The mediating role of SARS-CoV-2 variants between income and hospitalisation due to COVID-19: A period-based mediation analysis.

The mechanisms facilitating the relationship between low income and COVID-19 severity have not been partitioned in the presence of SARS-CoV-2 variants of concern (VOC). To address this, we used causal mediation analysis to quantify the possible mediating role infection with VOC has on the relationship between neighbourhood income (exposure) and hospitalisation due to COVID-19 among cases (outcome). A population-based cohort of 65,629 individuals residing in British Columbia, Canada, was divided into three periods of VOC co-circulation in the 2021 calendar year whereby each period included co-circulation of an emerging and an established VOC. Each cohort was subjected to g-formula mediation techniques to decompose the relationship between exposure and outcome into total, direct and indirect effects. In the mediation analysis, the total effects indicated that low income was associated with increased odds of hospitalisation across all periods. Further decomposition of the effects revealed that income is directly and indirectly associated with hospitalisation. The resulting indirect effect through VOC accounted for approximately between 6 and 13% of the total effect of income on hospitalisation. This study underscores, conditional on the analysis, the importance of addressing underlying inequities to mitigate the disproportionate impact on historically marginalised communities by adopting an equity lens as central to pandemic preparedness and response from the onset.

Impact of COVID-19 pandemic on hepatocellular carcinoma surveillance in British Columbia, Canada: An interrupted time series study.

We assessed the impact of the COVID-19 pandemic on hepatocellular carcinoma (HCC) surveillance among individuals with HCV diagnosed with cirrhosis in British Columbia (BC), Canada. We used data from the British Columbia Hepatitis Testers Cohort (BC-HTC), including all individuals in the province tested for or diagnosed with HCV from 1 January 1990 to 31 December 2015, to assess HCC surveillance. To analyse the impact of the pandemic on HCC surveillance, we used pre-policy (January 2018 to February 2020) and post-policy (March to December 2020) periods. We conducted interrupted time series (ITS) analysis using a segmented linear regression model and included first-order autocorrelation terms. From January 2018 to December 2020, 6546 HCC screenings were performed among 3429 individuals with HCV and cirrhosis. The ITS model showed an immediate decrease in HCC screenings in March and April 2020, with an overall level change of -71 screenings [95% confidence interval (CI): -105.9, -18.9]. We observed a significant decrease in HCC surveillance among study participants, regardless of HCV treatment status and age group, with the sharpest decrease among untreated HCV patients. A recovery of HCC surveillance followed this decline, reflected in an increasing trend of 7.8 screenings (95% CI: 0.6, 13.5) per month during the post-policy period. There was no level or trend change in the number of individuals diagnosed with HCC. We observed a sharp decline in HCC surveillance among people living with HCV and cirrhosis in BC following the COVID-19 pandemic control measures. HCC screening returned to pre-pandemic levels by mid-2020.

Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec. METHODS: We have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis. RESULTS: The results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018. CONCLUSIONS: We estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Understanding the impact of mobility on COVID-19 spread: A hybrid gravity-metapopulation model of COVID-19.

The outbreak of the severe acute respiratory syndrome coronavirus 2 started in Wuhan, China, towards the end of 2019 and spread worldwide. The rapid spread of the disease can be attributed to many factors including its high infectiousness and the high rate of human mobility around the world. Although travel/movement restrictions and other non-pharmaceutical interventions aimed at controlling the disease spread were put in place during the early stages of the pandemic, these interventions did not stop COVID-19 spread. To better understand the impact of human mobility on the spread of COVID-19 between regions, we propose a hybrid gravity-metapopulation model of COVID-19. Our modeling framework has the flexibility of determining mobility between regions based on the distances between the regions or using data from mobile devices. In addition, our model explicitly incorporates time-dependent human mobility into the disease transmission rate, and has the potential to incorporate other factors that affect disease transmission such as facemasks, physical distancing, contact rates, etc. An important feature of this modeling framework is its ability to independently assess the contribution of each factor to disease transmission. Using a Bayesian hierarchical modeling framework, we calibrate our model to the weekly reported cases of COVID-19 in thirteen local health areas in Metro Vancouver, British Columbia (BC), Canada, from July 2020 to January 2021. We consider two main scenarios in our model calibration: using a fixed distance matrix and time-dependent weekly mobility matrices. We found that the distance matrix provides a better fit to the data, whilst the mobility matrices have the ability to explain the variance in transmission between regions. This result shows that the mobility data provides more information in terms of disease transmission than the distances between the regions.

Clinical Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Relative to Delta in British Columbia, Canada: A Retrospective Analysis of Whole-Genome Sequenced Cases.

BACKGROUND: In late 2021, the Omicron severe acute respiratory syndrome coronavirus 2 variant emerged and rapidly replaced Delta as the dominant variant. The increased transmissibility of Omicron led to surges in case rates and hospitalizations; however, the true severity of the variant remained unclear. We aimed to provide robust estimates of Omicron severity relative to Delta. METHODS: This retrospective cohort study was conducted with data from the British Columbia COVID-19 Cohort, a large provincial surveillance platform with linkage to administrative datasets. To capture the time of cocirculation with Omicron and Delta, December 2021 was chosen as the study period. Whole-genome sequencing was used to determine Omicron and Delta variants. To assess the severity (hospitalization, intensive care unit [ICU] admission, length of stay), we conducted adjusted Cox proportional hazard models, weighted by inverse probability of treatment weights (IPTW). RESULTS: The cohort was composed of 13 128 individuals (7729 Omicron and 5399 Delta). There were 419 coronavirus disease 2019 hospitalizations, with 118 (22%) among people diagnosed with Omicron (crude rate = 1.5% Omicron, 5.6% Delta). In multivariable IPTW analysis, Omicron was associated with a 50% lower risk of hospitalization compared with Delta (adjusted hazard ratio [aHR] = 0.50, 95% confidence interval [CI] = 0.43 to 0.59), a 73% lower risk of ICU admission (aHR = 0.27, 95% CI = 0.19 to 0.38), and a 5-day shorter hospital stay (aß = -5.03, 95% CI = -8.01 to -2.05). CONCLUSIONS: Our analysis supports findings from other studies that have demonstrated lower risk of severe outcomes in Omicron-infected individuals relative to Delta.

A population-based study of reported hepatitis C diagnoses from 1998 to 2018 in immigrants and nonimmigrants in Quebec, Canada.

Immigrants living in low hepatitis C (HCV) prevalence countries bear a disproportionate HCV burden, but there are limited HCV population-based studies focussed on this population. We estimated rates and trends of reported HCV diagnoses over a 20-year period in Quebec, Canada, to investigate subgroups with the highest rates and changes over time. A population-based cohort of all reported HCV diagnoses in Quebec (1998-2018) linked to health administrative and immigration databases. HCV rates, rate ratios (RR) and trends overall and stratified by immigrant status and country of birth were estimated using Poisson regression. Among 38,348 HCV diagnoses, 14% occurred in immigrants, a median of 7.5 years after arrival. The average annual HCV rate/100,000 decreased for immigrants and nonimmigrants, but the risk (RR) among immigrants increased over the study period [35.7 vs. 34.5 (RR = 1.03) and 18.4 vs. 12.7 (1.45) between 1998-2008 and 2009-2018]. Immigrants from middle-income Europe & Central Asia [55.8 (RR = 4.39)], sub-Saharan Africa [51.7 (RR = 4.06)] and South Asia [32.8 (RR = 2.58)] had the highest rates between 2009 and 2018. Annual HCV rates decreased more slowly among immigrants vs. nonimmigrants (-5.9% vs. -8.9%, p < 0.001), resulting in a 2.5-fold (9%-21%) increase in the proportion of HCV diagnoses among immigrants (1998-2018). The slower decline in HCV rates among immigrants over the study period highlights the need for targeted screening for this population, particularly those from sub-Saharan Africa, Asia and middle-income Europe. These data can inform micro-elimination efforts in Canada and other low-HCV-prevalence countries.

The viral hepatitis B care cascade: A population-based comparison of immigrant groups.

BACKGROUND AND AIMS: The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS: In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS: In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.

Clinical severity of Omicron subvariants BA.1, BA.2, and BA.5 in a population-based cohort study in British Columbia, Canada.

The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct subvariants of Omicron, BA.1, BA.2, and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 subvariants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity, and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2, or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between December 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and intensive care unit (ICU) admission (aHRhospital = 1.17; 95% confidence interval [CI] = 1.096-1.252; aHRICU = 1.368; 95% CI = 1.152-1.624), whereas BA.5 infections were associated with an 18% higher risk of hospitalization (aHRhospital = 1.18; 95% CI = 1.133-1.224) after accounting for age, sex, comorbidities, vaccination status, geography, and social determinants of health. Phylogenetic analysis revealed no specific subclades associated with more severe clinical outcomes for any Omicron subvariant. In summary, BA.1, BA.2, and BA.5 subvariants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues.

The Impact of Current Opioid Agonist Therapy on Hepatitis C Virus Treatment Initiation Among People Who Use Drugs From the Direct-acting Antiviral (DAA) Era: A Population-Based Study.

BACKGROUND: Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset. METHODS: The British Columbia Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in British Columbia, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT. RESULTS: In total, 13 803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2704/5770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT had started HCV treatment. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95% confidence interval {CI}, 1.50, 2.26]). CONCLUSIONS: Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Geographic concentration of SARS-CoV-2 cases by social determinants of health in metropolitan areas in Canada: a cross-sectional study.

BACKGROUND: Understanding inequalities in SARS-CoV-2 transmission associated with the social determinants of health could help the development of effective mitigation strategies that are responsive to local transmission dynamics. This study aims to quantify social determinants of geographic concentration of SARS-CoV-2 cases across 16 census metropolitan areas (hereafter, cities) in 4 Canadian provinces, British Columbia, Manitoba, Ontario and Quebec. METHODS: We used surveillance data on confirmed SARS-CoV-2 cases and census data for social determinants at the level of the dissemination area (DA). We calculated Gini coefficients to determine the overall geographic heterogeneity of confirmed cases of SARS-CoV-2 in each city, and calculated Gini covariance coefficients to determine each city's heterogeneity by each social determinant (income, education, housing density and proportions of visible minorities, recent immigrants and essential workers). We visualized heterogeneity using Lorenz (concentration) curves. RESULTS: We observed geographic concentration of SARS-CoV-2 cases in cities, as half of the cumulative cases were concentrated in DAs containing 21%-35% of their population, with the greatest geographic heterogeneity in Ontario cities (Gini coefficients 0.32-0.47), followed by British Columbia (0.23-0.36), Manitoba (0.32) and Quebec (0.28-0.37). Cases were disproportionately concentrated in areas with lower income and educational attainment, and in areas with a higher proportion of visible minorities, recent immigrants, high-density housing and essential workers. Although a consistent feature across cities was concentration by the proportion of visible minorities, the magnitude of concentration by social determinant varied across cities. INTERPRETATION: Geographic concentration of SARS-CoV-2 cases was observed in all of the included cities, but the pattern by social determinants varied. Geographically prioritized allocation of resources and services should be tailored to the local drivers of inequalities in transmission in response to the resurgence of SARS-CoV-2.

Hospital Costs of Injection Drug Use in Florida.

People who inject drugs (PWID) experience significant injection-related infections (IRIs) at significant healthcare system cost. This study used and validated an algorithm based on the International Classification of Diseases, Tenth Revision, to estimate hospitalized PWID populations, assess the total statewide morbidity for IRIs among PWID, and calculate associated costs of care.

Opportunities to Enhance Linkage to Hepatitis C Care Among Hospitalized People With Recent Drug Dependence in New South Wales, Australia: A Population-based Linkage Study.

BACKGROUND: People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. METHODS: We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016-December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. RESULTS: Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. CONCLUSIONS: Among people who have evidence of recent drug dependence, frequent hospitalization-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care.

High hepatitis C treatment uptake among people with recent drug dependence in New South Wales, Australia.

BACKGROUND & AIMS: High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. METHODS: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. RESULTS: 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24-2.36), recent incarceration (aOR 1.10; 95% CI 1.01-1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13-1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72-0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69-0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78-0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82-0.98), HBV coinfection (aOR 0.69; 95% CI 0.59-0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84-0.98). CONCLUSIONS: These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. LAY SUMMARY: To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

BACKGROUND & AIMS: We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada. METHODS: We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality. RESULTS: Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality. CONCLUSIONS: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs. LAY SUMMARY: We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.

Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression.

BACKGROUND: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality. MATERIAL AND METHODS: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers. RESULTS: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 109 /L (2.76, 4.87), lymphocytes (ALC) at -0.34 × 109 /L (-0.45, -0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression. CONCLUSION: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.

Viral hepatitis C cascade of care: A population-level comparison of immigrant and long-term residents.

BACKGROUND & AIMS: Viral hepatitis C represents a major global burden, particularly among immigrant-receiving countries such as Canada, where knowledge of disparities in hepatitis C virus among immigrant groups for micro-elimination efforts is lacking. We quantify the hepatitis C cascades of care among immigrants and long-term residents prior to the introduction of direct-acting antiviral medications. METHODS: Using laboratory and health administrative records, we described the hepatitis C virus cascades of care in terms of diagnosis, engagement with care, treatment initiation, and clearance in Ontario, Canada (1997-2014). We stratified the cascade by immigrant and long-term resident groups and identify drivers at each stage using multivariable Poisson regression. RESULTS: We included 940 245 individuals in the study with an estimated hepatitis C prevalence of 167 923 (1.4%) overall, 23 759 (0.7%) among all immigrants, and 6019 (1.1%) among immigrants from hepatitis C endemic countries. Overall there were 104 616 individuals with reactive antibody results, 73 861 tested for viral RNA, 52 388 with viral RNA detected, 50 805 genotyped, 13 159 on treatment and 3919 with evidence of viral clearance. Compared to long-term residents, immigrants showed increased nucleic-acid testing (aRR: 1.09 [95%CI: 1.08, 1.10]), treatment initiation (aRR: 1.46 [95%CI: 1.38, 1.54]), and higher clearance rates (aRR: 1.07 [95%CI: 1.03, 1.11]). CONCLUSIONS: Hepatitis C virus is more prevalent among long-term residents compared to immigrants overall, however, immigrants from endemic countries are an important subgroup to consider for future screening and linkage to care initiatives. These findings are prior to the introduction of newer medications and provide a population-based benchmark for follow-up studies and evaluation of treatment programs and surveillance activities.

Impact of COVID-19-related public health measures on HCV testing in British Columbia, Canada: An interrupted time series analysis.

BACKGROUND & AIMS: Public health measures introduced to limit transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), also disrupted various healthcare services in many regions worldwide, including British Columbia (BC), Canada. We assessed the impact of these measures, first introduced in BC in March 2020, on hepatitis C (HCV) testing and first-time HCV-positive diagnoses within the province. METHODS: De-identified HCV testing data for BC residents were obtained from the provincial Public Health Laboratory. Weekly changes in anti-HCV, HCV RNA and genotype testing episodes and first-time HCV-positive (anti-HCV/RNA/genotype) diagnoses from January 2018 to December 2020 were assessed and associations were determined using segmented regression models examining rates before vs after calendar week 12 of 2020, when measures were introduced. RESULTS: Average weekly HCV testing and first-time HCV-positive diagnosis rates fell immediately following the imposition of public health measures by 62.3 per 100 000 population and 2.9 episodes per 1 000 000 population, respectively (P < .0001 for both), and recovered in subsequent weeks to near pre-March 2020 levels. Average weekly anti-HCV positivity rates decreased steadily pre-restrictions and this trend remained unchanged afterwards. CONCLUSIONS: Reductions in HCV testing and first-time HCV-positive diagnosis rates, key drivers of progression along the HCV care cascade, occurred following the introduction of COVID-19-related public health measures. Further assessment will be required to better understand the full impact of these service disruptions on the HCV care cascade and to inform strategies for the re-engagement of people who may have been lost to care because of these measures.

HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men.

BACKGROUND & AIMS: Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada. METHODS: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018. RESULTS: Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk. CONCLUSIONS: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.

Quantifying the impact of COVID-19 control measures using a Bayesian model of physical distancing.

Extensive non-pharmaceutical and physical distancing measures are currently the primary interventions against coronavirus disease 2019 (COVID-19) worldwide. It is therefore urgent to estimate the impact such measures are having. We introduce a Bayesian epidemiological model in which a proportion of individuals are willing and able to participate in distancing, with the timing of distancing measures informed by survey data on attitudes to distancing and COVID-19. We fit our model to reported COVID-19 cases in British Columbia (BC), Canada, and five other jurisdictions, using an observation model that accounts for both underestimation and the delay between symptom onset and reporting. We estimated the impact that physical distancing (social distancing) has had on the contact rate and examined the projected impact of relaxing distancing measures. We found that, as of April 11 2020, distancing had a strong impact in BC, consistent with declines in reported cases and in hospitalization and intensive care unit numbers; individuals practising physical distancing experienced approximately 0.22 (0.11-0.34 90% CI [credible interval]) of their normal contact rate. The threshold above which prevalence was expected to grow was 0.55. We define the "contact ratio" to be the ratio of the estimated contact rate to the threshold rate at which cases are expected to grow; we estimated this contact ratio to be 0.40 (0.19-0.60) in BC. We developed an R package 'covidseir' to make our model available, and used it to quantify the impact of distancing in five additional jurisdictions. As of May 7, 2020, we estimated that New Zealand was well below its threshold value (contact ratio of 0.22 [0.11-0.34]), New York (0.60 [0.43-0.74]), Washington (0.84 [0.79-0.90]) and Florida (0.86 [0.76-0.96]) were progressively closer to theirs yet still below, but California (1.15 [1.07-1.23]) was above its threshold overall, with cases still rising. Accordingly, we found that BC, New Zealand, and New York may have had more room to relax distancing measures than the other jurisdictions, though this would need to be done cautiously and with total case volumes in mind. Our projections indicate that intermittent distancing measures-if sufficiently strong and robustly followed-could control COVID-19 transmission. This approach provides a useful tool for jurisdictions to monitor and assess current levels of distancing relative to their threshold, which will continue to be essential through subsequent waves of this pandemic.