In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics.
BackgroundHepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients.MethodsA retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon’s Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI).ResultsHBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120–360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85–294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02).ConclusionThe prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.
In the EU/EEA, subgroups of international migrants have an increased prevalence of certain infectious diseases. The objective of this study was to examine migrants’ acceptability, value placed on outcomes, and accessibility of infectious disease interventions. We conducted a systematic review of qualitative reviews adhering to the PRISMA reporting guidelines. We searched MEDLINE, EMBASE, CINAHL, DARE, and CDSR, and assessed review quality using AMSTAR. We conducted a framework analysis based on the Health Beliefs Model, which was used to organize our preliminary findings with respect to the beliefs that underlie preventive health behavior, including knowledge of risk factors, perceived susceptibility, severity and barriers, and cues to action. We assessed confidence in findings using an adapted GRADE CERQual tool. We included 11 qualitative systematic reviews from 2111 articles. In these studies, migrants report several facilitators to public health interventions. Acceptability depended on migrants’ relationship with healthcare practitioners, knowledge of the disease, and degree of disease-related stigma. Facilitators to public health interventions relevant for migrant populations may provide clues for implementation. Trust, cultural sensitivity, and communication skills also have implications for linkage to care and public health practitioner education. Recommendations from practitioners continue to play a key role in the acceptance of infectious disease interventions.
HCV infection is associated with chronic kidney disease due to several mechanisms. Patients treated with interferon-based regimens demonstrate improved renal function and reduced incidence of chronic kidney disease. There is scarce evidence on the effect of direct acting antiviral regimens (DAAs) on renal function. We evaluated serial measures of renal function in a cohort of HCV-infected participants following completion of DAA-based treatment regimens. Measures of glomerular filtration rate (GFR) were estimated by the CKD-EPI equation. Data was recorded at end of treatment, and at 6–12 months, 12–24 months, and greater than 24 months following treatment completion. Group-based trajectory modeling was used to determine distinct GFR trajectories. Predictors of group membership were determined by multinomial regression analysis. Six trajectories were identified. One trajectory comprising 27% of the cohort demonstrated declining renal function and the others demonstrated no change in renal function over time. Baseline GFR did not predict SVR. Diabetes was associated with lower post-treatment GFR but patients with diabetes did not demonstrate a decrease in GFR over the period of evaluation. Cirrhosis and SVR were not significant predictors of GFR or GFR trajectory. There is no clinically relevant change in renal function among the majority of HCV-infected patients following completion of DAA-based treatments. Renal function does not influence the efficacy of DAA-based regimens. No consistent effect of DAA treatment and/or SVR on renal function was observed over a 2-year period following treatment completion.
BACKGROUND: Alcohol use and hepatitis C virus (HCV) are two leading causes of liver disease. Alcohol use is prevalent among the HCV-infected population and accelerates the progression of HCV-related liver disease. Despite barriers to care faced by HCV-infected patients who use alcohol, few studies have analyzed uptake of direct-acting antiviral (DAA) treatment. OBJECTIVE: We compared rates of treatment uptake and sustained virological response (SVR) between patients with and without alcohol use. METHODS: Prospective data were obtained from the Canadian Network Undertaking against Hepatitis C (CANUHC) cohort. Consenting patients assessed for DAA treatment between January 2016 and December 2019 were included. Demographic and clinical characteristics were compared between patients with and without alcohol use by means of t-tests, χ2 tests, and Fisher’s Exact Tests. Univariate and multivariate analyses were used to determine predictors of SVR and treatment initiation. RESULTS: Current alcohol use was reported for 217 of 725 (30%) patients. The proportion of patients initiating DAA treatment did not vary by alcohol use status (82% versus 83%; p = 0.99). SVR rate was similar between patients with alcohol use and patients without alcohol use (92% versus 94%; p = 0.45). Univariate and multivariate analysis found no association between alcohol use and SVR or treatment initiation. CONCLUSION: Patients engaged in HCV treatment have highly favourable treatment uptake and outcomes regardless of alcohol use. Public health interventions should be directed toward facilitating access to care for all patients irrespective of alcohol use. Research into high-level alcohol use and DAA outcomes is needed.
Due to shared modes of exposure, HIV‐HBV co‐infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co‐infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross‐sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV‐HBV patients and a comparator HBV group. From a total of 5996 HBV‐infected patients, 335 HIV‐HBV patients were identified. HIV‐HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti‐HBV therapy use (91% vs. 30%) than the HBV‐positive / HIV seronegative comparator group. A history of reported high‐risk exposure activities (drug use, high‐risk sexual contact) was more common in HIV‐HBV patients. HIV‐HBV patients with reported high‐risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV‐HBV patients born in an endemic country. In the main cohort, age ≥60 years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34–1.67]). In conclusion, Canadian co‐infected patients differed considerably from those with mono‐infection. Furthermore, HIV‐HBV‐infected patients who report high‐risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.
Objective Hepatitis C virus (HCV), cirrhosis, and HCV medications including direct-acting antivirals (DAAs) ±ribavirin may all influence the metabolic milieu. While interferon-based regimens improve glucose tolerance, evidence is limited on DAAs. Cases of elevated lactate have recently been reported in patients treated with DAAs, and lactic acidosis is a known complication of antivirals used to treat hepatitis B virus and HIV. Patients and methods Measures were evaluated at baseline, week 4, end of treatment, and 12–24 weeks after treatment. Mixed-effects modeling was used to determine factors influencing glucose and lactate over time. Results In total, 442 patients were treated (mean age 56, 65% male, 72% genotype 1, 48% cirrhotic). Glucose did not change on or after DAA treatment from baseline (P=0.51) aside from those with untreated diabetes, which declined (P=0.02). Overall, there was a decline in lactate following HCV treatment (mean 2.4–2.1 mmol/l; P<0.001). Lactate initially increased on treatment and then decreased after treatment completion in male patients treated with ribavirin. This pattern was not observed in other groups. There was no evidence of lactic acidosis with HCV nucleotide use. Conclusion Distinct glucose and lactate trajectories were identified without evidence of DAA metabolic toxicity. HCV treatment does not improve random glucose levels aside from perhaps in untreated diabetic patients.
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