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

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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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