Outpatient Practice

Designing A Long-COVID Clinic

Long-COVID is also known as PASC (post-acute sequela of COVID). A study in this week’s JAMA found that 10% of people infected with COVID had symptoms lasting for more than 6 months. These symptoms negatively affect quality of life and can result in significant impairment. There is a need for hospitals to create specialty clinics for PASC patients.

Long-COVID symptoms

Development of long-COVID symptoms depends on several variables. For example, women are twice as likely to develop long-COVID symptoms after an infection than men. People with repeated COVID infections are more likely to develop long-COVID symptoms than those with a single infection. People infected with the Delta variant are more likely to develop long-COVID symptoms than those infected with the Omicron variant. The severity of the initial infection also affects the likelihood of developing long-COVID: infected persons requiring hospitalization or ICU care are twice as likely to develop long-COVID symptoms compared to those with milder infections treated as outpatients. Other risk factors for developing long-COVID symptoms are being unvaccinated, older age, smoking, pre-existing chronic medical conditions, and obesity.

Long-COVID is a heterogeneous condition and patients can have a wide variety of symptoms. Most of these symptoms are non-specific. Among those who develop long-COVID symptoms, the most common include:

  • Post-exertional malaise (87%)
  • Fatigue (85%)
  • Brain fog (64%)
  • Dizziness (62%)
  • GI symptoms (59%)
  • Palpitations (57%)
  • Hearing difficulties (54%)
  • Joint pain (42%)
  • Weakness (42%)
  • Sexual impairment (42%)
  • Smell/taste impairment (41%)
  • Headache/muscle pain (39%)
  • Shortness of breath (36%)
  • Cough (33%)

Long-COVID clinic structure

Because of the wide variety of symptoms that people with long-COVID can develop, the evaluation of patients should be tailored to the specific presenting symptoms. The key purposes of a long-COVID clinic should be (1) to measure quantifiable impairment, (2) exclude other conditions that mimic long-COVID, (3) prescribe treatments to relieve symptoms, and (4) direct rehabilitation efforts. The long-COVID clinic should in a location that has on-site EKG testing, phlebotomy for lab testing, and radiology for chest x-rays. It should also be in close proximity for schedulable tests such as pulmonary function tests and echocardiograms.

A full set of vital signs (including resting pulse oximetry) should be performed for each visit. The clinic should be able to refer patients for speciality consultation including cardiology, pulmonary, rheumatology, physical medicine, sleep medicine, physical therapy, occupational therapy, and dietary. Ideally, there should also be access to a pulmonary rehabilitation and cardiac rehabilitation program in the area. Because of their protocol-driven nature, long-COVID clinics are an opportunity for advance practice providers (nurse practitioners and physician assistants).

For most patients, symptoms of acute COVID infection can take many days or even several weeks to fully resolve. The majority of these patients do not require evaluation in a specialized long-COVID clinic. It is reasonable to set a threshold of symptoms persisting for more than 6 – 12 weeks as criteria for referral to a long-COVID clinic. The initial evaluation should include a complete history and physical examination with attention to symptoms during the acute phase of the COVID infection, severity of the infection, vaccination status, age, BMI, smoking status, and co-morbid medical conditions.

Special effort should be given to medication reconciliation at the initial visit. Patients who were hospitalized for acute COVID infection are particularly likely to have had previous medications discontinued during hospitalization and/or new medications started. Sometimes these changes were because a chronic medication was not needed during hospitalization. Sometimes a chronic medication was stopped or changed during hospitalization due to a prohibitory drug-drug interaction with a medication necessary to treat the COVID infection. Or sometimes a drug was changed during hospitalization because that drug was not on the inpatient hospital formulary. During medication reconciliation, attention should be directed toward eliminating duplicate medications, discontinuing unnecessary medications, and resuming maintenance medications held during the acute infection.

Symptom-directed diagnostic testing

The history and physical exam may dictate initial testing. For example, the finding of dry crackles on pulmonary auscultation may dictate pulmonary function tests and a high resolution chest CT. On the other hand, pedal edema, an S3, and moist crackles may dictate a BNP test and an echocardiogram. Sudden onset of dyspnea and pleuritic chest pain shortly after resolution of an acute COVID infection may dictate a d-Dimer test and/or a CT pulmonary angiogram. Diagnostic testing in other patients should be ordered based on the specific long-COVID symptoms each patient has:

Fatigue: Laboratory testing should include: CBC, TSH, chemistry panel, and LFTs. An EKG should be performed. Oxygen saturation at rest and during exercise should be measured (for example, using the 6-minute walk test). Because many of the risk factors of long-COVID are also risk factors for obstructive sleep apnea, patients with fatigue should be screened for sleep apnea (for example, using the STOP-BANG questionnaire). Patients who received corticosteroids as part of their acute COVID treatment should be tested for adrenal insufficiency.

      • Mimics include: anemia, chronic kidney disease. chronic liver disease, sleep apnea, adrenal insufficiency, and hypothyroidism

Shortness of breath: Initial testing should include: BNP, CBC, TSH, chemistry panel, LFTs, chest x-ray, 6-minute walk test and EKG. If these tests are unremarkable, then additional testing could include a full set of pulmonary function tests (spirometry, flow-volume loop, lung volumes, diffusing capacity) and an echocardiogram. If these tests are also unremarkable, then a cardiopulmonary exercise test (CPET) should be considered. If post-inflammatory pulmonary fibrosis is suspected based on chest x-ray abnormalities (or crackles on pulmonary auscultation), a high resolution chest CT should be obtained. Patients with resting or exertion hypoxemia in the absence of radiographic abnormalities should be screened for thromboembolic disease with a d-Dimer test or CT pulmonary angiogram.

      • Mimics include anemia, heart failure, hypothyroidism, chronic kidney disease, chronic lung disease (asthma, COPD, interstitial lung disease), pulmonary embolism, and vocal cord dysfunction

Cough: Initial testing should include a chest x-ray and spirometry with flow-volume loop.

      • Mimics include asthma, gastroesophageal reflux, post-nasal drip, use of ACE inhibitor medications, and vocal cord dysfunction

Brain fog: Initial testing should include CBC, chemistry panel, LFTs, TSH, and 6-minute walk test. A screening test for cognitive impairment should be performed; in the past, this was typically the Mini-Mental State Examination (MMSE) but because that test now requires a fee to perform, the free SAGE test may be preferred. Another screening test for cognitive dysfunction is the Montreal Cognitive Assessment (MoCA); however completion of a mandatory 1-hour training program is required to perform this test.

      • Mimics include anemia, hypothyroidism, chronic liver disease, hypoxemia, sleep apnea, and early dementia

Dizziness or palpitations: Initial testing should include CBC, BNP, EKG, orthostatic blood pressure measurement, and 6-minute walk test. If these tests are unremarkable, additional testing could include Holter monitor, echocardiogram, and tilt-test.

      • Mimic include anemia, heart failure, orthostatic hypotension, and cardiac arrhythmias

GI symptoms: Initial testing should include CBC and LFTs. Patients with diarrhea should be tested for C. difficile if they received antibiotics or were hospitalized. Older age is a risk factor for both long-COVID and lactose intolerance.

      • Mimics include C. diff gastroenteritis, lactose intolerance, and irritable bowel syndrome

Weakness or muscle pain: Initial testing should include chemistry panel, CK, TSH, and LFTs.

      • Mimics include electrolyte disorders, drug side effects (statins), and hypothyroidism

Taste and olfactory dysfunction: These are common after COVID infection, particularly with the earlier Delta variants. There is no particular testing required but nutritional assessment may be useful in those losing weight due to altered diet resulting from abnormal taste and smell. Patients with smell dysfunction should be advised to have working smoke detectors in their homes.

      • Mimics include chronic sinusitis

Chest x-ray abnormalities: Patients with pulmonary infiltrates at the time of the initial COVID infection should have a follow-up x-ray. If infiltrates persist beyond 12 weeks, a chest CT should be performed. It should be noted that 50% of patients hospitalized with COVID who have x-ray abnormalities at the time of initial infection will still have x-ray abnormalities 6 months after the infection. However, because older age and cigarette smoking are risk factors for both long-COVID and lung cancer, resolution of chest x-ray abnormalities must be confirmed.

      • Mimics include lung cancer


Patients with severe impairment, particularly those with neuromuscular impairment, may require referral to a physical medicine specialist to direct rehabilitation. Patients with fatigue, mild-moderate exercise limitation, cardiac symptoms, and pulmonary symptoms can usually have rehabilitation efforts overseen from a long-COVID clinic. Prior to recommending a rehabilitation regimen, patients should complete diagnostic testing to exclude other medical conditions mimicking long-COVID and to identify any objective evidence of cardiorespiratory impairment.

Deconditioning is common following COVID infection. Patients are often sedentary for many days and often sustain weight loss and nutritional deficits during the acute COVID infection. In these patients, dietary guidance to restore body mass coupled with a regular exercise program can be very effective. There is not a single “best” exercise for patients with long-COVID symptoms, rather the best exercise is whatever exercise the patient will actually do consistently. In general, patients should be given a target of 150 minutes of weekly aerobic exercise (walking, stationary bike, treadmill, swimming, etc.). Patients with moderate or severe deconditioning may require several weeks to work up to 150 minutes per week. One of the barriers to aerobic exercise is the fear that exercise-induced dyspnea is a warning sign that the body is being harmed from exercise. A pulse oximeter can be very helpful to reassure patients that their oxygen level remains normal despite dyspnea and to help guide the heart rate during exercise. Patients should target keeping their heart rate during exercise at < 60% of their maximum predicted heart rate (maximum predicted heart rate = 220 – age).

Formal cardiac rehabilitation and pulmonary rehabilitation programs can be beneficial but Medicare will only cover these programs if there is objective evidence of cardiac or pulmonary impairment (some commercial insurance companies have less strict criteria for admission into these programs). For patients not eligible for cardiac or pulmonary rehabilitation, referral to a physical therapist can be useful, not only to define physical capabilities but for exercise guidance.

The special case of athletes

Vaccine skeptics often point to vaccine-induced myocarditis as a reason to avoid vaccination. However, a 2022 study found that people are 11-times more likely to get myocarditis from a COVID infection than they are from a COVID vaccination. Moreover, previous vaccination cut the chances of getting myocarditis after a COVID infection by half. Fortunately, most people who develop myocarditis (from either infection or vaccination) go on to have complete recovery. Nevertheless, those who have myocarditis at the time of their initial COVID infection should undergo cardiology consultation prior to resuming athletic activities.

Long-COVID can be devastating for a young athlete. Missing one season of their sport can mean an end to their high school or college athletic career. It is especially important to evaluate young athletes with long-COVID symptoms for exercise-induced bronchospasm and vocal cord dysfunction since these conditions can be readily treated. This should start with spirometry before and (if obstructed) after a bronchodilator to screen for asthma. A flow-volume loop should also be performed and if inspiratory notching is observed, vocal cord dysfunction should be suspected. In athletes with exertional cough and normal spirometry, a bronchoprovocation study should be performed. If available, a eucapneic voluntary hyperventilation study is the preferred test to identify athletes with exercise-induced bronchospasm. If unavailable, then a methacholine challenge test is an alternative.

If there is no evidence of asthma or vocal cord dysfunction in athletes with persistent dyspnea on exertion following COVID infection, a cardiopulmonary exercise test should be considered. This is an under-utilized test that can be extremely helpful in the evaluation of unexplained dyspnea.

Long-COVID disability determination

For some patients, impairment from long-COVID symptoms can be disabling. Most organizations require objective evidence of impairment before granting permanent disability. In general, subjective symptoms such as fatigue and pain must have objective correlates on diagnostic testing to qualify for disability. Patients with cardiac symptoms, such as chest pain, palpitations, dizziness, or dyspnea should undergo appropriate cardiovascular tests to determine if there is objective evidence of impairment. These tests could include echocardiograms, tilt tests, or cardiac stress tests.

Patients with pulmonary symptoms such as cough or dyspnea on exertion should undergo appropriate pulmonary diagnostic tests to determine if there is objective evidence of pulmonary impairment. These tests should include pulmonary function tests (spirometry, lung volumes, diffusing capacity). If these are normal and disability is still being considered, a cardiopulmonary exercise testing (CPET) should be performed.

Patients seeking disability for brain fog should be evaluated for objective evidence of cognitive impairment with neuropsychological testing.

Long-COVID prevention

The best way to prevent long-COVID symptoms is to prevent COVID infection. All persons should be recommended to get a bivalent COVID vaccine. Not only does vaccination reduce the chance of becoming infected in the first place but those who get infected despite being vaccinated are less likely to develop long-COVID symptoms than those who were never vaccinated. Those with risk factors for long-COVID such as being older, obese, or smokers should continue to take precautions against acute COVID infection including wearing masks in crowded indoor settings and avoiding contact with other people with acute infections. It is important to emphasis that recovery from a previous COVID infection is not protective because repeated COVID infection is an independent risk for developing long-COVID symptoms.

Long-COVID is very real and very common. But by listening to our patients and by using a symptom-driven approach to evaluation and rehabilitation, we can improve their lives.

May 26, 2023

By James Allen, MD

I am a Professor Emeritus of Internal Medicine at the Ohio State University and former Medical Director of Ohio State University East Hospital