Researchers found that prolonged symptoms after COVID-19 infection were significantly more common in individuals who were infected in the pre-Delta period compared with those infected during the Delta or Omicron periods. These study results were published in Clinical Infectious Diseases.
Researchers conducted a multicenter prospective study to investigate the occurrence of prolonged COVID-19 symptoms at 3 months following infection. The prevalence and differences in prolonged symptoms were evaluated across 3 variant-specific periods, including the pre-Delta, Delta, and Omicron periods. Eligible participants were adults with self-reported symptoms suggestive of COVID-19 infection who were tested for infection within the previous 42 days. Participants self-reported data through an online survey at baseline and at 3 months. The primary outcome was the occurrence of prolonged fatigue, defined as 3 or more months of fatigue with a severity score of at least 25. Two multivariable logistic regression models were used to evaluate the risk for prolonged symptoms across the 3 variant-specific periods. The first model was adjusted for potential confounders and the second was adjusted for vaccination status.
A total of 3223 participants were included in the final analysis, of whom 74.5% were positive and 25.5% were negative for COVID-19 infection. Among participants (n=2402) who tested positive, 49.9%, 30.8%, and 19.3% were infected during the Delta, Omicron (30.8%), and pre-Delta periods (19.3%), respectively.
Of COVID-19-positive participants, those infected in the pre-Delta period were significantly more likely to report severe fatigue at 3 months compared with those infected during the Delta or Omicron periods (16.7% vs 11.5% and 12.3%, respectively; P =.017).
After adjustments for potential confounders and vaccination status, the risk for prolonged severe fatigue did not significantly differ between participants infected in the Delta vs pre-Delta periods (adjusted odds ratio [aOR], 0.79; 95% CI, 0.52-1.20). Similar results were observed for participants infected in the Omicron vs pre-Delta periods (aOR, 0.94; 95% CI, 0.56-1.60) and for those infected in the Omicron vs Delta periods (aOR, 1.20; 95% CI, 0.82-1.75).
Higher rates prolonged severe fatigue were reported among participants who tested negative vs positive for COVID-19 infection (17.8% vs 12.7%), potentially owing to other infectious conditions or pandemic-related influences, including psychosocial impact, isolation, and physical inactivity.
Self-reports of any prolonged COVID-19 symptoms were significantly more likely among participants infected in the pre-Delta period (52.6%) compared with those infected in either the Delta or Omicron periods (both 41.5%; P <.001). Of note, the occurrence of 3 or more prolonged symptoms in COVID-19-positive participants did not significantly differ by variant-specific period after adjustment for vaccination status.
Study limitations include potential misclassification and selection bias, as well as insufficient data on vaccination timing, doses, and specific vaccine type.
According to the researchers, “[N]ewer 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.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Gottlieb M, Wang R, Yu H, et al; on behalf of the INSPIRE group. Severe fatigue and persistent symptoms at three months following SARS-COV-2 infections during the pre-delta, Delta, and Omicron Time Periods: A multicenter prospective cohort study. Clin Infect Dis. Published online January 27, 2023. doi:10.1093/cid/ciad045