This article summarizes the best available evidence for the diagnosis and management of postacute sequelae of COVID-19 (PASC), also called long COVID, in adults. Proposed etiologies for long COVID include residual damage from acute infection, ongoing viral activity within an intrahost viral reservoir, complications from a hyperinflammatory state, immune dysfunction, and unmasking of preexisting health conditions.^1,2

Epidemiology

• Data show that long COVID affects approximately 10% to 30% of the hundreds of millions of people who have had acute COVID-19.^3,4 The Centers for Disease Control and Prevention reports that 19% of adults who had COVID-19 in the past are still experiencing symptoms.⁵

• Reliable data on long COVID in children are lacking.^1,6

• Illness from COVID-19 has immediate and long-term consequences that can be conceptualized in three phases. Patients do not routinely develop all three.⁷

  ○ Phase 1. An acute illness with varying degrees of severity caused by viral replication and initial immune response lasts days to weeks. Asymptomatic patients can also progress to later phases of the illness.⁷

  ○ Phase 2. A rare hyperinflammatory illness known as multisystem inflammatory syndrome may occur two to five weeks after onset of the infection.^7–10 Multisystem inflammatory syndrome can affect children and adults and is caused by a dysregulated immune response with signs and symptoms similar to Kawasaki disease.^7,8

  ○ Phase 3. Long COVID may develop and can last for months.^1–4

• A 2022 study identified type 2 diabetes mellitus, SARS-CoV-2 viremia, Epstein-Barr virus viremia, and specific autoantibodies as risk factors for long COVID.¹¹ Additional risk factors suggested by other studies include age older than 50 years, female sex, more severe acute infection, more than five symptoms in the first week of acute infection, immunosuppressive conditions, underlying health conditions (e.g., hypertension, obesity, psychiatric condition), and partial or no vaccination.^12–17

• In a large community-based sample, the risk of long COVID in fully vaccinated individuals with breakthrough COVID-19 is less than in partially or unvaccinated individuals.^14,18

• Patients with long COVID report decreased quality of life on standardized testing.¹⁷

Diagnosis

• The Centers for Disease Control and Prevention defines long COVID as the presence of new, returning, or ongoing symptoms associated with acute COVID-19 that persist beyond 28 days,¹⁸ whereas the World Health Organization defines long COVID as symptoms that last for at least two months.¹⁹

• The diagnosis of long COVID can be based on a prior clinical diagnosis of COVID-19 with ongoing symptoms. A prior positive polymerase chain reaction or antigen test result to confirm SARS-CoV-2 infection is not required.¹ People with COVID-19 may have been asymptomatic or may not have had access to testing, and 10% to 20% do not produce detectable antibodies.^1,20,21

• The differential diagnosis includes acute sequelae of COVID-19, previous comorbidities, unmasking of preexisting health conditions, reinfection, new acute concerns, and complications of prolonged illness, hospitalization, or isolation.^1,15,22

• Review of the patient’s medical history should assess for conditions that could impact severity of COVID-19, including asthma, chronic fatigue, chronic kidney disease, diabetes, heart conditions, pulmonary disease, mood disorders, and trauma.¹

• Physicians should advise patients that long COVID is not fully understood and be sensitive to patient concerns that symptoms could be misattributed to psychiatric causes.¹