Long COVID: Experts Weigh in on Increasingly Common Syndrome

Further research on long COVID may reveal overlapping etiologies and markers to improve treatment for this broader class of disorders.⁸

Risk Factors & Incidence

Dr. Sparks

Like other post-acute infection syndromes, long COVID appears to be more common in women. Jeffrey Sparks, MD, MMSc, an assistant professor of medicine at Harvard Medicine School, Boston, and a rheumatologist at Brigham and Women’s Hospital, Boston, explains that the most well-established risk factor is probably increased severity of COVID-19 infection. However, long COVID also occurs in some patients who had a mild disease course.

With Zachary Wallace, MD, MSc, an assistant professor of medicine at Harvard Medical School and a rheumatologist at Massachusetts General Hospital, Dr. Sparks is leading several National Institutes of Health-funded prospective studies of post-COVID symptoms in patients with rheumatic diseases. One such study demonstrated that vaccinated patients with systemic autoimmune rheumatic disease had lower rates of PASC.³

Some data also indicate that long COVID may be less frequent following infection with omicron variants than earlier variants.⁹ A preprint study reveals that long COVID may be less common in patients treated with nirmatrelvir in combination with ritonavir (Paxlovid).¹⁰

We don’t currently know how having an immune-mediated rheumatic disease may impact the presentation of long COVID or its overall risk. “That’s one of the research agenda items that we will be looking at,” says Dr. Calabrese.

Partly because of these differing definitions and changing variables of the pandemic itself, we don’t have good estimates of the incidence of long COVID or of PASC more broadly, but some estimates put it in the 15%-30% range.⁴ A study from the COVID-19 Global Rheumatology Alliance found that almost 10% of patients with systemic autoimmune rheumatic diseases reported persistent symptoms 90 days after infection.¹¹

“Fortunately, dying from COVID is really uncommon these days,” says Dr. Sparks. “But as the mortality rate goes down, the importance of PASC rises, because there are a lot more survivors.”

Diagnosis, Treatment & Prognosis

Because no known biomarker for long COVID exists, diagnosis is clinical. Not all new-onset illness after a SARS-CoV-2 infection or a presumed SARS-CoV-2 infection is long COVID, but physicians can make a reasonable presumptive diagnosis after carefully excluding other potential causes of symptoms.

“It is really challenging to figure out what to do for long COVID patients because we don’t have a good under­standing of how this phenotype mechanistically occurs,” says Alfred H. Kim, MD, PhD, assistant professor in the Division of Rheumatology at Washington University School of Medicine in St. Louis.