Effectiveness of the neutralizing antibody sotrovimab among high-risk patients with mild-to-moderate SARS-CoV-2 in Qatar

ObjectivesTo estimate the real-world effectiveness of sotrovimab against severe, critical, or fatal COVID-19 in Qatar at a time in which most SARS-CoV-2 incidences occurred due to the BA.2 Omicron subvariant. MethodsWe conducted a matched case-control study among all individuals eligible for sotrovimab treatment per United States Food and Drug Administration guidelines in the resident population of Qatar. The odds of progression to severe forms of COVID-19 were compared in cases (treatment group) versus controls (eligible patients who opted not to receive the treatment). Subgroup analyses were conducted. ResultsA total of 3364 individuals were eligible for sotrovimab treatment during the study period, of whom 519 individuals received the treatment, whereas the remaining 2845 constituted the controls. The adjusted odds ratio of disease progression to severe, critical, or fatal COVID-19 comparing the treatment group to the control group was 2.67 (95% confidence interval 0.60-11.91). In the analysis including only the subgroup of patients at higher risk of severe forms of COVID-19, the adjusted odds ratio was 0.65 (95% confidence interval 0.17-2.48). ConclusionThere was no evidence for a protective effect of sotrovimab in reducing COVID-19 severity in a setting dominated by the BA.2 subvariant

Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar.

BACKGROUND: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear. METHODS: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021. RESULTS: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months. CONCLUSIONS: BNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.)

Protection against the omicron variant from previous SARS-CoV-2 infection

Natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits strong protection against reinfection with the B.1.1.7 (alpha),1,2 B.1.351 (beta),1 and B.1.617.2 (delta)3 variants. However, the B.1.1.529 (omicron) variant harbors multiple mutations that can mediate immune evasion. We estimated the effectiveness of previous infection in preventing symptomatic new cases caused by omicron and other SARS-CoV-2 variants in Qatar. In this study, we extracted data regarding coronavirus disease 2019 (Covid-19) laboratory testing, vaccination, clinical infection data, and related demographic details from the national SARS-CoV-2 databases, which include all results of polymerase-chain-reaction (PCR) testing, vaccinations, and hospitalizations and deaths for Covid-19 in Qatar since the start of the pandemic

Bivalent mRNA-1273.214 vaccine effectiveness against SARS-CoV-2 omicron XBB* infections

In October of 2022, Qatar introduced COVID-19 bivalent vaccination for persons ≥ 12 years using the 50-μg mRNA-1273.214 vaccine combining SARS-CoV-2 ancestral and omicron BA.1 strains.1 We estimated this vaccine’s effectiveness against SARS-CoV-2 infection. Using Qatar’s national SARS-CoV-2 databases, we conducted a matched, retrospective, cohort study to compare infection incidence in the national cohort of persons who received the vaccine (bivalent cohort) to that in the national cohort of Qatar residents whose last vaccination was ≥6 months before follow-up start (no-recent-vaccination cohort; Supplementary Appendix 1). The 6-month cut-off was chosen because of negligible effectiveness of first-generation vaccines against omicron infection ≥ 6 months after vaccination.2 Incidence of infection was defined as the first SARS-CoV-2 PCR-positive or rapid-antigen-positive test after the start of follow-up, regardless of symptoms. Cohorts were balanced on observed confounders through exact matching. Follow-up started 7 days after the person in the bivalent cohort received their vaccine dose. Associations were estimated using Cox proportional-hazards models adjusted for the matching factors and testing rate

Economic Evaluation of the Cyp2c19 Genotype-Guided Antiplatelet Therapy Compared To Universal Use of Ticagrelor or Clopidogrel in Qatar

Background: Clopidogrel requires activation primarily by cytochrome P450 2C19 (CYP2C19). Patients with CYP2C19 loss-of-function alleles (LOF) are at increased risk of major adverse cardiovascular events. Ticagrelor is a more effective and expensive alternative antiplatelet agent that is unaffected by the CYP2C19 polymorphism. The main aim of the current thesis is to evaluate the cost-effectiveness of CYP2C19*2/*3 genotype-guided therapy compared to the universal use of ticagrelor or clopidogrel after a percutaneous coronary intervention (PCI) with acute coronary syndrome (ACS). With the increasing size of relevant economic literature, another aim of the thesis was to perform a systematic review to answer the question about whether the overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost effective strategy in post-PCI ACS. Methods: A two-parts model, including a one-year decision-analytic model and a 20 years follow-up Markov model, was created from the Qatari healthcare provider's perspective, to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratio (ICER) of genotype guided therapy. Therapy success was defined as survival without myocardial infarction, stroke, stent thrombosis, cardiovascular death, or the no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. Via a Monte Carlo simulation, the model was based on multivariate analysis. For the systematic review, a literature search of PubMed, Embase, EconLit, and PharmGKB was done to identify all of the economic evaluations related to genotype guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment. Results: Genotype-guided therapy was between dominant and cost-effective compared to universal clopidogrel in 100%, over the one-year duration (mean ICER of QAR 22,215 per case of success) and the long-term follow up. Genotype-guided therapy was dominant compared to universal ticagrelor in 60% of the cases over the one-year model, and cost-effective in 96% of the cases over the long term (ICUR of QAR 5,036 per QALY). Universal clopidogrel was dominant in 63% of the cases in the clinical outcomes over the one-year model, and cost-effective in 99% of the cases over the long term (ICUR of QAR 38,650 per QALY). One-way and multivariate sensitivity analyses confirmed the robustness of the study results. The literature systematic review identified 13 articles. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while five studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in five, one, and three studies, respectively. Only two studies reported that universal ticagrelor was cost-effective compared to genotype guided treatment. All of the included articles had good quality. Conclusion: CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy over the universal use of ticagrelor or clopidogrel for post-PCI patients in Qatar. Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS post-PCI

Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review.

Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS. A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all the economic evaluations related to genotype-guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment. The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality. Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS undergoing PCI

Economic Evaluation of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to Universal Use of Ticagrelor or Clopidogrel in Qatar

Background: Patients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is a more effective and expensive antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI). Methods: A two-part simulation model, including a one-year decision-analytic model and a 20-year follow-up Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/quality-adjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes. Results: Against universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6,102 /success), and dominant over the long-term. Genotype-guided therapy was dominant over universal ticagrelor over the one-year duration, and cost-effective over the long term (ICUR, USD 1,383 /QALY). Universal clopidogrel was dominant over ticagrelor over the short term, and cost-effective over the long-term (ICUR, 10,616 /QALY). Conclusion: CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qata

Short- and long-term cost-effectiveness analysis of CYP2C19 genotype-guided therapy, universal clopidogrel, versus universal ticagrelor in post-percutaneous coronary intervention patients in Qatar

BackgroundPatients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is an effective antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI). MethodsA two-part decision-analytic model, including a one-year model and a 20-year follow-up Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/quality-adjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes, including against variations in drug acquisition costs. ResultsAgainst universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6102 /success), and dominant over the long-term. Genotype-guided therapy was dominant against universal ticagrelor over the one-year duration, and cost-effective over the long term (ICUR, USD 1383 /QALY). Universal clopidogrel was dominant over ticagrelor for the short term, and cost-effective over the long-term (ICUR, USD 10,616 /QALY). ConclusionCYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.This research is supported by award# GRA5-2-0521-18060 from Qatar National Research Fund, Qatar Foundation, Qatar

Epidemiology of herpes simplex virus type 1 in Canada: systematic review, meta-analyses, and meta-regressions

Background: The objective of this study was to characterize herpes simplex virus type 1 (HSV-1) epidemiology in Canada. Methods: HSV-1 publications as recent as December 6, 2021 were systematically reviewed, synthesized, and reported following PRISMA guidelines. Meta-analyses and meta-regressions were conducted. Results: HSV-1 measures were extracted from 22 studies and included 32 overall seroprevalence measures (79 stratified), 2 overall proportions of HSV-1 detection in clinically diagnosed genital ulcer disease (2 stratified), and 8 overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (27 stratified). Pooled mean seroprevalence was 19.1% [95% confidence interval (CI): 12.6–26.4%] among healthy children and 51.4% (95% CI: 47.3–55.5%) among healthy adults. Pooled mean seroprevalence among healthy general populations increased with age, with the lowest being 35.7% (95% CI: 29.1–42.6%) among individuals <20 years of age, and the highest being 70.0% (95% CI: 54.8–83.2) among individuals ≥40 years. Seroprevalence increased by 1.02-fold (95% CI: 1.01–1.04) per year. Pooled mean proportion of HSV-1 detection in genital ulcer disease was 30.8% (95% CI: 12.6–52.8%). Pooled mean proportion of HSV-1 detection in genital herpes was 37.4% (95% CI: 29.5–45.6%) and was highest in women and in young persons. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI: 1.00–1.08) per year. Conclusions: HSV-1 epidemiology in Canada appears to be shifting toward less oral acquisition in childhood and more genital acquisition in adulthood, particularly among youth. Both HSV-1 seroprevalence and proportion of HSV-1 detection in genital herpes are increasing with time.The authors gratefully acknowledge Professor Emeritus Rhoda Ashley-Morrow of the University of Washington, for her support in assessing the quality of study diagnostic methods. The authors are also grateful to Adona Canlas for administrative support. This publication was made possible by NPRP grant number 9-040-3-008 from the Qatar National Research Fund (a member of Qatar Foundation). The findings achieved herein are solely the responsibility of the authors. The authors are also grateful for pilot funding by the Biomedical Research Program and infrastructure support provided by the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine in Qatar.Scopu

Epidemiology of herpes simplex virus type 1 and genital herpes in Australia and New Zealand: Systematic review, meta-analyses and meta-regressions

Herpes simplex virus type 1 (HSV-1) infection is a lifelong infection that is acquired primarily orally and during childhood. We aimed to characterise HSV-1 epidemiology in Australia and New Zealand. HSV-1-related data as recent as 6 December 2021 were systematically reviewed, synthesised and reported, following PRISMA guidelines. Pooled mean seroprevalence and proportions of HSV-1 detection in genital ulcer disease (GUD) and in genital herpes were calculated using random-effects meta-analyses. Meta-regressions were also conducted. HSV-1 measures were retrieved from 21 eligible publications. Extracted HSV-1 measures included 13 overall seroprevalence measures (27 stratified) in Australia, four overall proportions of HSV-1 detection in clinically diagnosed GUD (four stratified) in Australia, and ten overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (26 stratified) in Australia and New Zealand. Pooled mean seroprevalence among healthy adults in Australia was 84.8% (95% confidence interval (CI) 74.3-93.1%). Pooled mean seroprevalence was 70.2% (95% CI 47.4-88.7%) among individuals <35 years of age and 86.9% (95% CI 79.3-93.0%) among individuals ≥35 years. Seroprevalence increased by 1.05-fold (95% CI 1.01-1.10) per year. Pooled mean proportion of HSV-1 detection in GUD was 8.2% (95% CI 0.4-22.9%). Pooled mean proportion of HSV-1 detection in genital herpes was 30.5% (95% CI 23.3-38.3%), and was highest in young individuals. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI 1.00-1.08) per year. Included studies showed heterogeneity, but 30% of the heterogeneity in seroprevalence and 42% of the heterogeneity in proportion of HSV-1 detection in genital herpes were explained in terms of epidemiological factors. HSV-1 seroprevalence is higher in Australia than in other Western countries. HSV-1 epidemiology in Australia and New Zealand appears to be transitioning towards less oral acquisition in childhood, but more genital acquisition among youth.Qatar National Research Fund (QNRF) - grant No. [NPRP 9-040-3-008]