The association of non-prescription drug use preceding out-of-hospital cardiac arrest and clinical outcomes.

BACKGROUND: Clinicians may make prognostication decisions for out-of-hospital cardiac arrest (OHCA) using historical details pertaining to non-prescription drug use. However, differences in outcomes between OHCAs with evidence of non-prescription drug use, compared to other OHCAs, have not been well described. METHODS: We included emergency medical service-treated OHCA in the British Columbia Cardiac Arrest Registry (January/2019-June/2023). We classified cases as "non-prescription drug-associated cardiac arrests" (DA-OHCA) if there was evidence of non-prescription drug use preceding the OHCA, including witness accounts of use within 24 h or paraphernalia at the scene. We fit logistic regression models to investigate the association between DA-OHCA (vs. other cases) and favourable neurological outcome (Cerebral Performance Category [CPC] 1-2) and survival at hospital discharge, and return of spontaneous circulation (ROSC). RESULTS: Of 18,426 OHCA, 2,171 (12%) were classified as DA-OHCA. DA-OHCA tended to be younger, unwitnessed, occur during the evening or night, and present with a non-shockable rhythm, compared to other OHCA. DA-OHCA (221 [10%]) had a greater proportion (difference 1.8%; 95% CI 0.49-3.2) with favourable neurological outcomes compared to other OHCA (1,365 [8.4%]). Adjusted models did not identify an association of DA-OHCA with favourable neurological outcome (OR 1.08, 95% CI 0.87-1.33) or survival to hospital discharge (OR 1.13, 95% CI 0.93-1.38), but did demonstrate an association with ROSC (OR 1.13, 95% CI 1.004-1.27). CONCLUSION: In unadjusted models, DA-OHCA was associated with an improved odds of survival and favourable neurological outcomes at hospital discharge, compared to other OHCA. However, we did not detect an association in adjusted analyses.

Canada's approach to SARS-CoV-2 sero-surveillance: Lessons learned for routine surveillance and future pandemics.

SETTING: In Canada's federated healthcare system, 13 provincial and territorial jurisdictions have independent responsibility to collect data to inform health policies. During the COVID-19 pandemic (2020-2023), national and regional sero-surveys mostly drew upon existing infrastructure to quickly test specimens and collect data but required cross-jurisdiction coordination and communication. INTERVENTION: There were 4 national and 7 regional general population SARS-CoV-2 sero-surveys. Survey methodologies varied by participant selection approaches, assay choices, and reporting structures. We analyzed Canadian pandemic sero-surveillance initiatives to identify key learnings to inform future pandemic planning. OUTCOMES: Over a million samples were tested for SARS-CoV-2 antibodies from 2020 to 2023 but siloed in 11 distinct datasets. Most national sero-surveys had insufficient sample size to estimate regional prevalence; differences in methodology hampered cross-regional comparisons of regional sero-surveys. Only four sero-surveys included questionnaires. Sero-surveys were not directly comparable due to different assays, sampling methodologies, and time-frames. Linkage to health records occurred in three provinces only. Dried blood spots permitted sample collection in remote populations and during stay-at-home orders. IMPLICATIONS: To provide timely, high-quality information for public health decision-making, routine sero-surveillance systems must be adaptable, flexible, and scalable. National capability planning should include consortiums for assay design and validation, defined mechanisms to improve test capacity, base documents for data linkage and material transfer across jurisdictions, and mechanisms for real-time communication of data. Lessons learned will inform incorporation of a robust sero-survey program into routine surveillance with strategic sampling and capacity to adapt and scale rapidly as a part of a comprehensive national pandemic response plan.

RéSUMé: CONTEXTE: Au Canada, où le système de santé est fédéré, les 13 juridictions provinciales et territoriales ont la responsabilité individuelle de recueillir les données qui leur permettent d'élaborer leurs politiques de santé. Lors de la pandémie de COVID-19 (2020­2023), pour réaliser les enquêtes de séroprévalence à l'échelle régionale et nationale, les autorités ont principalement utilisé l'infrastructure existante pour pouvoir analyser les échantillons et recueillir des données rapidement, mais cela a également nécessité de la communication et de la coordination entre les différentes juridictions. INTERVENTION: Au Canada, il y a eu quatre enquêtes nationales et sept enquêtes régionales sur la séroprévalence du SARS-CoV-2 dans la population générale. Les méthodologies utilisées différaient selon la méthode de sélection des participants, le choix des tests d'analyses et les structures de rapports. Nous avons analysé la façon dont ces enquêtes avaient été réalisées afin d'en dégager des éléments essentiels qui permettront de planifier pour les futures pandémies. RéSULTATS: Entre 2020 et 2023, plus d'un million d'échantillons, répartis en 11 ensembles de données distincts, ont été analysés afin de rechercher la présence d'anticorps au SARS-CoV-2. Dans la plupart des enquêtes nationales, la taille de l'échantillon était insuffisante pour pouvoir estimer la prévalence à l'échelle régionale. La disparité des méthodologies utilisées a entravé la comparaison des enquêtes régionales. Seules quatre enquêtes fournissaient les données recueillies à partir des questionnaires. Il a été impossible de comparer les enquêtes entre elles en raison de la diversité des tests d'analyse utilisés, des méthodes d'échantillonnage et de la durée des enquêtes. Seules trois provinces avaient couplé leurs données avec les archives médicales. Pour réaliser les enquêtes dans les populations éloignées et lors des périodes de confinement, la méthode d'analyse sur gouttes de sang séché a été utilisée. CONCLUSION: Afin de pouvoir fournir, en temps et en heure, des données de haute qualité pour la prise de décisions en matière de santé publique, un système de sérosurveillance continuelle doit être adaptable, modulable et évolutif. En cas de pandémie, un plan national doit prévoir des consortiums pour la conception et la validation des tests d'analyse, des moyens d'amélioration de la capacité de dépistage, des documents de base pour le couplage des données, un mode de transfert du matériel entre les différentes juridictions et des moyens pour une communication en temps réel des données. Les leçons tirées de cette analyse permettront de mettre en place un solide programme d'enquêtes de séroprévalence au sein des systèmes de sérosurveillance continuelle, et que ce programme sera accompagné d'une stratégie d'échantillonnage et d'un plan d'intervention national, rapide et complet en cas de pandémie.

Investigating the Antibody Imprinting Hypothesis among Canadian Paramedics after SARS-CoV-2 Omicron Variant Circulation.

Recent research has highlighted the Omicron variant's capacity to evade immune protection conferred by wild-type (WT) mRNA vaccines. Despite this observation, the potential involvement of antigenic sin phenomena remains unclear. Our hypothesis posited that a greater number of prior WT vaccine doses might lead to reduced anti-Omicron neutralization Abs following Omicron infection. To investigate this, we analyzed blood samples from human participants in the COVID-19 Occupational Risk, Seroprevalence, and Immunity among Paramedics (CORSIP) study who had received at least one WT mRNA vaccine before contracting Omicron. The exposure variable was the number of WT mRNA vaccines administered, and the outcome was the angiotensin-converting enzyme 2 (ACE-2) percent inhibition specific to the BA.4/BA.5 Omicron Ag. Contrary to expectations, our findings revealed that more WT-based vaccines were associated with an enhanced Omicron-specific immune response.

The association of extreme environmental heat with incidence and outcomes of out-of-hospital cardiac arrest in British Columbia: A time series analysis.

Background: The impact of extreme heat on out-of-hospital cardiac arrest (OHCA) incidence and outcomes is under-studied. We investigated OHCA incidence and outcomes over increasing temperatures. Methods: We included non-traumatic EMS (Emergency Medical Services)-assessed OHCAs in British Columbia during the warm seasons of 2020-2021. We fit a time-series quasi-Poisson generalized linear model to estimate the association between temperature and incidence of both EMS-assessed, EMS-treated, and EMS-untreated OHCAs. Second, we employed a logistic regression model to estimate the association between "heatwave" periods (defined as a daily mean temperature > 99th percentile for ≥ 2 consecutive days, plus 3 lag days) with survival and favourable neurological outcomes (cerebral performance category ≤ 2) at hospital discharge. Results: Of 5478 EMS-assessed OHCAs, 2833 were EMS-treated. OHCA incidence increased with increasing temperatures, especially exceeding a daily mean temperature of 25 °C Compared to the median daily mean temperature (16.9 °C), the risk of EMS-assessed (relative risk [RR] 3.7; 95%CI 3.0-4.6), EMS-treated (RR 2.9; 95%CI 2.2-3.9), and EMS-untreated (RR 4.3; 95%CI 3.2-5.7) OHCA incidence were higher during days with a temperature over the 99th percentile. Of EMS-treated OHCAs, during the heatwave (n = 179) and non-heatwave (n = 2654) periods, 4 (2.2%) and 270 (10%) survived and 4 (2.2%) and 241 (9.2%) had favourable neurological outcomes, respectively. Heatwave period OHCAs had decreased odds of survival (adjusted OR 0.28; 95%CI 0.10-0.79) and favourable neurological outcome (adjusted OR 0.31; 95%CI 0.11-0.89) at hospital discharge, compared to other periods. Conclusion: Extreme heat was associated with a higher incidence of OHCA, and lower odds of survival and favourable neurological status at hospital discharge.

The Association of Post-COVID-19-Related Symptoms and Preceding Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Fully Vaccinated Paramedics in Canada.

This study investigated the association between previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of symptoms associated with post-COVID conditions among fully vaccinated paramedics in Canada. We included vaccinated paramedics who provided blood sample and questionnaire data on the same date during the study period. We examined the presence of symptoms associated with post-COVID conditions and depression severity against prior SARS-CoV-2 infection categories. Compared to the "no previous SARS-CoV-2 infection" group, there was no detected association between known prior SARS-CoV-2 infection (odds ratio [OR], 1.42 [95% confidence interval {CI}, 0.96-2.09]), nor unknown prior SARS-CoV-2 infection (OR, 0.54 [95% CI, 0.29-1.00]), and the presence of symptoms associated with post-COVID conditions.

Non-prescription drug-associated out-of-hospital cardiac arrest: Changes in incidence over time and the odds of receiving resuscitation.

BACKGROUND: Multiple jurisdictions reported a significant increase in out-of-hospital cardiac arrest (OHCA) incidence over the past decade, however the reasons for this remain unclear. We investigated how drug-associated OHCA (DA-OHCA) contributed to overall OHCA incidence, and whether the likelihood of treatment by emergency medical services (EMS) was associated with DA-OHCA classification. METHODS: Using a large provincial cardiac arrest registry, we included consecutive, non-traumatic adult OHCA from 2016-2022. We classified as drug-associated if there were historical accounts of non-prescription drug use within the preceding 24 hours or evidence of paraphernalia at the scene. We examined year-by-year trends in OHCA and DA-OHCA incidence. We also investigated the association between DA-OHCA and odds of EMS treatment using an adjusted logistic regression model. RESULTS: Of 33,365 EMS-assessed cases, 1,985/18,591 (11%) of EMS-treated OHCA and 887/9,200 (9.6%) of EMS-untreated OHCA were DA-OHCA. Of EMS-treated DA-OHCA, the median age was 40 years (IQR 31-51), 1,059 (53%) had a known history of non-prescription drug use, and 570 (29%) were public-location. From 2016 to 2022, EMS-treated OHCA incidence increased from 60 to 79 per 100,000 person-years; EMS-treated DA-OHCA incidence increased from 3.7 to 9.1 per 100,000 person-years. The proportion of overall OHCA classified as DA-OHCA increased from 6.1% to 11.5%. DA-OHCA was associated with greater odds of EMS treatment (AOR 1.34; 95%CI 1.13-1.58). CONCLUSION: Although EMS-treated DA-OHCA incidence increased by nearly three-fold, it comprised a minority of the overall OHCA increase during the study period. DA-OHCA was associated with an increased likelihood of EMS treatment.

The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post-initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273]). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post-initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33-50) and 251 (42 %) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61 % (IQR 39.44-92.82) and 98.60 % (IQR 83.07-99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Whttps://www.covid19immunitytaskforce.ca/citf-databank/#accessing https://www.covid19immunitytaskforce.ca/citf-databank/#accessinguhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.

Eleven-month SARS-CoV-2 binding antibody decay, and associated factors, among mRNA vaccinees: implications for booster vaccination.

Background: We examined the 11 month longitudinal antibody decay among two-dose mRNA vaccinees, and identified factors associated with faster decay. Methods: The study included samples from the COVID-19 Occupational Risk, Seroprevalence and Immunity among Paramedics (CORSIP) longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11 months post-vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time. Results: This analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the twenty-first day (antibody level 9042 U ml-1) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter, with a half-life of 94 [95 % CI: 70, 143] days, with levels plateauing at 295 days (antibody level 1021 U ml-1). Older age, vaccine dosing interval <35 days, and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay. Conclusion: Antibody levels declined after the initial mRNA series with a half-life of 94 days, plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay.

The association of tibial vs. humeral intraosseous vascular access with patient outcomes in adult out-of-hospital cardiac arrests.

AIM: Humeral and tibial intraosseous (IO) vascular access can deliver resuscitative medications for out-of-hospital cardiac arrest (OHCA), however the optimal site is unclear. We examined the association between IO tibia vs. humerus as the first-attempted vascular access site with OHCA outcomes. METHODS: We used prospectively-collected data from the British Columbia Cardiac Arrest registry, including adult OHCAs treated with IO humerus or IO tibia as the first-attempted intra-arrest vascular access. We fit logistic regression models on the full study cohort and a propensity-matched cohort, to estimate the association between IO site and both favorable neurological outcomes (Cerebral Performance Category 1-2) and survival at hospital discharge. RESULTS: We included 1041 (43%) and 1404 (57%) OHCAs for whom IO humerus and tibia, respectively, were the first-attempted intra-arrest vascular access. Among humerus and tibia cases, 1010 (97%) and 1369 (98%) had first-attempt success, and the median paramedic arrival-to-successful access interval was 6.7 minutes (IQR 4.4-9.4) and 6.1 minutes (IQR 4.1-8.9), respectively. In the propensity-matched cohort (n = 2052), 31 (3.0%) and 44 (4.3%) cases had favourable neurological outcomes in the IO humerus and IO tibia groups, respectively; compared to IO humerus, we did not detect an association between IO tibia with favorable neurological outcomes (OR 1.44; 95% CI 0.90-2.29) or survival to hospital discharge (OR 1.29; 95% CI 0.83-2.01). Results using the full cohort were similar. CONCLUSIONS: We did not detect an association between the first-attempted intra-arrest IO site (tibia vs. humerus) and clinical outcomes. Clinical trials are warranted to test differences between vascular access strategies.

The effect of recognition on survival after out-of-hospital cardiac arrest and implications for biosensor technologies.

BACKGROUND: Biosensor technologies have been proposed as a solution to provide recognition and facilitate earlier responses to unwitnessed out-of-hospital cardiac arrest (OHCA) cases. We sought to estimate the effect of recognition on survival and modelled the potential incremental impact of increased recognition of unwitnessed cases on survival to hospital discharge, to demonstrate the potential benefit of biosensor technologies. METHODS: We included cases from the British Columbia Cardiac Arrest Registry (2019-2020), which includes Emergency Medical Services (EMS)-assessed OHCAs. We excluded cases that would not have benefitted from early recognition (EMS-witnessed, terminal illness, or do-not-resuscitate). Using a mediation analysis, we estimated the relative benefits on survival of a witness recognizing vs. intervening in an OHCA; and estimated the expected additional number of survivors resulting from increasing recognition alone using a bootstrap logistic regression framework. RESULTS: Of 13,655 EMS-assessed cases, 11,412 were included (6314 EMS-treated, 5098 EMS-untreated). Survival to hospital discharge was 191/8879 (2.2%) in unwitnessed cases and 429/2533 (17%) in bystander-witnessed cases. Of the total effect attributable to a bystander witness, recognition accounted for 84% (95% CI: 72, 86) of the benefit. If all previously unwitnessed cases had been bystander witnessed, we would expect 1198 additional survivors. If these cases had been recognized, but no interventions performed, we would expect 912 additional survivors. CONCLUSION: Unwitnessed OHCA account for the majority of OHCAs, yet survival is dismal. Methods to improve recognition, such as with biosensor technologies, may lead to substantial improvements in overall survival.

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.

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.

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.

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.

Association Between Medication Adherence and Risk of COPD in Adult Asthma Patients: A Retrospective Cohort Study in Canada.

Background: Poor adherence to prescribed asthma medications and risk of severe asthma exacerbations have been well established. However, the effects of changes in asthma medication compliance levels and subsequent risk of COPD is unknown and yet to be investigated. This study investigated the independent effect of medication adherence (MA) and asthma severity levels on the risk of COPD. Methods: We used four linked administrative health databases from the Population data BC to identify asthma patients aged 18 years and older between January 1, 1998 and December 31, 1999 without diagnosis of COPD. The primary event was time-to-COPD diagnosis during the follow-up period (January 1, 2000 to December 31, 2018). The proportion of days covered (PDC) - was used as a surrogate measure for medication adherence (MA) assessed at optimal-level (≥ 0.80), Intermediate-level (0.50-0.79), and low-level (< 0.5) of adherence. A propensity adjusted analysis with Marginal Structural Cox (MSC) model was employed to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for the effect of medication adherence and asthma severity over time. Results: At cohort entry, the sample included 68,211 asthma patients with an overall mean age of 48.2 years. The 18-year incidence of COPD in asthma patients was 9.8 per 1000-persons year. In an inverse weighted propensity adjusted analysis of the MSC model, higher MA levels were significantly associated with decreased risk of COPD as follows: optimal-level (aHR: 0.19, 95% CI: 0.17-0.24); Intermediate-level (aHR: 0.20, 95% CI: 0.18, 0.23) compared to the low-level adherence group. A significant increase in COPD risk was observed in severe asthma patients with low medication adherence (aHR: 1.72, 95% CI: 1.52-1.93), independent of other patient factors. Conclusion: Optimal (≥ 0.80) and intermediate adherence (0.5 to 0.79) levels were associated with reduced risk of COPD incidence over time. Interventions aimed at improving adherence to prescribed medications in adult asthma patients should be intensified to reduce their risk of COPD.

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.

Are higher antibody levels against seasonal human coronaviruses associated with a more robust humoral immune response after SARS-CoV-2 vaccination?

The SARS-CoV-2 belongs to the coronavirus family, which also includes common endemic coronaviruses (HCoVs). We hypothesized that immunity to HCoVs would be associated with stronger immunogenicity from SARS-CoV-2 vaccines. The study included samples from the COSRIP observational cohort study of adult paramedics in Canada. Participants provided blood samples, questionnaire data, and results of COVID-19 testing. Samples were tested for anti-spike IgG against SARS-CoV-2, HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 antigens. We first compared samples from vaccinated and unvaccinated participants, to determine which HCoV antibodies were affected by vaccination. We created scatter plots and performed correlation analysis to estimate the extent of the linear relationship between HCoVs and SARS-CoV-2 anti-spike antibodies. Further, using adjusted log-log multiple regression, we modeled the association between each strain of HCoV and SARS-CoV-2 antibodies. Of 1510 participants (mean age of 39 years), 94 (6.2%) had a history of COVID-19. There were significant differences between vaccinated and unvaccinated participant in anti-spike antibodies to HCoV-HKU1, and HCoV-OC43; however, levels for HCoV-229E and HCoV-NL63 were similar (suggesting that vaccination did not affect these baseline values). Among vaccinated individuals without prior COVID-19 infection, SARS-COV-2 anti-spike IgG demonstrated a weak positive relationship between both HCoV-229E (r = 0.11) and HCoV-NL63 (r = 0.12). From the adjusted log-log multiple regression model, higher HCoV-229E and HCoV-NL63 anti-spike IgG antibodies were associated with increased SARS-COV-2 anti-spike IgG antibodies. Vaccination appears to result in measurable increases in HCoV-HKU1, and HCoV-OC43 IgG levels. Anti-HCoV-229E and HCoV-NL63 antibodies were unaffected by vaccination, and higher levels were associated with significantly higher COVID-19 vaccine-induced SARS-COV-2 antibodies.

Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals.

SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher's Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.

Sensitivity of the Elecsys Nucleocapsid Assay for the Detection of Preceding SARS-CoV-2 Infections.

Nucleocapsid serological assay sensitivity to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among vaccinees and for Omicron cases is unclear. In this prospective study, the Elecsys nucleocapsid assay was 89% sensitive in identifying SARS-CoV-2 infections 14-607 days pre-blood collection. Sensitivity was similar when comparing by vaccination status, and in Omicron (vs pre-Omicron) cases.

A Prospective Observational Cohort Comparison of SARS-CoV-2 Seroprevalence Between Paramedics and Matched Blood Donors in Canada During the COVID-19 Pandemic.

STUDY OBJECTIVE: SARS-CoV-2 represents an occupational risk to paramedics, who work in uncontrolled environments. We sought to identify the occupation-specific risk to paramedics by comparing their seroprevalence of SARS-CoV-2 infection-specific antibodies to that of blood donors in Canada. METHODS: In this prospective cohort study, we performed serology testing (Elecsys Anti-SARS-CoV-2 nucleocapsid assay) on samples from paramedics and blood donors (January to July 2021) in Canada. Paramedic samples were compared to blood donor samples through 1:1-matched (based on age, sex, location, date of blood collection, and vaccination status) and raking weighted comparisons. We compared the seroprevalence with a risk difference (and 95% confidence interval [CI]) and performed secondary analyses within subgroups defined by vaccination status. RESULTS: The 1:1 match included 1,627 cases per group; in both groups, 723 (44%) were women, with a median age of 38. The raking weighted comparison included 1,713 paramedic samples and 19,515 blood donor samples, with similar characteristics. In the 1:1 match, the seroprevalence was similar (difference 1.2; 95% CI -0.20 to 2.7) between paramedics (5.2%) and blood donors (3.9%). The raking weighted comparison was consistent (difference 0.97; 95% CI -0.10 to 2.0). The unvaccinated paramedic samples, in comparison to the blood donor samples, demonstrated a higher seroprevalence in the 1:1 (difference 5.9; 95% CI 1.8 to 10) and weighted (difference 6.5; 95% CI 1.8 to 10) comparisons. Among vaccinated cases, the between-group seroprevalence was similar. CONCLUSION: Overall, paramedics demonstrated similar evidence of prior SARS-CoV-2 infection to that of blood donors. However, among unvaccinated individuals, evidence of prior infection was higher among paramedics compared to blood donors.