Predictors of SARS-CoV-2 RNA From Nasopharyngeal Swabs and Concordance With Other Compartments in Nonhospitalized Adults With Mild to Moderate COVID-19

Carlee Moser; Jonathan Z Li; Joseph J Eron; Evgenia Aga; Eric S Daar; David A Wohl; Robert W Coombs; Arzhang Cyrus Javan; Rachel A Bender Ignacio; Prasanna Jagannathan; Justin Ritz; Scott F Sieg; Urvi M Parikh; Michael D Hughes; Judith S Currier; Davey M Smith; Kara W Chew; ACTIV-2/A5401 Study Team

doi:10.1093/ofid/ofac618

Predictors of SARS-CoV-2 RNA From Nasopharyngeal Swabs and Concordance With Other Compartments in Nonhospitalized Adults With Mild to Moderate COVID-19

Open Forum Infect Dis. 2022 Nov 11;9(11):ofac618. doi: 10.1093/ofid/ofac618. eCollection 2022 Nov.

Authors

Carlee Moser¹, Jonathan Z Li², Joseph J Eron³, Evgenia Aga¹, Eric S Daar⁴, David A Wohl³, Robert W Coombs⁵, Arzhang Cyrus Javan⁶, Rachel A Bender Ignacio^{7

8}, Prasanna Jagannathan⁹, Justin Ritz¹, Scott F Sieg¹⁰, Urvi M Parikh¹¹, Michael D Hughes¹², Judith S Currier¹³, Davey M Smith¹⁴, Kara W Chew¹³; ACTIV-2/A5401 Study Team

Collaborators

ACTIV-2/A5401 Study Team:
Lara Hosey, Jhoanna Roa, Nilam Patel, Emily Degli-Angeli, Erin Goecker, Glenda Daza, Socorro Harb, Joan Dragavon, Grace Aldrovandi, William Murtaugh, Marlene Cooper, Howard Gutzman, Kevin Knowles, Rachel Bowman, Bill Erhardt, Stacey Adams

Affiliations

¹ Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
² Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
⁴ Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
⁵ Department of Laboratory Medicine and Pathology, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁶ National Institutes of Health, Rockville, Maryland, USA.
⁷ Department of Medicine, University of Washington, Seattle, Washington, USA.
⁸ Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.
⁹ Department of Medicine, Stanford University, Palo Alto, California, USA.
¹⁰ Department of Medicine, Case Western University, Cleveland, Ohio, USA.
¹¹ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹² Department of Biostatistics and Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
¹³ Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
¹⁴ Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Abstract

Background: Identifying characteristics associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding may be useful to understand viral compartmentalization, disease pathogenesis, and risks for viral transmission.

Methods: Participants were enrolled August 2020 to February 2021 in ACTIV-2/A5401, a placebo-controlled platform trial evaluating investigational therapies for mild-to-moderate coronavirus disease 2019 (COVID-19), and underwent quantitative SARS-CoV-2 RNA testing on nasopharyngeal and anterior nasal swabs, oral wash/saliva, and plasma at entry (day 0, pretreatment) and days 3, 7, 14, and 28. Concordance of RNA levels (copies/mL) across compartments and predictors of nasopharyngeal RNA levels were assessed at entry (n = 537). Predictors of changes over time were evaluated among placebo recipients (n = 265) with censored linear regression models.

Results: Nasopharyngeal and anterior nasal RNA levels at study entry were highly correlated (r = 0.84); higher levels of both were associated with greater detection of RNA in plasma and oral wash/saliva. Older age, White non-Hispanic race/ethnicity, lower body mass index (BMI), SARS-CoV-2 immunoglobulin G seronegativity, and shorter prior symptom duration were associated with higher nasopharyngeal RNA at entry. In adjusted models, body mass index and race/ethnicity associations were attenuated, but the association with age remained (for every 10 years older, mean nasopharyngeal RNA was 0.27 log₁₀ copies/mL higher; P < .001). Examining longitudinal viral RNA levels among placebo recipients, women had faster declines in nasopharyngeal RNA than men (mean change, -2.0 vs -1.3 log₁₀ copies/mL, entry to day 3; P < .001).

Conclusions: SARS-CoV-2 RNA shedding was concordant across compartments. Age was strongly associated with viral shedding, and men had slower viral clearance than women, which could explain sex differences in acute COVID-19 outcomes.

Keywords: COVID-19; SARS-CoV-2 RNA; nasal swabs; nasopharyngeal swabs; predictors; serostatus; sex differences.

Abstract

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