Elevated HbA1c levels in pre-Covid-19 infection increases the risk of mortality: A sistematic review and meta-analysis

Abstract

Aims: Diabetes is emerging as a risk factor for coronavirus disease (COVID)-19 prognosis. However, contradictory findings have been reported regarding the impact of glycaemic control on COVID-19 outcome. The aim of this meta-analysis was to explore the impact of hospital pre-admission or at-admission values of HbA1c on COVID-19 mortality or worsening in patients with diabetes.

Materials and methods: We searched PubMed, Embase and Scopus up to 30th December 2020. Eligibility criteria for study selection were the following: (1)enrolling patients with any form of diabetes mellitus and hospitalized for COVID-19 and (2) reporting data regarding HbA1c values before infection or at hospital admission in relation to COVID-19 mortality or worsening. Descriptive statistics, HbA1c values, odds ratios (ORs) and hazard ratios were extracted from seven observational studies and generic inverse variance (random effects) of OR was used to estimate the effect of HbA1c on COVID-19 outcome.

Results: HbA1c was linearly associated with an increased COVID-19 mortality or worsening when considered as a continuous variable (OR 1.01 [1.01, 1.01]; p < 0.00001). Similarly, when analysing studies providing the number of events according to the degree of glycaemic control among various strata, a significantly increased risk was observed with poor glycaemic control (OR 1.15 [1.11, 1.19]; p < 0.00001), a result corroborated by sensitivity analysis.

Conclusions: Notwithstanding the large heterogeneity in study design and patients' characteristics in the few available studies, data suggest that patients with diabetes and poor glycaemic control before infection might have an increased risk of COVID-19 related mortality.

Keywords: COVID-19; COVID-19 prognosis; HbA1c; SARS-CoV-2; glycaemic control; mortality; outcomes; type 1 diabetes mellitus; type 2 diabetes mellitus.

FIGURE 1

(A) Forest plot showing the association between HbA1c as continuous variable and COVID‐19 worsening or mortality. (B) Forest plot showing the association between HbA1c as continuous variable and COVID‐19 mortality which excluded two manuscripts not providing data for mortality alone

FIGURE 2

Forest plot showing the association between the degree of glycaemic control, categorized as a dichotomous variable, and COVID‐19 mortality considering the manuscripts by either Holman et al. (A) or Open Safely (B). Sensitivity analysis performed by calculating OR with a different approach considering either Holman et al. (C) or Open Safely (D). Data for mortality alone were extracted from the Coronado study