Effects of hyperglycaemia on complications of COVID‐19: A meta‐analysis of observational studies

To the Editor We read with great interest the article by Ceriello et al. regarding the worsened prognosis for coronavirus disease 2019 (COVID-19) in patients with hyperglycaemia and the potential reasons for this phenomenon. COVID-19 is currently the greatest public health concern, with global cases surpassing 12 million and attributed deaths reaching over half a million. There are concerns that patients with hyperglycaemia may face a high risk of severe COVID-19 with reports of association between high blood glucose and poor prognosis of COVID-19, as in the case of the severe acute respiratory syndrome (SARS) epidemic in 2003. Despite this, the literature specifically assessing the outcomes of COVID-19 in hyperglycaemic patients is scarce. Hence, this meta-analysis aims to determine if hyperglycaemia may be associated with an increased severity of COVID-19. This review was registered with PROSPERO (CRD42020195937). PubMed, Embase and China National Knowledge Infrastructure were searched for articles examining the outcomes of COVID-19 in hyperglycaemic and normoglycaemic patients. Terms including COVID-19, 2019-n-CoV and SARS-CoV-2 were used in the search strategy, which is shown in supplementary material 1. Original articles that examined the severity of COVID-19 in hyperglycaemic patients, determined by variables such as mortality and ICU admissions were included and full-text articles were reviewed for relevant outcomes. Binary data reporting the COVID-19 outcomes among both hyperglycaemic and normoglycaemic patients diagnosed with SARS-CoV-2 were extracted and analysed with the metaprop function and pooled in random effects. Dichotomous data were analysed in random effects using the DerSimonian and Laird model. Continuous data measuring hospital stay duration were extracted as mean and standard deviation and pooled as the mean difference. In total, 189 articles were retrieved using the search strategy, and subsequently 51 full-text articles were reviewed, of which eight studies satisfied our inclusion criteria to be included in the final analysis. The results of the analysis are summarized in supplementary material 2, 3 and 4. In total, 1447 hyperglycaemic and 1282 normoglycaemic patients with COVID-19 were included in the analysis. Among hyperglycaemic patients with COVID-19, which included patients with diabetes mellitus and those without the condition, 17% died [confidence interval (CI): 0.10-0.25], 11% required ICU admissions (CI: 0.05-0.19) and 23% required mechanical or non-mechanical ventilation (CI: 0.13-0.36). Furthermore, 72% of patients developed severe or critical COVID-19 (CI: 0.44-0.93), 14% had acute cardiac injury (CI: 0.07-0.24), 5% had acute kidney injury (CI: 0.02-0.09) and 15% developed acute respiratory distress syndrome (CI: 0.06-0.28). The duration of hospital stay trended higher among hyperglycaemic patients compared with normoglycaemic patients but did not reach statistical difference (mean difference: 1.834, CI: −1.234 to 4.901, P = .24). Compared with normoglycaemic patients, hyperglycaemic patients had a higher risk of mortality and would probably need admission to ICU, or mechanical or non-mechanical ventilation (supplementary material 2). Hyperglycaemic patients also probably developed severe or critical COVID-19, acute kidney injury and acute respiratory distress syndrome compared with normoglycaemic patients (supplementary material 2). Among diabetic COVID-19 patients with hyperglycaemia (n = 681), 16% died (CI: 0.09-0.25), 15% required ICU admission (CI: 0.10-0.21) and 16% required mechanical or non-mechanical ventilation (CI: 0.13-0.19). In addition, 89% of patients developed severe or critical COVID-19 (CI: 0.82-0.94), 15% had acute cardiac injury (CI: 0.070.25), 6% acute kidney injury (CI: 0.01-0.16) and 15% developed acute respiratory distress syndrome (CI: 0.08-0.23). When compared with diabetic COVID-19 patients with controlled blood glucose, diabetic COVID-19 patients with hyperglycaemia were more significantly associated with death and the need for mechanical or non-mechanical ventilation. Diabetic COVID-19 patients with hyperglycaemia were also at higher risk of developing acute cardiac injury, acute kidney injury or acute respiratory distress syndrome (supplementary material 3). Of the non-diabetic patients with hyperglycaemia (n = 158), 5% died (CI: 0.020.10), 5% required ICU admissions (CI: 0.02-0.10) and 38% needed mechanical or non-mechanical ventilation (CI: 0.21-0.59). Additionally, 75% of patients developed severe or critical COVID-19 (CI: 0.68-0.82), 20% had acute cardiac injury (CI: 0.14-0.28), 3% acute kidney injury (CI: 0.01-0.08) and 2% developed acute respiratory distress syndrome (CI: 0.00-0.06). When compared with normoglycaemic COVID-19 patients, non-diabetic patients with hyperglycaemia had a higher risk of ICU admission, mechanical or non-mechanical ventilation and severe or critical COVID-19 (supplementary material 4). Hyperglycaemia has been reported to be a predisposing factor for death in COVID-19, as well as for the progression of non-critical disease to critical disease. Our analysis affirms the higher risk of death among COVID-19 patients with hyperglycaemia, including patients with diabetes and those without diabetes. We urge for close surveillance for hyperglycaemia of patients with COVID-19 individuals in non-diabetics as it might alter the prognosis of these patients. In our analysis, hospitalization stay trended higher among Received: 14 July 2020 Revised: 20 August 2020 Accepted: 25 August 2020