November 1, 2021/COVID-19

Caring for ‘Long-Haulers’: A Review of the Latest Guidance on Evaluation and Treatment

Prolonged symptoms of COVID-19 are likely multifactorial


As the understanding of COVID-19 has evolved, so has the understanding of caring for COVID-19 survivors with long-term symptoms. The prolonged form of COVID-19, which the National Institutes of Health (NIH) has termed post-acute sequelae of SARS-CoV-2 infection (PASC), does not yet have a formal definition. Currently it is identified as COVID-19 symptoms persisting for 28 days or longer. The symptoms can vary from fatigue to diarrhea, and patients can vary from those who had mild acute illness at home to those who were treated in an intensive care unit.


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Pulmonologist and intensivist Michelle Biehl, MD, and a team of Cleveland Clinic authors recently published a review of the condition in Cleveland Clinic Journal of Medicine, including the latest guidance on evaluating and treating COVID-19 “long-haulers.” The article is part of a collection of COVID-19 Curbside Consults.

Because of the variations in reported symptoms, duration and definition of PASC among research studies, assessing the incidence of PASC is difficult, say the authors. Some reports estimate that about 10% of patients with COVID-19 have symptoms for longer than three weeks. Symptoms persist for more than six months in some patients. The incidence of PASC may be higher among minority populations and other groups at risk for health disparities. While older age, obesity and chronic medical conditions are potential risk factors of PASC, almost 20% of cases are in patients age 18-34 who are otherwise healthy.

In the review, authors summarize:

  • Possible mechanisms of PASC. To date, the pathophysiology of PASC is undetermined. However, it is possible that the condition is the result of hyperinflammation, ongoing viral activity, hypercoagulability or multiple other factors. Some researchers are studying mitochondrial dysfunction and metabolic changes, dysautonomia and more. “The prolonged symptoms are likely multifactorial and may be difficult to attribute to a single cause,” wrote the authors.
  • Range of symptoms. Fatigue, cough and shortness of breath are some of the most common symptoms, but other, less common symptoms are as varied as red eyes, vertigo and palpitations. See the full article for a table of more than a dozen symptoms of COVID-19 reported in patients 60 days after onset.
  • Guidelines for evaluation. Guidelines are still being developed, but multidisciplinary approaches have been established at post-COVID-19 clinics at various medical centers. Care teams often include experts in primary care, pulmonology, cardiology, infectious disease, neuropsychiatry, behavioral health and other specialties. At Cleveland Clinic, patients with persistent symptoms four weeks after diagnosis with COVID-19 or hospital discharge have in-person follow-up assessments including chest X-ray, spirometry, and psychiatric and neurocognitive screenings.
  • Treatments. No specific treatment for PASC currently exists. Authors report that treatment should focus on managing symptoms, comorbidities, pulmonary rehabilitation and continued follow-up, and that patients should be referred to a dedicated post-COVID-19 clinic, if available.
  • Impact of vaccination. One survey showed that more than 50% of people with PASC reported improved symptoms after they received vaccination against SARS-CoV-2. Data also indicate that people with COVID-19 who have been vaccinated are less likely to develop PASC than people with COVID-19 who haven’t been vaccinated.


Concluding the review is a brief look at studies investigating numerous treatments — including antihistamines, antidepressants, antioxidants, melatonin and hyperbaric oxygen. The NIH has earmarked more than $1 billion in grant funding for initiatives focused on improving the understanding and treatment of PASC.

Read the full article for free at Cleveland Clinic Journal of Medicine.


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