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- Title
Nasopharyngeal Viral Load Is the Major Driver of Incident Antibody Immune Response to SARS-CoV-2 Infection.
- Authors
Xu, Meng; O'Brien, Meagan P; Hooper, Andrea T; Forleo-Neto, Eduardo; Isa, Flonza; Hou, Peijie; Chan, Kuo-Chen; Cohen, Myron S; Marovich, Mary A; Hamilton, Jennifer D; Hirshberg, Boaz; Herman, Gary A; Musser, Bret J
- Abstract
Background Virologic determinants of seroconversion to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were defined in a post hoc analysis of prospectively studied vaccine- and infection-naïve individuals at high risk for coronavirus disease 2019 (COVID-19). Methods This phase 3 COVID-19 prevention trial (NCT04452318) with casirivimab and imdevimab was conducted in July 2020–February 2021, before widespread vaccine availability. Placebo-treated participants who were uninfected (SARS-CoV-2 quantitative reverse transcription polymerase chain reaction [RT-qPCR] negative) and seronegative were assessed weekly for 28 days (efficacy assessment period [EAP]) for COVID-19 symptoms and SARS-CoV-2 infection by RT-qPCR of nasopharyngeal swab samples and for serostatus by antinucleocapsid immunoglobulin (Ig) G. Regression-based modeling, including causal mediation analysis, estimated the effects of viral load on seroconversion. Results Of 157/1069 (14.7%) uninfected and seronegative (for antispike IgG, antispike IgA, and antinucleocapsid IgG) participants who became infected during the EAP, 105 (65%) seroconverted. The mean (SD) maximum viral load of seroconverters was 7.23 (1.68) log10 copies/mL vs 4.8 (2.2) log10 copies/mL in those who remained seronegative; viral loads of ∼6.0log10 copies/mL better predicted seroconversion. The mean of the maximum viral load was 7.11 log10 copies/mL in symptomatic participants vs 5.58 log10 copies/mL in asymptomatic participants. The mean duration of detectable viral load was longer in seroconverted vs seronegative participants: 3.24 vs 1.63 weeks. Conclusions Maximum SARS-CoV-2 viral load is a major driver of seroconversion and symptomatic COVID-19, with high viral loads (∼6.0 log10 copies/mL) better predicting seroconversion. Serology underestimates infection rates, incidence, and prevalence of SARS-CoV-2 infection.
- Subjects
HIV seroconversion; SARS-CoV-2; VIRAL load; REVERSE transcriptase polymerase chain reaction; ANTIBODY formation; COVID-19
- Publication
Open Forum Infectious Diseases, 2023, Vol 10, Issue 12, p1
- ISSN
2328-8957
- Publication type
Article
- DOI
10.1093/ofid/ofad598