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Background: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. Methods: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. Results: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results: were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Conclusions: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo.

With the World Health Organization plan for hepatitis C elimination by the year 2030, and recent guideline recommendations to screen all women during pregnancy for HCV, data on HCV in pregnancy are needed to determine the association of HCV viremia with adverse pregnancy outcomes and mother-to-child transmission (MTCT).This retrospective cohort study was performed in Ontario, Canada, using population-based administrative healthcare data. Individuals were stratified based on whether they had active HCV viremia during pregnancy or resolved viremia at time of pregnancy. Peak HCV viral load was determined. Logistic regression was used to determine the association of viremia with adverse pregnancy outcomes; maternal HCV RNA levels were evaluated as a predictor of MTCT.We identified a total of 2,170 pregnancies in 1,636 women who were HCV RNA positive prior to pregnancy; 1,780 (82%) pregnancies occurred in women who were HCV RNA positive during pregnancy. Patients who were HCV RNA positive during pregnancy were more likely to have preterm delivery (18% vs. 12%, p = 0.002), intrahepatic cholestasis of pregnancy (4% vs.2%, p = 0.003), and post-partum hemorrhage (9% vs. 5%, p = 0.013), and less likely to have gestational diabetes (6% vs. 10%, p = 0.008) than those with resolved infection. Only 511 (29%) infants had screening consistent with guidelines after birth; there was an estimated 3.5% risk of MTCT. HCV RNA ≥6.0 logActive HCV viremia among individuals with a history of HCV infection significantly increases adverse pregnancy outcomes. Few infants are screened for MTCT. Higher HCV RNA is associated with increased risk of MTCT.The prevalence of hepatitis C has increased in women of child-bearing age and has important implications for women who become pregnant and their infants. We evaluated the effect that hepatitis C has on pregnancy outcomes as well as the rate of hepatitis C transmission to infants in a large database with linked mother-infant records. We found that active hepatitis C during pregnancy increased the risk of pregnancy complications. We also identified very low rates of testing of infants born to mothers with hepatitis C, but found higher rates of hepatitis C transmission to infants in mothers with higher virus levels.

Background COVID-19 presents with a breadth of symptomatology including a spectrum of clinical severity requiring intensive care unit (ICU) admission. We investigated the mucosal host gene response at the time of gold standard COVID-19 diagnosis using clinical surplus RNA from upper respiratory tract swabs. Methods Host response was evaluated by RNA-sequencing, and transcriptomic profiles of 44 unvaccinated patients including outpatients and in-patients with varying levels of oxygen supplementation were included. Additionally, chest X-rays were reviewed and scored for patients in each group. Results Host transcriptomics revealed significant changes in the immune and inflammatory response. Patients destined for the ICU were distinguished by the significant upregulation of immune response pathways and inflammatory chemokines, including cxcl2 which has been linked to monocyte subsets associated with COVID-19 related lung damage. In order to temporally associate gene expression profiles in the upper respiratory tract at diagnosis of COVID-19 with lower respiratory tract sequalae, we correlated our findings with chest radiography scoring, showing nasopharygeal or mid-turbinate sampling can be a relevant surrogate for downstream COVID-19 pneumonia/ICU severity. Conclusions This study demonstrates the potential and relevance for ongoing study of the mucosal site of infection of SARS-CoV-2 using a single sampling that remains standard of care in hospital settings. We highlight also the archival value of high quality clinical surplus specimens, especially with rapidly evolving COVID-19 variants and changing public health/vaccination measures.

Chronic liver disease (CLD) has become a silent epidemic in our country and has resulted in significant physical, psychosocial, and financial burden. Although other international liver associations have published frameworks for the principal actions required to improve liver health across health systems, Canada does not have a strategy to address the growing concerns of CLD. Thus, a multidisciplinary group of care providers involved in CLD management in Canada gathered to review the current burden of disease, gaps in management, and key opportunities for improving the identification and management of people at risk of developing progressive CLD.

BACKGROUND: Widespread screening and treatment of hepatitis C virus (HCV) is required to decrease late-stage liver disease and liver cancer. Clinical practice guidelines and Canadian Task Force on Preventative Health Care recommendations differ on the value of one-time birth cohort (1945–75) HCV screening in Canada. To assess the utility of this approach, we conducted a real-world analysis of HCV antibody (Ab) prevalence among birth cohort individuals seen in different clinical contexts. METHODS: Cross-sectional study of individuals born between 1945 and 1975 who completed HCV Ab testing at multiple participating centres in Ontario, Canada between January 2016 and December 2020. Differences in prevalence were compared by year of birth, gender, and setting. RESULTS: Among 16,672 birth cohort individuals tested, HCV Ab prevalence was 3.2%. Prevalence was higher among younger individuals which increased from 0.9% among those born between 1945 and 1956 to 4.6% among those born between 1966 and 1975. Prevalence was higher among males (4.4%) compared with females (2.0%) and differed by test site. In primary care, the prevalence was 0.5%, whereas the prevalence was highest among those tested at drug treatment centres (28.7%) and through community outreach (14.0%). CONCLUSIONS: HCV Ab prevalence remains high in the 1945–1975 birth cohort. These data highlight the need to re-evaluate existing Canadian Preventative Task Force recommendations, to consider incorporating one-time birth cohort and/or other population-based approaches to HCV screening into the clinical workflow as a preventative health measure, and to increase training among community providers to screen for and treat HCV.