On-demand, hospital-based, severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic epidemiology to support nosocomial outbreak investigations: A prospective molecular epidemiology study.

Objectives: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings. Design and setting: This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures. Results: Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases. Conclusion: SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available. Trial registration: clinicaltrials.gov identifier: NCT05411562.

Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine.

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects' symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Séroprévalence du SRAS-CoV-2 chez les travailleurs de la santé de 10 hôpitaux du Québec, au Canada: étude transversale.

CONTEXTE: La pandémie de COVID-19 a affecté de manière disproportionnée les travailleurs de la santé. Nous avons voulu mesurer la séroprévalence du SRAS-CoV-2 chez les travailleurs de la santé dans les hôpitaux du Québec, au Canada, après la première vague de la pandémie, afin d'explorer les facteurs associés à la SRAS-CoV-2-séropositivité. MÉTHODES: Entre le 6 juillet et le 24 septembre 2020, nous avons recruté des travailleurs de la santé de 10 hôpitaux, dont 8 d'une région où l'incidence de la COVID-19 était élevée (région de Montréal) et 2 de régions du Québec où l'incidence était faible. Les travailleurs de la santé admissibles étaient des médecins, des infirmières, des préposées aux bénéficiaires et des préposés à l'entretien ménager travaillant dans 4 types d'unité de soins (urgences, soins intensifs, unité hospitalière COVID-19 et unité hospitalière non-COVID-19). Les participants ont répondu à un questionnaire et subi un dépistage sérologique du SRAS-CoV-2. Nous avons identifié les facteurs ayant un lien indépendant avec une séroprévalence plus élevée. RÉSULTATS: Parmi les 2056 travailleurs de la santé recrutés, 241 (11,7 %) se sont révélés SRAS-CoV-2-positifs. Parmi eux, 171 (71,0 %) avaient déjà reçu un diagnostic de COVID-19. La séroprévalence a varié d'un hôpital à l'autre, de 2,4 %­3,7 % dans les régions où l'incidence était faible, à 17,9 %­32,0 % dans les hôpitaux ayant connu des éclosions touchant 5 travailleurs de la santé ou plus. La séroprévalence plus élevée a été associée au fait de travailler dans un hôpital où des éclosions sont survenues (rapport de prévalence ajusté 4,16, intervalle de confiance [IC] à 95 % 2,63­6,57), au fait d'être infirmière ou auxiliaire (rapport de prévalence ajusté 1,34, IC à 95 % 1,03­1,74), préposée aux bénéficiaires (rapport de prévalence ajusté 1,49, IC à 95 % 1,12­1,97) et d'ethnicité noire ou hispanique (rapport de prévalence ajusté 1,41, IC à 95 % 1,13­1,76). La séroprévalence moindre a été associée au fait de travailler dans une unité de soins intensifs (rapport de prévalence ajusté 0,47, IC à 95 % 0,30­0,71) ou aux urgences (rapport de prévalence ajusté 0,61, IC à 95 % 0,39­0,98). INTERPRÉTATION: Les travailleurs de la santé des hôpitaux du Québec ont été exposés à un risque élevé d'infection par le SRAS-CoV-2, particulièrement lors des éclosions. Il faudra travailler à mieux comprendre la dynamique de la transmission du SRAS-CoV-2 dans les milieux de soins.

Infectivity of healthcare workers diagnosed with coronavirus disease 2019 (COVID-19) approximately 2 weeks after onset of symptoms: A cross-sectional study.

We performed viral culture of respiratory specimens in 118 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-infected healthcare workers (HCWs), ∼2 weeks after symptom onset. Only 1 HCW (0.8%) had a positive culture. No factors for prolonged viral shedding were identified. Infectivity is resolved in nearly all HCWs ∼2 weeks after symptom onset.

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec, Canada: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity. METHODS: Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence. RESULTS: Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63-6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03-1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12-1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13-1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30-0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39-0.98). INTERPRETATION: Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.