- Gottlieb, Michael;
- Wang, Ralph C;
- Yu, Huihui;
- Spatz, Erica S;
- Montoy, Juan Carlos C;
- Rodriguez, Robert M;
- Chang, Anna Marie;
- Elmore, Joann G;
- Hannikainen, Paavali A;
- Hill, Mandy;
- Huebinger, Ryan M;
- Idris, Ahamed H;
- Lin, Zhenqiu;
- Koo, Katherine;
- McDonald, Samuel;
- O'Laughlin, Kelli N;
- Plumb, Ian D;
- Santangelo, Michelle;
- Saydah, Sharon;
- Willis, Michael;
- Wisk, Lauren E;
- Venkatesh, Arjun;
- Stephens, Kari A;
- Weinstein, Robert A;
- Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) Group
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.