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Clinical Trial
. 2024 Dec 16;230(6):1384-1389.
doi: 10.1093/infdis/jiae400.

Association Between SARS-CoV-2 Viral Load and COVID-19 Vaccination in 4 Phase 3 Trials

Holly Janes  1 , Leigh H Fisher  1 , Jia Jin Kee  1 , Lalitha Parameswaran  2 , Paul A Goepfert  3 , Ann R Falsey  4 , James Ludwig  1 , Craig A Magaret  1 , Peter B Gilbert  1 , James G Kublin  1 , Nadine Rouphael  5 , Magdalena E Sobieszczyk  6 , Hana M El Sahly  7 , Lindsey R Baden  8 , Beatriz Grinsztejn  9 , Stephen R Walsh  8 , Glenda E Gray  10 , Karen L Kotloff  11 , Cynthia L Gay  12 , Alexander L Greninger  13 , Milagritos D Tapia  11 , E Adrianne Hammershaimb  11 , Frances H Priddy  14 , Justin A Green  15 , Frank Struyf  16 , Lisa Dunkle  17 , Kathleen M Neuzil  18 , Lawrence Corey  1 , Yunda Huang  1
Affiliations
Clinical Trial

Association Between SARS-CoV-2 Viral Load and COVID-19 Vaccination in 4 Phase 3 Trials

Holly Janes et al. J Infect Dis. .

Abstract

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802.

Keywords: COVID-19 transmission; COVID-19 vaccine; SARS-CoV-2 viral load; infectiousness; randomized trial.

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Conflict of interest statement

Potential conflicts of interest. A. F. had/has research grants from Pfizer, Merck, Janssen, CyanVac, VaxCo, Moderna, and BioFire Diagnostics; fees for advisory boards from GSK, ADMA Biologics, and Sanofi Pasteur; and fees for data safety monitoring board from Novavax. M. E. S. had/has grants from the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) during the conduct of the study (5UM1AI069470); grants from NIH/NIAID and Gates Foundation outside the submitted work; and grants to her institution from Merck Sharpe and Dohme, Sanofi, and Gilead outside of the submitted work. S. R. W. has received institutional funding from the NIH/NIAID; institutional grants or contracts from Sanofi Pasteur, Janssen Vaccines/Johnson & Johnson, Moderna Tx, Pfizer, Vir Biotechnology, and Worcester HIV Vaccine; has participated on data safety monitoring or advisory boards for Janssen Vaccines/Johnson & Johnson and BioNTech; and his spouse holds stock/stock options in Regeneron Pharmaceuticals. C. M. E. has received research grants from Merck and AstraZeneca; and has participated in Sanofi, Janssen, and Gilead advisory board meetings. N. R. is a paid safety consultant for ICON, CyanVac, and EMMES; served on selected advisory boards for Sanofi, Seqirus, Pfizer, and Moderna; and receives funds to their institution to conduct research from Sanofi, Lilly, Merck, Quidel, Immorna, Vaccine Company, and Pfizer. C. L. G. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies; and grants to her institution from Gilead and ViiV outside of the submitted work. K. L. K. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689); and from Novavax outside of the submitted work. J. A. G. is employed by and holds stock in AstraZeneca. E. A. H. received fees from Oxford University for time spent adjudicating end points for the AstraZeneca/Oxford SARS-CoV-2 vaccine trials conducted in the UK, South Africa, and Brazil. M. D. T. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
SARS-CoV-2 viral load at COVID-19 diagnosis, by parent protocol and randomization group. Viral load measured in nasal/nasopharyngeal swab at COVID-19 diagnosis in the 4 trials, from left to right: Moderna, AstraZeneca, Janssen, and Novavax. Treatment shown in color on the left and placebo in grey on the right for each trial. Filled circles indicated SARS-CoV-2 sequences that were measured, open triangles indicate those where sequences are missing. The midline of the box denotes the median and the ends of the box denote the 25th and 75th percentiles.
Figure 2.
Figure 2.
Estimated mean differences in SARS-CoV-2 viral load in nasopharyngeal swab at COVID-19 diagnosis, vaccine versus placebo, by parent protocol. Forest plot shows estimated mean difference in log10 copies/mL SARS-CoV-2 viral load between vaccine and placebo groups, along with 95% confidence intervals (CI). Estimates are based on the multivariate linear regression model that includes age at baseline, sex assigned at birth, self-identified race, ethnicity, baseline self-reported presence of comorbidities associated with higher likelihood of severe COVID-19, country of residence, detected SARS-CoV-2 variant, COVID-19 severity, and days since protocol-defined COVID-19 onset, with the exception of the Novavax trial which is based on an unadjusted analysis due to the small number of cases. Regression models are fit separately to each trial.
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