Omicron BA.1/1.1 SARS-CoV-2 infection among vaccinated Canadian adults

To the editor:

The incidence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron BA.1/1.1 variant, which spread rapidly worldwide even among vaccinated people, is not fully defined.one We quantified the incidence of SARS-CoV-2 infection during the initial variant wave of omicron BA.1/1.1 among Canadian adultstwo and the contribution of prior infection and concurrent vaccination to active age-specific immunity (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).3

From May 2020 to March 2022, in the Action to Beat Coronavirus (Ab-C) study, we conducted four serial assessments of SARS-CoV-2 seropositivity, each involving 5,000 to 9,000 adults, using the Angus Reid Forum, a national representative online voting platform (Fig. S2). Dried blood samples obtained by participants were analyzed with highly sensitive and specific chemiluminescence-based enzyme-linked immunosorbent assays targeting the spike protein, receptor-binding domain, and nucleocapsid (N) protein.2.4 Vaccines that have been used in Canada contain only spike protein and therefore should not cause N protein positivity.5 Approval for the study was obtained from the Unity Health Toronto Institutional Review Board.

The 5,031 adults who were surveyed in phase 4 of the Ab-C study and whose dried blood samples were received between January 24 and March 15, 2022, were broadly representative of Canadian adults. The study population had similar prevalences of obesity, smoking, diabetes, and SARS-CoV-2 vaccination as the general Canadian adult population, but the study population included a lower percentage of adults with low educational attainment (Table S1 ). More women than men and more vaccinated adults than unvaccinated adults provided dried blood samples in phase 4 of the study.

Peak protein titers for IgG antibodies in Canadian adults and the cumulative incidence of age-specific infection before and during the Omicron BA.1/1.1 variant wave.

Enhancement titers are shown, representing the relative proportions of IgG antibody titers against enhancement protein relative to control samples (Section S1 in the Supplementary Appendix), with stratification by infection and vaccination status in adults. Canadians (Panel A) and age. Specific cumulative incidence of infection in each stratum of prior infection and vaccination before and during the omicron variant wave BA.1/1.1 (Panel B). Dots represent participants who received their last dose of vaccine (or were unvaccinated) at least 1 month before dried blood spot samples were obtained. (A total of 3344 participants had complete information available at the time of the analyses, after exclusion of 21 low-quality samples.) In box-and-whisker plots, the solid line represents the median, the box represents the interquartile range, and the whiskers represent 1.5 times the interquartile range. The results with the use of the antigen receptor-binding domain were similar to those of the spike protein (Fig. S3). Cumulative incidences of Canadian adults in each vaccination and infection category (assessed on the basis of nucleocapsid protein positivity or rapid molecular or antigen tests) were drawn from groups of 3,481 participants in phase 3 (before the wave omicron BA.1/1.1). ) and 4,032 participants in phase 4 (during the omicron BA.1/1.1 wave, with a reference period beginning December 1, 2021) for whom complete testing, vaccination, and antibody data were available at the time of the analysis. The first column in the overall and age-specific sets represents viral and antibody test positivity throughout the period prior to the omicron BA.1/1.1 surge, and the second column represents values ​​during the omicron BA surge .1/1.1. Percentages may not add to 100 due to rounding.

Among the 3,468 adults who tested negative for protein N in phase 3 of the study (August through October 2021), 1,040 tested positive for protein N in phase 4 (education-weighted incidence between phases, 30%; interval confidence of 95%). [CI], 26 to 33). Among the 91 unvaccinated, uninfected participants in phase 3 of the study, 36 had a positive result in phase 4 (education-weighted incidence between phases, 40%; 95% CI, 25 to 54). After exclusion of participants who had been vaccinated less than 1 month before dried blood spot samples were obtained, peak protein titers were negligible among participants who were neither infected nor vaccinated. Peak protein titers were lower among participants who had received only one dose of vaccine than among those who had received multiple doses of vaccine (Figure 1A). Peak protein titers were higher among participants who had received three doses of vaccines and had been infected.

When we examined phases 3 and 4 separately, we found that the cumulative incidence of N protein positivity prior to wave variant omicron BA.1/1.1 was 11% (95% CI, 10 to 12; of 5,155 participants tested). , 571 had a positive result) but increased during the omicron BA.1/1.1 wave at an education-weighted cumulative incidence of 37% (95% CI, 35 to 39; of 5,031 participants tested, 1,869 had a positive result). When we applied the between-phase incidence among vaccinated or unvaccinated participants to the 29.7 million adults in Canada, we found that approximately 9.0 million adults (95% CI, 7.9 to 10.2 million) had recently infected during omicron BA.1/ wave 1.1, including 0.9 million infections (95% CI, 0.6 to 1.2 million) among 2.3 million unvaccinated adults. Figure 1B shows the age-specific patterns of cumulative infection (defined as N protein positivity or viral test positivity) or cumulative vaccination among participants before and during the omicron BA.1/1.1 wave. The incidence of infection with the omicron variant BA.1/1.1 increased to a lesser extent among older adults than among younger adults.

The use of N protein positivity may have resulted in an underestimation of the true incidence of infection with the omicron BA.1/1.1 variant because an antibody response was not elicited in vaccinated adults with mild cases or because the participants did not have seroconversion during the sampling period.one Section S1 provides more details on laboratory methods and analyses.

Despite the finding of widespread infection, age-specific patterns caution against the notion that the omicron BA.1/1.1 variant will immunize everyone. Unlike younger adults, people age 60 and older face the highest rates of hospitalization and death, but have the lowest rates of infection and vaccination combined. Strategies to build a wall of immunity will continue to rely on high levels of vaccination coverage, especially among people who have not yet received any vaccinations, including those who have recovered from infection.3 Continuous evaluation of the incidence of infection by the omicron BA.2 variant and future variants of SARS-CoV-2 is essential.

Patrick E. Brown, Ph.D.
Hang Fu size, MSA
Aiyush Bansal, MD
Leslie Newcombe, B.Sc.
Unity Health Toronto, Toronto, ON, Canada

Karen Colwill, Ph.D.
Geneviève Mailhot, M.Sc.
Melanie Delgado-Brand, B.Sc.
Anne-Claude Gingras, Ph.D.
Sinai Health, Toronto, ON, Canada

Arthur S. Slutsky, M.D.
Maria Pasic, Ph.D.
Jeffrey’s partner, MLT
Unity Health Toronto, Toronto, ON, Canada

Isaac I. Bogoch, MD
Toronto General Hospital, Toronto, ON, Canada

Ed Morawski, MA
teresa lam
Angus Reid, Ph.D.
Angus Reid Institute, Vancouver, BC, Canada

Prabhat Jha, MD, D.Phil.
Unity Health Toronto, Toronto, ON, Canada
[email protected]

for Ab-C Study Collaborators

Supported by the Covid-19 Immunity Task Forcethe Canadian Institutes of Health Research, Pfizer Global Medical GrantsY St. Michael’s Hospital Foundation.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on May 18, 2022 on NEJM.org.

A complete list of Ab-C study collaborators is provided in the Supplementary Appendix, available at NEJM.org.

  1. one. Ritchie H., Mathieu E., Rodés-Guirao L, et al. Coronavirus pandemic (COVID-19). our world in data, 2022 (https://ourworldindata.org/coronavirus).

  2. two. Spike X, Sharma A, passive m, et al. Assessment of SARS-CoV-2 seropositivity during the first and second viral waves in 2020 and 2021 among Canadian adults. JAMA Network Open 2022;5(2):e2146798e2146798.

  3. 3. Hammer A, Serge R., Fridge M, et al. Efficacy of the BNT162b2 vaccine after recovery from Covid-19. N English J Med 2022;386:12211229.

  4. Four. colwill k, galipeau and, Stible M, et al. A “made in Canada” serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination. October 26, 2021 (https://www.medrxiv.org/content/10.1101/2021.10.25.21265476v1). prepress

  5. 5. duarte n, Yanes-Lane M, Arora RK, et al. Adaptation of serological surveys for the SARS-CoV-2 vaccine era. Open Forum Infect Dis 2022;9:ofab632ofab632.

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