Among seronegative individuals with a high risk for COVID-19, maximal viral load is the major factor in seroconversion to SARS-CoV-2, and low viral load infections may not stimulate antibody immune responses, according to study findings published in Open Forum Infectious Diseases.
Researchers defined virologic determinants of seroconversion to SARS-CoV-2 infection in vaccine- and infection-naïve individuals at high risk for COVID-19 through a post-hoc analysis of a prospective, placebo-controlled phase 3 COVID-19 prevention trial (ClinicalTrials.gov Identifier: NCT04452318), conducted from July 2020 to February 2021.
The post hoc analysis involved trial participants who had received placebo and had never been infected at baseline, were vaccine-naïve, and had an increased risk for infection owing to close contact exposure to COVID-19. They had been assessed for COVID-19 symptoms, SARS-CoV-2 infection, and serostatus over 28 days.
The participants underwent active surveillance with weekly nasopharyngeal swab sampling for SARS-CoV-2 with quantitative reverse transcription polymerase chain reaction (RT-qPCR) testing in the efficacy assessment period (EAP) and were interviewed weekly for symptoms associated with COVID-19. Anti-SARS-CoV-2 serology testing was performed at baseline for anti-spike (anti-S) immunoglobulin G (IgG), anti-S IgA, and anti-nucleocapsid (anti-N) IgG.
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[M]aximal NP viral load, rather than duration of infection or presence of symptomatic infection, is a major driver of seroconversion within 32 days of COVID-19 infection.
Among 1069 uninfected, placebo-treated participants who were seronegative at baseline, 157 (14.7%) were infected in the 28-day EAP. Of those with infection, 102 (65.0%) seroconverted by day 32. A total of 144 participants (91.7%) who were infected had a positive RT-qPCR test result, and 13 who seroconverted did not have a positive RT-qPCR test.
Among the 144 participants with a positive SARS-CoV-2 RT-qPCR test result during the EAP, 89 (61.8%) seroconverted and 43 (29.9%) were seronegative.
Of the 157 individuals who became infected during the 28-day EAP, 78 had symptomatic infection and 79 had asymptomatic infection. Symptomatic COVID-19 was observed in 58 of 89 (65%) patients who seroconverted and in 15 of 43 (35%) patients who did not seroconvert. The odds ratio of seroconversion was 4.39 (log-odds=1.48, P =.0013) for patients who were symptomatic vs asymptomatic after controlling for covariates.
Seroconversion was associated with a higher viral load. The mean (SD) maximum viral load in participants who seroconverted by day 32 was 7.23 (1.68) log10 copies/mL vs 4.8 (2.2) log10 copies/mL in those who remained seronegative and 6.2 (2.3) log10 copies/mL in those with unknown seroconversion status.
A mean viral load of 6.08 log10 copies/mL (95% CI, 4.21-6.83) accurately predicted seroconversion at day 32, according to Youden’s index, which was maximized at 6.08 log10 copies/mL, with sensitivity of 85% and specificity of 67%.
A longer detectable viral load duration was associated with an increased chance of seroconversion postinfection. The mean duration of detectable viral load among seroconverted patients was 3.24 (1.85) weeks vs 1.63 (1.09) weeks in those who remained seronegative.
Study limitations include the potential for missing peak maximum viral load due to use of weekly RT-qPCR testing of nasopharyngeal swabs for viral load. The researchers also noted that the study was conducted in the US, Romania, and Moldova in 2020 to 2021, before widespread vaccination and emergence of the Omicron (B.1.1.529) and Omicron-lineage variants.
“The findings of this analysis in participants who were uninfected and seronegative at baseline and who were closely monitored for infection after a close contact exposure to COVID-19, conclusively demonstrate that maximal NP viral load, rather than duration of infection or presence of symptomatic infection, is a major driver of seroconversion within 32 days of COVID-19 infection, with high viral loads approximating over 6.0 log10 copies/mL being most associated with seroconversion,” the study authors concluded.
Disclosure: This study was supported by Regeneron Pharmaceuticals, Inc, and F. Hoffmann-La Roche Ltd. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
