Diabetes, obesity, hypertension and risk of severe COVID-19: a protocol for systematic review and meta-analysis

Introduction: previous evidence from several countries, including China, Italy, Mexico, UK and the USA, indicates that among patients with confirmed COVID-19 who were hospitalised, diabetes, obesity and hypertension might be important risk factors for severe clinical outcomes. Several preliminary systematic reviews and meta-analyses have been conducted on one or more of these non-communicable diseases, but the findings have not been definitive, and recent evidence has become available from many more populations. Thus, we aim to conduct a systematic review and meta-analysis of observational studies to assess the relationship of diabetes, obesity and hypertension with severe clinical outcomes in patients with COVID-19.Method and analysis: we will search 16 major databases (MEDLINE, Embase, Global Health, CAB Abstracts, PsycINFO, CINAHL, Academic Research Complete, Africa Wide Information, Scopus, PubMed Central, ProQuest Central, WHO Virtual Health Library, Homeland Security COVID-19 collection, SciFinder, Clinical Trials and Cochrane Library) for articles published between December 2019 and December 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2016 guidelines for the design and reporting the results. We will include observational studies that assess the associations of pre-existing diabetes, obesity and hypertension in patients with COVID-19 with risk of severe clinical outcomes such as intensive care unit admission, receiving mechanical ventilation or death. Stata V.16.1 and R-Studio V.1.4.1103 statistical software will be used for statistical analysis. Meta-analysis will be used to estimate the pooled risks and to assess potential heterogeneities in risks.Ethics and dissemination: the study was reviewed for human subjects concerns by the US CDC Center for Global Health and determined to not represent human subjects research because it uses data from published studies. We plan to publish results in a peer-reviewed journal and present at national and international conferences

Associations of diabetes, hypertension and obesity with COVID-19 mortality: a systematic review and meta-analysis

Introduction Despite a growing body of scholarly research on the risks of severe COVID-19 associated with diabetes, hypertension and obesity, there is a need for estimating pooled risk estimates with adjustment for confounding effects. We conducted a systematic review and meta-analysis to estimate the pooled adjusted risk ratios of diabetes, hypertension and obesity on COVID-19 mortality.Methods We searched 16 literature databases for original studies published between 1 December 2019 and 31 December 2020. We used the adapted Newcastle-Ottawa Scale to assess the risk of bias. Pooled risk ratios were estimated based on the adjusted effect sizes. We applied random-effects meta-analysis to account for the uncertainty in residual heterogeneity. We used contour-funnel plots and Egger’s test to assess possible publication bias.Results We reviewed 34 830 records identified in literature search, of which 145 original studies were included in the meta-analysis. Pooled adjusted risk ratios were 1.43 (95% CI 1.32 to 1.54), 1.19 (95% CI 1.09 to 1.30) and 1.39 (95% CI 1.27 to 1.52) for diabetes, hypertension and obesity (body mass index ≥30 kg/m2) on COVID-19 mortality, respectively. The pooled adjusted risk ratios appeared to be stronger in studies conducted before April 2020, Western Pacific Region, low- and middle-income countries, and countries with low Global Health Security Index scores, when compared with their counterparts.Conclusions Diabetes, hypertension and obesity were associated with an increased risk of COVID-19 mortality independent of other known risk factors, particularly in low-resource settings. Addressing these chronic diseases could be important for global pandemic preparedness and mortality prevention.PROSPERO registration number CRD42021204371

Associations of diabetes, hypertension and obesity with COVID-19 mortality: a systematic review and meta-analysis

Introduction: despite a growing body of scholarly research on the risks of severe COVID-19 associated with diabetes, hypertension and obesity, there is a need for estimating pooled risk estimates with adjustment for confounding effects. We conducted a systematic review and meta-analysis to estimate the pooled adjusted risk ratios of diabetes, hypertension and obesity on COVID-19 mortality.Methods: we searched 16 literature databases for original studies published between 1 December 2019 and 31 December 2020. We used the adapted Newcastle-Ottawa Scale to assess the risk of bias. Pooled risk ratios were estimated based on the adjusted effect sizes. We applied random-effects meta-analysis to account for the uncertainty in residual heterogeneity. We used contour-funnel plots and Egger’s test to assess possible publication bias.Results: we reviewed 34 830 records identified in literature search, of which 145 original studies were included in the meta-analysis. Pooled adjusted risk ratios were 1.43 (95% CI 1.32 to 1.54), 1.19 (95% CI 1.09 to 1.30) and 1.39 (95% CI 1.27 to 1.52) for diabetes, hypertension and obesity (body mass index ≥30 kg/m2) on COVID-19 mortality, respectively. The pooled adjusted risk ratios appeared to be stronger in studies conducted before April 2020, Western Pacific Region, low- and middle-income countries, and countries with low Global Health Security Index scores, when compared with their counterparts.Conclusions: diabetes, hypertension and obesity were associated with an increased risk of COVID-19 mortality independent of other known risk factors, particularly in low-resource settings. Addressing these chronic diseases could be important for global pandemic preparedness and mortality prevention

Lysophosphatidic acid is a potential mediator of cholestatic pruritus

BACKGROUND & AIMS: Pruritus is a common and disabling symptom in cholestatic disorders. However, its causes remain unknown. We hypothesized that potential pruritogens accumulate in the circulation of cholestatic patients and activate sensory neurons. METHODS: Cytosolic free calcium ([Ca2(+)](i)) was measured in neuronal cell lines by ratiometric fluorometry upon exposure to serum samples from pruritic patients with intrahepatic cholestasis of pregnancy (ICP), primary biliary cirrhosis (PBC), other cholestatic disorders, and pregnant, healthy, and nonpruritic disease controls. Putative [Ca2+](i)-inducing factors in pruritic serum were explored by analytical techniques, including quantification by high-performance liquid chromatography/ mass spectroscopy. In mice, scratch activity after intradermal pruritogen injection was quantified using a magnetic device. RESULTS: Transient increases in neuronal [Ca2+](i) induced by pruritic PBC and ICP sera were higher than corresponding controls. Lysophosphatidic acid (LPA) could be identified as a major [Ca2+](i) agonist in pruritic sera, and LPA concentrations were increased in cholestatic patients with pruritus. LPA injected intradermally into mice induced scratch responses. Autotaxin, the serum enzyme converting lysophosphatidylcholine into LPA, was markedly increased in patients with ICP versus pregnant controls (P <.0001) and cholestatic patients with versus without pruritus (P <.0001). Autotaxin activity correlated with intensity of pruritus (P <.0001), which was not the case for serum bile salts, histamine, tryptase, substance P, or mu-opioids. In patients with PBC who underwent temporary nasobiliary drainage, both itch intensity and autotaxin activity markedly decreased during drainage and returned to preexistent levels after drain removal. CONCLUSIONS: We suggest that LPA and autotaxin play a critical role in cholestatic pruritus and may serve as potential targets for future therapeutic intervention