Hyperinflammatory conditions, gender differences and mortality in Indian COVID-19 patients

Shoeb, F.; Hussain, I.; Afrin, G.; Mufti, S. T.; Raza, S. T.; Mahdi, F.

Purpose Evidence suggests that COVID-19 induces hyperinflammatory conditions and causes relatively more deaths in males than females. The purpose of this study was to analyze gender differences associated with various hyperinflammatory conditions (HIC) and mortality in the Indian COVID-19 patients Methods: This study was conducted at the Era's Lucknow Medical College and Hospital (ELMCH), ERA University, which is located in the northern part of India. Starting from July 4, 2020 till December 3, 2020 a total of 2997 patients were treated at ELMCH. We randomly collected blood samples from 150 severe COVID-19 patients (required oxygen) between August 10 and September 15, 2020 for analyzing the following HIC and associated laboratory markers: hyperferritinaemia (serum ferritin), hematological dysfunctions (lymphocytopenia and neutrophil to lymphocyte ratio), cytokinaemia (C-reactive protein), coagulopathy (D-dimer), liver inflammation (aspartate aminotransferase), renal inflammation (blood urea and creatinine), and hyperglycemia (random blood glucose). The threshold values/cut off limits of these laboratory markers used for analyzing the risk of mortality in male and female COVID-19 patients were set according to the scale validated recently by Webb et al, (2020). Results: In the above cohort of consecutively admitted COVID-19 patients, analysis of various HIC revealed hyperferritinaemia (odd ratio: 2.9, 95% CI 1.4-6.0), hematological dysfunctions (odd ratio: 2.10, 95% CI 1.0-4.2), hepatic inflammation (odd ratio: 2.0, 95% CI 0.52-7.40), and coagulopathy (odd ratio: 1.5, 95% CI 1.50, 95% CI 0.50-4.60) were more prevalent and sever in male COVID-19 patients. Approximately 86% male to 64% female COVID-19 patients developed lymphocytopenia. Regarding mortality, while hyperferritinaemia (odd ratio: 1.70, 95% CI 0.37-7.43) and cytokinaemia (odd ratio: 1.60, 95% CI 0.37 -7.30) were strongly associated with mortality in male COVID-19 patients, coagulopathy (odd ratio: 3.30, 95% CI 0.31-35), and hematological dysfunctions (odd ratio: 1.70, 95% CI 0.27-10) were more commonly associated with mortality in female COVID-19 patients. Nearly 80% male and female COVID-19 patients, who died had developed [≥]2 criteria of HIS criteria. Chronic renal disease was associated with more deaths in female than male COVID-19 patients (odd ratio: 2.0, 95% CI 0.54 - 7.4). While the mortality proportion was slightly higher in male (6.3%) than female (4.5%) COVID-19 patients, survival curves of the two genders were not different (hazard ratio: 1.02, 95% CI 0.71-1.40, P = 0. 953). Conclusion: Distinct HIC were associated with the severity, and mortality in male and female COVID-19 patients. Coagulopathy and renal injury were detrimental, specifically, for female COVID-19 patients. The overall mortality proportion was around 5.3%. The above results suggest that gender differences associated with COVID-19 severity and mortality arise due to differences in various HIC. These results may help in developing personalized or gender based treatments for COVID-19 patients. Keywords: COVID-19; Gender susceptibility; hyperinflammatory syndrome; Hyperferritinaemia; Hematological dysfunctions; Cytokinaemia; Coagulopathy; live inflammation; renal inflammation; hyperglycemia