The Relationship Between Anti-Spike SARS-CoV-2 Antibody Levels and Risk of Breakthrough COVID-19 Among Fully Vaccinated Adults.

The relationship between antibodies to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and the risk of breakthrough infections is unclear, especially during circulation of the Omicron strain. We investigated the association of anti-spike and anti-receptor binding domain antibody levels and the risk of subsequent breakthrough coronavirus disease 2019 (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 postvaccination 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.

Effect of vaccine dosing intervals on Omicron surrogate neutralization after three doses of BNT162b2.

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.

The association of the post-resuscitation on-scene interval and patient outcomes after out-of-hospital cardiac arrest.

BACKGROUND: After resuscitation from out-of-hospital cardiac arrest (OHCA) by Emergency Medical Services (EMS), the amount of time that should be dedicated to pre-transport stabilization is unclear. We examined whether the time spent on-scene after return of spontaneous circulation (ROSC) was associated with patient outcomes. METHODS: We examined consecutive adult EMS-treated OHCAs from the British Columbia Cardiac Arrest registry (January 1/2019-June 1/2021) that had on-scene ROSC (sustained to scene departure). The primary outcome was favourable neurological outcome (Cerebral Performance Category ≤ 2) at hospital discharge; secondary outcomes were re-arrest during transport and hospital-discharge survival. Using adjusted logistic regression models, we estimated the association between the post-resuscitation on-scene interval (divided into quartiles) and outcomes. RESULTS: Of 1653 cases, 611 (37%) survived to hospital discharge, and 523 (32%) had favourable neurological outcomes. The median post-resuscitation on-scene interval was 18.8 minutes (IQR:13.0-25.5). Compared to the first post-resuscitation on-scene interval quartile, neither the second (adjusted odds ratio [AOR] 1.19; 95% CI 0.72-1.98), third (AOR 1.10; 95% CI 0.67-1.81), nor fourth (AOR 1.54; 95% CI 0.93-2.56) quartiles were associated with favourable neurological outcomes; however, the fourth quartile was associated with a greater odds of hospital-discharge survival (AOR 1.73; 95% CI 1.05-2.85), and both the third (AOR 0.40; 95% CI 0.22-0.72) and fourth (AOR 0.44;95% CI 0.24-0.81) quartiles were associated with a lower odds of intra-transport re-arrest. CONCLUSION: Among resuscitated OHCAs, increased post-resuscitation on-scene time was not associated with improved neurological outcomes, but was associated with improved survival to hospital discharge and decreased intra-transport re-arrest.

Determining the Optimal SARS-CoV-2 mRNA Vaccine Dosing Interval for Maximum Immunogenicity.

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.

Temporal trends of suicide-related non-traumatic out-of-hospital cardiac arrest characteristics and outcomes with the COVID-19 pandemic.

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.

Performance of the medical priority dispatch system in correctly classifying out-of-hospital cardiac arrests as appropriate for resuscitation.

BACKGROUND: Emergency dispatch centres receive emergency calls and assign resources. Out-of-hospital cardiac arrests (OHCA) can be classified as appropriate (requiring emergent response) or inappropriate (requiring non-emergent response) for resuscitation. We sought to determine system accuracy in emergency medical services (EMS) OHCA response allocation. METHODS: We analyzed EMS-assessed non-traumatic OHCA records from the British Columbia (BC) Cardiac Arrest registry (January 1, 2019-June 1, 2021), excluding EMS-witnessed cases. In BC the "Medical Priority Dispatch System" is used. We classified EMS dispatch as "emergent" or "non-emergent" and compared to the gold standard of whether EMS personnel decided treatment was appropriate upon scene arrival. We calculated sensitivity, specificity, and positive and negative predictive values (PPV, NPV), with 95% CI's. RESULTS: Of 15,371 non-traumatic OHCAs, the median age was 65 (inter quartile range 51-78), and 4834 (31%) were women; 7152 (47%) were EMS-treated, of whom 651 (9.1%) survived). Among EMS-treated cases 6923/7152 had an emergent response (sensitivity = 97%, 95% CI 96-97) and among EMS-untreated cases 3951/8219 had a non-emergent response (specificity = 48%, 95% CI, 47 to 49). Among cases with emergent dispatch, 6923/11191 were EMS-treated (PPV = 62%, 95% CI 61-62), and among those with non-emergent dispatch, 3951/4180 were EMS-untreated (NPV = 95%, 95% CI 94-95); 229/4180 (5.5%) with a non-emergent dispatch were treated by EMS. CONCLUSION: The dispatch system in BC has a high sensitivity and moderate specificity in sending the appropriate responses for OHCAs deemed appropriate for treatment by paramedics. Future research may address strategies to increase system specificity, and decrease the incidence of non-emergent dispatch to EMS-treated cases.