients recovering from sepsis [114]. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Post-discharge management'.)

For all patients with persistent symptoms, particularly those with multisystem complaints or symptoms lasting beyond 12 weeks, we refer for an evaluation in a specialized outpatient COVID-19 recovery clinic, if available, or a subspecialty clinic relevant to the patient's specific symptoms.

Assess disease severity, complications, and treatments — During the initial follow-up evaluation, we obtain a comprehensive history of the patient's acute COVID-19 illness, including the illness timeline, duration and severity of symptoms, type and severity of complications (eg, venous thromboembolism, presence and degree of kidney injury, supplemental oxygen requirements [including the need for noninvasive or invasive ventilation], cardiac complications, delirium), COVID-19 testing results, and initial treatments used. We review hospital and outpatient records and the patient's medication list. This information is compared with their pre-COVID-19 medical history.

Laboratory testing

General laboratory testing — The need for laboratory testing in patients who have recovered from acute COVID-19 is determined by the severity and abnormal test results during their acute illness and current symptoms. Most patients who have abnormal laboratory testing at the time of diagnosis improve during recovery [30].

For most patients who have recovered from mild acute COVID-19, laboratory testing is not necessary.

For patients recovering from more severe illness, those with identified laboratory abnormalities, patients who were discharged from hospital or an inpatient rehabilitation facility, or for those with unexplained continuing symptoms, it is reasonable to obtain the following:

Complete blood count

Blood chemistries, including electrolytes, blood urea nitrogen (BUN) and serum creatinine

Liver function studies, including serum albumin

Additional laboratory tests that might be appropriate for select patients include:

Brain natriuretic peptide (BNP) and troponin in patients whose course was complicated by heart failure or myocarditis or in those with possible cardiac symptoms from covert myocarditis (eg, dyspnea, chest discomfort, edema).

D-dimer in patients with unexplained persistent or new dyspnea or in any patient in whom there is a concern for thromboembolic disease.

Thyroid studies in those with unexplained fatigue or weakness.

Creatinine kinase in patients with weakness or muscle tenderness.

We generally do not monitor coagulation parameters (eg, fibrinogen, fibrinogen degradation products, activated thromboplastin time, international normalized ratio, and D-dimer levels) or inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein, ferritin, interleukin-6) to resolution.

COVID-19 testing and serology — We do not routinely re-test patients for active infection with SARS-CoV-2 at the time of follow-up outpatient evaluation. Instead, we follow a non-test-based approach to removing infectious precautions. This approach is supported by the World Health Organization and the Centers for Disease Control and Prevention (table 2). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Discontinuation of precautions' and "COVID-19: Diagnosis", section on 'Persistent or recurrent positive NAAT during convalescence' and "COVID-19: Epidemiology, virology, and prevention", section on 'Viral shedding and period of infectiousness' and "COVID-19: Epidemiology, virology, and prevention", section on 'Immune responses following infection'.)

In addition, there is no clinical utility in obtaining SARS-CoV-2 serology (antibodies) in patients who had their acute infection documented by a positive molecular test (ie, nucleic acid amplification test [NAAT], reverse transcriptase polymerase chain reaction [RT-PCR] test) or antigen test. However, for patients with prior COVID-19 based upon symptoms but without a documented positive molecular or antigen test, the value of obtaining SARS-CoV-2 serology is unclear. Regardless, we sometimes obtain serology to guide additional testing or decision-making (eg, convalescent plasma donation, evaluation of unexplained symptoms). (See "COVID-19: Diagnosis", section on 'Serology to identify prior/late infection'.)

EVALUATION AND MANAGEMENT OF COMPLICATIONS AND PERSISTENT SYMPTOMS — Following the acute illness, we encourage patients to resume their daily activities as tolerated. While most patients, particularly those with mild illness, are expected to have resolution of symptoms over the first few weeks following acute illness, some may experience a slower than expected recovery course or develop new or progressive symptoms. Patients who have failure of their symptoms to resolve or new or progressive symptoms should be evaluated promptly (see 'Persistent symptoms' above). As part of the initial patient evaluation in our post-COVID-19 clinic, we typically use standardized screening measures to complement our routine symptom-directed clinical assessment. As examples, we use the screening tests recommended by the Critical Care International Consensus Conference to predict and identify long-term physical and mental impairments after critical illness (table 3) [113]. These can help identify important information on medical and psychological issues, which may prompt additional assessments, treatments, and referrals to specialist providers, if appropriate.

Cardiopulmonary symptoms

Clinical evaluation — We inquire about ongoing dyspnea (at rest and exertion), cough, chest discomfort, pleuritic pain, and wheezing. We also inquire about orthopnea, chest pain (exertional, positional), peripheral edema, palpitations, dizziness, orthostasis, and pre-syncope or syncope. We typically use the modified Borg dyspnea scale to assess overall dyspnea symptoms (table 4). We also ask about supplemental oxygen needs and obtain pulse oximetry (SpO2) data, if available.

We determine whether symptoms are persistent, worsening, and/or new, since the latter may reflect the development of late complications of COVID-19, such as secondary bacterial pneumonia, empyema, pulmonary embolism, or COVID-19-related myocardial injury or inflammation. (See "Diagnostic evaluation of a pleural effusion in adults: Initial testing" and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "COVID-19: Cardiac manifestations in adults".)

During in-person visits, we check complete vital signs, with special attention to SpO2, and in patients with orthostasis, pre-syncope or syncope, postural blood pressure (up to 10 minutes after standing) and pulse rate. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".)

We perform a complete chest examination to evaluate for the following:

Fibrosis (eg, coarse crackles). (See "Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis".)

Pleural effusion (eg, dullness on percussion). (See "Diagnostic evaluation of a pleural effusion in adults: Initial testing".)

Consolidation (eg, egophony). (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

Cardiovascular system including evaluation for murmurs, pericardial rub, third or fourth heart sounds, jugular venous distension, fine basilar crackles, peripheral edema, and orthostasis. (See "Diagnostic evaluation of a pleural effusion in adults: Initial testing" and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Heart failure: Clinical manifestations and diagnosis in adults" and "Clinical manifestations and diagnosis of myocarditis in adults" and "COVID-19: Evaluation and management of cardiac disease in adults" and "Mechanisms, causes, and evaluation of orthostatic hypotension".)

Cardiopulmonary testing — In recovering COVID-19 patients with cardiopulmonary symptoms, we obtain chest imaging and electrocardiography (ECG). Additional tests, such as echocardiography, Holter monitoring, and pulmonary function tests may also be necessary in select patients.

Chest imaging – The need for chest imaging is determined by previous abnormal imaging obtained during the course of their illness as well as current symptoms.

For patients who did not have chest imaging during the course of their illness and who have no current cardiopulmonary symptoms, chest imaging is not necessary.

For all patients who had a pulmonary infiltrate or other abnormality identified on imaging obtained during the course of COVID-19 illness, we obtain follow-up chest imaging. In addition, in any patient with new or worsening respiratory symptoms or an abnormal cardiopulmonary physical examination, we obtain chest imaging.

-Type of imaging – For most patients, chest radiography is sufficient. However, in patients with abnormalities on chest imaging performed during their acute illness that are concerning for another pathology, we typically obtain chest computed tomography (CT). For example, we obtain a contrast-enhanced chest CT if malignancy is suspected or non-contrast enhanced high resolution chest CT (HRCT) for patients with suspected interstitial lung disease from severe pulmonary involvement (eg, acute respiratory distress syndrome [ARDS]).

-Timing – Few guidelines are available to inform the timing of follow-up imaging [105]. Based upon accumulating data in patients recovering from COVID-19, we expect lung damage (ie, ground glass opacities, consolidation, interlobular septal thickening) to resolve in two to four weeks, but full resolution may require 12 weeks or longer with some studies suggesting changes up to a year, especially in those with severe disease [27,30,31,34,37,38,40,46,110,115-117]. Thus, it is reasonable to perform chest radiography at 12 weeks following discharge to ensure complete radiographic resolution [118].

For patients who have persistent radiographic abnormalities at 12 weeks, we typically obtain CT of the chest and consult with a pulmonologist. However, lung abnormalities may persist on chest CT for six months or longer in 50 percent of previously hospitalized patients, even among those with non-severe respiratory disease [27,46,117]. Infrequent cases of residual lung fibrosis requiring lung transplantation have been reported [119].

Some patients may require earlier imaging earlier than 12 weeks including patients with worsening or new respiratory symptoms, patients with a new or evolving infiltrate, or those in whom an alternate or complicating pathology is suspected (eg, malignancy, interstitial lung disease, tracheal stenosis).

For patients with resolving ARDS, the clinical utility of interval HRCT (eg, repeat imaging at 3, 6, 12, 24 months) is unclear. We do not routinely perform HRCT at predetermined intervals due to the lack of high-quality evidence demonstrating benefit and risk of radiation exposure. However, a subsequent HRCT for follow-up is reasonable in select patients (eg, patients with slower than expected improvement, patients with severe residual symptoms). (See "Acute respiratory distress syndrome: Prognosis and outcomes in adults", section on 'Lung function'.)

For patients with unexplained cardiopulmonary symptoms and/or low peripheral oxygen saturation despite normal chest radiograph, we recommend clinicians have a high index of suspicion for venous thromboembolism and evaluate with an appropriate imaging exam, such as CT pulmonary angiography. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

In addition, patients may rarely experience chest or neck discomfort related to venous stenosis from previous central venous catheterization [120]; this is often a clinical diagnosis, but confirmation by ultrasound may be appropriate.

Cardiac testing

For patients with any intermittent or persistent cardiopulmonary symptoms, including palpitations, or those with generalized, constitutional complaints such as weakness or fatigue, we typically perform a 12-lead ECG. (See "Evaluation of palpitations in adults".)

For patients with persistent cardiac symptoms, particularly palpitations or symptoms of dysautonomia, despite an unremarkable ECG, we perform extended Holter monitoring (see "Evaluation of palpitations in adults"). For patients who develop exaggerated symptoms with standing and have nondiagnostic postural blood pressure testing in clinic, tilt table testing can be used to further assess for changes in vital signs with change to upright posture. (See "Postural tachycardia syndrome".)

We do not routinely perform transthoracic echocardiography (TTE) on recovering COVID-19 patients. However, we obtain TTE in patients with a history or biochemical evidence of myocardial injury or myocarditis or patients with dyspnea and other signs and symptoms suggestive of an underlying cardiac disorder (eg, orthopnea, elevated jugular venous pressure, peripheral edema, inspiratory crackles, new murmurs, rubs, gallops). If TTE is unrevealing, cardiopulmonary exercise testing may be warranted. Limited data are available regarding follow-up echocardiography in patients with COVID-19. One study reported that among those who were admitted to the intensive care unit (ICU) with COVID-19 and had persistent symptoms at four months following discharge, 10 percent had an ejection fraction less than 50 percent [34]. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Cardiopulmonary exercise testing in the evaluation of dyspnea".)

The clinical utility of cardiac magnetic resonance imaging (MRI) to identify evidence of myocarditis that was not clinically evident during the acute phase of COVID-19 remains controversial [121,122]. For patients in whom myocarditis is suspected, we typically refer to a cardiologist for further evaluation [123]. (See "COVID-19: Evaluation and management of cardiac disease in adults" and "Myocarditis: Causes and pathogenesis".)

Pulmonary function testing – In patients with absent, mild, or resolving respiratory symptoms, we do not obtain pulmonary function tests (PFTs). For patients recovering from COVID-19 who have persistent, progressive, or new respiratory symptoms, we obtain PFTs including spirometry, lung volumes, and diffusion capacity. We also obtain PFTs in recovering COVID-19 patients with severe pulmonary involvement or COVID-19-related ARDS, which applies to many patients who required hospitalization. For patients with suspected neuromuscular weakness, maximal inspiratory and expiratory pressure (maximal inspiratory pressure [MIP], maximal expiratory pressure [MEP]) measurements can be used to assess respiratory muscle strength. (See "Overview of pulmonary function testing in adults".)

The optimal timing to obtain PFTs in the recovering patient is unknown. However, based upon accumulating data from COVID-19 patients and indirect evidence from the non-COVID-19 ARDS population (in whom PFTS are indicated), we typically obtain the studies at 6 to 12 weeks following hospital discharge. For patients with COVID-19-related ARDS, if PFT abnormalities are detected, we advise obtaining follow-up PFTs at six months and yearly thereafter for five years. (See "Acute respiratory distress syndrome: Prognosis and outcomes in adults", section on 'Lung function' and "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Radiographic response'.)

Data on pulmonary function following COVID-19 are evolving, and the data suggest that pulmonary function abnormalities may persist, particularly reduction in diffusion capacity, especially among those with more severe lung involvement [27,28,30,37-40,90-92,110,116,124]. Similar abnormalities in lung function have been reported in patients following recovery from systemic acute respiratory syndrome (SARS) [125-127]. (See "Severe acute respiratory syndrome (SARS)".)

As examples:

In one retrospective study including 110 patients with non-critical COVID-19, persistent lung function abnormalities were detected at 29 to 34 days following onset of illness [92]. The most common abnormalities were reduced diffusion capacity and restrictive defects; abnormalities were most pronounced among those with severe pneumonia. However, critical care cases were excluded from the analysis, baseline PFTs were unavailable, and long-term follow-up testing was not included.

In another study that included 59 critically ill patients who survived COVID-19, the majority had normal lung function at six weeks following discharge, while 15 percent had obstructive abnormalities, 19 percent had restrictive abnormalities, and 27 percent had reduced diffusion capacity [124].

In an observational study of over 1700 patients previously hospitalized with COVID-19 in Wuhan, China, among the 86 patients with severe pulmonary involvement (ie, requiring high flow nasal canula oxygen, noninvasive, or mechanical ventilation), 56 percent had persistently abnormal diffusion capacity at six months [27].

Evaluating exercise capacity and oxygenation – For any patient with unexplained respiratory symptoms after initial cardiopulmonary evaluation, including evaluation of venous thromboembolic disease and heart disease, as well as in patients who were hospitalized due to acute COVID-19, we typically obtain a six-minute walk test (table 5). Although not designed to be an oxygen titration study, it is a good index of physical and respiratory function and may identify any oxygenation issue to help explain a patient's dyspnea. Nocturnal oximetry measurement is typically not needed unless the patient is symptomatic during sleep (eg, recurrent awakening, chest pain, dyspnea) or if severe underlying heart or lung disease is suspected. (See "Pulse oximetry" and "Overview of pulmonary function testing in adults", section on 'Six-minute walk test' and "Long-term supplemental oxygen therapy", section on 'Prescribing oxygen'.)

If dyspnea remains unexplained after this evaluation, we refer to pulmonology for consideration of further evaluation with, for example, cardiopulmonary exercise testing (CPET) (table 6) and/or to cardiology, for evaluation of silent myocardial ischemia or COVID-19-related myocarditis. (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis", section on 'Diagnosis' and "COVID-19: Evaluation and management of cardiac disease in adults".)

CPET may identify the etiology of symptoms and may also identify those who may benefit from pulmonary or physical rehabilitation (eg, patients with deconditioning) (algorithm 1). (See "Cardiopulmonary exercise testing in the evaluation of dyspnea".)

For most patients, an arterial blood gas (ABG) is typically not warranted. However, in patients with acute hypercapnia who required noninvasive ventilation (NIV; eg, continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BPAP]) during their acute illness, an ABG may guide further management, particularly in patients requiring continued NIV.

Management — High quality data to inform the management of persistent cardiopulmonary symptoms following recovery from acute COVID-19 are limited. Our approach is based upon the management of symptoms following similar illnesses.

Dyspnea – COVID-19 pneumonia-related dyspnea is likely to improve slowly but may have a protracted course, especially in those with more severe pulmonary involvement or neuromuscular weakness (eg, up to 6 to 12 months). Management is similar to that in non-COVID-19 patients. (See "Approach to the patient with dyspnea".)

As a general treatment strategy following COVID-19, we address the underlying reason(s) for dyspnea, which is often multifactorial (eg, resolving pneumonia, organizing pneumonia, deconditioning, neuromuscular weakness, exacerbation of underlying lung disease, tracheal stenosis from intubation, heart failure).

For all patients, we optimize pharmacotherapy for any identified underlying cardiac or pulmonary disease.

For those with mild symptoms (eg, Borg score ≤3) (table 4) who are without an oxygen requirement and do not have a cardiac etiology for their symptoms, we prescribe breathing exercises and breathlessness management strategies (table 7).

For patients who have moderate to severe dyspnea (eg, Borg score >3) (table 4), persistent desaturations (SpO2 ≤92 percent), continue to have a new requirement for supplemental oxygen, or have other concerning respiratory symptoms, we advise referral to a pulmonary specialist for additional investigation and consideration of pulmonary rehabilitation [128].

In some cases, oral corticosteroids may need to be considered for patients with organizing pneumonia from resolving ARDS. For example, in one retrospective study of 837 survivors of COVID-19, 5 percent had evidence of organizing pneumonia [129]. Corticosteroid treatment resulted in improved symptoms, imaging, and function. An open-label, randomized trial reported similar improvements, although there was no difference between high-dose (prednisolone 40 mg/day for one week, 30 mg/day for one week, 20 mg/day for two weeks, 10 mg/day for two weeks) compared with low-dose (prednisolone 10 mg/day for six weeks) corticosteroid regimens [130]. Additional randomized trials are needed to inform this clinical consideration. (See "Approach to the patient with dyspnea" and "Pulmonary rehabilitation" and "Cryptogenic organizing pneumonia".)

Cough – Cough following recovery from acute COVID-19 is managed in a similar fashion to cough in patients with postviral cough syndrome, ensuring that other causes of cough are not exacerbating or contributing to symptoms (eg, gastrointestinal reflux disease, asthma). (See "Evaluation and treatment of subacute and chronic cough in adults".)

Therapy is supportive. We typically advise use of over-the-counter cough suppressants (eg, benzonatate, guaifenesin, dextromethorphan) as needed. Inhaled therapies (eg, inhaled bronchodilators or glucocorticoids) are infrequently prescribed, although they may be helpful in some cases. Opioids are rarely justified for treatment of cough due to the potential risks of harm, and they are used only in patients with intractable cough that is severe, intolerable, interfering with sleep, and/or reducing quality of life.

Chest discomfort/tightness/pain – Persistent chest discomfort following recovery from acute COVID-19 may resolve slowly. It does not generally require treatment unless it is interfering with the patient's quality of life. For persistent, severe, discomfort, nonsteroidal antiinflammatory drugs (NSAIDs) may be administered in the absence of renal dysfunction or other contraindications. We advise using the lowest effective dose for the shortest period of time (eg, ibuprofen 400 to 600 mg orally every eight hours as needed for one to two weeks). (See "Nonselective NSAIDs: Overview of adverse effects" and "Clinical evaluation of musculoskeletal chest pain" and "Outpatient evaluation of the adult with chest pain".)

If chest tightness is thought to be due to bronchospasm, therapy with an inhaled bronchodilator is appropriate. (See "Evaluation and treatment of subacute and chronic cough in adults", section on 'Asthma'.)

Chest pain due to COVID-19-related myocardial injury or myocarditis requires urgent evaluation, if appropriate, or referral to cardiology for further evaluation [123]. (See "COVID-19: Evaluation and management of cardiac disease in adults" and "COVID-19: Myocardial infarction and other coronary artery disease issues" and "Clinical manifestations and diagnosis of myocarditis in adults".)

Known cardiac injury – Patients with an established diagnosis of cardiac injury (eg, acute myocardial infarction, cardiac arrest, atrial fibrillation) or myocarditis related to COVID-19 should be evaluated by a cardiologist. (See "COVID-19: Cardiac manifestations in adults" and "COVID-19: Myocardial infarction and other coronary artery disease issues" and "Clinical manifestations and diagnosis of myocarditis in adults".)

In addition, patients recovering from cardiac injury with resulting functional limitations (eg, New York Heart Association [NYHA] class II or higher) (table 8) should undergo cardiac rehabilitation rather than a traditional physical therapy program, if available, as long as there are no contraindications (table 9). (See "Cardiac rehabilitation programs" and "Cardiac rehabilitation in older adults" and "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary heart disease" and "Cardiac rehabilitation in patients with heart failure".)

Orthostasis – For patients with orthostasis and dysautonomia (eg, unexplained sinus tachycardia, dizziness on standing) following COVID-19, we initially treat conservatively with compression stockings, abdominal binder, hydration, physical therapy, and behavioral modifications. (see "Treatment of orthostatic and postprandial hypotension"). For those with evidence of postural tachycardia on orthostatic testing and failure of conservative management, we sometimes consider medications. (See "Postural tachycardia syndrome".)

Neurologic and neurocognitive sequalae — For patients with neurologic complications of acute COVID-19 (eg, stroke, seizures, hypoxic encephalopathy, neuromuscular weakness related to critical illness [131], Guillain-Barré syndrome, encephalitis), we perform a complete neurological history and examination and evaluate the degree of residual deficits and their impact on the patient's functional status. We do not typically obtain neurological imaging unless there is an unexplained neurologic deficit or concern for a focal lesion or other condition.

Patients with neurologic complications following COVID-19 should be managed in the same way as with other patients. For example, for patients with unexplained muscle weakness or sensory complaints, evaluation with electromyography and nerve conduction studies are appropriate. These issues are discussed separately.

(See "COVID-19: Neurologic complications and management of neurologic conditions".)

(See "Neuromuscular weakness related to critical illness".)

(See "Guillain-Barré syndrome in adults: Treatment and prognosis".)

(See "Overview of secondary prevention of ischemic stroke".)

(See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".)

In addition, similar to the experience of sepsis survivors, many COVID-19 survivors report concentration and memory problems (in lay terms also known as "brain-fog"). In most patients, we screen for cognitive impairment (which may be subtle) using the Montreal Cognitive Assessment (MoCA) (table 3). We typically refer patients with scores indicating moderate-severe cognitive impairment for neuropsychological or speech-language pathology evaluation and management. The MoCA-BLIND (MoCA without the visuospatial/executive and naming sections of the test) can be used during telehealth evaluation. Further details are provided separately.

(See "COVID-19: Neurologic complications and management of neurologic conditions".)

(See "Mental status scales to evaluate cognition".)

(See "Evaluation of cognitive impairment and dementia".)

(See "The mental status examination in adults".)

(See "Mild cognitive impairment: Prognosis and treatment".)

Hypercoagulability/thromboses — Many patients with COVID-19 demonstrate laboratory evidence of hypercoagulability during the acute illness and some develop venous and arterial thromboses, especially those with severe or critical acute illness. We evaluate all patients for signs and symptoms of deep venous thromboses (DVT) of the upper and lower extremities, pulmonary embolism, or arterial thromboses (eg, digital ischemia). For patients taking anticoagulants, we review the duration and indication for anticoagulation, confirming appropriateness and safety as we do in any patient on anticoagulation. Further details are provided separately:

(See "COVID-19: Hypercoagulability".)

(See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

(See "Primary (spontaneous) upper extremity deep vein thrombosis".)

(See "Catheter-related upper extremity venous thrombosis in adults".)

(See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

(See "COVID-19: Acute limb ischemia", section on 'Management'.)

Patients diagnosed with documented thromboses are treated in a similar fashion to thrombosis in patients who did not have COVID-19 (table 10):

(See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Monitoring and follow-up'.)

(See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'Monitoring and follow-up'.)

(See "Catheter-related upper extremity venous thrombosis in adults", section on 'Treatment' and "Overview of thoracic central venous obstruction".)

(See "Peripherally inserted central catheter (PICC)-related venous thrombosis in adults", section on 'Treatment'.)

(See "Initial assessment and management of acute stroke", section on 'Acute therapy'.)

(See "Atrial fibrillation in adults: Use of oral anticoagulants".)

The duration of hypercoagulability in COVID-19 is unknown. For the majority of patients who have recovered from acute COVID-19, who were therapeutically anticoagulated for a hypercoagulable state alone, without evidence of a thrombosis, and in whom no other clear indication exists, anticoagulants are discontinued upon hospital discharge. Indications for postdischarge thromboprophylaxis are the same as for non-COVID-19 patients, the details of which are discussed separately.

(See "COVID-19: Hypercoagulability", section on 'Outpatient thromboprophylaxis'.)

(See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Duration'.)

(See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Duration of prophylaxis'.)

(See "Prevention of venous thromboembolism in adult orthopedic surgical patients".)

Olfactory/gustatory symptoms — For patients who experienced a loss or decrease in their sense of smell or taste with acute COVID-19, we inquire about the degree of residual impairment and if their appetite or weight have been affected. Weight loss can be significant for some patients after critical illness for multifactorial reasons, and taste and smell impairment may contribute. (See "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Smell and taste disorders' and "Taste and olfactory disorders in adults: Anatomy and etiology".)

In most cases, symptoms resolve slowly over several weeks and do not require intervention except for education regarding food and home safety.

Patients with persistent gustatory and/or olfactory dysfunction may benefit from olfactory training, and self-guided programs are available online. If symptoms fail to resolve, further evaluation by an otolaryngologist may be needed, particularly in the setting of accompanying upper airway symptoms. Although not widely available, referral to a specialized taste and smell clinic may also be considered. (See "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Smell and taste disorders' and "Taste and olfactory disorders in adults: Evaluation and management".)

Fatigue, poor endurance, and functional status — The American Academy of Physical Medicine and Rehabilitation has developed a multidisciplinary collaborative consensus guidance statement on the assessment and management of fatigue following COVID-19 illness [132]. We generally follow the recommendations of this guidance statement as outlined in this section.

Some, although not all, patients with fatigue may have symptoms consistent with and meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome. In those cases, a similar assessment and management strategy can be used. (See "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome", section on 'Diagnosis and evaluation'.)

Clinical evaluation — Consensus-based recommendations for the evaluation of fatigue have been published (table 11) [132]. Patients should be screened for fatigue patterns to help guide activity and monitor the response to initiating and escalating activity as well as monitor the effects on daily functioning (eg activities and instrumental activities of daily living such as feeding, dressing, bathing, toileting, driving, housekeeping, and grocery shopping).

To inform the patient's rehabilitation plan, we compare their current symptoms with their preillness functional status (eg, decline in exercise tolerance, weakness, or reduced mobility). As part of the evaluation, we also determine whether the patient has any conditions that may exacerbate or lead to fatigue, including medication use/polypharmacy, deconditioning, weakness, muscle atrophy, pain, sleep disturbances, endocrine disorders, mood disorders, and/or cardiopulmonary symptoms.

As screening tools, we typically use the six-minute walk test (table 5) and one or more of the following: EuroQol-5D-5L, Timed Up and Go (TUG), and Short Physical Performance Battery (SPPB) [113,133]. As part of the EuroQol-5D-5L, we also assess for persistent pain. These standardized functional assessment tools can also be used to monitor the patient's progress over time. A functional assessment tool specific to COVID-19 has been developed, although it has not been validated [134,135]. (See "Overview of pulmonary function testing in adults", section on 'Six-minute walk test'.)

We consider laboratory testing in new patients and in patients without laboratory work-up in the three months prior to the visit. Potential laboratory work-up is outlined above. (See 'Laboratory testing' above.)

Management — Consensus based recommendations for the evaluation and management of fatigue have been published (table 12) [132].

General guidance for management of patients with persistent fatigue and impaired functional status includes:

For patients with fatigue, we encourage adequate rest, good sleep hygiene, and specific fatigue management strategies [59,105]. One method that is helpful is the "four-P" approach to energy conservation: Planning, Pacing, Prioritizing, and Positioning. Details can be found at this website.

For the majority of patients, we advise an individualized and structured, titrated return-to-activity program based on the level of fatigue. These programs are based on identifying the level of activity that the patient is comfortable with and slowly progressing it, if tolerated. If the patient is unable to tolerate progression or experiences worsening symptoms or malaise following activity, we recommend maintenance at the previously tolerated level. For patients having difficulty advancing activity, we refer to a rehabilitation specialist (ie, physical therapy or physiatrist) to help guide an individualized rehabilitation program. We do not have patients undergo a structured graduated/progressive exercise program. Those with fatigue or poor exercise performance due to cardiopulmonary pathology may be more likely to benefit from a specialized cardiac or pulmonary rehabilitation program. (See "Overview of geriatric rehabilitation: Patient assessment and common indications for rehabilitation" and "Pulmonary rehabilitation" and "Cardiac rehabilitation programs".)

Although we encourage a healthy diet and hydration for all patients, there has not been a specific diet shown to be beneficial. There is currently insufficient evidence to support the use of specific nutritional supplements.

There is currently no evidence for the use of specific pharmacologic agents in the treatment of fatigue related to COVID-19 infection.

Other (renal, hepatic, endocrine, gastrointestinal, dermatologic, infectious, sleep, psychological, quality of life)

Renal and hepatic – In patients who suffer from acute renal and liver dysfunction during acute COVID-19 infection, we assess for hypertension, anemia, and signs of persistent kidney and liver disease. (See "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension" and "COVID-19: Issues related to liver disease in adults".)

Although in most patients with non-critical COVID-19 the kidney and liver injury generally self-resolve, those with kidney or liver injury during acute illness require appropriate follow-up laboratory testing to assess for organ recovery. New-onset chronic kidney disease is unusual but may be seen in those who had acute kidney injury during ICU hospitalization [34]. Patients with long-term kidney or liver dysfunction should be managed by specialists. These issues are discussed separately:

(See "COVID-19: Issues related to liver disease in adults".)

(See "COVID-19: Issues related to gastrointestinal disease in adults".)

(See "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension".)

(See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)

(See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'Hepatic manifestations'.)

Endocrine – During, and in the three to six months following, acute COVID-19 illness, patients may rarely develop new diabetes mellitus, and those with diabetes may become newly insulin-dependent or develop an increased insulin requirement [136-138]. During our initial evaluation, we review diabetic treatment regimens and assess the ability of the patient to administer insulin (if necessary) and monitor their own blood sugars. (See "COVID-19: Issues related to diabetes mellitus in adults".)

Previous studies have also demonstrated accelerated loss of bone mineral density following critical illness [139]. Thus, we ask patients about orthopedic pain (eg, from vertebral fracture) and assess their risk for the development of osteoporosis (eg, comorbidities, postmenopausal status, smoking, glucocorticoid use). (See "Screening for osteoporosis in postmenopausal women and men" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men".)

For patients who have fatigue, myalgia, orthostasis, decreased appetite, nausea, and weight loss, clinicians should consider the diagnosis of adrenal insufficiency, particularly in patients who received corticosteroids during their hospitalization. The presentation and diagnosis of adrenal insufficiency is reviewed elsewhere. (See "Clinical manifestations of adrenal insufficiency in adults" and "Diagnosis of adrenal insufficiency in adults".)

Gastrointestinal/nutritional – Persistent COVID-19 symptoms of nausea and diarrhea may slowly resolve after acute infection. However, for patients with new or progressive symptoms or symptoms that are not resolving, an alternative diagnosis, such as antibiotic-associated diarrhea or Clostridioides difficile enterocolitis should be considered, particularly in patients who received antibiotics. (See "Approach to the adult with acute diarrhea in resource-rich settings" and "COVID-19: Issues related to gastrointestinal disease in adults".)

Weight loss due to acute illness is often multifactorial and may involve malnutrition, loss of appetite, catabolic state, swallowing dysfunction, and disordered taste and smell. We encourage patients to eat small, frequent meals with protein and calorie supplementation. For patients with severe weight loss and ongoing appetite issues, nutrition consultation is appropriate. Speech pathology evaluation is necessary for patients with swallowing dysfunction. (See "Nutrition support in critically ill patients: An overview", section on 'Coronavirus disease 2019' and "Post-intensive care syndrome (PICS)", section on 'Other' and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management", section on 'Swallowing rehabilitation and nutrition'.)

Psychological and emotional issues – We assess anxiety and depression symptoms by direct questioning of the patient and/or their caregiver, including evaluation of mood, anxiety, feelings of isolation, and stress level [113]. We also attempt to discern whether psychological and emotional symptoms may be secondary to physical symptoms or the patient's social environment. In patients with affective symptoms, we further ask about suicidality [140,141].

We use screening questionnaires including the Hospital Anxiety and Depression Scale (HADS) to evaluate for anxiety and depression and the Impact of Event Scale to evaluate for posttraumatic stress disorder (PTSD). (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis", section on 'Medical illness'.)

For patients with symptoms consistent with anxiety, depression, and/or PTSD, we evaluate the severity of symptoms and determine the most appropriate treatment. For those with mild to moderate anxiety and depression, treatment may be provided by a primary care clinician, depending upon practice setting and clinician experience. For patients with severe anxiety and depression and for patients with PTSD, referral for psychiatric evaluation may be warranted. Social work services and occupational therapy support may also be helpful resources. The management of anxiety, depression, and PTSD are reviewed in detail elsewhere. (See "Management of posttraumatic stress disorder in adults" and "Post-intensive care syndrome (PICS)", section on 'Psychiatric impairment' and "Unipolar major depression in adults: Choosing initial treatment" and "Generalized anxiety disorder in adults: Management".)

Dermatologic – We ask about alopecia and skin lesions (including any residual effects from "COVID toes" or pernio-like acral lesions), other COVID-19 related skin lesions, necrotic skin lesions related to vasopressor use, or decubitus ulcers. We examine any affected areas, assess for healing, and evaluate for secondary infection. Wound care consultation may be warranted. Some patients recovering from COVID-19 have reported alopecia [4]. Alopecia should be managed similarly to non-COVID-19 patients, and in patients where malnutrition may be a contributor, nutritional status should be addressed. (See "COVID-19: Cutaneous manifestations and issues related to dermatologic care" and "Overview of treatment of chronic wounds" and "Alopecia areata: Management".)

Infectious – Case reports of invasive fungal infections, such as rhino-orbital mucormycosis, have been reported in patients recovering from COVID-19. Risk factors for mucormycosis include treatment with corticosteroids and poorly controlled diabetes mellitus [142-144]. Mucormycosis should be suspected in patients with these risk factors who have sinus congestion, blackish or discolored nasal discharge, facial or ocular pain, or visual symptoms following acute COVID-19 illness [145,146]. (See "Mucormycosis (zygomycosis)", section on 'Coronavirus disease 2019-associated'.)

Other infectious complications have been observed in COVID-19 patients with similar risk factors (eg, immunosuppression, poorly controlled diabetes mellitus), including pulmonary aspergillosis [147] and strongyloides hyperinfection (disseminated disease due to autoinfection in the setting of remote initial infection) [148,149]. Although these infectious complications have been typically observed as a late complication of acute illness, delayed presentation may occur and should be considered in patients recovering from acute, moderate to severe COVID-19. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids' and "Strongyloidiasis" and "Epidemiology and clinical manifestations of invasive aspergillosis".)

Insomnia/poor-quality sleep – Sleep disturbance following acute COVID-19 is common [150], and we ask all patients about quality and duration of sleep. All patients with insomnia receive counseling on sleep hygiene, relaxation techniques, and stimulus control (table 13). Further discussion of the evaluation and management of insomnia is found elsewhere. (See "Overview of the treatment of insomnia in adults".)

Quality of life – We evaluate patients for general well-being and health-related quality of life. We use the EuroQol-visual analogue scale (EQ-VAS) as a self-reported measure of overall health. Using this scale, patients are asked to report their overall health on a visual 0 to 100 scale; we use this to track recovery from COVID-19 over time.

Economic and social concerns – Patients with prolonged recovery from COVID-19 may be unable to return to work or may face familial or personal stress due to prolonged home isolation. We ask all patients about changes in employment, issues related to potential lost income, and their home environment and social support. We refer patients to appropriate social services support whenever necessary.

Vaccination – Although data in this population are limited, symptoms do not generally appear to worsen after vaccination in individuals with persistent symptoms, and in some cases, improvement in symptoms has been noted [151]. We adopt the same vaccination approach in this population as that recommended for the general population. (See "COVID-19: Vaccines".)

Family outcomes – Preliminary data suggest that family members of patients diagnosed with COVID also undergo significant stress and can suffer from anxiety [152]. (See "COVID-19: Psychiatric illness", section on 'Family members of COVID-19 patients' and "COVID-19: Management in children", section on 'Loss of a parent or caregiver'.)

REHABILITATION: SETTING AND PRESCRIPTION — Many patients who have recovered from severe acute COVID-19 require rehabilitation services, including physical and occupational therapy, pulmonary or cardiac rehabilitation, and speech and swallowing therapy [89]. We refer all patients with a need for rehabilitation services as early as is feasible, typically within 30 days of recovery from initial infection [153]. All patients should be screened for cardiac symptoms prior to beginning any exercise program; if necessary, a full cardiac evaluation may be warranted before commencing rehabilitation therapy based upon symptoms. In the absence of concerning symptoms, we generally do not require any cardiac screening prior to initiating rehabilitation. (See 'Cardiopulmonary symptoms' above.)

Rehabilitation programs generally last for six to eight weeks and are followed by a clinical reassessment to determine the need for ongoing treatment.

Outpatient rehabilitation – There are a wide variety of available outpatient rehabilitation programs including in-person rehabilitation and in-home or web-based rehabilitation programs. In general, we prefer in-person programs since they are better validated [154], but home or web-based rehabilitation may be appropriate for patients who cannot easily access a rehabilitation facility.

In-person rehabilitation – Some experts suggest waiting for six to eight weeks or obtaining a negative COVID-19 test before commencing in-person rehabilitation [105]. However, we prefer a non-test-based strategy to determine when to remove infectious precautions and refer for in-person rehabilitation (table 2).

Some rehabilitation programs are multidisciplinary and address a wide array of issues including general physical rehabilitation, pulmonary and/or cardiac rehabilitation, and occupational therapy, as well as the nutritional needs of the individual. Further details regarding in-person rehabilitation programs are provided separately.

-(See "Overview of geriatric rehabilitation: Patient assessment and common indications for rehabilitation".)

-(See "Pulmonary rehabilitation".)

-(See "Geriatric rehabilitation interventions".)

-(See "Cardiac rehabilitation programs".)

-(See "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary heart disease".)

-(See "Cardiac rehabilitation in patients with heart failure".)

-(See "Cardiac rehabilitation in older adults".)

Home- or web-based rehabilitation ("telerehabilitation") – For some patients, telerehabilitation is another option [155-157]. Remote delivery of rehabilitation services may be preferable in areas of high infection prevalence to minimize the potential spread of COVID-19. However, rehabilitation at home models vary widely in the services provided and are of unproven benefit in patients recovering from COVID-19.

Telerehabilitation can be delivered either synchronously (ie, in real-time) or asynchronously (eg, a prerecorded customized exercise plan). Systems need to be established in order to use these methods successfully given the wide range of patient rehabilitation needs and varying access and patient comfort with technology. Telerehabilitation may be supplemented with one or more in-person visits. (See "Telemedicine for adults".)

Prescription – It has been postulated that graded exercise therapy is not appropriate for patients with COVID-19-related fatigue and debility given concern for worsening postexertional malaise [158]. Despite these concerns and based upon our experience with post-sepsis patients [3] and our initial experience with patients recovering from COVID-19, we generally use a cautious approach to initiating a comprehensive therapy program (eg, two to three days per week). We find that a structured and supervised program can improve endurance and reduce fatigue and dyspnea. In addition, this approach gives patients confidence and provides reassurance that they are safely resuming activity. We advise patients that if they feel worse (instead of better) after participation, they may need to cut back on their therapy to the previous level or stop all together. The development of concerning symptoms (eg, new chest discomfort) or symptoms that are disproportionate to the degree of underlying system dysfunction may warrant additional evaluation by specialty clinicians (eg, pulmonary, cardiac, neurology).

We generally start with a progressive aerobic and strength training rehabilitation program. We begin with breathing exercises, gentle stretching, and light muscle strengthening prior to any targeted cardiovascular program. Once the patient is able to tolerate light stretching and strengthening, we introduce an aerobic training program. For aerobic training, we begin at one to three metabolic equivalents (METs) and slowly increase activity as tolerated, often over multiple sessions. We monitor vital signs and initially maintain the heart rate (HR) at <60 percent of the maximum predicted HR (MPHR). We also monitor pulse oximetry and blood pressure before, periodically during, and after therapeutic activities. (See "Pulmonary rehabilitation", section on 'Components' and "Cardiac rehabilitation in older adults", section on 'Exercise prescription' and "Cardiac rehabilitation programs", section on 'Exercise training'.)

We also advocate for a program that incorporates nutritional support, particularly for those who have lost muscle mass during their acute illness. (See "Malnutrition in advanced lung disease".)

Outcomes – Data examining the outcome of rehabilitation in patients with COVID-19 are limited. In one study including 72 older patients with COVID-19 who were discharged from the hospital, participation in a six-week rehabilitation program was associated with improvement in pulmonary function, exercise capacity, and quality of life compared with patients who did not undergo rehabilitation [159].

ADDITIONAL CONSIDERATIONS FOR THE INPATIENT REHABILITATION PATIENT — Some patients recovering from COVID-19 require postacute care services, including admission to a long-term acute care facility (LTAC), an inpatient rehabilitation facility (IRF), or a skilled nursing facility (SNF). Prior to hospital discharge, patients should be assessed for any functional impairment that would require inpatient rehabilitation services. One report suggested that among 1250 patients with COVID-19 who were discharged from a hospital, 12.6 percent required admission to an IRF or SNF [66].

The initial evaluation of recovering COVID-19 patients who are admitted to an inpatient rehabilitation facility are similar to that described in the outpatient population. This involves a detailed assessment of the hospital course, complications, evaluation of current symptoms, and appropriate follow-up testing and management. Further details are provided above. (See 'General evaluation' above.)

Management is also similar to that in the outpatient setting. However, inpatients discharged from the intensive care unit (ICU) to LTACs commonly have a tracheostomy, and most suffer from post-intensive care syndrome (PICS), which includes physical impairment from ICU-acquired neuromuscular weakness, cognitive, and neuropsychological impairment. For such patients, in the early stages of rehabilitation, there is a heavy emphasis placed on ventilator weaning, physical therapy for improving muscle strength and endurance, and optimizing nutrition. For these patients, non-urgent medical issues and testing are often deferred until the patient has been weaned from mechanical ventilation. Further details regarding these issues are provided separately.

(See "Post-intensive care syndrome (PICS)".)

(See "Geriatric rehabilitation interventions".)

(See "Pulmonary rehabilitation".)

(See "Cardiac rehabilitation programs".)

(See "Neuromuscular weakness related to critical illness".)

(See "Nutrition support in critically ill patients: An overview".)

(See "Geriatric nutrition: Nutritional issues in older adults".)

Resource allocation — In some regions with high volumes of acute care COVID-19 patients, rural hospitals, unused buildings (such as university dormitories), or unused hospital floors have been repurposed with the goal of rehabilitating patients recovering from COVID-19 [160].

It is preferable for patients to receive their rehabilitation at an LTAC, IRF, or SNF, as the staff are appropriately trained and best suited to deliver these services. In cases of prolonged admission, possibly due to limited capacity in inpatient rehabilitation settings or rehabilitation facility infection control procedures, rehabilitation (including ventilator weaning) may need to begin in the hospital or ICU. Specific guidelines for intensive care rehabilitation are available [161]. For patients who remain infectious, rehabilitation therapy should be provided one-on-one in patients' rooms using appropriate personal protective equipment. Personnel should be minimized, shared equipment must be decontaminated after use, and when feasible, single-use equipment should be used.

Infection precautions — Federal, state, county, and local guidance on infection precaution strategies for new admissions and readmissions to IRFs, SNFs, and LTACs have been variable and sometimes conflicting. In general, we suggest the following:

SNFs and IRFs – Patients recovering from COVID-19 who are being discharged from the hospital and have met criteria for discontinuing precautions do not require additional isolation precautions upon discharge to SNFs and IRFs. This includes those who met criteria using a non-test-based strategy (table 2). Details of infection precautions in these patients are reviewed elsewhere. (See "COVID-19: Management in nursing homes", section on 'Approach to new/returning residents'.)

LTACs – Recommendations for discontinuing isolation and precautions for the critically ill continue to evolve. As of October 2020, the Centers for Disease and Control and Prevention guidelines stated that "persons with more severe to critical illness or severe immunocompromise likely remain infectious no longer than 20 days after symptom onset." However, given the severity of COVID-19 that may include compromised patients, many LTACs request test-based strategies (eg, two negative severe acute respiratory syndrome coronavirus-2 reverse transcriptase-polymerase chain reaction [SARS-CoV-2 RT-PCR] tests performed 24 hours apart) before accepting a patient with COVID-19.

If transfer to a facility is delayed, rehabilitation (and ventilator weaning, if applicable) should begin at the acute care facility when medically indicated. For patients who remain infectious, rehabilitation therapy should be provided one-on-one in patients' rooms using appropriate personal protective equipment. Personnel should be minimized, shared equipment must be decontaminated after use and, when feasible, single-use equipment should be used.

Tracheostomy care and weaning — Weaning patients with COVID-19 from mechanical ventilation is similar to weaning non-COVID-19 patients, the details of which are discussed separately. (See "Management and prognosis of patients requiring prolonged mechanical ventilation".)

However, appropriate precautions should be taken in patients who are considered infectious particularly during aerosol-generating procedures.

Initial weaning trials of pressure support ventilation (PSV) are typically performed through a closed-loop system, which is considered non-aerosol-generating. This system is sufficient for patients undergoing spontaneous breathing trials (SBTs) with incremental periods of prolonged PSV which typically occur over a few days or a few weeks. This practice is similar to that in non-COVID-19 patients.

Once the patient can breathe spontaneously for 16 to 24 hours on PSV, they typically progress to SBTs through a tracheostomy collar. However, an SBT using a tracheostomy collar is an open system. As a result, some institutions consider tracheostomy collar an aerosol-generating procedure (AGP), although it remains controversial. At our institution, given the available evidence, if flow is less than 15 liters per minute, we do not consider it an AGP, and at higher flow, deem it a low-risk procedure. Regardless, once the tracheostomy collar SBT is completed, closed-loop ventilation should be resumed.

Given the potential need for tracheal suctioning, ideally, a tracheostomy collar SBT should be performed in an airborne isolation room. An alternative includes using a portable HEPA filter to generate negative pressure in a room during a tracheostomy collar SBT. A surgical mask over the tracheostomy itself may also theoretically limit droplet spread but is not ideal.

Once the patient can breathe for 24 hours on a tracheostomy collar (or modified T-piece), they can undergo trials of a speaking valve and "capping" with the balloon deflated. Placing a speaking valve and capping would be considered aerosol-generating, so airborne precautions are warranted. However, once a speaking valve is in place or the tracheostomy is capped, aerosolization is less of a consideration and is the equivalent of a patient with a cough and on low-flow oxygen; in such cases, the patients may wear a mask over their nose and mouth.

Tracheostomy placement, bronchoscopy, and decannulation (ie, removal of the tracheostomy) are each considered aerosol-generating procedures, and provided the patient remains infectious, all the usual airborne precautions should be taken. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

Outcome data for patients with a tracheostomy and undergo weaning are limited but suggest the outcomes may be better than patients without COVID-19. One retrospective study of 158 patients who required tracheostomy for prolonged mechanical ventilation reported successful weaning in 71 percent and a mortality of 10 percent [162]. Weaning duration was 8 days. By the end of the study period, 19 percent were discharged home while 70 percent were discharged to other facilities (eg, rehabilitation facilities [46 percent], acute care hospital [17 percent], or nursing facility [7 percent]). In another retrospective study of patients who underwent tracheostomy for COVID-19, 90 percent were alive 90 days later, 2.7 percent still had the tracheostomy, 33 percent still had a PEG, and almost two-thirds were at home [163]. Another retrospective analysis suggested that liberation rates may be higher in patients with COVID-19 compared with non-COVID-19 illnesses (91 versus 56 percent) [164].

Venous thromboembolism prophylaxis — We typically place inpatients recovering from acute COVID-19 on venous thromboembolism prophylaxis until the acute illness fully resolves and/or the patient becomes fully mobile, although the efficacy of this approach is unknown. Guidance on duration of therapeutic anticoagulation varies with the indication and is similar to that described for the outpatient. (See 'Hypercoagulability/thromboses' above.)

RETURN TO WORK OR EXERCISE — The ability of patients to return to work or exercise should be assessed on an individual basis and will likely vary depending upon their baseline pre-COVID-19 functional status, the severity of their illness and any complications, and the intensity of planned activity [109]. In general, for most patients recovering from their acute illness, we encourage gradual resumption of exercise as tolerated, starting at a low-intensity level and slowly increasing activity over the next several weeks [108].

For patients who remain asymptomatic, we advise slow escalation of higher-intensity exercise toward their pre-COVD-19 baseline with close monitoring for symptoms (table 14). (See "COVID-19: Return to sport or strenuous activity following infection", section on 'Schedules and guidance for return to activity and full play'.)

Patients who have new or progressive symptoms during resumption of physical activity or difficulty with advancing to pre-COVID-19 activity levels should have a formal clinical evaluation and consideration of exercise testing (algorithm 2). (See 'Cardiopulmonary testing' above and "COVID-19: Return to sport or strenuous activity following infection", section on 'Medical clearance in athletes'.)

In general, patients planning to return to high-level sport or a physically demanding occupation following confirmed myocarditis should be first evaluated by a cardiologist [104]. This and other issues related to resuming strenuous activity following COVID-19 are reviewed in detail elsewhere. (See "COVID-19: Return to sport or strenuous activity following infection", section on 'Myocardial injury' and "Treatment and prognosis of myocarditis in adults", section on 'Follow-up'.)

VACCINATION — Details regarding optimal timing for COVID-19 vaccination are provided elsewhere. (See "COVID-19: Vaccines", section on 'History of SARS-CoV-2 infection'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: COVID-19 overview (The Basics)" and "Patient education: Recovery after COVID-19 (The Basics)" and "Patient education: COVID-19 and pregnancy (The Basics)")

SUMMARY AND RECOMMENDATIONS

Terminology – The COVID-19 pandemic has resulted in a growing population of individuals with a wide range of persistent symptoms after acute SARS-CoV-2 infection. This comprises patients with symptoms that develop during or after COVID-19, continue for ≥4 weeks, and are not explained by an alternative diagnosis. Several terms have been used to describe prolonged symptoms following COVID-19 illness, such as "post-COVID conditions," "long COVID," "postacute sequelae of SARS-CoV-2 infection (PASC)," "postacute COVID-19," "chronic COVID-19," and "post-COVID syndrome." Whether the constellation of symptoms represents a new syndrome unique to COVID-19 or if there is overlap with the recovery from similar illnesses has not been determined. (See 'Terminology and stages of recovery' above and 'Challenges with defining and evaluating post-COVID conditions' above.)

Recovery symptoms and course

Physical and psychological symptoms are common following COVID-19. (See 'Persistent symptoms' above.)

-Persistent physical symptoms are common and typically include fatigue, dyspnea, chest pain, and cough (table 1). Less common persistent physical symptoms include anosmia, joint pain, headache, sicca syndrome, rhinitis, dysgeusia, poor appetite, dizziness, myalgias, insomnia, alopecia, sweating, and diarrhea.

-Patients may also experience psychological or cognitive complaints including posttraumatic stress disorder (PTSD), anxiety, depression, and poor memory and concentration.

While most patients with mild acute COVID-19 disease are expected to recover quickly (eg, two weeks), a longer recovery should be expected in those with moderate to severe acute disease (eg, two to three months, sometimes longer in those who survive critical illness). The wide variability in time to symptom resolution likely also depends upon premorbid risk factors as well as illness severity during acute COVID-19. (See 'Expected recovery time course' above.)

General evaluation (see 'General evaluation' above)

We assess the patient's symptom severity to determine the timing of follow-up evaluation. In patients with mild to moderate disease not requiring hospitalization, we do not routinely schedule a COVID-19 follow-up visit unless the patient requests it or has persistent, progressive, or new symptoms. For patients with more severe acute COVID-19 disease requiring hospitalization (with or without the need for postacute care such as inpatient rehabilitation), we ideally follow-up within one week but no later than two to three weeks after discharge from the hospital or rehabilitation facility. (See 'Timing and location of follow-up evaluation' above.)

During the initial follow-up evaluation, we obtain a comprehensive history of the patient's COVID-19 illness, including the illness timeline, duration and severity of symptoms, types and severity of complications, COVID-19 testing results, and any management strategies. The need for laboratory testing is determined by illness severity, prior abnormal testing during their illness, and current symptoms. We do not routinely re-test patients for active infection with SARS-CoV-2 at the time of follow-up outpatient evaluation. Instead, we follow a non-test-based approach to removing infectious precautions. (See 'Assess disease severity, complications, and treatments' above and 'General laboratory testing' above and 'COVID-19 testing and serology' above.)

Cardiopulmonary issues (see 'Cardiopulmonary symptoms' above)

We perform a comprehensive cardiopulmonary evaluation, including a comprehensive history and physical examination. We inquire about ongoing dyspnea (at rest and exertion) (table 4), cough, chest discomfort, pleuritic pain, wheezing, orthopnea, chest pain (exertional, positional), peripheral edema, palpitations, dizziness, orthostasis, and pre-syncope or syncope. (See 'Cardiopulmonary symptoms' above and 'Clinical evaluation' above.)

Based on clinical history and findings, the following cardiopulmonary testing strategy is appropriate (see 'Cardiopulmonary testing' above):

-For all patients who had a pulmonary infiltrate or other abnormality identified on imaging during the acute course of COVID-19 illness, we obtain follow-up chest imaging, typically chest radiography, at 12 weeks. For patients with new or progressive symptoms, earlier imaging is indicated. Chest computed tomography (CT) is preferred for patients in whom another etiology (eg, malignancy) is suspected, and high resolution CT (HRCT) is an appropriate imaging study for patients with suspected interstitial lung disease from severe pulmonary involvement (eg, acute respiratory distress syndrome [ARDS]).

-For patients with intermittent or persistent cardiopulmonary symptoms, including palpitations, or those with generalized, constitutional complaints such as weakness or fatigue, we typically perform a 12-lead electrocardiogram. We do not routinely perform transthoracic echocardiography (TTE). However, we have a low threshold to obtain a TTE in patients with a history or biochemical evidence of myocardial injury or myocarditis or in patients with dyspnea and other signs and symptoms suggestive of a potential cardiac disorder.

-For patients with persistent, progressive, or new respiratory symptoms and patients recovering from ARDS, we obtain pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusion capacity and a six-minute walk test.

-If cardiopulmonary symptoms remain unexplained, we typically refer the patient to a cardiologist or pulmonologist for further evaluation and testing.

Our approach to management is based upon the management of symptoms following similar illnesses (see 'Management' above):

-Dyspnea (see "Approach to the patient with dyspnea")

-Cough (see "Evaluation and treatment of subacute and chronic cough in adults")

-Chest discomfort (see "Clinical evaluation of musculoskeletal chest pain" and "Outpatient evaluation of the adult with chest pain")

-Cardiac injury or myocarditis (see "COVID-19: Cardiac manifestations in adults" and "Clinical manifestations and diagnosis of myocarditis in adults")

Some patients may benefit from cardiac or pulmonary rehabilitation. (See "Cardiac rehabilitation programs" and "Pulmonary rehabilitation".)

Neurologic or neurocognitive issues (see 'Neurologic and neurocognitive sequalae' above)

We perform a complete neurological history and examination and evaluate any deficits and their impact on the patient's functional status. Patients are managed in a similar way to non-COVID-19 patients with the same issues. We do not typically obtain neurological imaging unless there is an unexplained neurologic deficit or concern for a focal lesion or other condition. These issues are discussed separately.

-(See "COVID-19: Neurologic complications and management of neurologic conditions".)

-(See "Neuromuscular weakness related to critical illness".)

-(See "Guillain-Barré syndrome in adults: Treatment and prognosis".)

-(See "Overview of secondary prevention of ischemic stroke".)

-(See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".)

-(See "Treatment of orthostatic and postprandial hypotension", section on 'Nonpharmacologic measures'.)

We screen for cognitive impairment using the Montreal Cognitive Assessment (MoCA) (table 3). We typically refer patients with scores indicating moderate to severe cognitive impairment (ie, score <18) for neuropsychological or speech language evaluation. These issues are discussed separately.

-(See "COVID-19: Neurologic complications and management of neurologic conditions".)

-(See "Mental status scales to evaluate cognition".)

-(See "Evaluation of cognitive impairment and dementia".)

-(See "The mental status examination in adults".)

-(See "Mild cognitive impairment: Prognosis and treatment".)

Hypercoagulability – We evaluate all patients for signs and symptoms of deep venous thromboses (DVT) of the upper and lower extremities, pulmonary embolism, or arterial thromboses (eg, digital ischemia). For patients taking anticoagulants, we review the duration and indication for anticoagulation, confirming appropriateness and safety. Patients with documented thromboses are treated in a similar fashion to thrombosis in non-COVID-19 patients (table 10). These issues are discussed separately.

(See "COVID-19: Hypercoagulability".)

(See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

(See "Primary (spontaneous) upper extremity deep vein thrombosis".)

(See "Catheter-related upper extremity venous thrombosis in adults".)

(See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

(See "COVID-19: Acute limb ischemia", section on 'Management'.)

Olfactory/gustatory – In most cases, these symptoms resolve slowly over several weeks and do not require intervention except for education regarding food and home safety. Patients with persistent gustatory and/or olfactory dysfunction may benefit from further evaluation and management, including olfactory training by referral to an otolaryngologist or a taste and smell clinic, if available. (See "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Smell and taste disorders' and "Taste and olfactory disorders in adults: Evaluation and management".)

Fatigue and functional assessment – We typically screen patients for functional impairment using the six-minute walk test (table 5) and one or more of the following: EuroQol-5D-5L, Timed Up and Go (TUG), and Short Physical Performance Battery (SPPB). We typically advise an individualized and structured, titrated return-to-activity program as tolerated for the patient. We encourage adequate rest, good sleep hygiene, and specific fatigue management strategies. If patients have symptoms consistent with or meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome, a similar evaluation and management strategy is warranted. (See 'Fatigue, poor endurance, and functional status' above and "Treatment of myalgic encephalomyelitis/chronic fatigue syndrome" and "Approach to the adult patient with fatigue".)

Other – Other conditions which may persist following recovery from COVID-19 can include renal failure, hepatic injury, endocrine disorders (diabetes, bone loss, adrenal insufficiency), gastrointestinal symptoms (diarrhea, weight loss, malnutrition), dermatologic conditions (alopecia, skin lesions, decubitus ulcers), impaired sleep (eg, insomnia), psychological effects (anxiety, depression, PTSD), quality of life, and social and economic concerns. (See 'Other (renal, hepatic, endocrine, gastrointestinal, dermatologic, infectious, sleep, psychological, quality of life)' above.)

Outpatient rehabilitation – When rehabilitation services are indicated, we typically refer patients within 30 days of recovery from initial infection. All patients should be screened for cardiac symptoms prior to beginning any exercise program; if necessary, a full cardiac evaluation may be warranted before commencing rehabilitation therapy. While we prefer in-person rehabilitation programs that last six to eight weeks, outpatient and web-based programs are also available, although the latter are less well-validated. (See 'Rehabilitation: Setting and prescription' above.)

Inpatient rehabilitation – The evaluation and management of patients recovering from acute COVID-19 who are admitted to a long-term acute care facility (LTAC), an inpatient rehabilitation facility (IRF), or a skilled nursing facility (SNF) are similar to those described in the outpatient population. In addition, such patients commonly have a tracheostomy and most suffer from post-intensive care syndrome (PICS), which includes physical impairment from intensive care unit (ICU)-acquired neuromuscular weakness, cognitive, and neuropsychological impairment. If there is a delay in transferring the patient to an inpatient facility, ventilator weaning should begin in the acute care facility. If the patient remains infectious, appropriate precautions should be taken during tracheostomy collar weaning. Most patients in inpatient facilities require venous thromboembolism prophylaxis until the acute illness fully resolves and/or the patient becomes fully mobile. (See 'Additional considerations for the inpatient rehabilitation patient' above.)

Return to work/exercise – The ability of patients to return to work or exercise should be assessed on an individual basis and will likely vary depending upon their baseline pre-COVID-19 functional status, the severity of their illness and any complications, and the intensity of planned activity. In general, patients planning to return to strenuous activity or a physically demanding occupation following myocarditis should be first evaluated by a cardiologist. (See 'Return to work or exercise' above.)

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Topic 129312 Version 52.0

References