A new study has shed light on key risk factors associated with post-acute sequelae of SARS-CoV-2, including reinfections, vaccination status, and the severity of the initial illness. The study, conducted by Teslemm K. Babalola and colleagues from Stony Brook University, NY, offers insights into the long-term implications of COVID-19, especially among essential workers.

"Although researchers have not yet provided a clear answer to the pathogenetic mechanism of PASC, identifying risk factors can assist in better understanding and managing the health condition," noted Babaloa and colleagues. "Linking these factors to other identified potential pathologies, especially with similar clinical pictures and etiological causes, could better help understand the pathology and health impact."

The retrospective study analyzed data from 2,511 essential workers, primarily first responders, who tested positive for COVID-19 between March 2020 and February 2024. Researchers identified that 18.9% of participants developed post-acute sequelae of SARS-CoV-2 (PASC), characterized by symptoms persisting or emerging at least 3 months after initial infection and lasting at least 2 months. Researchers highlighted three significant risk factors:

1. Multiple Reinfections: Participants who experienced 2 or more SARS-CoV-2 infections had a 41% higher risk of developing PASC compared with those infected only once.
2. Severe Initial Infection: Those with severe cases of COVID-19 were over three times more likely to develop PASC than those with mild or asymptomatic infections.
3. Vaccination Status: Unvaccinated individuals at the time of their first infection were at a significantly higher risk of developing PASC, with a relative risk over three times greater than their vaccinated counterparts.

Neurological symptoms like brain fog, headaches, and dizziness were common, alongside respiratory issues such as chronic cough and shortness of breath. Other symptoms included musculoskeletal pain, fatigue, and gastrointestinal disturbances.

The prevalence of PASC observed in this study aligns with findings from other international research efforts, which estimate that 10% to 20% of individuals who contract COVID-19 may develop long-term symptoms. In the U.S. alone, millions of individuals report persistent symptoms years after their initial infection, researchers reported in The Lancet Regional Health.

Researchers proposed that multiple reinfections may hinder the body’s ability to clear viral loads, prolonging inflammation and increasing susceptibility to long-term symptoms.

“Each subsequent infection could potentially increase the burden on the immune system, leaving individuals vulnerable to the cumulative effects of the virus,” the authors noted. This insight underscores the critical need for ongoing protective measures, especially for high-risk populations.

Vaccinated individuals were significantly less likely to report persistent symptoms, even if they contracted the virus.

"Our study findings are consistent with some findings in the literature, which indicate that the incidence of PASC among COVID-19-vaccinated individuals would be lower than among unvaccinated individuals," the researchers concluded.

The study was funded by the CDC and the National Institute on Aging (NIH). No relevant conflicts of interest were disclosed.