Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections during the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

Michael Gottlieb, Ralph C. Wang, Huihui Yu, Erica S. Spatz, Juan Carlos C. Montoy, Robert M. Rodriguez, Anna Marie Chang, Joann G. Elmore, Paavali A. Hannikainen, Mandy Hill, Ryan M. Huebinger, Ahamed H. Idris, Zhenqiu Lin, Katherine Koo, Samuel McDonald, Kelli N. O'Laughlin, Ian D. Plumb, Michelle Santangelo, Sharon Saydah, Michael WillisLauren E. Wisk, Arjun Venkatesh, Kari A. Stephens, Robert A. Weinstein

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-Term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). Methods: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. Results: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P =. 017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P <. 001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. Conclusions: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-Term symptoms. Clinical Trials Registration. NCT04610515.

Original languageEnglish (US)
Pages (from-to)1930-1941
Number of pages12
JournalClinical Infectious Diseases
Volume76
Issue number11
DOIs
StatePublished - Jun 1 2023

Keywords

  • COVID-19
  • Delta
  • Long COVID
  • Omicron
  • SARS-CoV-2

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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