Risk Phenotypes of Diabetes and Association with COVID-19 Severity and Death – A Living Systematic Review and Meta-Analysis

Background: Diabetes has been identified as a risk factor for poor prognosis of COVID-19. The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death. Methods: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19 regarding death and COVID-19 severity. Four different databases were searched up to October 10th 2020. We used random effects meta-analysis to calculate summary relative risks (SRR) with 95% confidence intervals (CI). The certainty of evidence was evaluated by GRADE. This study is registered with PROSPERO, CRD42020193692. Findings: A total of 22 articles met our inclusion criteria. There was high to moderate certainty of evidence for associations between male sex [SRR (95% CI): 1·28 (1·02, 1·61), n=10 studies], older age [>65 years: 3·49 (1·82, 6·69), n=6], pre-existing comorbidities [cardiovascular disease: 1·56 (1·09, 2·24), n=8; chronic kidney disease: 1·93 (1·28, 2·91), n=6; chronic obstructive pulmonary disease: 1·40 (1·21, 1·62), n=5], diabetes treatment [insulin use: 1·75 (1·01, 3·03), n=5; metformin use: 0·50 (0·28, 0·90), n=4] and blood glucose at admission [blood glucose ≥11 mmol/L: 8·60 (2·25, 32·83), n=2] regarding death among individuals with diabetes and COVID-19. Similar, but in general weaker and less precise, associations were observed for severity of COVID-19. Interpretation: Individuals with more severe course of diabetes have a poorer prognosis of COVID-19 compared to individuals with a milder course of disease. To strengthen the evidence still more studies accounting for potential confounders are warranted. Funding Statement: The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Science and Culture of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD). Declaration of Interests: SS: none. MN: none. AL: none. KP: none. OK: none. CH: received speaker’s honoraria from Sanofi-Aventis and Lilly and research support from Sanofi-Aventis. MR: received personal fees from Boehringer-Ingelheim Pharma, Eli Lilly, Fishawack Group, Novo Nordisk, Sanofi US, Target NASH, Terra Firma and investigator-initiated research support from Boehringer-Ingelheim, Nutricia/Danone and Sanofi-Aventis.