Anti-nucleocapsid antibodies following SARS-CoV-2 infection in the blinded phase of the mRNA-1273 Covid-19 vaccine efficacy clinical trial

Abstract

Importance: The performance of immunoassays for determining past SARS-CoV-2 infection, which were developed in unvaccinated individuals, has not been assessed in vaccinated individuals. Objective: To evaluate anti-nucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 vaccine efficacy trial participants after SARS-CoV-2 infection during the trial's blinded phase. Design: Nested analysis in a Phase 3 randomized, placebo-controlled vaccine efficacy trial. Nasopharyngeal swabs for SARS-CoV-2 PCR testing were taken from all participants on Day 1 and Day 29 (vaccination days), and during symptom-prompted illness visits. Serum samples from Days 1, 29, 57, and the Participant Decision Visit (PDV, when participants were informed of treatment assignment, median day 149) were tested for anti-N Abs. Setting: Multicenter, randomized, double-blind, placebo-controlled trial at 99 sites in the US. Participants: Trial participants were ≥ 18 years old with no known history of SARS-CoV-2 infection and at appreciable risk of SARS-CoV-2 infection and/or high risk of severe Covid-19. Nested sub-study consists of participants with SARS-CoV-2 infection during the blinded phase of the trial. Intervention: Two mRNA-1273 (Moderna) or Placebo injections, 28 days apart. Main Outcome and Measure: Detection of serum anti-N Abs by the Elecsys (Roche) immunoassay in samples taken at the PDV from participants with SARS-CoV-2 infection during the blinded phase. The hypothesis tested was that mRNA-1273 recipients have different anti-N Ab seroconversion and/or seroreversion profiles after SARS-CoV-2 infection, compared to placebo recipients. The hypothesis was formed during data collection; all main analyses were pre-specified before being conducted. Results: We analyzed data from 1,789 participants (1,298 placebo recipients and 491 vaccine recipients) with SARS-CoV-2 infection during the blinded phase (through March 2021). Among participants with PCR-confirmed Covid-19 illness, seroconversion to anti-N Abs at a median follow up of 53 days post diagnosis occurred in 21/52 (40%) of the mRNA-1273 vaccine recipients vs. 605/648 (93%) of the placebo recipients (p < 0.001). Higher SARS-CoV-2 viral copies at diagnosis was associated with a higher likelihood of anti-N Ab seropositivity (odds ratio 1.90 per 1-log increase; 95% confidence interval 1.59, 2.28). Conclusions and Relevance: As a marker of recent infection, anti-N Abs may have lower sensitivity in mRNA-1273-vaccinated persons who become infected. Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing Trial Registration: ClinicalTrials.gov NCT04470427

Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

“…(v) We defined previous infection in participants as previously testing PCR positive for SARS-CoV-2, or seroconversion to anti-N positivity during the study. However, some of the group labelled as naïve could have been exposed to SARS-CoV-2, and anti-N seroconversion is less likely in vaccinated people and differs between variants (Follmann et al, 2022; Whitaker et al, 2021). (vi) For people with vaccine breakthrough infections since the second vaccine dose, infecting sequence data was not always available.…”

Accounting for assay performance when estimating the temporal dynamics in SARS-CoV-2 seroprevalence in the U.S

“…Furthermore, biases in the sampling could also vary over time and across states, for instance as a function of the numbers of cases and underlying demographics. Rates of seroconversion and reversion might also be different preand post-vaccination (e.g., Follmann et al, 2022 ; Goldberg et al, 2022 ; Carazo et al, 2022 ). We use numbers of tests that were positive and negative in the models, meaning that we do not make explicit adjustments for race, ethnicity, age, or sex, although these factors are, to an extent, captured in the model with state-specific intercepts.…”

Awareness of SARS-CoV-2 Omicron Variant Infection Among Adults With Recent COVID-19 Seropositivity

“…The ability to detect seroconversion may have been limited by the technical sensitivity of the assay used and by the potential delay or attenuation of IgG-N antibody response in individuals who were immunocompromised or received mRNA vaccination. 29,30 Thus, the established criterion for seroconversion used in this analysis may have underestimated the true prevalence of seroconversion during the study period. The modest sample size had limited statistical power to detect multiple factors associated with Omicron variant infection awareness; larger studies could identify additional potentially important factors.…”