Study identifies female sex, heart disease as long-COVID risk factors, vaccination as protective

Worker at desk with long COVID

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Women and adults with preexisting conditions such as cardiovascular disease are less likely to recover from COVID-19 within 3 months, while vaccination and Omicron-variant infection were linked to a quicker recovery, reveals a study posted yesterday in JAMA Network Open. It also showed that more than one in five adults had protracted recoveries.

From April 2020 to February 2023, Columbia University researchers tracked 4,708 first-time COVID-19 patients participating in 1 of 14 ongoing nationwide cohorts that have followed participants as early as 1971. Patients underwent physical exams before the pandemic and answered questionnaires during the crisis. 

The average patient age was 61.3 years, 62.7% were women, 44.3% were Hispanic, 33.5% were White, 13.2% were Black, 7.9% were American Indian or Alaska Native, and 1.1% were Asian. In total, 12.6% of patients were hospitalized, and 3.1% needed critical care. One in five participants (20.5%) were vaccinated before infection, of whom 5.9% had received only one dose.

Median time to recovery was 20 days

The median self-reported time to recovery from COVID-19 was 20 days, and about 22.5% of patients were still experiencing symptoms at 90 days. Sociodemographic, clinical, and lifestyle factors differed significantly by 90 days, especially for infection severity (outpatient vs critical hospitalization, 32.9 vs 57.6 days). 

Our study underscores the important role that vaccination against COVID has played, not just in reducing the severity of an infection but also in reducing the risk of long COVID.

Elizabeth Oelsner, MD, MPH

Recovery by 90 days was tied to pre-infection vaccination (hazard ratio [HR], 1.30) and infection during the Omicron variant wave (HR, 1.25). These associations were mediated by less severe infection by 33.4% and 17.6%, respectively. Risk factors for long COVID, or post-COVID condition (PCC) were female sex (HR, 0.85) and pre-existing cardiovascular disease (HR, 0.84). The results were similar for reinfections.

"Our study underscores the important role that vaccination against COVID has played, not just in reducing the severity of an infection but also in reducing the risk of long COVID," lead author Elizabeth Oelsner, MD, MPH, said in a Columbia University press release.

"Our study clearly establishes that long COVID posed a substantial personal and societal burden," she added. "By identifying who was likely to have experienced a lengthy recovery, we have a better understanding of who should be involved in ongoing studies of how to lessen or prevent the long-term effects of SARS-CoV-2 infection."

Further research needed on racial, sex disparities

Noting the propensity for American Indian or Alaska Native participants to have prolonged recoveries in models that didn't account for cohort effects, the authors said more research is needed on how much the pandemic may have worsened US social and health disparities, including among Indigenous populations. 

"Inclusion of racially and ethnically diverse participants in PCC mechanistic research and clinical trials remains essential to identifying and equitably distributing interventions," they wrote.

Likewise, women had slower recoveries despite a lower rate of severe infection. "Sex differences in risk of PCC, and particularly PCC subphenotypes characterized by neurologic, musculoskeletal, and autoimmune conditions, could be explained by multiple mechanisms, including differences in the immune response and higher risk of autoreactivity and thrombosis in women (vs men), that merit further study," the researchers wrote.

"Further investigation on the longer-term prognosis and mechanisms of PCC, including comparisons of multiorgan structure and function before and after infection, is critical to inform treatment and prevention," they concluded.

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