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 ,Jill Anderson ,Michael Willis ,Nikki Gentile ,Angela Wong ,Ryan Huebinger Site ,Cecilia Lara Chavez ,Minna Hassaballa ,Senyte Pierce ,Grace Amadio ,Lauren E Wisk ,Kelli N O’laughlin ,Morgan Kelly ,Christopher W Chandler ,Arun Kane ,Arjun K Venkatesh ,Michelle Santangelo ,Zenoura Maat ,Kevin Schaeffer ,Hongbo Yu ,Ryan Jerger ,Michelle L’hommedieu ,D L Morse ,Zhenqiu Lin ,David Cheng ,Zohaib Ahmed ,Kate Diaz Roldan ,Carly Shutty ,Rachel E Geyer ,Samuel Mcdonald ,Summer Chavez ,Dylan T Grau ,Jocelyn Dorney ,Nicole Renzi ,Marshall Kaadan ,Aron J Hall ,Kerry Malone ,Alex Charlton ,Hailey Shughart ,Anna Marie Chang ,Robert M Rodriguez ,Ahamed H Idris ,Kari A Stephens ,Ian D Plumb ,Michael Choi ,Sharon Saydah ,Guang Yang ,Raul Moreno ,Jasmine Park ,Andrew Ulrich ,Robert A Weinstein ,Mireya Arreguin ,D.p Gallegos ,Efrat Kean ,Joann G Elmore ,Erica S Spatz ,Ralph Wang ,Peter Nikonowicz ,Phillip B Watts ,Megan Eguchi ,Antonia Derden ,Robin Kemball ,Paavali Hannikainen ,Zimo Yang ,Karen Adams ,Lindsey Shughart ,Kristin L Rising ,Riley Martin ,Diego Guzmán ,Jessica Miao ,Juan Carlos C Montoy ,Luis Ruiz ,Ryan M Huebinger ,Shuxia Li ,Imtiaz Ebna Mannan ,Katherine Koo ,Tracy Stober ,Virginia Chan ,Kristyn Gatling ,Mandy J Hill ,Jeremiah Kinsman ,Xavier Puente ,Graham Nichol ,Melissa Briggs-Hagen

doi:10.1093/cid/ciad045

Abstract

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). 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. 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. 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.

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