Introduction Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette–Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. Methods In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18–60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. Results There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54–2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20–0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28–80%) for likely symptomatic COVID-19 infection. Conclusions BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. Clinical Trials Registry Clinical Trials Registry India (CTRI/2020/07/026668).

A cytokine storm is an important cause of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19). The objective of the study was to determine the prognostic significance of pro-inflammatory cytokines with the overall final outcome of patients with COVID-19. We conducted a retrospective study of 142 patients admitted with COVID-19 in the Department of Medicine at All India Institute of Medical Sciences, New Delhi, from May 2021 to June 2021. We obtained their demographic, clinical, and biochemical characteristics at baseline and 48-72 hours prior to the terminal event (survival/death). The data were analyzed to determine the prognostic significance of these markers on the final outcome. Higher levels of inflammatory markers were associated with a worse final outcome (ferritin p-value <0.001, c-reactive protein (CRP) p-value <0.001, interleukin 6 (IL-6) p-value 0.007, procalcitonin p-value 0.005, and lactic acid p-value 0.004). Optimal probability cut-offs for these markers for predicting mortality were: ferritin: 963 ng/mL (sensitivity - 67.35%, specificity - 67.50%), CRP: 66.3 mg/L (sensitivity - 78.43%, specificity - 74.12%), IL-6: 46.2 pg/mL (sensitivity - 59.26%, specificity - 59.57%), procalcitonin: 0.3ng/mL (sensitivity - 65.38 %, specificity - 66.67%), lactic acid: 1.5 mg/dL (sensitivity - 59.26%, specificity - 58.57%). Multivariate logistic regression analysis was done, which showed that pre-terminal event CRP was associated with a statistically significant higher risk of mortality (Unadjusted OR 18.89, Adjusted OR 1.008, p=0.002, 95% CI 6.815 - 47.541). Inflammatory markers have a prognostic significance in patients with COVID-19, with higher levels being associated with worse outcomes.

This meta-analysis aims to highlight the impact of cardio-metabolic comorbidities on COVID-19 severity and mortality. A thorough search on major online databases was done for studies describing the clinical outcomes of COVID-19 patients. We used random-effects model to compute pooled estimates for critical or fatal disease. A total of 20,475 patients from 33 eligible studies were included. Maximum risk of development of critical or fatal COVID-19 disease was seen in patients with underlying cardiovascular disease [OR: 3.44, 95% CI: 2.65–4.48] followed by chronic lung disease, hypertension and diabetes mellitus. Of the total cases, 64% had one of the four comorbidities with the most prevalent being hypertension with a pooled prevalence of 27%. Presence of comorbidities like cardiovascular disease, chronic lung disease, hypertension and diabetes mellitus led to a higher risk of development of critical or fatal COVID-19 disease, with maximum risk seen with underlying cardiovascular disease.

During the coronavirus disease 2019 (COVID-19) pandemic in India, several characteristics of hospitalized COVID-19 patients, based on demographics, mortality predictors, and presence of comorbidities, were found to be associated with poor outcomes. The objective of this study was to identify such epidemiological and clinical characteristics among the patients admitted at a tertiary-care center in India that may have predisposed them to COVID-19-related mortality. This retrospective observational study conducted at the Department of Medicine, All India Institute of Medical Sciences, New Delhi, in May 2021 included 141 COVID-19 confirmed patients. The medical history, demographic characteristics, comorbidities, clinical findings, and laboratory data of each patient were obtained. The data were analyzed to identify significant clinical and laboratory parameters that led to the adverse final outcomes. Hypertension was the most common comorbidity and the presence of diabetes with hypertension led to poorer final outcomes. Lower oxygen saturation and requirement of oxygen supplementation at admission along with worse prognostic scores during admission led to poorer outcomes. Twenty-seven patients needed non-invasive ventilation (NIV) during the hospital course, and all ultimately landed up among the 56 patients who were managed on invasive mechanical ventilation (IMV). Multivariate logistic regression analysis performed identified COVID-19 severity at admission, co-existence of hypertension and diabetes mellitus, systolic blood pressure less than 90 mm Hg, and serum creatinine greater than 1.2 mg/dL to be associated with higher COVID-19 mortality. COVID-19 patients having the co-existence of diabetes and hypertension constitute a high-risk group and may be targeted by prompt vaccination strategies. The presence of severe disease along with a need for oxygen therapy and other intensive care interventions ultimately led to unfavorable outcomes.