A Comparative Study of the Patterns of Mortality in COVID-19 Patients in Juxtaposition with Non-COVID-19 Mortality in the First and Second Waves of the Pandemic.

BACKGROUND AND OBJECTIVES: The Coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to the public healthcare system worldwide like none before, producing far-reaching global economic, humanitarian, and social crises. It is estimated to have affected more than 1.8 million people worldwide. India has faced two phases of the pandemic, being the country with 2nd most number of deaths with varying mortality patterns across the two waves. In this study, we compare the patterns of mortality between the two phases of pandemics in association with COVID-19 and non-COVID-19 deaths. MATERIALS AND METHODS: A retrospective observational study at a tertiary care center in Central India was carried out. Demographic patterns of mortality have been studied in each of the groups, and a comparative analysis was done between COVID-19 and non-COVID-19 mortality patterns in each phase of the study, that is, from 20th March 2020 to 19th September 2020 and from 20th September 2020 to May 2021, as well as between the two phases. RESULTS: The case fatality rate of COVID-19 positive patients in the second phase of the study was 22.04%, whereas the those of non-COVID-19 patients in the second phase were found to be 15.95%. A maximum number of COVID-19 positive deaths during the first wave of the pandemic occurred in September 2020 and during the second wave in April 2021. In the first phase of the study, 69.6% of patients who died were males, and 30.3% were females, whereas in the second phase among COVID-19 positive subjects, 65% deaths were among males, and 35% deaths were among females. COVID-19 positive mortality in the second phase showed, 26.53% to be hypertensive, while 13.8% were diabetic. CONCLUSION: It was found that most of the deaths in both phases of COVID-19 amongst COVID-19 positive patients and non-COVID patients were amongst the elderly population (>60 years) with male predominance. Most deaths in both populations occurred during the first 3 days of admission whereas it was relatively less in the second phase. Noncommunicable diseases like systemic hypertension, and DM had a significant influence on all-cause mortality and morbidity in both COVID-19 positive and non-COVID-19 patients in the first and second waves of COVID-19. Noncommunicable diseases thus played a major role in mortality among both the populations under study.

In vitro apoptotic effect on human lymphatic filarial parasite by piperidine derivatives and thymidine reversal study.

A novel library of synthetic piperidine derivatives was used to screen against human lymphatic filarial parasite Brugia malayi. Piperidine has earlier been reported to have effect against parasites including rodent filarial nematodes. Compounds with hydroxyl substitutions (4Q and 4H) showed marked antifilarial effect. Molecular docking of 4H derivative showed more favorable thermodynamic parameters against thymidylate synthase of B. malayi than human counterpart. A wide difference between IC50 and LD50 ensured the therapeutic safety of the candidates against the filarial parasites. Addition of thymidine to the treatment regimen led to a significant reversal of antifilarial effect of 4H that confirmed inhibition of thymidylate synthase as pharmacological rationale. Apoptosis induced in the parasite as a consequence of probable inhibition of thymidylate synthase was studied by acridine orange/ethidium bromide fluorescent staining and poly (ADP-ribose) polymerase activity inhibition. Involvement of mitochondria was confirmed by decreased 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) conversion and increased cytosolic cytochrome c level in 4H treated microfilariae, compared with the untreated microfilariae. Moreover, Michael adduct of chalcone targeting dihydrofolate reductase and piperidine targeting thymidylate synthase demonstrated synergistic effect on the parasite, indicating the importance of inhibition of DNA synthesis by combined effect. In conclusion, piperidine derivatives with hydroxyl substitution have a great therapeutic potential with an apoptotic rationale involving mitochondrial pathway, due to possible inhibition of parasitic thymidylate synthase.