Long COVID Symptoms More Common in Those Infected During Pre-Delta Variant Period

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Up to half of patients infected with SARS-CoV-2 may experience symptoms lasting beyond three months post-infection, including severe fatigue, organ system-based symptoms and other persistent symptoms.

Experiencing prolonged or long-COVID symptoms following a SARS-CoV-2 infection was more common to those infected during the pre-Delta variant period compared with the Delta and Omicron periods.

According to results from a recent study published in the Clinical Infectious Diseases journal, up to half of patients infected with SARS-CoV-2 may experience symptoms lasting beyond three months post-infection, including severe fatigue, organ system-based symptoms and other persistent symptoms.

In the cohort Centers for Disease Control and Prevention-funded INSPIRE collaboration, researchers observed patients across eight major healthcare systems in the U.S., which were intentionally selected for diversity of geography and participant populations. Patients who both tested positive and negative for COVID, and were symptomatic at the time of testing, were observed three months after their infection for over 18 months.

Patients were observed to identify the difference in long-term symptoms between variants to help patients, clinicians, researchers, and policy advisors plan for longer-term impacts of COVID-19, according to the study.

Out of 3,223 participants, (2,402 COVID-positive and 821 COVID-negative) 463 (19.3%) of the COVID-positive cohort were pre-Delta, 1,198 (49.9%) were during Delta, and 741 (30.8%) were during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts, as was presence of 3 or more prolonged symptoms.

Results show there was no difference seen in the COVID-negative cohort between variant time periods. In multivariable models, there was no difference in severe fatigue between variants. However, there were decreased odds of having 3 or more symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status.

COVID-19 has been dynamic with numerous variants of concern (VOC) throughout the pandemic, creating challenges for clinicians, patients, and researchers. Results shared variants are considered more severe due to increased transmissibility, more severe disease, reduced neutralization by antibodies, reduced treatment response, and/or diagnostic detection failures.

To date, the CDC has identified six major VOC, of which Delta and Omicron (including subvariants) are generally considered most important given ramifications for diagnosis, treatment, and public health efforts.

In a recent webinar titled “3 Years Later, What’s Known About Long COVID?,” Michael Gottlieb, MD, RDMS of Mercer Medical Center, mentioned that many things have changed over the course of pre-Delta variant to the Omnicron — more specifically the development of vaccinations and patients in different populations being affected differently.

“The impact we're seeing on prolonged fatigue and multiple symptoms, well, it differed when you look at just the pure numbers, but when you account for other variables, specifically things like vaccination, the populations affected, that number went away,” Gottlieb said. “(The results are) suggesting there seems to be an impact on vaccination to reducing the risk of long- COVID across these variants.”

Paul E. Sax, MD, FIDSA, clinical director of the Division of Infectious Disease at Brigham and Women’s Hospital, responded in the webinar by stating the study shows “people who might be hesitant about getting vaccinated should think about this as a potential benefit beyond the one that is probably most widely publicized, which is prevention of severe disease.”

When asked of the likelihood of developing long-COVID after an initial infection versus reinfection, the group said they are actively studying reinfection and it’s planned to be a feature paper to come out.

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