Protection against Omicron BA.2 reinfection conferred by primary Omicron or pre-Omicron infection with and without mRNA vaccination

BackgroundWe estimated the protection against the Omicron BA.2 variant associated with prior primary infection (PI) due to pre-Omicron or Omicron BA.1 virus, with and without mRNA vaccination. MethodsA test-negative case-control study was conducted among healthcare workers (HCWs) tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 predominated and was presumptively diagnosed. Logistic regression models compared the likelihood of BA.2 reinfection (second positive test [≥]30 days after PI) among HCWs with history of PI and none to three doses of mRNA vaccine versus infection-naive, unvaccinated HCWs. FindingsAmong 37,732 presumed BA.2 cases, 2,521 (6.7%) and 659 (1.7%) were reinfections following pre-Omicron or BA.1 PI, respectively. Among 73,507 controls, 7,360 (10.0%) and 12,315 (16.8%) had a pre-Omicron or BA.1 PI, respectively. Pre-Omicron PI was associated with 38% (95%CI:19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those also vaccinated with one (56%), two (69%) or three (70%) vaccine doses. Omicron BA.1 PI was associated with greater protection against BA.2 (72%; 95%CI:65-78), higher among two-dose vaccinated at 96% (95%CI:95-96) but not improved with a third dose (96%; 95%CI:95-97). Hybrid Omicron BA.1 PI plus two or three dose vaccine-induced protection persisted for five months post-infection. InterpretationTwice-vaccinated individuals who experienced BA.1 infection were subsequently well-protected for a prolonged period against BA.2 reinfection and derived no meaningful added benefit against BA.2 from a third dose of mRNA vaccine.

Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination

ImportanceOmicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification. ObjectiveTo estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine. DesignTest-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022. SettingPopulation-based, province of Quebec, Canada ParticipantsCommunity-dwelling [≥]12-year-olds tested for SARS-CoV-2. ExposuresPrior laboratory-confirmed infection with/without mRNA vaccination. OutcomesLaboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. ResultsWithout vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses. Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively). Conclusions and relevancePrior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.

Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada

BackgroundThe Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canadas larger provinces. MethodsTwo-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults [≥]18-years-old in British Columbia (BC) and Quebec, Canada. FindingsIn both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with [~]95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at [~]70% when both doses were ChAdOx1. Estimates were similar by age group (including adults [≥]70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained [≥]80%. InterpretationTwo doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.

Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a sixteen-week interval between doses

While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them, raising concerns about vaccine efficacy. Here, we analyzed longitudinal humoral responses including antibody binding, Fc-mediated effector functions and neutralizing activity against the D614G strain but also variants of concern and SARS-CoV-1 in a cohort of SARS-CoV-2 naive and previously infected individuals, with an interval of sixteen weeks between the two doses. While the administration of a second dose to previously infected individuals did not significantly improve humoral responses, we observed a significant increase of humoral responses in naive individuals after the 16-weeks delayed second shot, achieving similar levels as in previously infected individuals. We compared these responses to those elicited in individuals receiving a short (4-weeks) dose interval. For the naive donors, these responses were superior to those elicited by the short dose interval.

Single-dose mRNA vaccine effectiveness against SARS-CoV-2 in healthcare workers extending 16 weeks post-vaccination: a test-negative design from Quebec, Canada

IntroductionIn Canada, first and second doses of mRNA vaccines against SARS-CoV-2 were uniquely spaced 16 weeks apart, but the duration of single-dose protection remains uncertain. We estimated one- and two-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Quebec, Canada including protection against varying outcome severity, variants of concern (VOC), and the stability of single-dose protection out to 16 weeks post-vaccination. MethodsA test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly-matched (10:1), randomly-sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by one dose [≥]14 days or two doses [≥]7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. ResultsPrimary analysis included 5,316 cases and 53,160 controls. Single-dose VE was 70% (95%CI: 68-73) against SARS-CoV-2 infection, 73% (95%CI: 71-75) against COVID-19 illness and 97% (95%CI: 92-99) against associated hospitalization. Two-dose VE was 86% (95%CI: 81-90) and 93% (95%CI: 89-95), respectively, with no associated hospitalizations. VE was higher for non-VOC than VOC (73% Alpha) among single-dose (77%, 95%CI: 73-81 versus 63%, 95%CI: 57-67) but not two-dose recipients (87%, 95%CI: 57-96 versus 94%, 95%CI: 89-96). Across 16 weeks, no decline in single-dose VE was observed with appropriate stratification based upon prioritized vaccination determined by higher versus lower likelihood of direct patient contact. ConclusionOne mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least four months post-vaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy to consider.