Understanding and managing long COVID

Although 90% of non-hospitalized patents with acute COVID-19 have complete symptom resolution by 21 days, the rest suffer from a wide range of nonspecific symptoms for weeks to months, collectively known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. An AFP editorial on long COVID published last December advised that family physicians perform limited testing in these patients guided by the clinical assessment; for those with normal results, "recommended management ... consists of emotional support, ongoing monitoring, symptomatic treatment (e.g., acetaminophen for fever), and attention to comorbidities." A virtual workshop convened that month by the National Institutes of Health (NIH) noted that long COVID symptoms "have been reported among persons of all ages," including children, and that this syndrome potentially represents an enormous chronic health burden; since at least 32 million people have had COVID-19 in the U.S. alone, 3 million or more could be affected. 

Evidence gaps highlighted by workshop speakers included the epidemiology, clinical spectrum, and natural history, and pathophysiology of long COVID. In January, Dr. Francis Collins announced that the NIH would use a Congressional appropriation of $1.15 billion over four years to fund a PASC Initiative to support "a combination of ongoing and new research studies and the creation of core resources ... to help us understand the long-term effects of SARS-CoV-2 infection, and how we may be able to prevent and treat these effects moving forward." 

Two recent electronic health record studies have advanced our understanding of long COVID in the U.S. A cohort study of more than 73,000 non-hospitalized COVID-19 survivors in the Veterans Health Administration (VHA) found that compared to non-hospitalized VHA users who did not have COVID-19, the former group had an increased risk of death beyond the first 30 days of illness (HR 1.59, 95% CI 1.46-1.73) and were more likely to seek outpatient care and have more frequent visits. In addition, the study found an excess burden of respiratory conditions, nervous system conditions, mental health disorders, metabolic disorders, cardiovascular conditions, and gastrointestinal disorders in the COVID-19 cohort at 6 months of follow-up. Similarly, a Centers for Disease Control and Prevention (CDC) study of 3,171 non-hospitalized adults at Kaiser Permanente Georgia who had a positive SARS-CoV-2 polymerase chain reaction result from April to September 2020 found that 69% attended one or more outpatient visits 28 to 180 days after their COVID-19 diagnosis. 68% of these patients had visits for a new primary diagnosis; although most visits were with primary care clinicians, 38% visited with a new specialist. The volume of visits for symptoms potentially related to COVID-19 (throat or chest pain, shortness of breath, malaise and fatigue) declined after 60 days, but some continued through 120 to 180 days.

In a perspective paper in The Milbank Quarterly, Dr. Zackary Berger and colleagues observed that primary care clinicians will play important roles in providing and coordinating care for vulnerable patients with long COVID. The racial health disparities seen in acute COVID-19 will likely translate into similar disparities in long COVID, exacerbated by structural barriers to health and care access (economic, geographical, housing and segregation, and occupational) that could impede recovery. The authors recommended boosting health system resources devoted to primary care and addressing the root causes of inequity though actions to mitigate the social determinants of health. Whether the upcoming CDC guidelines on long COVID heed these sensible recommendations remains to be seen.