In a recent publication in the journal Clinical Infectious Diseases, researchers sought to examine the incidence of prolonged symptoms 3 months post-SARS-CoV-2 infection across three variant time periods, including pre-Delta, Delta, and Omicron periods.

In the INSPIRE trial, which is a national study across eight major healthcare systems purposely selected for the diversity of geography and participant populations across three variant time periods, researchers compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of three or more total symptoms among participants with and without “long COVID.” Study participants were followed for 18 months.

INSPIRE was established to prospectively and longitudinally evaluate the symptoms and outcomes of participants who test positive for SARS-CoV-2 compared with symptomatic adults testing negative. Employing a standardized questionnaire, data were self-reported by participants. In this study, the participants received surveys either by email or text about an assortment of issues, including symptoms during and after COVID-19; demographics; vaccination status; and physical, mental, and social well-being. Participants also answered questions about their cognitive status and when they returned to work or resumed daily activities.

The study included 2,402 COVID-positive and 821 COVID-negative participants. Among COVID-positive participants, 463 (19.3%) were pre-Delta, 1,198 (49.9%) were Delta, and 741 (30.8%) were Omicron.

The results revealed that the pre-Delta COVID-positive cohort presented with more prolonged severe fatigue (16.7% vs. 11.5% vs. 12.3%; P = .017) and the existence of three or more prolonged symptoms (28.4% vs. 21.7% vs. 16.0%; P <.001) compared with the Delta and Omicron cohorts.

Moreover, across time periods, no variations were found in the COVID-negatives. In multivariable models adjusted for vaccination, severe fatigue, and odds of having three or more symptoms were no longer significant across variants.

The authors noted that among participants infected during pre-Delta than with Delta and Omicron periods, prolonged symptoms following SARS-CoV-2 infection were more common; yet, these variances were no longer significant after adjusting for vaccination status, signifying a valuable effect of vaccination on risk of long-term symptoms.

The authors wrote, “Our study suggests that newer variants such as Delta and Omicron might have a different distribution of symptoms post-illness, but no significant difference in fatigue severity or symptom quantity after accounting for vaccination status. Despite this, persistent symptoms remain common at three months post-COVID-19 among our COVID-positive and COVID-negative cohorts, with 1 in 8 participants reporting severe fatigue.”

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