key: cord-0862412-bide13uo authors: Eng, Pei Chia; Distaso, Walter; Durreshahwar, Hashmi; Shaikhali, Yusuf; Narendranathan, Divani; Cassin‐Scott, Rebecca; Misra, Shivani; Hill, Neil E.; Tharakan, George; Oliver, Nick S.; Tan, Tricia M.; Izzi‐Engbeaya, Chioma; Salem, Victoria title: The benefit of dexamethasone in patients with COVID‐19 infection is preserved in patients with diabetes date: 2022-04-03 journal: Diabetes Obes Metab DOI: 10.1111/dom.14692 sha: e0d264fc13a54cf2b1be70bff3884132cb7142fe doc_id: 862412 cord_uid: bide13uo nan Dexamethasone significantly reduces mortality 1 and is now standard treatment for patients with COVID-19 who require supplemental oxygen and/or mechanical ventilation. However, supraphysiological doses of glucocorticoids may exacerbate dysglycaemia and precipitate hyperglycaemic complications, particularly in those with or at risk of type 2 diabetes. 2 The RECOVERY trial 1 reported a low incidence of hyperglycaemic complications (2/1996, 0.1%), although the real-world incidence is likely to be much higher. 3 Type 2 diabetes itself increases the risk of severe COVID-19, 4 and hyperglycaemia independently predicts poor outcomes. 5 We investigated the possibility that patients with diabetes may derive less survival benefit from steroid therapy in the setting of severe COVID-19 infection. We performed a retrospective analysis of the characteristics of all nonpregnant adults hospitalized with COVID-19 infection between 9 March 2020 and 22 April 2020 (UK COVID-19 Wave 1) 6 We also recorded dexamethasone-induced hyperglycaemic complications in Wave 2, as well as length of stay in hospital in Wave 1 and Wave 2. GraphPad Prism 9.0 statistical software was used to perform Mann-Whitney tests on nonparametric data, and Fisher's exact tests were used for univariate analyses. Matlab code and STATA software were used to perform unbiased multivariate logistic regression analysis to determine factors associated with death and/or ICU admission or 30-day mortality alone. The multivariate analysis was performed on all 2261 patients studied (Wave 1 6 plus Wave 2) and we report both the logit coefficients and associated odds ratios. In brief, this analysis aims to identify and quantify the contribution of both preexisting conditions and presenting clinical features that are independently (eg, all other measured features being equal) associated with death from COVID-19. One of the measures that were chosen a priori was FiO 2 , that is, the maximum oxygen requirement during admission-a direct measure of disease severity. Rather than arbitrarily remove this factor from this analysis, we elected to control for the potential endogeneity 7 of FiO 2 (which would otherwise invalidate the statistical analysis), we ran a first stage regression of FiO 2 on a set of exogenous regressors (clinical frailty score, admission temperature, respiratory rate, heart rate and systolic blood pressure), which showed a good fit (R 2 of 30%). Thereafter the logit specifications were run in STATA, adding the residuals from the first stage regressions. Both regressions displayed a good fit, with adjusted R 2 equal to 36% for the composite primary endpoint of death and/or ICU admission and 31% for 30-day mortality alone. This increased our confidence that our findings were unbiased. During Wave 2, 1372 adults were admitted to ICHNT hospitals with COVID-19 compared with 889 admissions in Wave 1. 6 Table 1 . Ischaemic heart disease and renal failure were independent predictors of poor outcome, over and above a diagnosis of diabetes per se, suggesting that multimorbidity rather than any one risk factor alone is the major driver for COVID-19 mortality. 9 For the composite outcome of ICU admission/death ( between these two groups (all other cofactors being equal). Dexamethasone use was associated with a lower probability of ICU admission/ death (Table 1) , and its effect was very similar in patients with and without diabetes (P = 0.82 using an F-test for equality of the logit coefficients). However, dexamethasone use was not associated with a reduction in mortality in patients with diabetes and in patients without diabetes (Table 2) . Dexamethasone was not used as a treatment for COVID-19 during All authors declare no potential conflicts of interest. to the data, and accepts full responsibility for integrity of the data and the accuracy of the data analysis. The peer review history for this article is available at https://publons. com/publon/10.1111/dom.14692. Full access to primary data and statistical analyses are available upon request to the corresponding author. 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