A new study of more than 4,700 people from the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) reveals that more than one in five people who contracted COVID from 2020 to 2023 did not recover within 90 days after infection. The study also revealed that those people who had been vaccinated and those infected with the Omicron variant suffered milder infections and recovered quicker. The research, led by investigators at the  Columbia University Vagelos College of Physicians and Surgeons is published in JAMA Network Open.

“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,” says Elizabeth C. Oelsner, PhD, the study’s lead author and the Herbert Irving Associate Professor of Medicine at Columbia.

At present, it is still unclear exactly why some people suffer from “long COVID” or symptoms and conditions that develop, linger, or reoccur weeks or months after an initial infection. The new study, however, does provide information on people who are at greater risk of experiencing long-lasting symptoms.

Women and adults with pre-pandemic cardiovascular disease were less likely to recover from COVID after three months. Other pre-pandemic health conditions such as chronic kidney disease, diabetes, asthma, chronic lung disease, depressive symptoms, and a history of smoking were linked with longer recovery times, though the researchers noted that these associations weren’t significant after accounting for sex, cardiovascular disease, vaccination, and variant exposure.

“Longer recovery times were observed in participants with pre-pandemic health conditions. With simultaneous adjustment for all pre-pandemic conditions, only clinical CVD was associated with recovery; infection severity mediated this association by 20.0%, suggesting the importance of alternative pathways, such as systemic inflammation or endotheliopathy,” the researchers wrote.

Other groups disproportionately affected by long COVID—sometimes call post COVID-19 condition (PCC)—were American Indian and Alaska Native study participants who showed more severe infections and longer recovery periods.

“Additional research is needed on the extent to which the pandemic may have exacerbated U.S. social and health disparities, including among Indigenous communities,” the investigators noted. “Inclusion of racially and ethnically diverse participants in (long COVID) mechanistic research and clinical trials remains essential to identifying and equitably distributing interventions.”

The results of the new analysis were consistent with prior studies into the burden of PCC on the U.S. population, namely the Researching COVID to Enhance Recovery (RECOVER) initiative—a large, prospective, case-control study of PCC. RECOVER had a longer follow period (six months vs. 90 days) and from patient self-reporting of 12 symptoms, found a 10% prevalence of symptom score–defined PCC at six-month follow-up.

The team also noted their research was in line with earlier efforts data showing women had worse recovery rates than men, despite having lower rates of severe acute illness. “This finding could be due to a reporting bias differential by sex, although other possibilities must be considered,” the reporters noted. “Sex differences in risk of PCC, and particularly PCC sub-phenotypes 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.”

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