Impact of chronic comorbidities on hospitalization, intensive care unit admission and death among adult vaccinated and unvaccinated COVID-19 confirmed cases during the Omicron wave.

Background: Comorbidities are important risk factors of severe COVID-19 complications. Their impact during the Omicron wave among vaccinated and unvaccinated COVID-19 cases is not well documented. Purpose: The objective of this study was to estimate the association between the number of comorbidities and the risk of hospitalization, intensive care unit (ICU) admission, and death among vaccinated and unvaccinated confirmed adult COVID-19 cases during the Omicron wave. Research Design and Study sample: We performed a cohort study of COVID-19 adult cases of primo-infection occurring during the Omicron wave, from December 5, 2021 to January 9, 2022 using surveillance database of the province of Québec, Canada. The database included all laboratory-confirmed cases in the province and the related information on 21 pre-existing comorbidities, hospitalization, ICU admission, death related to COVID-19 and vaccination status. Analysis: We performed a robust Poisson regression model to estimate the impact of the number of comorbidities on each complication by vaccination status adjusted for age, sex, socioeconomic status, and living environment. Results: We observed that the risk of complication increased for each additional comorbidity in both vaccinated and unvaccinated individuals and that this risk was systematically higher among unvaccinated individuals. Compared with vaccinated individuals without comorbidities (reference group), the risks of hospitalization, ICU admission, and death were respectively: 9X (95% CI [7.77-12.01]), 13X (95% CI [8.74-18.87]), and 12X (95% CI [7.57-18.91]) higher in vaccinated individuals with ≥3 comorbidities; 22X (95% CI [19.07-25.95]), 45X (95% CI [29.06-69.67]) and 38X (95% CI [23.62-61.14]) higher in unvaccinated individuals with ≥3 comorbidities. Conclusion: Our results support the importance of promoting vaccination in all individuals, and especially those with pre-existing medical conditions, to reduce severe complications, even during the Omicron wave.

Protection against omicron (B.1.1.529) BA.2 reinfection conferred by primary omicron BA.1 or pre-omicron SARS-CoV-2 infection among health-care workers with and without mRNA vaccination: a test-negative case-control study.

BACKGROUND: There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination. METHODS: We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection. FINDINGS: 258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47-63), two (69%, 64-73), or three (70%, 66-74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65-78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95-96), but was not improved with a third dose (96%, 95-97). INTERPRETATION: Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant. FUNDING: Ministère de la Santé et des Services Sociaux du Québec.

Estimated Protection of Prior SARS-CoV-2 Infection Against Reinfection With the Omicron Variant Among Messenger RNA-Vaccinated and Nonvaccinated Individuals in Quebec, Canada.

Importance: The Omicron variant is phylogenetically and antigenically distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron reinfection, with and without vaccination, requires quantification. Objective: To estimate the protection against Omicron reinfection and hospitalization conferred by prior heterologous non-Omicron SARS-CoV-2 infection and/or up to 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine. Design, Setting, and Participants: This test-negative, population-based case-control study was conducted between December 26, 2021, and March 12, 2022, and included community-dwelling individuals aged 12 years or older who were tested for SARS-CoV-2 infection in the province of Quebec, Canada. Exposures: Prior laboratory-confirmed SARS-CoV-2 infection with or without mRNA vaccination. Main Outcomes and Measures: The main outcome was laboratory-confirmed SARS-CoV-2 reinfection and associated hospitalization, presumed to be associated with the Omicron variant according to genomic surveillance. The odds of prior infection with or without vaccination were compared for case participants with Omicron infection and associated hospitalizations vs test-negative control participants. Estimated protection was derived as 1 - the odds ratio, adjusted for age, sex, testing indication, and epidemiologic week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results: This study included 696 439 individuals (224 007 case participants and 472 432 control participants); 62.2% and 63.9% were female and 87.4% and 75.5% were aged 18 to 69 years, respectively. Prior non-Omicron SARS-CoV-2 infection was detected for 9505 case participants (4.2%) and 29 712 control participants (6.3%). Among nonvaccinated individuals, prior non-Omicron infection was associated with a 44% reduction (95% CI, 38%-48%) in Omicron reinfection risk, which decreased from 66% (95% CI, 57%-73%) at 3 to 5 months to 35% (95% CI, 21%-47%) at 9 to 11 months postinfection and was below 30% thereafter. The more severe the prior infection, the greater the risk reduction. Estimated protection (95% CI) against Omicron infection was consistently significantly higher among vaccinated individuals with prior infection compared with vaccinated infection-naive individuals, with 65% (63%-67%) vs 20% (16%-24%) for 1 dose, 68% (67%-70%) vs 42% (41%-44%) for 2 doses, and 83% (81%-84%) vs 73% (72%-73%) for 3 doses. For individuals with prior infection, estimated protection (95% CI) against Omicron-associated hospitalization was 81% (66%-89%) and increased to 86% (77%-99%) with 1, 94% (91%-96%) with 2, and 97% (94%-99%) with 3 mRNA vaccine doses, without signs of waning. Conclusions and Relevance: The findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization. In the context of program goals to prevent severe outcomes and preserve health care system capacity, a third mRNA vaccine dose may add limited protection in twice-vaccinated individuals with prior SARS-CoV-2 infection.

Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada.

BACKGROUND: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada's larger provinces. METHODS: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22-47) 2021. RESULTS: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7-8-week versus manufacturer-specified 3-4-week intervals between mRNA doses. CONCLUSIONS: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

Impact of the first vaccine dose on COVID-19 and its complications in long-term care facilities and private residences for seniors in Québec, Canada.

Background: Residents of long-term care facilities (LTCFs) and private residences for seniors (PRSs) were given priority for vaccination against coronavirus disease 2019 (COVID-19). Given the shortage of vaccine in the winter of 2021, the Comité sur l'immunisation du Québec recommended postponing the administration of second doses to ensure more rapid and widespread administration of first doses. The objective of this study was to measure the impact of first-dose vaccination on 1) the incidence of cases and complications in LTCFs and PRSs and 2) the frequency of outbreaks in LTCFs. Methods: In this ecological study, COVID-19 incidence and complications in residents of LTCFs and PRSs in Québec were compared with the general (community) population at a point in time when there was still only limited eligibility for vaccination. Results: After vaccination in LTCFs, the incidence rate of COVID-19 decreased by 92% compared with 49% in the community, and deaths decreased by 95%. By six weeks post-vaccination, almost no facility reported five or more cases per 100 beds per week. The incidence rate decreased by 91% in PRSs compared with 2% in the community. Hospitalizations and deaths in PRSs decreased by 94% and 90%, respectively. Conclusion: As a result of 1) vaccination of residents with one dose, 2) natural immunity already acquired in LTCFs and PRSs, 3) vaccination of healthcare workers and 4) other non-pharmaceutical prevention measures implemented, the circulation of the coronavirus in these settings was largely interrupted.

Exploring the associations between polypharmacy and COVID-19-related hospitalisations and deaths: a population-based cohort study among older adults in Quebec, Canada.

OBJECTIVES: To study the association between polypharmacy and the risk of hospitalisation and death in cases of COVID-19 in the population over the age of 65. DESIGN: Population-based cohort study. SETTING: Quebec Integrated Chronic Disease Surveillance System, composed of five medico-administrative databases, in the province of Quebec, Canada. PARTICIPANTS: 32 476 COVID-19 cases aged over 65 whose diagnosis was made between 23 February 2020 and 15 March 2021, and who were covered by the public drug insurance plan (thus excluding those living in long-term care). We counted the number of different medications they claimed between 1 April 2019 and 31 March 2020. OUTCOME MEASURES: Robust Poisson regression was used to calculate relative risk of hospitalisation and death associated with the use of multiple medications, adjusting for age, sex, chronic conditions, material and social deprivation and living environment. RESULTS: Of the 32 476 COVID-19 cases included, 10 350 (32%) were hospitalised and 4146 (13%) died. Compared with 0-4 medications, polypharmacy exposure was associated with increased hospitalisations, with relative risks ranging from 1.11 (95% CI 1.04 to 1.19) for those using 5-9 medications to 1.62 (95% CI 1.51 to 1.75) for those using 20+. Similarly, the risk of death increased with the number of medications, from 1.13 (95% CI 0.99 to 1.30) for those using (5-9 medications to 1.97 (95% CI 1.70 to 2.27) (20+). Increased risk was mainly observed in younger groups. CONCLUSIONS: Polypharmacy was significantly associated with the risk of hospitalisations and deaths related to COVID-19 in this cohort of older adults. Polypharmacy may represent a marker of vulnerability, especially for younger groups of older adults.

Single-Dose Messenger RNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Workers Extending 16 Weeks Postvaccination: A Test-Negative Design From Québec, Canada.

BACKGROUND: In Canada, first and second doses of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were uniquely spaced 16 weeks apart. We estimated 1- and 2-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Québec, Canada, including protection against varying outcome severity, variants of concern (VOCs), and the stability of single-dose protection up to 16 weeks postvaccination. METHODS: A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly matched (10:1), randomly sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by 1 dose ≥14 days or 2 doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. RESULTS: Primary analysis included 5316 cases and 53 160 controls. Single-dose VE was 70% (95% confidence interval [CI], 68%-73%) against SARS-CoV-2 infection; 73% (95% CI, 71%-75%) against illness; and 97% (95% CI, 92%-99%) against hospitalization. Two-dose VE was 86% (95% CI, 81%-90%) and 93% (95% CI, 89%-95%), respectively, with no hospitalizations. VE was higher for non-VOCs than VOCs (73% Alpha) among single-dose recipients but not 2-dose recipients. Across 16 weeks, no decline in single-dose VE was observed, with appropriate stratification based upon prioritized vaccination determined by higher vs lower likelihood of direct patient contact. CONCLUSIONS: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least 4 months postvaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy.

Relative Severity of Common Human Coronaviruses and Influenza in Patients Hospitalized With Acute Respiratory Infection: Results From 8-Year Hospital-Based Surveillance in Quebec, Canada.

BACKGROUND: Few data exist concerning the role of common human coronaviruses (HCoVs) in patients hospitalized for acute respiratory infection (ARI) and the severity of these infections compared with influenza. METHODS: Prospective data on the viral etiology of ARI hospitalizations during the peaks of 8 influenza seasons (from 2011-2012 to 2018-2019) in Quebec, Canada, were used to compare patients with HCoV and those with influenza infections; generalized estimation equations models were used for multivariate analyses. RESULTS: We identified 340 HCoV infections, which affected 11.6% of children (n = 136) and 5.2% of adults (n = 204) hospitalized with ARI. The majority of children (75%) with HCoV infections were also coinfected with other respiratory viruses, compared with 24% of the adults (P < .001). No deaths were recorded in children; 5.8% of adults with HCoV monoinfection died, compared with 4.2% of those with influenza monoinfection (P = .23). The risk of pneumonia was nonsignificantly lower in children with HCoV than in those with influenza, but these risks were similarly high in adults. Markers of severity (length of stay, intensive care unit admissions, and case-fatality ratio) were comparable between these infections in multivariate analyses, in both children and adults. CONCLUSIONS: In children and adults hospitalized with ARI, HCoV infections were less frequent than influenza infections, but were as severe as influenza monoinfections.

Respiratory tract samples collected from patients in a region of Quebec, Canada, indicate the absence of early circulation of SARS-CoV-2 infection.

Background: The first documented case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Quebec was confirmed on February 27, 2020. Retracing the first cases that occur within a geographical region may provide insight regarding the evolution and spread of SARS-CoV-2 in that region because the spread of undiagnosed cases may facilitate the initial community amplification of the virus. Methods: We performed a retrospective analysis of respiratory tract samples collected for influenza testing in a region of Quebec, Canada, to look for evidence of early circulation of SARS-CoV-2. Frozen nucleic acid extracts initially collected for influenza testing between January 1 and February 20, 2020, were tested for SARS-CoV-2 using a reverse transcription-polymerase chain reaction assay. Results: During the study period, 1,440 of 2,121 (67.9%) nucleic acid extracts from individual patients were available for retrospective testing. None of the samples tested positive for SARS-CoV-2. Conclusions: The results suggest that SARS-CoV-2 was not circulating within the region before February 20, 2020, because many samples, representing more than two-thirds of all samples tested for influenza during early 2020, were tested. Further studies using a similar methodology to determine the date of onset of SARS-CoV-2 in different countries and geographic areas could enhance our understanding of the current pandemic.

Historique: Le premier cas démontré d'infection par le syndrome respiratoire aigu sévère à coronavirus 2 (SARS-CoV-2) au Québec a été confirmé le 27 février 2020. Le retraçage du premier cas survenu dans une région géographique peut donner un aperçu de l'évolution et de la propagation du virus SARS-CoV-2 dans cette région, car la transmission des cas non diagnostiqués peut favoriser l'amplification initiale du virus dans la communauté. Méthodologie: Les chercheurs ont procédé à l'analyse rétrospective des échantillons respiratoires prélevés pour le dépistage de la grippe dans une région du Québec, au Canada, afin de trouver des preuves de circulation précoce du virus SARS-CoV-2D. Les extraits d'acide nucléique congelés entre le 1er janvier et le 20 février 2020 ont été soumis au dépistage du virus SARS-CoV-2 au moyen de l'amplification en chaîne par polymérase après transcriptase inverse. Résultats: Pendant la période de l'étude, 1 440 des 2 121 extraits d'acide nucléique (67,9 %) provenant de patients différents étaient disponibles en vue de tests rétrospectifs. Aucun n'a été positif au virus SARS-CoV-2. Conclusions: D'après les résultats, le virus SARS-CoV-2 n'était pas en circulation dans la région avant le 20 février 2020, car de nombreux échantillons, représentant plus des deux tiers de tous ceux ayant servi au dépistage de la grippe au début de l'année 2020, ont été soumis au dépistage. D'autres études faisant appel à une méthodologie semblable pour déterminer la date d'apparition du virus SARS-CoV-2 dans divers pays et diverses régions géographiques pourraient permettre de mieux comprendre la pandémie en cours.