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Abstract Background The primary objective of this cross-sectional study, conducted in Québec and Bristish Columbia (Canada) between February 2021 and January 2022, was to measure the prevalence of viral RNA in oronasal and rectal swabs and serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amongst cats living in households with at least one confirmed human case. Secondary objectives included a description of potential risk factors for the presence of SARS-CoV-2 antibodies and an estimation of the association between the presence of viral RNA in swabs as well as SARS-CoV-2 antibodies and clinical signs. Oronasal and rectal swabs and sera were collected from 55 cats from 40 households at most 15 days after a human case confirmation, and at up to two follow-up visits. A RT-qPCR assay and an ELISA were used to detect SARS-CoV-2 RNA in swabs and serum SARS-CoV-2 IgG antibodies, respectively. Prevalence and 95% Bayesian credibility intervals (BCI) were calculated, and associations were evaluated using prevalence ratio and 95% BCI obtained from Bayesian mixed log-binomial models. Results Nine (0.16; 95% BCI = 0.08–0.28) and 38 (0.69; 95% BCI = 0.56–0.80) cats had at least one positive RT-qPCR and at least one positive serological test result, respectively. No risk factor was associated with the prevalence of SARS-CoV-2 serum antibodies. The prevalence of clinical signs suggestive of COVID-19 in cats, mainly sneezing, was 2.12 (95% BCI = 1.03–3.98) times higher amongst cats with detectable viral RNA compared to those without. Conclusions We showed that cats develop antibodies to SARS-CoV-2 when exposed to recent human cases, but detection of viral RNA on swabs is rare, even when sampling occurs soon after confirmation of a human case. Moreover, cats with detectable levels of virus showed clinical signs more often than cats without signs, which can be useful for the management of such cases.

Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 – June 2023 compared to the first “wave” of the outbreak in this region, which occurred April – August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in “Wave 2”, cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.

BackgroundSARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs). ObjectiveThis study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout. MethodsWe used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs. ResultsWe included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups. ConclusionsOur study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

Abstract Background Widespread human-to-human transmission of the severe acute respiratory syndrome coronavirus two (SARS-CoV-2) stems from a strong affinity for the cellular receptor angiotensin converting enzyme two (ACE2). We investigate the relationship between a patient’s nasopharyngeal ACE2 transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada. Methods Epidemiological case data from the outbreak investigations was merged with public health laboratory records and viral lineage calls, from whole genome sequencing, to reconstruct the concurrent outbreaks using infection tracing transmission network analysis. ACE2 transcription and RNA viral load were measured by quantitative real-time polymerase chain reaction. The transmission network was resolved to calculate the number of potential secondary cases. Bivariate and multivariable analyses using Poisson and Negative Binomial regression models was performed to estimate the association between ACE2 transcription the number of SARS-CoV-2 secondary cases. Results The infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on average ACE2 transcription did not differ between patients and healthcare workers (P = 0.86). High ACE2 transcription was observed in 98.6% of transmission events, either the primary or secondary case had above average ACE2. Multivariable analysis found that the association between ACE2 transcription (log2 fold-change) and the number of secondary transmission events differs between patients and healthcare workers. In health care workers Negative Binomial regression estimated that a one-unit change in ACE2 transcription decreases the number of secondary cases (β = -0.132 (95%CI: -0.255 to -0.0181) adjusting for RNA viral load. Conversely, in patients a one-unit change in ACE2 transcription increases the number of secondary cases (β = 0.187 (95% CI: 0.0101 to 0.370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship between ACE2 and secondary transmission in health care workers and confirmed the positive association among patients. Conclusion Our study suggests that ACE2 transcription has a positive association with SARS-CoV-2 secondary transmission in admitted inpatients, but not health care workers in concurrent hospital associated outbreaks, and it should be further investigated as a risk-factor for viral transmission.

In British Columbia, Canada, initial growth of the SARS-CoV-2 Delta variant was slower than that reported in other jurisdictions. Delta became the dominant variant (>50% prevalence) within ≈7–13 weeks of first detection in regions within the United Kingdom and United States. In British Columbia, it remained at

During 2006–2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population. Foodborne botulism in Indigenous communities accounted for 46% of all cases, which is down from 85% of all cases during 1990–2005. Among all cases, 52% were caused by botulinum neurotoxin type E, but types A (24%), B (16%), F (3%), and AB (1%) also occurred; 3% were caused by undetermined serotypes. Four outbreaks resulted from commercial products, including a 2006 international outbreak caused by carrot juice. Hospital data indicated that 78% of patients were transferred to special care units and 70% required mechanical ventilation; 7 deaths were reported. Botulinum neurotoxin type A was associated with much longer hospital stays and more time spent in special care than types B or E. Foodborne botulism often is misdiagnosed. Increased clinician awareness can improve diagnosis, which can aid epidemiologic investigations and patient treatment.

Abstract Background The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the accuracy and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada. Results We found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high accuracy when predicting epidemiologically informed clusters from sequence data. Conclusions Our new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.

We tested swab specimens from pets in households in Ontario, Canada, with human COVID-19 cases by quantitative PCR for SARS-CoV-2 and surveyed pet owners for risk factors associated with infection and seropositivity. We tested serum samples for spike protein IgG and IgM in household pets and also in animals from shelters and low-cost neuter clinics. Among household pets, 2% (1/49) of swab specimens from dogs and 7.7% (5/65) from cats were PCR positive, but 41% of dog serum samples and 52% of cat serum samples were positive for SARS-CoV-2 IgG or IgM. The likelihood of SARS-CoV-2 seropositivity in pet samples was higher for cats but not dogs that slept on owners’ beds and for dogs and cats that contracted a new illness. Seropositivity in neuter-clinic samples was 16% (35/221); in shelter samples, 9.3% (7/75). Our findings indicate a high likelihood for pets in households of humans with COVID-19 to seroconvert and become ill.

The real-time polymerase chain reaction (PCR), commonly known as quantitative PCR (qPCR), is increasingly common in environmental microbiology applications. During the COVID-19 pandemic, qPCR combined with reverse transcription (RT-qPCR) has been used to detect and quantify SARS-CoV-2 in clinical diagnoses and wastewater monitoring of local trends. Estimation of concentrations using qPCR often features a log-linear standard curve model calibrating quantification cycle (Cq) values obtained from underlying fluorescence measurements to standard concentrations. This process works well at high concentrations within a linear dynamic range but has diminishing reliability at low concentrations because it cannot explain “non-standard” data such as Cq values reflecting increasing variability at low concentrations or non-detects that do not yield Cq values at all. Here, fundamental probabilistic modeling concepts from classical quantitative microbiology were integrated into standard curve modeling approaches by reflecting well-understood mechanisms for random error in microbial data. This work showed that data diverging from the log-linear regression model at low concentrations as well as non-detects can be seamlessly integrated into enhanced standard curve analysis. The newly developed model provides improved representation of standard curve data at low concentrations while converging asymptotically upon conventional log-linear regression at high concentrations and adding no fitting parameters. Such modeling facilitates exploration of the effects of various random error mechanisms in experiments generating standard curve data, enables quantification of uncertainty in standard curve parameters, and is an important step toward quantifying uncertainty in qPCR-based concentration estimates. Improving understanding of the random error in qPCR data and standard curve modeling is especially important when low concentrations are of particular interest and inappropriate analysis can unduly affect interpretation, conclusions regarding lab performance, reported concentration estimates, and associated decision-making.

ABSTRACT: This article reports a case of a 21-year-old woman with refractory B-cell acute lymphocytic leukaemia who presented with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). She remained positive for SARS-CoV-2 by viral culture for 78 days and by polymerase chain reaction (PCR) for 97 days. Sequencing of repeat samples over time demonstrated an increasing and dynamic repertoire of mutations.

Background: The Kappa variant is designated as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest (VOI). We identified 195 Kappa variant cases in a region of British Columbia, Canada—the largest published cluster in North America. Objectives: To describe the epidemiology of the Kappa variant in relation to other circulating SARS-CoV-2 variants of concern (VOC) in the region to determine if the epidemiology of the Kappa variant supports a VOI or VOC status. Methods: Clinical specimens testing positive for SARS-CoV-2 collected between March 10 and May 2, 2021, were screened for the detection of known circulating VOCs; approximately 50% of specimens were subsequently selected for whole genome sequencing (WGS). Epidemiological analysis was performed comparing the characteristics of Kappa cases to the main circulating variants in the region (Alpha and Gamma) and to non-VOC/VOI cases. Results: A total of 2,079 coronavirus disease 2019 (COVID-19) cases were reported in the region during the study period, of which 54% were selected for WGS. The 1,131 sequenced cases were categorized into Kappa, Alpha, Gamma and non-VOC/VOI. While Alpha and Gamma cases were found to have a significantly higher attack rate among household contacts compared to non-VOI/VOC cases, Kappa was not. Conclusion: Epidemiological analysis supports the designation of Kappa as a VOI and not a VOC. The Alpha and Gamma variants were found to be more transmissible, explaining their subsequent dominance in the region and the rapid disappearance of the Kappa variant. Variant surveillance strategies should focus on both detection of established VOCs and detection of potential new VOCs.

Contexte : Le variant Kappa est désigné comme un variant d’intérêt (VI) du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). Nous avons recensé 195 cas du variant Kappa dans une région de la Colombie-Britannique, au Canada, le plus grand agrégat spatio-temporel publié en Amérique du Nord. Objectifs : Décrire l’épidémiologie du variant Kappa en relation avec d’autres variants préoccupants (VP) du SRAS-CoV-2 en circulation dans la région afin de déterminer si l’épidémiologie du variant Kappa demande un statut de VI ou de VP. Méthodes : Les échantillons cliniques qui se sont avérés positifs pour le SRAS-CoV-2 collectés entre le 10 mars et le 2 mai 2021 ont été examinés pour la détection des VP circulants connus; environ 50 % des échantillons ont ensuite été sélectionnés pour le séquençage du génome entier. Une analyse épidémiologique a été réalisée en comparant les caractéristiques des cas Kappa aux principaux variants circulant dans la région (Alpha et Gamma) et aux cas non VP/VI. Résultats : Au total, 2 079 cas de maladie à coronavirus 2019 (COVID-19) ont été signalés dans la région pendant la période d’étude, dont 54 % ont été sélectionnés pour le séquençage du génome entier. Les 1 131 cas séquencés ont été classés en Kappa, Alpha, Gamma et non VP/VI. Alors que les cas Alpha et Gamma se sont avérés avoir un taux d’attaque significativement plus élevé parmi les contacts familiaux par rapport aux cas non VI/VP, ce n’était pas le cas pour le variant Kappa. Conclusion : L’analyse épidémiologique soutient la désignation du variant Kappa comme un VI et non un VP. Les variants Alpha et Gamma se sont avérés plus transmissibles, ce qui explique leur domination ultérieure dans la région et la disparition rapide du variant Kappa. Les stratégies de surveillance des variants doivent mettre l’accent à la fois sur la détection des VP établis et sur la détection de nouveaux VP potentiels.

Contexte : En mars 2021, une éclosion de maladie à coronavirus 2019 (COVID-19) a été déclarée dans un grand établissement de soins de longue durée et de séjour de courte durée en Colombie-Britannique, au Canada, bien après l’introduction du programme de vaccination dans les établissements de soins de longue durée qui a entraîné une baisse spectaculaire du nombre d’éclosions dans ce type d’établissement. L’objectif de cette étude est de fournir l’épidémiologie descriptive de cette éclosion, dans le contexte de l’immunisation partielle des résidents et du personnel de l’établissement. Méthodes : Les renseignements sur les cas ont été extraits d’un système de renseignements provincial (Panorama). L’analyse descriptive a été réalisée à l’aide de Microsoft Excel et de SAS. Les contrôles de gestion de l’éclosion comprenaient, sans s’y limiter, des tests asymptomatiques et des efforts pour augmenter la vaccination. Résultats : Vingt-six cas parmi les 241 résidents et trois cas parmi les 418 membres du personnel (correspondant à des taux d’attaque de 10 % et moins de 1 %, respectivement) ont été trouvés. Le taux d’attaque chez les résidents était considérablement plus faible que le taux d’attaque moyen pour les éclosions de COVID-19 dans les établissements de soins de longue durée avant le déploiement du vaccin. Dix-sept cas résidents étaient partiellement ou totalement immunisés. Quatre des huit cas hospitalisés et deux des trois cas décédés étaient partiellement immunisés. Dix-sept cas étaient des résidents en séjour temporaire. Les trois cas du personnel n’ont pas été vaccinés. Dix cas ont été trouvés avec des tests asymptomatiques. Conclusion : L’introduction de la vaccination dans les établissements a contribué à la baisse des taux d’attaque et à l’augmentation du nombre de cas asymptomatiques dans cette éclosion. Le dépistage des personnes asymptomatiques a permis de trouver des cas supplémentaires parmi les résidents vaccinés. Les résultats soulignent l’importance d’atteindre une couverture vaccinale élevée, y compris chez les résidents en séjour temporaire, afin de prévenir l’introduction du virus et les possibilités de transmission ultérieures non reconnues.

Background: In March 2021, a coronavirus disease 2019 (COVID-19) outbreak was declared at a large long-term care and short stay facility in British Columbia, Canada—well after introduction of the vaccination program in long-term care facilities that resulted in a dramatic decline in the number of outbreaks in this type of setting. The objective of this study is to provide the descriptive epidemiology of this outbreak, in the context of partial immunization of both residents and staff at the facility. Methods: The cases’ information was extracted from a provincial information system (Panorama). Descriptive analysis was performed using Microsoft Excel and SAS. Outbreak management controls included, but were not limited to, asymptomatic testing and efforts to increase vaccination. Results: Twenty-six cases among the 241 resident and three cases among the 418 staff (corresponding to attack rates of 10% and less than 1%, respectively) were identified. The attack rate in residents was considerably lower than the average attack rate for COVID-19 outbreaks in long-term care facilities before the vaccine rollout. Seventeen resident cases were either partially or fully immunized. Four of the eight hospitalized cases and two of the three deceased cases were partially immunized. Seventeen cases were temporary stay residents. The three staff cases were not vaccinated. Ten cases were identified as part of asymptomatic testing. Conclusion: Introduction of vaccination at facilities contributed to lower attack rates and higher numbers of asymptomatic cases in this outbreak. Screening asymptomatic individuals identified additional cases among vaccinated residents. Findings underscore the importance of achieving high vaccine coverage, including among temporary stay residents, to prevent virus introduction and subsequent unrecognized transmission opportunities.

Several severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) emerged in late 2020; lineage B.1.1.7 initially dominated globally. However, lineages B.1.351 and P.1 represent potentially greater risk for transmission and immune escape. In British Columbia, Canada, B.1.1.7 and B.1.351 were first identified in December 2020 and P.1 in February 2021. We combined quantitative PCR and whole-genome sequencing to assess relative contribution of VOCs in nearly 67,000 infections during the first 16 weeks of 2021 in British Columbia. B.1.1.7 accounted for 50% by week 8. P.1 accounted for

SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have immunologically assessed serial Omicron infections. We characterized SARS-CoV-2 humoral responses in an individual who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to 124 COVID-19-naive vaccinees. One month post-second and -third vaccine doses, the participant’s wild-type and BA.1-specific IgG, ACE2-displacement and virus neutralization activities were average for a COVID-19-naive triple-vaccinated individual. BA.1 infection boosted the participant’s responses to the cohort ≥95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Reinfection increased BA.1 and BA.2-specific responses only modestly. Though vaccines clearly protect against severe disease, results highlight the continued importance of maintaining additional protective measures to counteract the immune-evasive Omicron variant, particularly as vaccine-induced immune responses naturally decline over time.

Background: Infant botulism is a rare toxicoinfectious disease caused by colonization of the infant’s intestine with botulinum neurotoxin-producing clostridia (i.e. Clostridium botulinum or neurotoxigenic strains of C. butyricum or C. baratii). Our goal was to examine data from laboratory-confirmed cases of infant botulism reported in Canada to summarize incidence over time, over geographic distribution by province or territory, and by sex, and to compare these parameters with data from the Canadian Notifiable Disease Surveillance System (CNDSS). The average age of onset, serotype of botulinum neurotoxin (BoNT), case outcomes, length of hospitalization and suitability of clinical specimens for laboratory confirmation were also determined. Methods: We examined laboratory records from the Health Canada Botulism Reference Service and the British Columbia Centre for Disease Control (BCCDC) Public Health Laboratory. The Discharge Abstract Database (DAD) and the Hospital Morbidity Database (HMDB) of the Canadian Institute of Health Information (CIHI) were queried for data on hospitalization of infant botulism cases. The CNDSS was queried for data on reported cases of infant botulism. Results: From 1979 to 2019, 63 laboratory-confirmed cases of infant botulism were confirmed by the Health Canada Botulism Reference Service and the BCCDC Public Health Laboratory for an annual rate of 4.30 cases per million live births. From 1983 to 2018, 57 cases of infant botulism were reported to the CNDSS. Of the 63 cases confirmed by the reference laboratories, the median age of onset was 16 weeks with a range of 2 to 52 weeks. The majority of cases were type A (76%) and B (21%), with single cases of type F and type AB. Of the 23 laboratory-confirmed cases with matched hospital records, 13 were transferred to special care and eight needed ventilator support; no deaths were reported. Conclusion: Spores of C. botulinum are present naturally in the environment, thus diagnosis of infant botulism does not require a history of exposure to high-risk foods such as honey. Stool samples are the most useful diagnostic specimen.

Background: Many healthcare facilities have faced the decision of conducting point prevalence testing (PPT) of healthcare workers (HCW) during COVID-19 outbreaks. As a containment strategy, PPT can identify asymptomatic or presymptomatic cases for isolation. It is less clear how useful testing asymptomatic HCW is in understanding the spread and possible routes of transmission in an outbreak. This study investigated HCW cases identified through PPT during acute-care outbreaks in Fraser Health (FH), British Columbia, incorporating both epidemiological and whole-genome sequencing (WGS) data to determine their epidemiological source. Methods: This study was a retrospective review of cases associated with COVID-19 acute-care outbreaks in FH occurring between December 2020 and June 2021, when most of these infections were of the alpha and gamma lineages. All patients and HCWs with a positive COVID-19 test and epidemiologically linked to the outbreaks were included in the study. WGS results supported determination of epidemiological source for cases. The proportion of patient and HCW cases related to the outbreak was compared. All analyses were conducted using SAS version 4.3 software with the PROC GLM package. Results: Between December 2020 and June 2021, 49 acute-care COVID-19 outbreaks were declared. Point-prevalence testing of HCWs, in addition to routine patient PPT, was conducted in 28 outbreaks (57%), with 2,167 eligible HCWs (63%) tested. Testing identified 14 previously unknown HCW cases, representing 12.96% of all HCW cases epidemiologically linked to the outbreaks. None of these HCWs were determined to be the index case for their associated outbreak. There was no statistically significant difference between HCWs and patients regarding WGS failure rate, and all failed samples were removed from further analysis. Patients were 3.8 times as likely as HCWs to present as symptomatic when testing positive. HCWs were 2.2 times as likely as patients to have WGS results unrelated to the outbreak. Discussion: Although point-prevalence testing of HCW identified previously unknown cases, these cases were more likely than patients to be unrelated to the outbreak and therefore less useful in understanding the epidemiology of the outbreak. It is difficult to determine whether HCW PPT was effective at preventing transmission, especially with robust infection prevention measures already in place. Patients were more likely than HCWs to present as asymptomatic, however this may be due to the attribution of symptoms to other conditions. Conclusions: Point prevalence testing of HCWs during COVID-19 outbreaks may assist with preventing transmission but is less likely to contribute meaningful information to the investigation.

BackgroundCOVID-19 vaccination is a key public health measure in the pandemic response. The rapid evolution of SARS-CoV-2 variants introduce new groups of spike protein mutations. These new mutations are thought to aid in the evasion of vaccine-induced immunity and render vaccines less effective. However, not all spike mutations contribute equally to vaccine escape. Previous studies associate mutations with vaccine breakthrough infections (BTI), but information at the population level remains scarce. We aimed to identify spike mutations associated with SARS-CoV-2 vaccine BTI in a community setting during the emergence and predominance of the Delta-variant.MethodsThis case-control study used both genomic, and epidemiological data from a provincial COVID-19 surveillance program. Analyses were stratified into two periods approximating the emergence and predominance of the Delta-variant, and restricted to primary SARS-CoV-2 infections from either unvaccinated individuals, or those infected ≥14 days after their second vaccination dose in a community setting. Each sample's spike mutations were concatenated into a unique spike mutation profile (SMP). Penalized logistic regression was used to identify spike mutations and SMPs associated with SARS-CoV-2 vaccine BTI in both time periods.Results and DiscussionThis study reports population level relative risk estimates, between 2 and 4-folds, of spike mutation profiles associated with BTI during the emergence and predominance of the Delta-variant, which comprised 19,624 and 17,331 observations, respectively. The identified mutations cover multiple spike domains including the N-terminal domain (NTD), receptor binding domain (RBD), S1/S2 cleavage region, fusion peptide and heptad regions. Mutations in these different regions imply various mechanisms contribute to vaccine escape. Our profiling method identifies naturally occurring spike mutations associated with BTI, and can be applied to emerging SARS-CoV-2 variants with novel groups of spike mutations.

ABSTRACT Wastewater-based genomic surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus shows promise to complement genomic epidemiology efforts. Multiplex tiling PCR is a desirable approach for targeted genome sequencing of SARS-CoV-2 in wastewater due to its low cost and rapid turnaround time. However, it is not clear how different multiplex tiling PCR primer schemes or wastewater sample matrices impact the resulting SARS-CoV-2 genome coverage. The objective of this work was to assess the performance of three different multiplex primer schemes, consisting of 150-bp, 400-bp, and 1,200-bp amplicons, as well as two wastewater sample matrices, influent wastewater and primary sludge, for targeted genome sequencing of SARS-CoV-2. Wastewater samples were collected weekly from five municipal wastewater treatment plants (WWTPs) in the Metro Vancouver region of British Columbia, Canada during a period of increased coronavirus disease 19 (COVID-19) case counts from February to April 2021. RNA extracted from clarified influent wastewater provided significantly higher genome coverage (breadth and median depth) than primary sludge samples across all primer schemes. Shorter amplicons appeared to be more resilient to sample RNA degradation but were hindered by greater primer pool complexity in the 150-bp scheme. The identified optimal primer scheme (400 bp) and sample matrix (influent) were capable of detecting the emergence of mutations associated with genomic variants of concern, for which the daily wastewater load significantly correlated with clinical case counts. Taken together, these results provide guidance on best practices for implementing wastewater-based genomic surveillance and demonstrate its ability to inform epidemiology efforts by detecting genomic variants of concern circulating within a geographic region. IMPORTANCE Monitoring the genomic characteristics of the SARS-CoV-2 virus circulating in a population can shed important insights into epidemiological aspects of the COVID-19 outbreak. Sequencing every clinical patient sample in a highly populous area is a difficult feat, and thus sequencing SARS-CoV-2 RNA in municipal wastewater offers great promise to augment genomic surveillance by characterizing a pooled population sample matrix, particularly during an escalating outbreak. Here, we assess different approaches and sample matrices for rapid targeted genome sequencing of SARS-CoV-2 in municipal wastewater. We demonstrate that the optimal approach is capable of detecting the emergence of SARS-CoV-2 genomic variants of concern, with strong correlations to clinical case data in the province of British Columbia. These results provide guidance on best practices on, as well as further support for, the application of wastewater genomic surveillance as a tool to augment current genomic epidemiology efforts.

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. Results: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14–56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45–3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = −0.24 [95%CI: −1.2-(−0.12)]). A positive association was found between COVID-19 vaccination and endemic human β-coronavirus IgG titer 14–56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45–3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. Conclusions: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.

Early virus detection and characterization is key to successful avian influenza virus (AIV) surveillance for the health of humans as well as domestic poultry. We explored a novel sampling approach and molecular strategy using sediment from wetlands and outdoor waterbodies on poultry farms as a population-level proxy of AIV activity in waterfowls. RNA was extracted using the MoBio RNA PowerSoil Total RNA isolation kit with additional chloroform extraction steps to reduce PCR inhibition. AIV matrix protein (MP) gene was detected in 42/345 (12.2%) samples by RT-qPCR; an additional 64 (18.6%) samples showed evidence of amplification below the threshold and were categorized as “suspect positive.” Enrichment-based targeted resequencing (TR) identified AIV sequences in 79/345 (22.9%) samples. TR probes were designed for MP, hemagglutinin (HA), and neuraminidase (NA), however PB2 and PA were also identified. Although RT-qPCR and TR only had fair-moderate agreement, RT-qPCR positivity was predictive of TR-positivity both when using only strictly positive RT-qPCR samples (OR = 11.29) and when coding suspect positives as positive (OR = 7.56). This indicates that RT-qPCR could be used as a screening tool to select samples for virus characterization by TR and that future studies should consider RT-qPCR suspect positives to be positive samples for subsequent resequencing when avoiding false negatives is the priority, for instance in a diagnostic test, and to consider suspect positives to be negative samples when cost efficiency over a large number of samples is the priority, for instance in a surveillance program. A total of 13 HA (H1-7, H9-13, H16) and 9 NA (N1-9) subtypes were identified, with a maximum of 8 HA and 8 NA subtypes detected in a single sample. The optimized RNA extraction and targeted resequencing methods provided increased virus detection and subtyping characterization that could be implemented in an AIV surveillance system.

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27; 95% CI = 1.17–1.37), older age (p-trend < 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30–39 years = 3.06; 95% CI = 2.32–4.03, to aRR 80+ years = 43.68; 95% CI = 33.41–57.10 compared to 20–29 years-old]), asthma (aRR = 1.15; 95% CI = 1.04–1.26), cancer (aRR = 1.19; 95% CI = 1.09–1.29), chronic kidney disease (aRR = 1.32; 95% CI = 1.19–1.47), diabetes (treated without insulin aRR = 1.13; 95% CI = 1.03–1.25, requiring insulin aRR = 5.05; 95% CI = 4.43–5.76), hypertension (aRR = 1.19; 95% CI = 1.08–1.31), injection drug use (aRR = 2.51; 95% CI = 2.14–2.95), intellectual and developmental disabilities (aRR = 1.67; 95% CI = 1.05–2.66), problematic alcohol use (aRR = 1.63; 95% CI = 1.43–1.85), immunosuppression (aRR = 1.29; 95% CI = 1.09–1.53), and schizophrenia and psychotic disorders (aRR = 1.49; 95% CI = 1.23–1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69; 95% CI = 1.42–5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

The dissemination of antibiotic resistant bacteria from anthropogenic sources into the environment poses an emerging public health threat. Antibiotic resistance genes (ARGs) and gene-capturing systems such as integron-associated integrase genes (intI) play a key role in alterations of microbial communities and the spread of antibiotic resistant bacteria into the environment. In order to assess the effect of anthropogenic activities on watersheds in southwestern British Columbia, the presence of putative antibiotic resistance and integrase genes was analyzed in the microbiome of agricultural, urban influenced, and protected watersheds. A metagenomics approach and high-throughput quantitative PCR (HT qPCR) were used to screen for elements of resistance including ARGs and intI. Metagenomic sequencing of bacterial genomic DNA was used to characterize the resistome of microbial communities present in watersheds over a 1-year period. There was a low prevalence of ARGs relative to the microbial population (

ABSTRACT Giardia causes the diarrheal disease known as giardiasis; transmission through contaminated surface water is common. The protozoan parasite’s genetic diversity has major implications for human health and epidemiology. To determine the extent of transmission from wildlife through surface water, we performed whole-genome sequencing (WGS) to characterize 89 Giardia duodenalis isolates from both outbreak and sporadic infections: 29 isolates from raw surface water, 38 from humans, and 22 from veterinary sources. Using single nucleotide variants (SNVs), combined with epidemiological data, relationships contributing to zoonotic transmission were described. Two assemblages, A and B, were identified in surface water, human, and veterinary isolates. Mixes of zoonotic assemblages A and B were seen in all the community waterborne outbreaks in British Columbia (BC), Canada, studied. Assemblage A was further subdivided into assemblages A1 and A2 based on the genetic variation observed. The A1 assemblage was highly clonal; isolates of surface water, human, and veterinary origins from Canada, United States, and New Zealand clustered together with minor variation, consistent with this being a panglobal zoonotic lineage. In contrast, assemblage B isolates were variable and consisted of several clonal lineages relating to waterborne outbreaks and geographic locations. Most human infection isolates in waterborne outbreaks clustered with isolates from surface water and beavers implicated to be outbreak sources by public health. In-depth outbreak analysis demonstrated that beavers can act as amplification hosts for human infections and can act as sources of surface water contamination. It is also known that other wild and domesticated animals, as well as humans, can be sources of waterborne giardiasis. This study demonstrates the utility of WGS in furthering our understanding of Giardia transmission dynamics at the water-human-animal interface. IMPORTANCE Giardia duodenalis causes large numbers of gastrointestinal illness in humans. Its transmission through the contaminated surface water/wildlife intersect is significant, and the water-dwelling rodents beavers have been implicated as one important reservoir. To trace human infections to their source, we used genome techniques to characterize genetic relationships among 89 Giardia isolates from surface water, humans, and animals. Our study showed the presence of two previously described genetic assemblages, A and B, with mixed infections detected from isolates collected during outbreaks. Study findings also showed that while assemblage A could be divided into A1 and A2, A1 showed little genetic variation among animal and human hosts in isolates collected from across the globe. Assemblage B, the most common type found in the study surface water samples, was shown to be highly variable. Our study demonstrates that the beaver is a possible source of human infections from contaminated surface water, while acknowledging that theirs is only one role in the complex cycle of zoonotic spread. Mixes of parasite groups have been detected in waterborne outbreaks. More information on Giardia diversity and its evolution using genomics will further the understanding of the epidemiology of spread of this disease-causing protozoan.

Background. Clostridium difficile is a major cause of gastrointestinal illness. Epidemic NAP1 strains contain toxins A and B, a deletion in repressor tcdC, and a binary toxin. Objectives. To determine the molecular epidemiology of C. difficile in British Columbia and compare between two time points in one region. Methods. C. difficile isolates from hospital and community laboratories (2008) and one Island Health hospital laboratory (2013) were characterized by pulsed-field gel electrophoresis, PCR-ribotyping, toxin possession, tcdC genotype, and antimicrobial susceptibility. Results. In 2008, 42.7% of isolates had NAP1 designation. Hospital-collected isolates were associated with older patients and more NAP1 types. Unlike other isolates, most NAP1 isolates possessed binary toxin and a 19 bp loss in tcdC. All isolates were susceptible to metronidazole and vancomycin. A 2013 follow-up revealed a 28.9% decrease in NAP1 isolates and 20.0% increase in isolates without NAP designation in one region. Then, community-associated cases were seen in younger patients, while NAP types were evenly distributed. Isolates without NAP designation did not cluster with a PFGE pattern or ribotype. Conclusions. Evaluation of C. difficile infections within British Columbia revealed demographic associations, epidemiological shifts, and characteristics of strain types. Continuous surveillance of C. difficile will enable detection of emerging strains.

A novel influenza A (H1N1) virus detected in April 2009 rapidly spread around the world. North American provincial and state laboratories have well-defined roles and responsibilities, including providing accurate, timely test results for patients and information for regional public health and other decision makers. We used the multidisciplinary response and rapid implementation of process changes based on Lean methods at the provincial public health laboratory in British Columbia, Canada, to improve laboratory surge capacity in the 2009 influenza pandemic. Observed and computer simulating evaluation results from rapid processes changes showed that use of Lean tools successfully expanded surge capacity, which enabled response to the 10-fold increase in testing demands.

BACKGROUND: The availability of direct-to-consumer personalized genetic testing has enabled the public to access and interpret their own genetic information. Various genetic traits can be determined including resistance to norovirus through a nonsense mutation (G428A) in the FUT2 gene. Although this trait is believed to confer resistance to the most dominant norovirus genotype (GII.4), the spectrum of resistance to other norovirus strains is unknown. The present report describes a cluster of symptomatic norovirus GI.6 infection in a family identified to have norovirus resistance through personalized genetic testing.

In association with the development of new microbial tests for source water quality (SWQ), focus groups with members of the public were conducted to gain insight into their perceptions of SWQ, behaviours and contaminants they think pose the greatest threat to its quality, and what/how they want to know about SWQ. Discussions revealed a low concern about SWQ in general, and in particular about microbial contamination. Participants identified behaviours that threaten SWQ, barriers to changing behaviour and suggestions for inducing change. A strong desire was expressed for water quality information to be interpreted and communicated in terms of how SWQ may impact human health and how their actions should be altered in response to test results. The information can be used to inform communication strategies and possibly impact policies associated with water quality testing and implementation of new tests. More broadly, awareness of the public's understanding and beliefs about source water can be used in working with the public to adopt water-friendly behaviours, influence the content and methods of communicating with the public about water issues and water quality, and could contribute to the direction of future research and investment into water technologies to align with the public's priorities.