Studies examine persistent symptoms of COVID-19

Vaccination after infection with SARS-CoV-2 was associated with a decreased likelihood of extended duration of symptoms, a study of U.K. adults found.

Researchers used data from adults who received at least one COVID-19 vaccine dose after testing positive for SARS-CoV-2 infection to estimate associations between COVID-19 vaccination and duration of symptoms. Presence of symptoms was tracked over a seven-month follow-up period (February to September 2021). Results were published May 18 by The BMJ.

Among 28,356 patients, 6,729 (24%) reported COVID-19 symptoms of any severity at least once during follow-up. Before vaccination, the odds of experiencing extended symptoms changed little over time. A first vaccine dose was associated with an initial 13% decrease in the odds of extended symptoms. The researchers noted that it was not clear whether this improvement was sustained over the following 12 weeks, until a second vaccine dose was given.

Receiving a second vaccine dose was associated with a 9% decrease in the odds of extended symptoms, and this improvement was sustained at least over an average follow-up of nine weeks, the researchers stated. “Our results suggest that vaccination of people previously infected may be associated with a reduction in the burden of long covid on population health, at least in the first few months after vaccination,” they concluded.

An editorial accompanying the study said that “Unfortunately, many unknowns remain about the long term prognosis of long covid, including the effect of booster vaccines or recurrent covid-19.” The editorialists said more research is needed “on the link between antibody titres and symptoms over time before we can hope to predict the effects of vaccination on individuals.”

A separate study, published by Annals of Internal Medicine on May 24, reported a high burden of persistent symptoms in patients after COVID-19. Researchers at the NIH examined self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least six weeks from symptom onset regardless of the presence of postacute sequelae of SARS-CoV-2 infection (PASC) and a control group of patients with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, regardless of their current health status. All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset of patients also received exploratory immunologic and virologic evaluations.

Overall, 189 patients with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and in none of the vaccinated COVID-19 cohort. In exploratory studies, no evidence was found for persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.

An accompanying editorial noted that there has been an “onslaught” of PASC, with these patients not being believed, being misdiagnosed as having anxiety disorder, or having their symptoms misattributed to pandemic stress. More research on PASC is urgently needed, the editorialists noted.

“Without a fuller understanding of pathophysiology and disease course, we must not allow normal objective tests to negate our patients' subjective experiences,” they wrote. “We need to explore whether real-world measurements during both restful and stressful conditions offer insight into the mechanisms of PASC. While we gather evidence, our patients deserve personalized care pathways that acknowledge the many biopsychosocial factors involved in illness recovery.”