Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies.

OBJECTIVES: We conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19 and to estimate the proportion of deaths attributable to these conditions. METHODS: Relevant observational studies were identified by searches in the PubMed, Cochrane library and Embase databases through 14 November 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% CIs. Certainty of evidence was assessed using the Cochrane methods and the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: A total of 186 studies representing 210 447 deaths among 1 304 587 patients with COVID-19 were included in this analysis. The SRR for death in patients with COVID-19 was 1.54 (95% CI 1.44 to 1.64, I2=92%, n=145, low certainty) for diabetes and 1.42 (95% CI 1.30 to 1.54, I2=90%, n=127, low certainty) for hypertension compared with patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI 1.31 to 1.61, I2=91%, n=54, high certainty) for patients with BMI ≥30 kg/m2 compared with those with BMI <30 kg/m2 and 1.12 (95% CI 1.07 to 1.17, I2=68%, n=25) per 5 kg/m2 increase in BMI. There was evidence of a J-shaped non-linear dose-response relationship between BMI and mortality from COVID-19, with the nadir of the curve at a BMI of around 22-24, and a 1.5-2-fold increase in COVID-19 mortality with extreme obesity (BMI of 40-45). The SRR was 1.28 (95% CI 1.17 to 1.40, I2=74%, n=28, low certainty) for ever, 1.29 (95% CI 1.03 to 1.62, I2=84%, n=19) for current and 1.25 (95% CI 1.11 to 1.42, I2=75%, n=14) for former smokers compared with never smokers. The absolute risk of COVID-19 death was increased by 14%, 11%, 12% and 7% for diabetes, hypertension, obesity and smoking, respectively. The proportion of deaths attributable to diabetes, hypertension, obesity and smoking was 8%, 7%, 11% and 2%, respectively. CONCLUSION: Our findings suggest that diabetes, hypertension, obesity and smoking were associated with higher COVID-19 mortality, contributing to nearly 30% of COVID-19 deaths. TRIAL REGISTRATION NUMBER: CRD42020218115.

Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review.

BACKGROUND: Vaccines are critical cost-effective tools to control the coronavirus disease 2019 (COVID-19) pandemic. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may threaten the global impact of mass vaccination campaigns. AIMS: The objective of this study was to provide an up-to-date comparative analysis of the characteristics, adverse events, efficacy, effectiveness and impact of the variants of concern for 19 COVID-19 vaccines. SOURCES: References for this review were identified through searches of PubMed, Google Scholar, BioRxiv, MedRxiv, regulatory drug agencies and pharmaceutical companies' websites up to 22nd September 2021. CONTENT: Overall, all COVID-19 vaccines had a high efficacy against the original strain and the variants of concern, and were well tolerated. BNT162b2, mRNA-1273 and Sputnik V after two doses had the highest efficacy (>90%) in preventing symptomatic cases in phase III trials. mRNA vaccines, AZD1222, and CoronaVac were effective in preventing symptomatic COVID-19 and severe infections against Alpha, Beta, Gamma or Delta variants. Regarding observational real-life data, full immunization with mRNA vaccines and AZD1222 seems to effectively prevent SARS-CoV-2 infection against the original strain and Alpha and Beta variants but with reduced effectiveness against the Delta strain. A decline in infection protection was observed at 6 months for BNT162b2 and AZD1222. Serious adverse event rates were rare for mRNA vaccines-anaphylaxis 2.5-4.7 cases per million doses, myocarditis 3.5 cases per million doses-and were similarly rare for all other vaccines. Prices for the different vaccines varied from $2.15 to $29.75 per dose. IMPLICATIONS: All vaccines appear to be safe and effective tools to prevent severe COVID-19, hospitalization, and death against all variants of concern, but the quality of evidence greatly varies depending on the vaccines considered. Questions remain regarding a booster dose and waning immunity, the duration of immunity, and heterologous vaccination. The benefits of COVID-19 vaccination outweigh the risks, despite rare serious adverse effects.

Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis.

BACKGROUND: Hydroxychloroquine or chloroquine with or without azithromycin have been widely promoted to treat coronavirus disease 2019 (COVID-19) following early in vitro antiviral effects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: The aim of this systematic review and meta-analysis was to assess whether chloroquine or hydroxychloroquine with or without azithromycin decreased COVID-19 mortality compared with the standard of care. DATA SOURCES: PubMed, Web of Science, Embase Cochrane Library, Google Scholar and MedRxiv were searched up to 25 July 2020. STUDY ELIGIBILITY CRITERIA: We included published and unpublished studies comparing the mortality rate between patients treated with chloroquine or hydroxychloroquine with or without azithromycin and patients managed with standard of care. PARTICIPANTS: Patients ≥18 years old with confirmed COVID-19. INTERVENTIONS: Chloroquine or hydroxychloroquine with or without azithromycin. METHODS: Effect sizes were pooled using a random-effects model. Multiple subgroup analyses were conducted to assess drug safety. RESULTS: The initial search yielded 839 articles, of which 29 met our inclusion criteria. All studies except one were conducted on hospitalized patients and evaluated the effects of hydroxychloroquine with or without azithromycin. Among the 29 articles, three were randomized controlled trials, one was a non-randomized trial and 25 were observational studies, including 11 with a critical risk of bias and 14 with a serious or moderate risk of bias. After excluding studies with critical risk of bias, the meta-analysis included 11 932 participants for the hydroxychloroquine group, 8081 for the hydroxychloroquine with azithromycin group and 12 930 for the control group. Hydroxychloroquine was not significantly associated with mortality: pooled relative risk (RR) 0.83 (95% CI 0.65-1.06, n = 17 studies) for all studies and RR = 1.09 (95% CI 0.97-1.24, n = 3 studies) for randomized controlled trials. Hydroxychloroquine with azithromycin was associated with an increased mortality (RR = 1.27; 95% CI 1.04-1.54, n = 7 studies). We found similar results with a Bayesian meta-analysis. CONCLUSION: Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality.

Hydroxychloroquine and mortality risk of patients with COVID-19: a systematic review and meta-analysis of human comparative studies (preprint)

BackgroundGlobal COVID-19 deaths reached at least 400,000 fatalities. Hydroxychloroquine is an antimalarial drug that elicit immunomodulatory effects and had shown in vitro antiviral effects against SRAS-CoV-2. This drug divided opinion worldwide in the medical community but also in the press, the general public and in public health policies. The aim of this systematic review and this meta-analysis was to bring a new overview on this controversial drug and to assess whether hydroxychloroquine could reduce COVID-19 mortality risk in hospitalized patients. Methods and FindingsPubmed, Web of Science, Cochrane Library, MedRxiv and grey literature were searched until 10 June 2020. Only studies of COVID-19 patients treated with hydroxychloroquine (with or without azithromycin) compared with a comparative standard care group and with full-text articles in English were included. Studies reporting effect sizes as Odds Ratios, Hazard Ratio and Relative Risk for mortality risk and the number of deaths per groups were included. This meta-analysis was conducted following PRISMA guidelines and registered on PROSPERO (Registration number: CRD42020190801). Independent extraction has been performed by two independent reviewers. Effect sizes were pooled using a random-effects model. The initial search leaded to 112 articles, from which 16 articles met our inclusion criteria. 15 studies were retained for association between hydroxychloroquine and COVID-19 survival including 15,081 patients (8,072 patients in the hydroxychloroquine arm and 7,009 patients in the standard care arm with respectively, 1,578 deaths and 1,423 deaths). 6 studies were retained for hydroxychloroquine with azithromycin. Hydroxychloroquine was not significantly associated with mortality risk (pooled Relative Risk RR=0.82 (95% Confidence Interval: 0.62-1.07, I2=82, Pheterogeneity<0.01, n=15)) within hospitalized patients, nor in association with azithromycin (pooled Relative Risk RR=1.33 (95% CI: 0.92-1.92, I2=75%, Pheterogeneity<0.01, n=6)), nor in the numerous subgroup analysis by study design, median age population, published studies (vs unpublished articles), level of bias risk. However, stratified analysis by continents, we found a significant decreased risk of mortality associated with hydroxychlroquine alone but not with azithromycin among European (RR= 0.62 (95%CI: 0.41-0.93, n=7)) and Asian studies (RR=0.36 (95%CI:0.18-0.73, n=1)), with heterogeneity detected across continent (Pheterogeneity between=0.003). These finding should be interpreted with caution since several included studies had a low quality of evidence with a small sample size, a lack of adjustment on potential confounders or selection and intervention biases. ConclusionOur meta-analysis does not support the use of hydroxychloroquine with or without azithromycin to reduce COVID-19 mortality in hospitalized patients. It raises the question of the hydroxychloroquine use outside of clinical trial. Additional results from larger randomised controlled trials are needed