COVID-19: Management of adults with persistent symptoms following acute illness ("long COVID")

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. During recovery, these patients may experience a wide range of symptoms, which is referred to by several terms (eg, "long COVID").

Patients with long COVID may have several symptoms following the acute illness. In this topic, we will discuss the management of organ-specific symptoms of long COVID. The clinical presentation and diagnosis of long COVID is described separately:

●(See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")".)

The management of adults with acute COVID-19 is reviewed elsewhere:

●(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".)

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".)

DEFINITION — We and others define long COVID as a syndrome with a broad range of persistent or new symptoms/symptom clusters that develop during or after COVID-19, are noted more than three months after the onset of their COVID-19 illness, have an impact on the patient's life, and are not explained by an alternative diagnosis. Further details on the definition of long COVID and terminology used to describe it are provided separately. (See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")", section on 'Terminology and stages of recovery'.)

CARDIOPULMONARY SYMPTOMS — Cardiopulmonary symptoms are common in patients with long COVID (eg, dyspnea, chest discomfort, cough).

Clinical evaluation — For patients who have persistent cardiopulmonary symptoms or complications during their illness, 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 presyncope or syncope. We typically use the modified Borg dyspnea scale to assess overall dyspnea symptoms (table 1). We also ask about supplemental oxygen needs and obtain pulse oximetry data (ie, peripheral oxygen saturation [SpO₂]), 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 "Pleural fluid analysis in adults with a pleural effusion" 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 vital signs, with special attention to blood pressure to look for new onset hypertension [1] and to SpO₂ to look for hypoxemia. In patients with orthostasis, presyncope, or syncope, we perform postural blood pressure (up to 10 minutes after standing) and check 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 "Pleural fluid analysis in adults with a pleural effusion".)

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

●Cardiac abnormalities including murmurs, pericardial rub, third or fourth heart sounds, jugular venous distension, fine basilar crackles, and peripheral edema. (See "Pleural fluid analysis in adults with a pleural effusion" 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 patients with cardiopulmonary symptoms or signs more than four weeks after the acute illness, we typically obtain testing based on clinical history and physical examination. Such testing may include chest imaging, electrocardiography (ECG), and evaluating exercise capacity and oxygenation. Additional tests, such as echocardiography, Holter monitoring, and pulmonary function tests (PFTs), may also be necessary in select patients.

Early referral to a pulmonologist and/or cardiologist is prudent, especially when cardiopulmonary symptoms remain unexplained after routine testing (eg, pulmonary hypertension, deconditioning, myocardial ischemia or myocarditis is suspected). (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Initial diagnostic evaluation (noninvasive testing)' and "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis", section on 'Diagnosis' and "COVID-19: Evaluation and management of cardiac disease in adults", section on 'Diagnostic approach'.)

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

●Indications – Who to image is poorly studied. Our approach is the following:

•For patients who did not have chest imaging during 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 performed during the course of their acute 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.

●Imaging type – The optimal imaging tool is also poorly studied. Our approach is the following:

•For most patients, chest radiography is sufficient (preferably upright posterior-anterior and lateral images).

•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 chest CT for patients with suspected malignancy (contrast-enhanced) or for patients with suspected interstitial lung disease from severe pulmonary involvement during the acute illness (eg, acute respiratory distress syndrome [ARDS]; non-contrast-enhanced).

•For patients with unexplained cardiopulmonary symptoms and/or low SpO₂ despite normal chest radiograph, we have a high index of suspicion for venous thromboembolism and evaluate with D-dimer levels and an appropriate imaging exam, such as CT pulmonary angiography. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

●Timing – For patients with abnormal lung imaging during their acute COVID-19 infection, few guidelines are available to inform the timing of follow-up imaging [2]. Our approach is the following:

•When indicated, we perform chest radiography at 12 weeks following diagnosis to ensure complete radiographic resolution [3]. Based upon accumulating data in patients recovering from COVID-19, we expect lung damage (ie, ground glass opacities, consolidation, interlobular septal thickening) to spontaneously resolve in two to four weeks, but full resolution may require 12 weeks or longer, with some studies suggesting changes up to two years, especially in those with severe disease [4-16].

For patients who have persistent radiographic abnormalities at 12 weeks, we typically obtain chest CT 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 nonsevere respiratory disease [4,11,15,16]. Infrequent cases of severe residual lung fibrosis have been reported [17].

•We image select patients earlier than 12 weeks. Examples include patients with worsening or new respiratory symptoms, patients with a new or evolving infiltrate on chest radiography, and patients in whom an alternate or complicating pathology is suspected (eg, malignancy, interstitial lung disease, tracheal stenosis).

•For patients with resolving ARDS, we do not routinely perform serial chest CT at predetermined intervals (eg, 3, 6, 12, 24 months) due to the risk of radiation exposure and lack of high-quality evidence demonstrating benefit. However, a subsequent CT 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'.)

Pulmonary function testing — Our approach to obtaining PFTs during COVID-19 recovery is the following:

●In patients with absent, mild, or resolving respiratory symptoms, we do not routinely obtain PFTs.

●For patients recovering from COVID-19 who have persistent, progressive, or new respiratory symptoms, we obtain PFTs.

●For patients who had severe pulmonary involvement or COVID-19-related ARDS, which applies to many patients who required hospitalization, we obtain PFTs.

When PFTs are indicated, we perform a full set of PFTs including spirometry, lung volumes, and diffusion capacity. For patients with suspected neuromuscular weakness, we additionally perform maximal inspiratory and expiratory pressures to assess respiratory muscle strength. (See "Overview of pulmonary function testing in adults" and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Respiratory muscle strength testing'.)

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 PFTs 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'.)

A reduction in diffusing capacity is the most common deficit seen (≥50 percent) [4]. Additional deficits include restriction (up to one-third) and obstruction (up to 15 percent) [18,19].

Cardiac testing — We follow the American College of Cardiology (ACC) consensus decision pathway for the selection of cardiac testing for individuals with long COVID [20]:

●For individuals without cardiac symptoms during their acute infection and without ongoing symptoms more than three months following acute infection, further cardiac testing is not necessary.

●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. We also obtain basic laboratory testing including complete blood count, basic metabolic panel, cardiac troponin, D-dimer, brain natriuretic peptide and c-reactive protein. (see "Evaluation of palpitations in adults").

●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 during the acute illness 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).

Limited data are available regarding follow-up TTE in patients with COVID-19. One study reported that among those who were admitted to the intensive care unit with COVID-19 and had persistent symptoms at four months following discharge, 10 percent had an ejection fraction less than 50 percent [7]. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Cardiopulmonary exercise testing in the evaluation of unexplained dyspnea".)

●We obtain cardiac consultation on those patients with abnormal cardiac test results, known cardiac disease, history of cardiac complications during acute COVID-19, as well as for patients with unexplained symptoms for which a cardiac etiology remains suspected.

●The clinical utility of cardiac magnetic resonance imaging to identify evidence of myocarditis that was not clinically evident during the acute phase of COVID-19 remains controversial [21,22]. For patients in whom myocarditis is suspected, we typically refer to a cardiologist for further evaluation [23]. The approach to suspected myocarditis in patients with COVID-19 is discussed in detail separately. (See "COVID-19: Evaluation and management of cardiac disease in adults", section on 'Diagnostic approach'.)

●For patients with persistent palpitations or symptoms of dysautonomia (eg, dizziness on standing) despite an unremarkable ECG, we follow the recommendations of the ACC consensus decision pathway as follows [20]:

•We perform an active 10-minute stand test with measurement of heart rate and blood pressure 5 minutes after laying supine and 2, 5, and 10 minutes after standing to evaluate for orthostatic hypotension and postural orthostatic tachycardia syndrome. Correlation between vital signs and symptoms should be monitored. (See "Postural tachycardia syndrome", section on 'Clinical evaluation'.)

•Extended Holter monitor testing is also appropriate. (See "Ambulatory ECG monitoring".)

•In addition to the ACC guidance, 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", section on 'Clinical evaluation' and "Postural tachycardia syndrome", section on 'Autonomic testing'.)

Evaluating exercise capacity and oxygenation — For patients with cardiorespiratory symptoms after initial evaluation, patients whose course was complicated by venous thromboembolic disease and heart disease, and patients who were hospitalized due to acute COVID-19, we typically obtain a six-minute walk test (table 2). 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'.)

For most patients, an arterial blood gas (ABG) is typically not warranted. However, in patients with acute hypercapnia who required noninvasive ventilation (NIV) during their acute illness, an ABG may guide further management, particularly in patients requiring continued NIV. We also consider an ABG in patients with unexplained symptoms and lower SpO₂ to detect occult hypoxemia [24].

Cardiopulmonary exercise testing (CPET) is not generally needed unless dyspnea remains unexplained (table 3); CPET may identify the etiology of symptoms and also identify those who may benefit from pulmonary or physical rehabilitation (eg, patients with deconditioning, chronotropic incompetence, dysfunctional breathing) (algorithm 1) [25]. (See "Cardiopulmonary exercise testing in the evaluation of unexplained dyspnea".)

Other — For patients with dyspnea and normal lung and cardiac function, diaphragmatic ultrasonography may identify residual weakness to explain dyspnea [26].

Rarely, patients may experience chest or neck discomfort related to venous stenosis from previous central venous catheterization [27]; this is often a clinical diagnosis, but confirmation by ultrasound may be appropriate.

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 and our experience to date in long COVID patients.

●Dyspnea – Dyspnea resolves slowly in most patients over two to three months, sometimes longer, especially in those with more severe pulmonary involvement or neuromuscular weakness (eg, up to 6 to 12 months) [11,19,28-31]. Similarly, pulmonary function abnormalities may persist for a year or longer, especially among those with more severe lung involvement [4,5,8-10,12,14,18,19,30-33].

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, reactive airway disease, tracheal stenosis from intubation, heart failure).

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

•For patients with mild dyspnea (eg, Borg score ≤3 (table 1)) who are without an oxygen requirement and do not have a cardiac etiology for their symptoms, we prescribe breathing exercises (eg, diaphragmatic breathing) and breathlessness management strategies (table 4) through self-directed educational resources, in-person rehabilitation, or online programs [34].

•For patients who have moderate to severe dyspnea (eg, Borg score >3 (table 1)), 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 [35]. (See "Pulmonary rehabilitation".)

•For patients with organizing pneumonia from resolving ARDS, we manage patients in a similar fashion to those with organizing pneumonia due to non-COVID-related conditions. (See "Cryptogenic organizing pneumonia".)

In some patients, this means the administration of oral glucocorticoids. In one retrospective study of 837 survivors of COVID-19, 5 percent had evidence of organizing pneumonia [36]. Glucocorticoid 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) glucocorticoid regimens [37]. Additional randomized trials are needed to inform this clinical consideration. Details on the indications for glucocorticoids in organizing pneumonia are provided separately. (See "Cryptogenic organizing pneumonia", section on 'Initial approach'.)

•Rare case reports of lung transplantation for severe residual fibrosis due to COVID-19 have been reported [17].

●Cough – Cough resolves in the majority of patients by 3 months [28] and is rarely persistent for 12 months [11].

Cough following recovery from acute COVID-19 is managed similar to postviral cough syndrome, ensuring that other causes of cough are not exacerbating or contributing to symptoms (eg, gastrointestinal reflux disease, asthma) and that more serious pathologies have been sufficiently excluded. (See "Evaluation and treatment of subacute and chronic cough in adults".)

•Most patients in whom cough is improving quickly do not require specific intervention other than as-needed, over-the-counter cough suppressants (eg, benzonatate, guaifenesin, dextromethorphan).

•For those with bothersome or persistent cough, inhaled therapies are infrequently prescribed (eg, inhaled bronchodilators or glucocorticoids), 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. While glucocorticoids may be prescribed for intractable cough in patients with asthma, it is unclear whether systemic glucocorticoids are effective in treating intractable cough due to COVID-19. (See "Evaluation and treatment of subacute and chronic cough in adults" and "Evaluation and treatment of subacute and chronic cough in adults", section on 'Asthma'.)

●Chest discomfort/tightness/pain – Chest discomfort, often considered to be related to inflammation and/or musculoskeletal strain from coughing, persists in 12 to 22 percent of patients approximately two to three months after acute COVID-19 infection (rarely longer) and generally improves spontaneously over weeks [11,28,38].

Persistent chest discomfort does not generally require treatment unless it is interfering with the patient's quality of life. For persistent, severe, discomfort, we prescribe nonsteroidal anti-inflammatory drugs in the absence of kidney 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). In some cases, we advise an exercise program for suspected costochondritis/musculoskeletal chest pain. (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 [23]. (See "COVID-19: Evaluation and management of cardiac disease in adults" and "Clinical manifestations and diagnosis of myocarditis in adults".)

If cough-induced rib fracture is suspected, we obtain chest imaging and treat accordingly. (See "Initial evaluation and management of rib fractures".)

●Known cardiac injury – Patients with an established diagnosis of COVID-19-related cardiac injury (eg, acute myocardial infarction, cardiac arrest, atrial fibrillation) or myocarditis should be evaluated by a cardiologist. (See "COVID-19: Cardiac manifestations in adults" 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 5)) should undergo cardiac rehabilitation (if available) rather than a traditional physical therapy program, provided there are no contraindications (table 6). (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".)

●Dysautonomia – For patients with orthostasis and dysautonomia (eg, unexplained sinus tachycardia with or without activity, dizziness on standing) following COVID-19, we initially treat conservatively with compression stockings, abdominal binder, hydration, and behavioral modifications. Lifestyle management tips are available online and a consensus statement has been published for patients with long COVID [39]. (See "Treatment of orthostatic and postprandial hypotension".)

We also advise a dedicated home exercise program or physical therapy program, which often includes starting from supine position and education on physical countermeasures, keeping in mind that patients should not go to the point of over-exertion or post-exertional malaise.

For those with evidence of postural tachycardia on orthostatic testing and failure of conservative management, we consider medications depending on the specific nature of ongoing autonomic symptoms [39]. (See "Postural tachycardia syndrome".)

FATIGUE, POOR ENDURANCE, AND FUNCTIONAL DISABILITY — Although fatigue and reduced functional status resolves in most patients, it can be profound, is one of the most common and bothersome symptoms, and may last for three months or longer, particularly among those who were hospitalized and intensive care unit survivors [28,29,38,40,41]. Fatigue and poor endurance may be directly related to the virus-induced physical weakness, but this issue is often multifactorial with other contributors, such as poor nutritional intake, musculoskeletal pain and myalgias, insomnia, and many psychological sequalae of COVID-19.

The American Academy of Physical Medicine and Rehabilitation has developed a multidisciplinary collaborative consensus guidance statement on the assessment (table 7) and management (table 8) of fatigue following COVID-19 illness [42]. We generally follow the recommendations of this guidance statement as outlined in this section. Consistent with the multifactorial nature of this issue, these recommendations encompass all potential medical and psychological manifestations of long COVID that can contribute to fatigue (eg, cardiopulmonary symptoms, anxiety/depression).

Some, although not all, patients with fatigue may have symptoms consistent with and meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In those cases, an ME/CFS 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 — Our approach is as follows:

●We evaluate the degree and pattern of fatigue (eg, daily or intermittent, worsening at certain periods during the day) and also evaluate for post-exertional malaise. Post-exertional malaise is a condition where patients report an exacerbation of fatigue (and sometimes other symptoms, such as impaired cognition) after activity or over-exertion (generally physical but can also be cognitive or emotional).

●We assess the impact of fatigue on daily functioning (eg, activities and instrumental activities of daily living, such as feeding, dressing, bathing, toileting, driving, housekeeping, and grocery shopping) (table 7).

●We determine whether the patient has any conditions that may exacerbate or lead to fatigue, including medication use/polypharmacy, deconditioning, weakness, muscle atrophy or tenderness, pain, sleep disturbances, endocrine disorders (eg, hypothyroidism), mood disorders, and/or cardiopulmonary symptoms.

●For patients in whom functional disability is suspected based on symptoms, we use objective evaluation tools. For example, we typically use the six-minute walk test (table 2) and one or more of the following: EuroQol-5D-5L, Timed Up and Go (TUG), and Short Physical Performance Battery (SPPB) [43,44]. 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 [45,46]. (See "Overview of pulmonary function testing in adults", section on 'Six-minute walk test'.)

●If not already performed at the initial visit or within three months of the visit, we perform routine laboratory testing, such as complete blood count, chemistries, and liver function tests, and occasionally thyroid function tests and creatinine kinase if hypothyroidism or muscle inflammation is suspected. Initial laboratory testing is discussed separately. (See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")", section on 'General laboratory testing'.)

Management — While fatigue is very common during the acute phase of COVID-19, patients with ongoing fatigue (>3 months) often need additional management strategies, although many will continue to slowly improve over time.

General guidance for management of patients with persistent fatigue and impaired functional status is shown on the table (table 8) and includes the following:

●For patients with fatigue, we encourage adequate rest, good sleep hygiene, and specific fatigue management strategies [2,47]. One method that is helpful is the "four-P" approach to energy conservation: Planning, Pacing, Prioritizing, and Positioning.

●For the majority of patients, we advise an individualized and structured, titrated return-to-activity program based upon 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. Some patients may benefit from starting in a supine or recombinant position or with more passive therapy before beginning a dedicated cardiovascular exercise program (see 'Cardiac testing' above). 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 for COVID-19-related fatigue. There is currently insufficient evidence to support the use of specific nutritional supplements.

●There is no evidence for the use of specific pharmacologic agents in the treatment of fatigue related to COVID-19 infection. In appropriate selected patients, trials of pharmacologic agents such as neurostimulants (eg, methylphenidate), modafinil, and amantadine may be beneficial [42].

PSYCHOLOGICAL AND NEUROCOGNITIVE SYMPTOMS — In general, psychological and cognitive symptoms improve over time (eg, six weeks) but may persist for more than 6 to 12 months for a subset of patients, especially those who were severely ill [11,28,29,48-50].

Neurologic and neurocognitive dysfunction

●Clinical evaluation for neurologic conditions – For patients with neurologic complications of acute COVID-19 (eg, stroke, seizures, hypoxic encephalopathy, neuromuscular weakness related to critical illness [51], Guillain-Barré syndrome, encephalitis) and those with new neurologic symptoms (numbness/tingling, tremors, headaches, tinnitus), we perform a complete neurologic history and examination and evaluate the degree of deficits and their impact on the patient's functional status. We do not typically obtain follow-up neurologic imaging unless there is an unexplained neurologic deficit or concern for a focal lesion or other condition.

●Management of neurologic conditions – Patients with neurologic complications following COVID-19 should be managed in the same way as other patients. These conditions 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".)

●Clinical evaluation for cognition – Many individuals with long COVID report persistent cognitive concerns including trouble with word finding, concentration, and memory (in lay terms also known as "brain-fog"). In most patients in whom concentration and memory is an issue, we evaluate for cognitive impairment (which may be subtle) using the Montreal Cognitive Assessment (MoCA) (table 9). We typically refer patients with persistent bothersome symptoms or scores indicating moderate to 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.

●Management of cognitive dysfunction – It is important to evaluate and treat comorbid medical issues that may be contributing to cognitive impairment (eg, pain, insomnia/sleep disorders, mood disorders, polypharmacy). Referral to speech-language pathology for cognitive therapy is also recommended [52]. In selected patients who fail conservative management, pharmacologic treatment can be considered (eg, neurostimulants). Further information about the treatment of cognitive impairment is provided separately:

•(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".)

Psychological sequalae

●Clinical evaluation – During the initial visit, we ask about symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD). If psychological sequalae are found, we attempt to discern whether they may be secondary to physical symptoms or the patient's social environment. In patients with affective symptoms, we further ask about suicidality [53,54].

For patients in whom depression, anxiety (table 10), or PTSD is suspected, we supplement clinical evaluation with rating tools including the Hospital Anxiety and Depression Scale (HADS) to evaluate for anxiety and depression and the Impact of Event Scale on managing cognitive dysfunction to evaluate for PTSD.

●Management – It is important for clinicians to recognize that psychological symptoms may be secondary to ongoing physical symptoms or that psychological symptoms may contribute to perceived physical symptoms without being the only or root cause. Discussion of psychiatric care should include recognition of this and that it may be valuable to treat these symptoms even if they are due to persistent physical symptoms.

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 is warranted. Psychological counseling/therapy, social work services, and occupational therapy support may also be helpful resources.

The evaluation and management are similar to that in other patients who have suspected non-COVID-related psychological dysfunction, which is discussed separately:

•(See "Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis".)

•(See "Generalized anxiety disorder in adults: Management".)

•(See "Major depressive disorder in adults: Approach to initial management" and "Unipolar minor depression in adults: Management".)

•(See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical features, assessment, and diagnosis".)

•(See "Posttraumatic stress disorder in adults: Treatment overview".)

•(See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Subsequent testing' and "Post-intensive care syndrome (PICS): Treatment and prognosis", section on 'Individual components of PICS'.)

OLFACTORY/GUSTATORY SYMPTOMS — The majority of patients with olfactory/gustatory symptoms have complete or near-complete recovery at one to three months following acute illness, although in a small proportion these symptoms persist longer (<5 percent; 6 to 12 months) [11,55-64]. Patients with hyposmia and male patients may recover more rapidly compared with those who have anosmia or are female [55,57,62].

Our general approach is similar to olfactory/gustatory symptoms that follow other respiratory viruses and includes the following:

●In most cases, symptoms resolve slowly over 2 to 12 weeks and do not require intervention except for education regarding food and home safety. If patients are bothered by their symptoms, we may advise olfactory training with self-guided programs, which are available online.

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, especially those who were critically ill due to COVID-19 for multifactorial reasons, and taste and smell impairment may contribute. (See "Taste and olfactory disorders in adults: Anatomy and etiology" and "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Smell and taste disorders'.)

●If symptoms fail to resolve or improve (eg, >3 months), 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. Preliminary data from specialized clinics report possible improvement with oral and intranasal glucocorticoids [65,66], zinc [67], palmitoylethanolamide and luteolin [68], bilateral stellate ganglion block [69], and intranasal insulin in refractory cases [70]. In addition, theophylline, intranasal vitamin A, intranasal sodium citrate, and alpha-lipoic acid have shown possible efficacy in non-COVID-19 postinfectious olfactory dysfunction [71,72].

Further details regarding the evaluation of olfactory/gustatory symptoms are provided separately. (See "Taste and olfactory disorders in adults: Evaluation and management".)

OTHER (MUSCULOSKELETAL, SLEEP, KIDNEY, HEPATIC, ENDOCRINE, GASTROINTESTINAL, DERMATOLOGIC, INFECTIOUS, HYPERCOAGULABILITY, QUALITY OF LIFE)

●Musculoskeletal – Myalgias and arthralgia are often persistent in 4 to 6 percent of patients at one to three months but typically resolve by six months [73].

We treat these symptoms supportively, typically with acetaminophen or nonsteroidal anti-inflammatory drugs until they resolve. We also assess for symptoms and physical exam findings consistent with fibromyalgia (eg, diffuse tenderness to muscle palpation). However, if symptoms are new or worsen during recovery or if there is clinical evidence of synovitis or other rheumatologic illness, we consider appropriate serologic testing and referral to a rheumatology specialist. (See "Approach to the patient with myalgia" and "Evaluation of the adult with polyarticular pain" and "Clinical manifestations and diagnosis of fibromyalgia in adults".)

●Insomnia/poor-quality sleep – Sleep disturbance following acute COVID-19 is common [74]. We ask all patients about quality and duration of sleep. We counsel patients on sleep hygiene, relaxation techniques, and stimulus control (table 11). Further discussion of the evaluation and management of insomnia is found elsewhere. (See "Overview of the treatment of insomnia in adults".)

●Kidney and hepatic – In patients who developed acute kidney 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 kidney and liver injury generally self-resolve in most patients with noncritical COVID-19, 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 intensive care unit hospitalization [7]. 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 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-onset diabetes mellitus and those with diabetes may become newly insulin-dependent or develop an increased insulin requirement [75-77]. 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 [78]. Thus, we ask patients about orthopedic pain (eg, from vertebral fracture) and assess their risk for the development of osteoporosis (eg, comorbidities, postmenopausal status, tobacco use, glucocorticoid use). Those with suspected osteoporosis are managed similarly to non-COVID-19 patients. (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 glucocorticoids during their hospitalization. The presentation and diagnosis of adrenal insufficiency is reviewed elsewhere. (See "Clinical manifestations of adrenal insufficiency in adults" and "Determining the etiology 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-abundant 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-language pathology evaluation is necessary for patients with swallowing dysfunction. (See "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Other' and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management", section on 'Swallowing rehabilitation and nutrition' and "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription", section on 'Coronavirus disease 2019'.)

●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. (See "COVID-19: Cutaneous manifestations and issues related to dermatologic care".)

We examine any affected areas, assess for healing, and evaluate for secondary infection. Wound care consultation may be warranted. (See "Overview of treatment of chronic wounds".)

Some patients recovering from COVID-19 have reported alopecia [28]. Alopecia should be managed similarly to non-COVID-19 patients, and nutritional status should be addressed in patients where malnutrition may be a contributor. (See "Alopecia areata: Management".)

●Infectious – Most infectious complications of COVID-19 have been observed typically as a late complication of acute illness, especially in those with moderate to severe illness. However, delayed presentation may occur. Evaluation and management are similar to that for non-COVID-19 patients. Examples include the following:

•Case reports of invasive rhino-orbital mucormycosis have been reported in patients recovering from COVID-19. Risk factors for mucormycosis include treatment with glucocorticoids and poorly controlled diabetes mellitus [79-81]. 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 [82,83]. They are managed similarly to non-COVID-19 patients. (See "Mucormycosis (zygomycosis)", section on 'Coronavirus disease 2019-associated'.)

•Invasive pulmonary aspergillosis [84] and strongyloides hyperinfection (disseminated disease due to autoinfection in the setting of remote initial infection) [85,86] have also been reported during recovery in COVID-19 patients with similar risk factors (eg, immunosuppression, poorly controlled diabetes mellitus). These illnesses should be suspected in patients with these risk factors who have progressive dyspnea and new unexplained gastrointestinal symptoms. They are managed similarly to non-COVID-19 patients. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids' and "Epidemiology and clinical manifestations of invasive aspergillosis" and "Strongyloidiasis".)

●Hypercoagulability – Patients with documented thromboses are treated in a similar fashion to non-COVID-19 patients with thrombosis (table 12), and indications for postdischarge thromboprophylaxis are the same as for non-COVID-19 patients. 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 "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

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

●Quality of life – In our clinic, we evaluate all 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. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)

●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, their home environment, and social support. We encourage facilitating work accommodations (eg, working from home, being able to sit at work) when needed in order to prevent work absences and/or exacerbation of post-exertional symptoms. We refer patients to appropriate social services support whenever necessary.

●Family outcomes – Preliminary data suggest that family members of patients diagnosed with COVID-19 also undergo significant stress and can suffer from anxiety [87]. (See "COVID-19: Psychiatric illness", section on 'Family members of COVID-19 patients' and "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation", section on 'Post-intensive care syndrome-family' and "Post-intensive care syndrome (PICS): Treatment and prognosis", section on 'Post-intensive care syndrome-family'.)

VACCINATION — We adopt the same vaccination approach in this population as that recommended for the general population. COVID-19 vaccination and impact of vaccination on long COVID symptoms are provided separately. (See "COVID-19: Vaccines" and "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")", section on 'Vaccination'.)

REHABILITATION — 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 [40]. When indicated, we refer all patients with a need for rehabilitation services as early as is feasible, typically within 30 days of recovery from initial infection [88]. 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.

In most cases, outpatient or home rehabilitation programs are appropriate, although inpatient programs may be needed for those who were hospitalized, especially patients who required intensive care unit admission.

Outpatient

In-person or home-based — There are a wide variety of available outpatient rehabilitation programs including in-person rehabilitation and home- or web-based rehabilitation programs. In general, we prefer in-person programs since they are better validated [89], but home- or web-based rehabilitation may be appropriate for patients who cannot easily access a rehabilitation facility.

●In-person rehabilitation – Most 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 [90-93], although home-based models vary widely in availability. One study reported that a home-based physical and mental health rehabilitation program improved quality of life at 3 and 12 months compared with usual care [93].

Telerehabilitation can be delivered either synchronously (ie, in real-time) or asynchronously (eg, a prerecorded customized exercise plan). Systems need to be established 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.

The value of telehealth is discussed in detail separately. (See "Telemedicine for adults".)

Therapy prescription — Based upon our experience with post-sepsis [94] as well as COVID-19 patients, we generally use a cautious approach to initiating a comprehensive physical 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, pulmonology, cardiology, neurology).

We generally 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 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. 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 [95-98]. A systematic review of 14 trials totaling 1244 COVID-19 patients reported that rehabilitation was associated with improved exercise capacity (standardized mean difference -0.56, 95% credible interval -0.87 to -0.22). Adverse events appeared to be low but were inadequately reported, decreasing the certainty of the result [96]. Another meta-analysis of 23 studies reported improvements in dyspnea, fatigue, depression, exercise tolerance, lung function, and quality of life [98]. Among the studies that reported adverse events (11 studies), no significant events were described.

Inpatient

General considerations — While inpatient rehabilitation was common in the earlier phases of the pandemic [58], it is likely less prevalent as the pandemic has progressed. 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, evaluation of current symptoms and complications, and appropriate follow-up testing and management. Further details are provided separately. (See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")", section on 'Diagnostic evaluation'.)

Tracheostomy care and ventilator liberation — Weaning patients with COVID-19 from mechanical ventilation is similar to that in non-COVID-19 patients, the details of which are discussed separately. (See "Weaning from mechanical ventilation: Readiness testing" and "Initial weaning strategy in mechanically ventilated adults" and "Management and prognosis of patients requiring prolonged mechanical ventilation".)

Outcome data for patients with a tracheostomy and who undergo ventilator 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 [99]. Weaning duration was eight 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 feeding tube, and 59 percent were at home [100]. 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) [101].

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 non-COVID-19 patients.

RETURN TO WORK OR EXERCISE — The ability of patients to return to work or exercise should be assessed on an individual basis and varies depending upon their baseline pre-COVID-19 functional status, the severity of their illness, complications of acute COVID-19, and the intensity of planned activity [102]. We facilitate work accommodations (eg, working from home, being able to sit at work) when needed in order to prevent work absences and/or exacerbation of post-exertional symptoms. In general, for most patients recovering from their acute illness without significant fatigue or post-exertional malaise, we encourage gradual resumption of physical activity as tolerated, starting at a low-intensity level and slowly increasing activity over the next several weeks [103].

●For patients who remain asymptomatic, we advise slow escalation of higher-intensity exercise toward their pre-COVID-19 baseline with close monitoring for symptoms (table 13). (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). Further details regarding return to sport or strenuous activity following COVID-19 are described separately. (See "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'.)

PROGNOSIS AND EXPECTED RECOVERY TIME COURSE — Symptoms generally improve with time. However, there is wide variability in time to symptom resolution, which depends upon premorbid risk factors as well as the severity of the acute illness and spectrum of symptoms experienced by the patient [38,105-109]. In the largest study to date, the estimated mean long COVID symptom duration was nine months in hospitalized individuals and four months in nonhospitalized individuals [110]. Among those with long COVID, 15 percent continued to experience symptoms at one year, but the range was wide (95% uncertainty interval, 10.3-21.1 percent). Additional studies have reported that some patients have at least one symptom at three years [111].

Some symptoms resolve more quickly than others. For example, fevers, chills, cough, and olfactory/gustatory symptoms typically resolve within two to six weeks while fatigue, dyspnea, chest tightness, musculoskeletal pain, cognitive deficits, and psychological effects may last for months (eg, 2 to 12 months) [11,28,29,38,41,55-57,59,73,112-114]. Expected recovery of individual symptoms are included in the sections above:

●(See 'Cardiopulmonary symptoms' above.)

●(See 'Psychological and neurocognitive symptoms' above.)

●(See 'Olfactory/gustatory symptoms' above.)

●(See 'Fatigue, poor endurance, and functional disability' above.)

●(See 'Other (musculoskeletal, sleep, kidney, hepatic, endocrine, gastrointestinal, dermatologic, infectious, hypercoagulability, quality of life)' above.)

A longer recovery course is expected in the following patients [4,11,29,38,41,58,105,115-117]:

●Patients requiring hospitalization (especially those who had a prolonged stay in the hospital or intensive care unit)

●Older patients

●Patients with pre-existing comorbidities

●Patients who experienced medical complications (eg, secondary bacterial pneumonia, venous thromboembolism)

Although hospitalized patients are at the greatest risk for prolonged symptoms (33 to 87 percent) [4,11,29,38,41,58,117], a lower proportion of patients with mild disease experience similar symptoms, but may not last as long (eg, 6 to 55 percent) [28,107,110,112,114,115,117-122]. In the vast majority of patients, most symptoms have resolved by one year. The spectrum of symptoms is similar between hospitalized and nonhospitalized patients.

Although not documented, the prognosis may also change as the pandemic evolves and variants emerge.

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 5^th to 6^th 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 10^th to 12^th 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: Long COVID (The Basics)" and "Patient education: COVID-19 and pregnancy (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – We define long COVID as a syndrome with a broad range of persistent or new symptoms/symptom clusters that develop during or after COVID-19, continue for more than three months after the onset of acute COVID-19 illness, have an impact on the patient's life, and are not explained by an alternative diagnosis. (See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")", section on 'Terminology and stages of recovery'.)

●Cardiopulmonary issues (see 'Cardiopulmonary symptoms' above):

•For patients with cardiopulmonary symptoms, we perform a detailed cardiopulmonary history and examination (table 1). (See 'Clinical evaluation' above.)

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

-For all patients with cardiopulmonary symptoms or signs or patients who had a pulmonary infiltrate or other abnormality identified on imaging during the acute course of COVID-19 illness, follow-up chest imaging (typically chest radiography) should be performed at 12 weeks. For patients with new or progressive symptoms, earlier imaging is indicated. For patients in whom another etiology is suspected (eg, malignancy, suspected interstitial lung disease, such as organizing pneumonia or fibrosis due to acute respiratory distress syndrome [ARDS]), chest CT is appropriate. (See 'Chest imaging' above.)

-For patients with intermittent or persistent cardiopulmonary symptoms (including palpitations) or those with generalized, constitutional complaints (such as weakness or fatigue), a 12-lead electrocardiogram should be performed. The threshold to obtain transthoracic echocardiography should be low 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. (See 'Cardiac testing' above.)

-For patients with persistent, progressive, or new respiratory symptoms and patients recovering from ARDS, pulmonary function tests should be performed, including spirometry, lung volumes, diffusion capacity, and a six-minute walk test. (See 'Pulmonary function testing' above.)

-For patients with cardiorespiratory symptoms, patients whose course was complicated by venous thromboembolic disease and heart disease, and patients who were hospitalized due to acute COVID-19, a six-minute walk test should be performed (table 2). (See 'Evaluating exercise capacity and oxygenation' above.)

-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".)

●Fatigue and functional disability – For patients with functional impairment following COVID-19, we typically evaluate using the six-minute walk test (table 2) and one or more of the following: EuroQol-5D-5L, Timed Up and Go (TUG), and Short Physical Performance Battery (SPPB). (See 'Clinical evaluation' above.)

For those with fatigue associated with identified cardiac or pulmonary pathology, a specialized cardiac or pulmonary rehabilitation program may offer benefit. (See 'Management' above.)

For those without cardiopulmonary disease, we suggest an individualized and structured, titrated return-to-activity program based upon level of fatigue (Grade 2C). These programs differ from structured graduated/progressive exercise programs by emphasizing maintenance at previously tolerated levels of activity for those with worsening symptoms or malaise after increases in activity. Those who have persistent difficulty advancing should be referred to a rehabilitation specialist. (See 'Management' above.)

Adequate rest, good sleep hygiene, and specific fatigue management strategies should be encouraged. (See 'Fatigue, poor endurance, and functional disability' above and "Approach to the adult patient with fatigue".)

If patients have symptoms consistent with or meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an ME/CFS evaluation and management strategy is warranted. (See "Treatment of myalgic encephalomyelitis/chronic fatigue syndrome".)

●Cognitive or neurologic symptoms (see 'Psychological and neurocognitive symptoms' above):

•Cognitive – For patients who complain of cognitive impairment (eg, impaired memory or concentration) following COVID, we evaluate for cognitive impairment using the Montreal Cognitive Assessment (MoCA) tool (table 9). We typically refer patients with scores indicating moderate to severe cognitive impairment (ie, score <18) for neuropsychological or speech-language pathology evaluation. These issues are discussed separately:

-(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".)

•Neurologic – For patients who had neurologic complications due to acute COVID-19, we perform a complete neurologic history and examination and evaluate any deficits and their impact on the patient's functional status. Patients are managed similar to non-COVID-19 patients with the same issues. Neurologic imaging is not typically needed 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'.)

●Olfactory/gustatory symptoms – 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 self-guided olfactory training or referral to an otolaryngologist or a taste and smell clinic, if available. (See 'Olfactory/gustatory symptoms' above and "Taste and olfactory disorders in adults: Evaluation and management" and "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Smell and taste disorders'.)

●Other – Other conditions that may persist following recovery from COVID-19 include musculoskeletal conditions (myalgias, arthralgias), impaired sleep (eg, insomnia), kidney failure, hepatic injury, endocrine disorders (diabetes, bone loss, adrenal insufficiency), gastrointestinal symptoms (diarrhea, weight loss, malnutrition), dermatologic conditions (alopecia, skin lesions, decubitus ulcers), psychological effects (anxiety, depression, posttraumatic stress disorder), quality of life, and social and economic concerns. These are all typically managed similar to non-COVID-19 patients. (See 'Other (musculoskeletal, sleep, kidney, hepatic, endocrine, gastrointestinal, dermatologic, infectious, hypercoagulability, quality of life)' above.)

●Rehabilitation – 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. When rehabilitation services are indicated, referring patients within 30 days of recovery from initial infection is reasonable.

•Outpatient rehabilitation – While in-person outpatient rehabilitation programs that last six to eight weeks are typical, web-based programs are also available, although they are less well-validated. We generally start with an individually titrated, structured return-to-activity program with progression as symptoms tolerate. (See 'Outpatient' above.)

•Inpatient rehabilitation – The evaluation and management of patients recovering from acute COVID-19 who are admitted to a long-term acute care facility, an inpatient rehabilitation facility, or a skilled nursing facility are similar to those described in the outpatient population but may also involve tracheostomy weaning. (See 'Inpatient' above.)

●Return to work/exercise – The ability of patients to return to work or exercise should be assessed on an individual basis and varies depending upon their baseline pre-COVID-19 functional status, the severity of their illness and any complications of acute COVID, and the intensity of planned activity. Appropriate work accommodations may be necessary to help employees return. In those without significant fatigue or post-exertional malaise, gradual resumption of physical activity as tolerated is typical, starting at a low-intensity level and slowly increasing activity over the next several weeks. In general, patients planning to return to strenuous activity or a physically demanding occupation following myocarditis should first be evaluated by a cardiologist. Further details regarding return to sport or strenuous activity following COVID-19 are described separately. (See 'Return to work or exercise' above and "COVID-19: Return to sport or strenuous activity following infection".)

●Prognosis – The outcome is generally good with most symptoms improving over time. However, there is wide variability in time to symptom resolution, and a small proportion of patients have persistent symptoms for a year or longer. Hospitalized patients are at the greatest risk for developing prolonged symptoms, as are older patients, patients with pre-existing comorbidities, and patients who developed COVID-19-related complications. (See 'Prognosis and expected recovery time course' above.)