Omicron incidence and seroprevalence among children in Montreal, Canada, in early 2023: final results from the longitudinal EnCORE serology study.

Since early 2022, routine testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on symptoms and exposure history has largely ceased in Canada. Consequently, seroprevalence studies, particularly longitudinal studies, have become critical for monitoring the rate of incident SARS-CoV-2 infections and the proportion of the population with evidence of immunity. EnCORE is a longitudinal SARS-CoV-2 seroprevalence study comprising five rounds of serology testing from October 2020 to June 2023, in a sample of 2- to 17-year-olds (at baseline), recruited from daycares and schools in four neighbourhoods of Montreal, Canada. We report on SARS-CoV-2 incidence and seroprevalence among the 509 participants in the fifth and final round of the study. Seroprevalence of antibodies from either infection or vaccination was 98% (95 per cent confidence interval [CI]: 97, 99). The infection-acquired seroprevalence was 78% (95% CI: 73-82), and the incidence rate was 113 per 100 person-years (95% CI: 94-132), compared to the seroprevalence of 58% and the incidence rate of 133 per 100 person-years, respectively, in the fourth round of testing (mid-late 2022). Of the 131 participants newly seropositive for infection in Round 4, only 18 were seronegative for infection in Round 5 (median follow-up: 326 days).

Increasing our knowledge about the epidemiology of Helicobacter pylori in Nunavik's Inuit population (Québec, Canada) using Qanuilirpitaa? 2017 cross-sectional survey.

Helicobacter pylori is a bacterium that may colonise and proliferate in human stomachs, leading invariably to chronic inflammation and, to a lesser extent, to peptic ulcers and cancer. The main objective of this study is to describe the epidemiology surrounding H. pylori in Nunavik's Inuit population using the 2004 and 2017 Health Surveys. Estimated prevalences were 70.9% for bacterial colonisation using a stool antigens test (SAT), 72.5% for anti-H. pylori antibodies, 12.7% for faecal occult blood in participants aged ≥ 50 and respectively of 28.4%, 11.2% and 2.4% for a prior diagnosis of colonisation, gastritis and peptic ulcer in the medical charts, with under five cases of gastric cancer reported. Variables associated with higher SAT+ prevalence were the number of household members (prevalence ratio [PR] = 1.03) and age (quadratic relationship), whereas mainly drinking municipal (PR = 0.84) and natural water (PR = 0.72) compared to bottled water, and increasing alcohol consumption (PR = 0.96) were associated with reduced prevalence. Despite current regional guidelines targeting high risk individuals in the context of high prevalence, Nunavik's health authorities must remain vigilant by following gastric cancer incidence and the rapid evolution of guidelines, while considering local realities.

SARS-CoV-2 seroprevalence and mental health of school staff: a cross-sectional study of schools from four areas of Montreal, Quebec in 2021.

OBJECTIVES: To assess the seroprevalence of infection-acquired SARS-CoV-2 and the mental health of school/daycare staff in the months after reopening of schools in Montreal, Quebec (Canada) in the Fall of 2020 and whether these varied by school and participant characteristics. DESIGN: A cross-sectional design based on a convenience sample of schools/daycares and staff was used as the originally planned longitudinal design was no longer feasible due to obstacles in recruitment, for example, teacher's strike. SETTING: Forty-nine schools/daycares in four Montreal neighbourhoods from March to October 2021. PARTICIPANTS: Three-hundred and sixty-two participants completed both questionnaires and serology tests. PRIMARY AND SECONDARY OUTCOME MEASURES: SARS-CoV-2 seroprevalence and prevalence of anxiety, depression, resilience and burnout/emotional exhaustion. RESULTS: The seroprevalence estimate made representative to the Quebec population of educators was 8.6% (95% CI 5.2 to 13.0). The adjusted seroprevalence in high school was 20% that of elementary school (aRR=0.20, 95% CI 0.07 to 0.58). Thirty per cent of seropositive staff were exposed to a household member with confirmed COVID-19. Prevalence of high emotional exhaustion/burnout was 35%, 44% and 53% in daycare, elementary school and high school staff, respectively. However, moderate/severe anxiety and depression and low resilience did not exceed 18%. After adjusting for confounders, being very afraid of catching COVID-19 at school was associated with moderate-severe anxiety, moderate-severe depression and high emotional exhaustion (aRR=4.4, 95% CI 2.2 to 8.9; aRR=2.8, 95% CI 1.5 to 5.4; aRR=2.2, 95% CI 1.6 to 3.0, respectively). CONCLUSION: The seroprevalence, anxiety and depression among school/daycare staff were comparable to the reported levels in the adult population of Quebec. The prevalence of emotional exhaustion/burnout was high across all school levels and exceeding the average across all occupations in the USA and in teachers in Germany.

Impact of recruitment strategies on individual participation practices in the Canadian National Vaccine Safety Network: prospective cohort study.

Background: The Canadian National Vaccine Safety (CANVAS) network conducted a multi-center, prospective vaccine safety study to collect safety data after dose 1 and 2 of COVID-19 vaccines and follow up safety information 7 months after dose 1. Objective: This study aimed to describe and evaluate the recruitment methods used by CANVAS and the retention of participants by each modality. Methods: CANVAS deployed a multi-pronged recruitment approach to reach a larger sample, without in-person recruitment. Three primary recruitment strategies were used: passive recruitment, technology-assisted electronic invitation through the vaccine booking system (auto-invitation), or auto-registration through the vaccine registries (auto-enrollment). Results: Between December 2020 and April 2022, approximately 1.3 million vaccinated adults either self-enrolled or were auto-enrolled in CANVAS, representing about 5% of the vaccinated adult Canadian population. Approximately 1 million participants were auto-enrolled, 300,000 were recruited by auto-invitation, and 5,000 via passive recruitment. Overall survey completion rates for dose 1, dose 2 and the 7-month follow-up surveys were 51.7% (681,198 of 1,318,838), 54.3% (369,552 of 681,198), and 66.4% (452,076 of 681,198), respectively. Completion rates were lower among auto-enrolled participants compared to passively recruited or auto-invited participants who self-enrolled. However, auto-enrolled samples were much larger, which offset the lower completion rates. Conclusion: Our data suggest that auto-enrollment provided an opportunity to reach and retain a larger number of individuals in the study compared to other recruitment modalities.

Incidence of SARS-CoV-2 during the Omicron wave: Results of a longitudinal serosurvey in Québec, Canada.

OBJECTIVES: Conventional serological approaches lack sensitivity for the detection of recent SARS-CoV-2 infections in vaccinated individuals, as these individuals exhibit a blunted anti-nucleocapsid (N) response. This limitation was recently addressed by the development of a "ratio-based approach", which compares longitudinally collected specimens. Here, we used this approach to estimate the incidence of SARS-CoV-2 infection and reinfection in Québec (Canada) during the Omicron wave. METHODS: Consenting plasma donors were included if they donated plasma before December 15, 2021 and during six consecutive periods of ~ 3 months between December 15, 2021 and July 7, 2023 (study period). Anti-N levels were measured with an enzyme-linked immunosorbent assay, and seroconversion was characterized by a ratio of ≥ 1.5 between the optical density of two consecutive samples. RESULTS: Among the 254 donors, the adjusted proportion of donors (95% confidence interval [CI]) with a new infection ranged between 18.1% (13.2‒23.0) and 24.2% (18.8‒29.7) over Periods 1-5 and fell to 7.9% (4.9‒11.0) during Period 6. During the study period, the proportion of newly infected donors decreased among those aged < 60 (Period 1 = 31.6%, Period 5 = 4.4%), but increased among those aged ≥ 70 (Period 1 = 0.3%, Period 6 = 10.3%). Throughout the study period, 72 (28.3%) reinfections occurred, including two seroconversion events in a single donor. Overall, 87.4% (95% CI = 82.7‒91.2) were infected by SARS-CoV-2 at least once during the study period. CONCLUSION: The vast majority of the Québec population may have been infected during the Omicron wave. This longitudinal survey demonstrates the usefulness of the "ratio-based approach" for identifying both new infections and reinfections in a vaccinated population.

RéSUMé: OBJECTIFS: Les approches sérologiques classiques démontrent un manque de sensibilité pour la détection des infections récentes par le SRAS-CoV-2 chez les personnes vaccinées, car ces dernières présentent une réponse anti-nucléocapside (N) peu élevée. Cette limitation a été récemment surmontée suite au développement d'une « approche basée sur les ratios ¼, qui compare des échantillons collectés de manière longitudinale. Nous avons utilisé cette approche pour estimer l'incidence de l'infection et de la réinfection par le SRAS-CoV-2 au Québec (Canada) pendant la vague Omicron. MéTHODES: Les donneurs de plasma consentants étaient inclus dans l'étude s'ils avaient donné du plasma avant le 15 décembre 2021 et pendant six périodes consécutives de 2 à 3 mois entre le 15 décembre 2021 et le 7 juillet 2023 (période d'étude). Les taux d'anti-N ont été mesurés par ELISA et la séroconversion a été caractérisée par un rapport ≥ 1,5 entre la densité optique de deux échantillons consécutifs. RéSULTATS: Parmi les 254 donneurs, le risque ajusté (IC 95 %) d'infection a varié entre 18,1 % (13,2‒23,0) et 24,2 % (18,8‒29,7) au cours des périodes 1 à 5 et a chuté à 7,9 % (4,9‒11,0) au cours de la période 6. Au cours de la période d'étude, le risque d'infection a diminué chez les donneurs âgés de moins de 60 ans (période 1 = 31,6 %, période 5 = 4,4 %), mais a augmenté chez ceux âgés de ≥ 70 ans (période 1 = 0,3 %, période 6 = 10,3 %). Tout au long de la période d'étude, 72 (28,3 %) réinfections se sont produites (c'est-à-dire deux événements de séroconversion chez un même donneur). Dans l'ensemble, 87,4 % (IC 95 % = 82,7‒91,2) ont été infectés par le SRAS-CoV-2 au moins une fois au cours de la période d'étude. CONCLUSION: La grande majorité de la population québécoise pourrait avoir été infectée lors de la vague Omicron. Cette enquête longitudinale démontre l'utilité de l'approche basée sur les ratios pour identifier les nouvelles infections et les réinfections dans une population vaccinée.

Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study.

BACKGROUND: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. METHODS: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. RESULTS: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. CONCLUSIONS: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

mRNA COVID-19 vaccine safety among older adults from the Canadian National Vaccine Safety Network.

This study examined short-to-medium term safety of COVID-19 vaccines among adults aged ≥65 years using the Canadian National Vaccine Safety Network active safety surveillance data. Both vaccinated and unvaccinated older adult participants recruited from seven provinces and territories were included in the analysis. Safety was assessed at 7 days after COVID-19 vaccination (dose 1, 2 and 3), and 7 months after dose 1. Multivariable logistic regression was used to examine the association between BNT162b2/mRNA-1273 COVID-19 vaccines and two short-term health events: 1) health event preventing daily activities and/or required medical consultation, 2) serious health events resulting in an emergency department visit and/or hospitalization within 7 days following each dose. We also assessed the rates of serious health events for the period between dose 1 and 2, and 7-months following dose 1. Between December 2020 and February 2022, a total of 173,038, 104,452, and 13,970 older adults completed dose 1, dose 2, and dose 3 surveys, respectively. The control survey was completed by 2,955 unvaccinated older adults. Health events occurred more frequently among recipients after dose 2 homologous mRNA-1273 (adjusted odds ratio [95 % confidence interval]: 2.91 [2.24-3.79]) and dose two heterologous (BNT162b2 followed by mRNA-1273): 1.50 [1.12-2.02] compared to unvaccinated counterparts. There was no difference in event rates after any dose of BNT162b2 and unvaccinated participants. The rates of serious health events following COVID-19 vaccination were very low (≤0.3 %) across all vaccine products and doses, and were not higher compared to unvaccinated controls, and were not associated with an emergency department visit or hospitalization within 7 days following vaccination. Reported symptoms were self-limited and rarely required medical assessment. Our findings further strengthen the current evidence that mRNA COVID-19 vaccines are safe and can be used to inform older adults about expected adverse events following COVID-19 vaccination.

Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

A multiprovincial retrospective analysis of the incidence of myocarditis or pericarditis after mRNA vaccination compared to the incidence after SARS-CoV-2 infection.

Objective: To compare myocarditis/pericarditis risk after COVID-19 mRNA vaccination versus SARS-CoV-2 infection, and to assess if myocarditis/pericarditis risk varies by vaccine dosing interval. Methods: In this retrospective cohort study, we used linked databases in Quebec, Ontario, and British Columbia between January 26, 2020, and September 9, 2021. We included individuals aged 12 or above who received an mRNA vaccine as the second dose or were SARS-CoV-2-positive by RT-PCR. The outcome was hospitalization/emergency department visit for myocarditis/pericarditis within 21 days of exposure. We calculated age- and sex-stratified incidence ratios (IRs) of myocarditis/pericarditis following mRNA vaccination versus SARS-CoV-2 infection. We also calculated myocarditis/pericarditis incidence by vaccine type, homologous/heterologous schedule, and dosing interval. We pooled province-specific estimates using meta-analysis. Results: Following 18,860,817 mRNA vaccinations and 860,335 SARS-CoV-2 infections, we observed 686 and 160 myocarditis/pericarditis cases, respectively. Myocarditis/pericarditis incidence was lower after vaccination than infection (IR [BNT162b2/SARS-CoV-2], 0.14; 95%CI, 0.07-0.29; IR [mRNA-1273/SARS-CoV-2], 0.28; 95%CI, 0.20-0.39). Within the vaccinated cohort, myocarditis/pericarditis incidence was lower with longer dosing intervals; IR (56 or more days/15-30 days) was 0.28 (95%CI, 0.19-0.41) for BNT162b2 and 0.26 (95%CI, 0.18-0.38) for mRNA-1273. Conclusion: Myocarditis/pericarditis risk was lower after mRNA vaccination than SARS-CoV-2 infection, and with longer intervals between primary vaccine doses.

Test negative design for vaccine effectiveness estimation in the context of the COVID-19 pandemic: A systematic methodology review.

BACKGROUND: During the height of the global COVID-19 pandemic, the test-negative design (TND) was extensively used in many countries to evaluate COVID-19 vaccine effectiveness (VE). Typically, the TND involves the recruitment of care-seeking individuals who meet a common clinical case definition. All participants are then tested for an infection of interest. OBJECTIVES: To review and describe the variation in TND methodology, and disclosure of potential biases, as applied to the evaluation of COVID-19 VE during the early vaccination phase of the pandemic. METHODS: We conducted a systematic review by searching four biomedical databases using defined keywords to identify peer-reviewed articles published between January 1, 2020, and January 25, 2022. We included only original articles that employed a TND to estimate VE of COVID-19 vaccines in which cases and controls were evaluated based on SARS-CoV-2 laboratory test results. RESULTS: We identified 96 studies, 35 of which met the defined criteria. Most studies were from North America (16 studies) and targeted the general population (28 studies). Outcome case definitions were based primarily on COVID-19-like symptoms; however, several papers did not consider or specify symptoms. Cases and controls had the same inclusion criteria in only half of the studies. Most studies relied upon administrative or hospital databases assembled for a different (non-evaluation) clinical purpose. Potential unmeasured confounding (20 studies), misclassification of current SARS-CoV-2 infection (16 studies) and selection bias (10 studies) were disclosed as limitations by some studies. CONCLUSION: We observed potentially meaningful deviations from the validated design in the application of the TND during the COVID-19 pandemic.

Effectiveness of BNT162b2 Vaccine Against Omicron-SARS-CoV-2 Subvariants in Children 5-11 Years of Age in Quebec, Canada, January 2022 to January 2023.

BACKGROUND: In premarketing clinical trials conducted before Omicron emergence, BNT162b2 vaccine efficacy against COVID-19 was 90% in children. We conducted postmarketing evaluation of 1- and 2-dose vaccine effectiveness (VE) against Omicron BA.1, BA.2 and BA.4/5 subvariants in 5- to 11-year olds. METHODS: We estimated VE against SARS-CoV-2 infection using a test-negative design. Specimens collected between January 9, 2022, and January 7, 2023, from children 5-11 years old in Quebec, Canada, and tested by nucleic acid amplification test were eligible. We estimated VE by time since last vaccine dose, interval between doses and by period of Omicron subvariant predominance. RESULTS: A total of 48,826 NAATs were included in overall analysis. From 14-55 to 56-385 days postvaccination, 2-dose VE against symptomatic infection decreased from 68% (95% CI, 62-74) to 25% (95% CI, 11-36). Two-dose VE with restriction to specimens collected from acute care hospitals (emergency rooms or wards) did not decline but was stable at ~40%. VE against symptomatic infection remained comparable at any interval between doses but increased with longer interval among children tested in acute care settings, from 18% (95% CI, -17 to 44) with 21- to 55-day interval to 69% (95% CI, 43-86) with ≥84-day interval. Two-dose VE against symptomatic infection dropped from 70% (95% CI, 63-76) during BA.1, to 32% (95% CI, 13-47) with BA.2 and to nonprotective during BA.4/5 dominance. CONCLUSIONS: In children 5-11 years of age, VE against symptomatic infection was stable at any interval between doses but decreased with time since the last dose and against more divergent omicron subvariants.

Single-dose Effectiveness of Mpox Vaccine in Quebec, Canada: Test-negative Design With and Without Adjustment for Self-reported Exposure Risk.

INTRODUCTION: During the 2022 mpox outbreak, the province of Quebec, Canada, prioritized first doses for pre-exposure vaccination of people at high mpox risk, delaying second doses due to limited supply. We estimated single-dose mpox vaccine effectiveness (VE) adjusting for virus exposure risk based only on surrogate indicators available within administrative databases (eg, clinical record of sexually transmitted infections) or supplemented by self-reported risk factor information (eg, sexual contacts). METHODS: We conducted a test-negative case-control study between 19 June and 24 September 2022. Information from administrative databases was supplemented by questionnaire collection of self-reported risk factors specific to the 3-week period before testing. Two study populations were assessed: all within the administrative databases (All-Admin) and the subset completing the questionnaire (Sub-Quest). Logistic regression models adjusted for age, calendar-time and exposure-risk, the latter based on administrative indicators only (All-Admin and Sub-Quest) or with questionnaire supplementation (Sub-Quest). RESULTS: There were 532 All-Admin participants, of which 199 (37%) belonged to Sub-Quest. With exposure-risk adjustment based only on administrative indicators, single-dose VE estimates were similar among All-Admin and Sub-Quest populations at 35% (95% confidence interval [CI]:-2 to 59) and 30% (95% CI:-38 to 64), respectively. With adjustment supplemented by questionnaire information, the Sub-Quest VE estimate increased to 65% (95% CI:1-87), with overlapping confidence intervals. CONCLUSIONS: Using only administrative data, we estimate one vaccine dose reduced the mpox risk by about one-third; whereas, additionally adjusting for self-reported risk factor information revealed greater vaccine benefit, with one dose instead estimated to reduce the mpox risk by about two-thirds. Inadequate exposure-risk adjustment may substantially under-estimate mpox VE.

Influenza Hospitalization Burden by Subtype, Age, Comorbidity, and Vaccination Status: 2012-2013 to 2018-2019 Seasons, Quebec, Canada.

BACKGROUND: Influenza immunization programs aim to reduce the risk and burden of severe outcomes. To inform optimal program strategies, we monitored influenza hospitalizations over 7 seasons, stratified by age, comorbidity, and vaccination status. METHODS: We assembled data from 4 hospitals involved in an active surveillance network with systematic collection of nasal samples and polymerase chain reaction testing for influenza virus in all patients admitted through the emergency department with acute respiratory infection during the 2012-2013 to 2018-2019 influenza seasons in Quebec, Canada. We estimated seasonal, population-based incidence of influenza-associated hospitalizations by subtype predominance, age, comorbidity, and vaccine status, and derived the number needed to vaccinate to prevent 1 hospitalization per stratum. RESULTS: The average seasonal incidence of influenza-associated hospitalization was 89/100 000 (95% confidence interval, 86-93), lower during A(H1N1) (49-82/100 000) than A(H3N2) seasons (73-143/100 000). Overall risk followed a J-shaped age pattern, highest among infants 0-5 months and adults ≥75 years old. Hospitalization risks were highest for children <5 years old during A(H1N1) but for highest adults aged ≥75 years during A(H3N2) seasons. Age-adjusted hospitalization risks were 7-fold higher among individuals with versus without comorbid conditions (214 vs 30/100 000, respectively). The number needed to vaccinate to prevent hospitalization was 82-fold lower for ≥75-years-olds with comorbid conditions (n = 1995), who comprised 39% of all hospitalizations, than for healthy 18-64-year-olds (n = 163 488), who comprised just 6% of all hospitalizations. CONCLUSIONS: In the context of broad-based influenza immunization programs (targeted or universal), severe outcome risks should be simultaneously examined by subtype, age, comorbidity, and vaccine status. Policymakers require such detail to prioritize promotional efforts and expenditures toward the greatest and most efficient program impact.

Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent COVID-19: A Prospective Observational Cohort Study.

BACKGROUND: There is a need to understand the duration of infectivity of primary and recurrent coronavirus disease 2019 (COVID-19) and identify predictors of loss of infectivity. METHODS: Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US Centers for Disease Control and Prevention (CDC) criteria (fever resolution, symptom improvement, and negative RADT) to predict loss of infectivity was also investigated. RESULTS: In total, 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n = 107, 88.4%) had received ≥3 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 odds ratio [OR], 0.14; P < .001]; day 7 OR, 0.04; P = .003]) and were all non-infective by day 10 (P = .02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; P = .003), an RT-PCR cycle threshold [Ct] value <23 (aOR on day 5, 22.75; P < .001) but not symptom improvement or RADT result.The CDC criteria would identify 36% (24/67) of all non-infectious individuals on day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. CONCLUSIONS: Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.

SARS-CoV-2 infection among healthcare workers: the role of occupational and household exposures during the first three pandemic waves in Quebec, Canada.

Objective: We described the evolution of SARS-CoV-2 source of infection in a cohort of healthcare workers (HCWs) of Quebec, Canada, during the first three pandemic waves. We also estimated their household secondary attack rate (SAR) and its risk factors. Design: Cross-sectional surveys. Participants: HCWs with a SARS-CoV-2 infection confirmed by polymerasa chain reaction and diagnosed between March 2020 and May 2021. Methods: We collected demographic, clinical, vaccination, and employment information, self-reported perceived source of infection, and transmission to household members during the first three pandemic waves. SAR was calculated for households with ≥2 members where the HCW was the index case. A Poisson regression model estimated the association between risk factors and SAR. Results: Among the 11,670 HCWs completing the survey, 91%, perceived their workplace as the source of infection during the first wave (March-July 2020), 71% during the second wave (July 2020-March 2021), and 40% during the third wave (March-May 2021). Conversely, HCWs reported an increasing proportion of household-acquired infections with each wave from 4% to 14% and 33%, respectively. The overall household SAR of 7,990 HCWs living with ≥1 person was 30% (95%CI: 29-30). SAR increased with the presence of symptoms, older age, and during Alpha-variant predominant period. Conclusions: HCWs and their household members were largely affected during the first pandemic waves of COVID-19, but the relative importance of occupational exposure changed overtime. Pandemic preparedness in healthcare settings is essential to protect HCWs from emerging biological hazard exposures.

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules?

BACKGROUND: In 2019, the 3 + 1 schedule for children's vaccination (2-4-6-18 months old) was changed for a reduced 2 + 1 schedule (2-4-12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. METHODS: We conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children's blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. RESULTS: A total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65-0.90), 0.66 (0.55-0.79), 0.72 (0.52-0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. CONCLUSION: Infant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children's protection.

Factors associated with intention for revaccination among patients with adverse events following immunization.

OBJECTIVES: Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. METHODS: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. RESULTS: Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]). CONCLUSION: Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.

Infection-induced seroconversion and seroprevalence of SARS-CoV-2 among a cohort of children and youth in Montreal, Canada.

The EnCORE study is a prospective serology study of SARS-CoV-2 in a cohort of children from Montreal, Canada. Based on data from our fourth round of data collection (May-October 2022), we estimated SARS-CoV-2 seroprevalence and seroconversion. Using multivariable regression, we identified factors associated with seroconversion. Our results show that previously seronegative children were approximately 9-12 times more likely to seroconvert during the early Omicron-dominant period compared to pre-Omicron rounds. Unlike the pre-Omicron rounds, the adjusted rate of seroconversion among 2- to 4-year-olds was higher than older age groups. As seen previously, higher seroconversion rates were associated with ethnic/racial minority status.

Effectiveness of previous infection-induced and vaccine-induced protection against hospitalisation due to omicron BA subvariants in older adults: a test-negative, case-control study in Quebec, Canada.

BACKGROUND: Older adults (aged ≥60 years) were prioritised for COVID-19 booster vaccination due to severe outcome risk, but the risk for this group is also affected by previous SARS-CoV-2 infection and vaccination. We estimated vaccine effectiveness against omicron-associated hospitalisation in older adults by previously documented infection, time since last immunological event, and age group. METHODS: This was a population-based test-negative case-control study done in Quebec, Canada, during BA.1 dominant (December, 2021, to March, 2022), BA.2 dominant (April to June, 2022), and BA.4/5 dominant (July to November, 2022) periods using provincial laboratory, immunisation, hospitalisation, and chronic disease surveillance databases. We included older adults (aged ≥60 years) with symptoms associated with COVID-19 who were tested for SARS-CoV-2 in acute-care hospitals. Cases were defined as patients who were hospitalised for COVID-19 within 14 days after testing positive; controls were patients who tested negative. Analyses spanned 3-14 months after last vaccine dose or previous infection. Logistic regression models compared COVID-19 hospitalisation risk by mRNA vaccine dose and previous infection versus unvaccinated and infection-naive participants. FINDINGS: Between Dec 26, 2021, and Nov 5, 2022, we included 174 819 specimens (82 870 [47·4%] from men and 91 949 [52·6%] from women; from 8455 cases and 166 364 controls), taken from 2951 cases and 48 724 controls in the BA.1 period; 1897 cases and 41 702 controls in the BA.2 period; and 3607 cases and 75 938 controls in the BA.4/5 period. In participants who were infection naive, vaccine effectiveness against hospitalisation improved with dose number, consistent with a shorter median time since last dose, but decreased with more recent omicron subvariants. Four-dose vaccine effectiveness was 96% (95% CI 93-98) during the BA.1 period, 84% (81-87) during the BA.2 period, and 68% (63-72) during the BA.4/5 period. Regardless of dose number (two to five doses) or timing since previous infection, hybrid protection was more than 90%, persisted for at least 6-8 months, and did not decline with age. INTERPRETATION: Older adults with both previous SARS-CoV-2 infection and two or more vaccine doses appear to be well protected for a prolonged period against hospitalisation due to omicron subvariants, including BA.4/5. Ensuring that older adults who are infection naive remain up to date with vaccination might reduce COVID-19 hospitalisations most efficiently. FUNDING: Ministère de la Santé et des Services Sociaux du Québec. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and teenagers in Montréal, Canada.

OBJECTIVES: To use serological testing to assess the pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montréal, Canada. DESIGN: This analysis is from a prospective cohort study of children aged 2-17 years (at baseline) that included blood spots for antibody detection. The serostatus of participants was determined by enzyme-linked immunosorbent assays using the receptor-binding domain from the spike protein and the nucleocapsid protein as antigens. We estimated seroprevalence, seroconversion rates, and the likelihood of seroreversion at 6 months and 1 year. RESULTS: The baseline (October 2020 to April 2021) seroprevalence was 5.8% (95% confidence interval [CI] 4.8-7.1), which increased to 10.5% (May to September 2021) and 11.0% (November 2021 to March 2022) for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The crude rate of seroconversion over the study period was 12.8 per 100 person-years (95% CI 11.0-14.7). The adjusted hazard rates of seroconversion by child characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes in the lowest tercile of our study population. The likelihood of remaining seropositive at 6 months was 68% (95% CI 60-77%) and dropped to 42% (95% CI 32-56%) at 1 year. CONCLUSION: Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels after infection.