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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.

Summary: Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

PurposeThe British Columbia COVID-19 Cohort (BCC19C) was developed from an innovative, dynamic surveillance platform and is accessed/analyzed through a cloud-based environment. The platform integrates recently developed provincial COVID-19 datasets (refreshed daily) with existing administrative holdings and provincial registries (refreshed weekly/monthly). The platform/cohort were established to inform the COVID-19 response in near “real-time” and to answer more in-depth epidemiologic questions.ParticipantsThe surveillance platform facilitates the creation of large, up-to-date analytic cohorts of people accessing COVID-19 related services and their linked medical histories. The program of work focused on creating/analyzing these cohorts is referred to as the BCC19C. The administrative/registry datasets integrated within the platform are not specific to COVID-19 and allow for selection of “control” individuals who have not accessed COVID-19 services.Findings to dateThe platform has vastly broadened the range of COVID-19 analyses possible, and outputs from BCC19C analyses have been used to create dashboards, support routine reporting and contribute to the peer-reviewed literature. Published manuscripts (total of 15 as of July, 2023) have appeared in high-profile publications, generated significant media attention and informed policy and programming. In this paper, we conducted an analysis to identify sociodemographic and health characteristics associated with receiving SARS-CoV-2 laboratory testing, testing positive, and being fully vaccinated. Other published analyses have compared the relative clinical severity of different variants of concern; quantified the high “real-world” effectiveness of vaccines in addition to the higher risk of myocarditis among younger males following a 2nd dose of an mRNA vaccine; developed and validated an algorithm for identifying long-COVID patients in administrative data; identified a higher rate of diabetes and healthcare utilization among people with long-COVID; and measured the impact of the pandemic on mental health, among other analyses.Future plansWhile the global COVID-19 health emergency has ended, our program of work remains robust. We plan to integrate additional datasets into the surveillance platform to further improve and expand covariate measurement and scope of analyses. Our analyses continue to focus on retrospective studies of various aspects of the COVID-19 pandemic, as well as prospective assessment of post-acute COVID-19 conditions and other impacts of the pandemic.

Summary: Background: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality. Methods: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders. Findings: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2–32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9–30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1–8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18–0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78–84%). Interpretation: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

We assessed the association between cirrhosis and severe COVID-19-related outcomes among people with laboratory-diagnosed COVID-19 infection in British Columbia, Canada. We used data from the British Columbia (BC) COVID-19 Cohort, a population-based cohort that integrates data on all individuals tested for COVID-19, with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions, and deaths in the Canadian province of BC. We included all individuals aged ≥18 who tested positive for SARS-CoV-2 by real-time reverse transcription-polymerase chain reaction from 1 January 2021 to 31 December 2021. Multivariable logistic regression models were used to assess the associations of cirrhosis status with COVID-19-related hospitalization and with ICU admission. Of the 162,509 individuals who tested positive for SARS-CoV-2 and were included in the analysis, 768 (0.5%) had cirrhosis. In the multivariable models, cirrhosis was associated with increased odds of hospitalization (aOR = 1.97, 95% CI: 1.58–2.47) and ICU admission (aOR = 3.33, 95% CI: 2.56–4.35). In the analyses stratified by age, we found that the increased odds of ICU admission among people with cirrhosis were present in all the assessed age-groups. Cirrhosis is associated with increased odds of hospitalization and ICU admission among COVID-19 patients.