Protection against omicron (B.1.1.529) BA.2 reinfection conferred by primary omicron BA.1 or pre-omicron SARS-CoV-2 infection among health-care workers with and without mRNA vaccination: a test-negative case-control study

Abstract

Background: There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination.

Methods: We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection.

Findings: 258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47-63), two (69%, 64-73), or three (70%, 66-74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65-78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95-96), but was not improved with a third dose (96%, 95-97).

Interpretation: Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant.

Funding: Ministère de la Santé et des Services Sociaux du Québec.

Figure 1

Weekly distribution of SARS-CoV-2 infections by infection history and weekly proportion of reinfections among all infections during the omicron BA.1 and BA.2 waves, December, 2021–June, 2022

Figure 2

Distribution of primary infections relative to reinfections during the study period, by definition of reinfection (≥30-day interval vs ≥90-day interval) Distribution of primary infections associated with a reinfection using the 30-day or longer interval definition (A) and using the 90-day or longer interval definition (B). Vertical dotted lines show start of study period.

Figure 3

Protection against omicron BA.2 infection (any infection or symptomatic infection) conferred by pre-omicron or omicron BA.1 primary infection with or without vaccination Protection against any BA.2 infection (A) and symptomatic BA.2 infection (B). Logistic regression models compared participants with previous primary infection or vaccination, or both, versus unvaccinated participants without previous primary infection. All estimates were adjusted for age, sex, type of employment, facility, indication for testing, and epidemiological week. Error bars are 95% CI. NI-V1=no previous infection, one vaccine dose. NI-V2=no previous infection, two vaccine doses. NI-V3=no previous infection, three vaccine doses. PI-NV=primary infection non-vaccinated. PI-V1=primary infection before one vaccine dose. PI-V2=primary infection before two vaccine doses. PI-V3=primary infection before three vaccine doses. V1-PI=primary infection after one vaccine dose. V1-PI-V2=primary infection after first but before second vaccine dose. V1-PI-V3=primary infection after first but before second and third vaccine doses. V2-PI=primary infection after two vaccine doses. V2-PI-V3=primary infection after second but before third vaccine dose. V3-PI=primary infection after three vaccine doses.