Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial

Ann Intern Med. 2022 Sep;175(9):1258-1265. doi: 10.7326/M22-1300. Epub 2022 Jul 5.

Abstract

Background: Immunoassays for determining past SARS-CoV-2 infection have not been systematically evaluated in vaccinated persons in comparison with unvaccinated persons.

Objective: To evaluate antinucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection.

Design: Nested substudy of a phase 3 randomized, double-blind, placebo-controlled vaccine efficacy trial. (ClinicalTrials.gov: NCT04470427).

Setting: 99 sites in the United States, July 2020 through March 2021.

Participants: Participants were aged 18 years or older, had no known history of SARS-CoV-2 infection, and were at risk for SARS-CoV-2 infection or severe COVID-19. Substudy participants were diagnosed with SARS-CoV-2 infection during the trial's blinded phase.

Intervention: 2 mRNA-1273 or placebo injections 28 days apart.

Measurements: Nasopharyngeal swabs from days 1 and 29 (vaccination days) and from symptom-prompted illness visits were tested for SARS-CoV-2 via polymerase chain reaction (PCR). Serum samples from days 1, 29, and 57 and the participant decision visit (PDV, when participants were informed of treatment assignment; median day 149) were tested for anti-N Abs by the Elecsys immunoassay.

Results: Among 812 participants with PCR-confirmed COVID-19 illness during the blinded phase of the trial (through March 2021), seroconversion to anti-N Abs (median of 53 days after diagnosis) occurred in 21 of 52 mRNA-1273 vaccinees (40% [95% CI, 27% to 54%]) versus 605 of 648 placebo recipients (93% [CI, 92% to 95%]). Each 1-log increase in SARS-CoV-2 viral copies at diagnosis was associated with 90% higher odds of anti-N Ab seroconversion (odds ratio, 1.90 [CI, 1.59 to 2.28]).

Limitation: The scope was restricted to mRNA-1273 vaccinees and the Elecsys assay, the sample size was small, data on Delta and Omicron infections were lacking, and the analysis did not address a prespecified objective of the trial.

Conclusion: Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing.

Primary funding source: National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Double-Blind Method
  • Humans
  • SARS-CoV-2
  • Seroepidemiologic Studies
  • United States
  • Vaccine Efficacy

Substances

  • COVID-19 Vaccines
  • 2019-nCoV Vaccine mRNA-1273

Associated data

  • ClinicalTrials.gov/NCT04470427