COVID-19 mortality in 1984 Bhopal gas tragedy survivors: implications for chemically exposed populations.

Leakage of methyl isocyanate from the Union Carbide plant in Bhopal, India, killed thousands and left deleterious trans-generational effects. Gas-exposed populations experience higher rates of lung and metabolic diseases, and immune dysregulation, all associated with adverse outcomes in coronavirus disease 2019 (COVID-19). We used publicly available, official data from government sources to estimate COVID-19-associated crude mortality in populations with and without a history of gas exposure. Overall, there were 1240 deaths among patients hospitalized with known COVID-19 in Bhopal, of which 453 (36.53%) were in gas-exposed individuals, 726 (58.55%) were in gas-unexposed individuals and the exposure status of 61 (4.92%) individuals could not be determined. There were 351 and 375 deaths in gas-unexposed people in the first (April 2020-February 2021) and second (March 2021-July 2021) waves, respectively; in the gas-exposed population, there were 300 and 153 deaths in the two respective waves. The overall annualized crude mortality of COVID-19 was 3.84 (95% CI 3.41 to 4.33) times higher in the gas-exposed population at 83.6 (95% CI 76.1 to 91.7) per 100 000 compared with the gas-unexposed population, at 21.8 (95% CI 20.2 to 23.4) per 100,000. When stratified by age, compared with unexposed people, the gas-exposed individuals experienced 1.88 (95% CI 1.61 to 2.21) and 1.24 (95% CI 1.02 to 1.50) times the mortality rates in the age groups of 35-65 and >65 y, respectively. These findings indicate that gas-exposed individuals are likely to have a higher risk of severe COVID-19 and death and need to be specifically targeted and recognized for preventive and promotive efforts.

Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis.

Liver is often exposed to plethora of chemical toxins. Owing to its profound physiological role and central function in metabolism and homeostasis, pertinent succession of cell cycle in liver epithelial cells is of prime importance to maintain cellular proliferation. Although recent evidence has displayed a strong association between exposures to methyl isocyanate (MIC), one of the most toxic isocyanates, and neoplastic transformation, molecular characterization of the longitudinal effects of MIC on cell cycle regulation has never been performed. Here, we sequentially delineated the status of different proteins arbitrating the deregulation of cell cycle in liver epithelial cells treated with MIC. Our data reaffirms the oncogenic capability of MIC with elevated DNA damage response proteins pATM and γ-H2AX, deregulation of DNA damage check point genes CHK1 and CHK2, altered expression of p53 and p21 proteins involved in cell cycle arrest with perturbation in GADD-45 expression in the treated cells. Further, alterations in cyclin A, cyclin E, CDK2 levels along with overexpression of mitotic spindle checkpoints proteins Aurora A/B, centrosomal pericentrin protein, chromosomal aberrations, and loss of Pot1a was observed. Thus, MIC impacts key proteins involved in cell cycle regulation to trigger genomic instability as a possible mechanism of developmental basis of liver carcinogenesis.

Association of microsatellite instability and chronic obstructive pulmonary disorder in isocyanate-Exposed population of Bhopal.

CONTEXT: Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR. AIMS: Molecular screening of the gas-affected population of Bhopal with COPD for microsatellite instability due to exposure of MIC. SETTINGS AND DESIGN: The isocyanate-exposed population of Bhopal city suffering from chronic obstructive pulmonary disorder. MATERIALS AND METHODS: Inter-(SSR) analysis was used to characterize microsatellite instability in 52 MIC victims of Bhopal, suffering from COPD using (CA)(8)RG and (CA)(8)R[Y-Q] primer. STATISTICAL ANALYSIS USED: Association analyses were performed using regression analysis. RESULTS: The study on the MIC-affected population in Bhopal showed weak association between microsatellite instability and age (r = + 0.37); exposure distance from site (r = -0.44); and smoking status(r = + 0.12); while regression analysis of the above parameters displayed supporting evidence. CONCLUSIONS: The high prevalence of smoking coupled with aging and poor living habits threatens, to further increase COPD incidences among this population, highlighting the need for enhanced screening efforts.