ABSTRACT
Background: Increasing the interval between the first and second SARS-CoV-2 vaccine doses enhances vaccine immunogenicity, however the optimal timing of the third vaccine is unknown. In this study, we investigated how the time interval between the first and second (V1-V2), or second and third (V2-V3) doses affects immunogenicity after three doses of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine. Methods: This is an observational cohort consisting of 360 participants enrolled in the COVID-19 Occupational Risks, Seroprevalence, and Immunity among Paramedics in Canada (CORSIP) study. Immune responses to BA.1 and other variants were measured from serum using an ACE2 competitive binding assay for surrogate SARS-CoV-2 neutralization. We fit a multiple linear regression model to estimate the independent association between both the V1-V2 and V2-V3 intervals and serum SARS-CoV-2 neutralization, while adjusting for age, sex, and the V3-to-blood collection interval. We examined vaccine dosing intervals as continuous variables and categorized them into quartiles. Results: The mean age was 40 years, 45% were female sex (at birth), and the median BA.1 surrogate neutralization was 61% (IQR 38-77%). The multivariate analysis indicated that longer V1-V2 (ß = 0.1292, 95% CI: 0.04807-0.2104) and V2-V3 (ß = 0.2653, 95% CI: 0.2291-0.3015) intervals were associated with increased surrogate neutralization of BA.1. These results were consistent when examining responses against Spike from other SARS-CoV-2 strains. When categorized into V2-V3 quartiles, the first (56-231 days), and second (231-266 days) quartiles demonstrated decreased BA.1 surrogate neutralization compared to the longest V2-V3 quartile (282-329 days). There was no significant difference in surrogate neutralization between the long (266-282 days) and longest (282-329 days) V2-V3 intervals. Conclusion: Longer intervals between first, second and third doses are independently associated with increased immunogenicity for all tested SARS-CoV-2 strains. Increasing the intervals between the second and third vaccine doses up to 8.9 months provided additive benefits increasing the immunogenicity of BNT162b2 vaccine schedules.
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IntroductionCanadian Paramedic services modified infection prevention and control (IPAC) practices in response to COVID-19. These changes may affect risk of exposure to infectious disease agents and can be used to inform future IPAC practices. We characterized COVID-19-related IPAC changes in the provinces of Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan.Materials & MethodsQuestionnaire data (January 2021-Feb 2022) from the national COVID-19 Occupational Risks, Seroprevalence and Immunity among Paramedics (CORSIP) project was used to identify which IPAC practices were in place prior to COVID-19, and which were modified in response to COVID-19, including the timing of changes (March-May 2020;June-Aug 2020;Sept-Nov 2020;Nov 2020-present).Results2939 participants were included (146, 1249, 139, 1317, 88 from Alberta, BC, Manitoba, Ontario, and Saskatchewan, respectively), of whom 2674 (91%) reported receiving IPAC training. IPAC measures that were common prior to COVID-19 included: personal protective equipment (PPE) training, patient screening, hand hygiene, N95/P100 respirators, gowns, impermeable suits, and cleaning/disinfection. COVID-related IPAC changes included: screening staff, social distancing, restricting aerosol generating procedures, masking patients, cloth face coverings, surgical masks, face shields, and elastomeric respirators. Changes were reported for all IPAC measures. Most (71%) of these changes were made early in the COVID-19 pandemic (March-May 2020). Differences in proportions across provinces, community practice settings, and professional regulation status were reported (p < .05) for hand hygiene, PPE training, screening of patients, face shields, and various respirator types.ConclusionCanadian paramedic services were quick to modify available IPAC measures. However, these changes were variable across provinces, regulation status, and setting for specific IPAC measures. Inconsistent IPAC measures across jurisdictions may contribute to variable risk of infectious disease exposure. An evidence-informed and nationally coordinated approach may provide more equitable exposure risk mitigation for paramedic workers.
ABSTRACT
OBJECTIVE: Emerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear. METHODS: This study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples six months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as "short" (first quartile), "moderate" (second quartile), "long" (third quartile), and "longest" interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included spike and receptor-binding domain (RBD) immunoglobulin G (IgG) antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations. RESULTS: A total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to "short interval" (≤30 days), vaccine dosing intervals of the long (39-73 days) group (ß= 0.31, 95% Confidence interval (CI): 0.10-0.52) and the longest (≥74 days) group (ß = 0.82. 95% CI: 0.36-1.28) were associated with increased spike total antibody concentration. Compared to the short interval, the longest interval quartile was associated with higher spike IgG antibodies, while the long and longest intervals were associated with higher RBD IgG antibody concentrations. Similarly, the longest dosing intervals increased inhibition of ACE-2 binding to viral spike protein. CONCLUSION: Increased mRNA vaccine dosing intervals longer than 38 days result in higher levels of anti-spike antibodies and ACE-2 inhibition when assessed six months after the first COVID-19 vaccine.
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The relationship between antibodies to wild-type SARS-CoV-2 antigens and the risk of breakthrough infections is unclear, especially during time periods of Omicron. We investigated the association of anti-spike and anti-receptor binding domain antibody levels and the risk of subsequent breakthrough COVID-19. We included adult paramedics from an observational cohort study who received ≥ 2 mRNA vaccines but did not have COVID-19 before the blood collection. Higher post-vaccine antibody levels to wild-type SARS-CoV-2 antigens were associated with a reduced risk of COVID-19. Further research into clinical utility of antibody levels, to inform a threshold for protection and timing of boosters, should be prioritized.
ABSTRACT
Background: Jurisdictions have reported COVID-19-related increases in the incidence and mortality of non-traumatic out-of-hospital cardiac arrest (OHCA). We hypothesized that changes in suicide incidence during the COVID-19 pandemic may have contributed to these changes. We investigated whether the COVID-19 pandemic was associated with changes in the: (1) incidence of suicide-related OHCA, and (2) characteristics and outcomes of such cases. Methods: We used the provincial British Columbia Cardiac Arrest Registry, including non-traumatic emergency medical system (EMS)-assessed OHCA, to compare suicide-related OHCA (defined as clear self-harm or a priori communication of intent) one-year prior to, and one year after, the start of the COVID-19 pandemic (March 15, 2020). We calculated differences in incidence (with 95% CI), overall and within subgroups of mechanism (hanging, suffocation, poisoning, or unclear mechanism), and in case characteristics and hospital-discharge favourable neurological outcomes (CPC 1-2). Results: Of 13,785 EMS-assessed OHCA, we included 274/6430 (4.3%) pre-pandemic and 221/7355 (3.0%) pandemic-period suicide-related cases. The median age was 43 years (IQR 30-57), 157 (32%) were female, and 7 (1.4%) survived with favourable neurological status. Suicide-related OHCA incidence decreased from 5.4 pre-pandemic to 4.3 per 100 000 person-years (-1.1, 95% CI -2.0 to -0.28). Hanging-related OHCA incidence also decreased. Patient characteristics and hospital discharge outcomes between periods were similar. Conclusion: Suicide-related OHCA incidence decreased with the COVID-19 pandemic and we did not detect changes in patient characteristics or outcomes, suggesting that suicide is not a contributor to increases in COVID-related OHCA incidence or mortality. Overall suicide-related OHCA outcomes in both time periods were poor.