Clinical characterisation, treatment outcomes, and case fatality risk of patients with different SARS-CoV-2 variants in Bangladesh.

Background: Bangladesh underwent four waves of the coronavirus disease 2019 (COVID-19) pandemic. Analysing them is essential for understanding changes in viral behaviour, disease patterns, severity, and response to treatment. Nevertheless, data are scarce in low- and middle-income countries. Therefore, we aimed to compare clinical manifestations; outcomes for therapy with oxygen, dexamethasone, and remdesivir; as well as the case fatality during the ancestral, alpha/beta, delta, and omicron-driven waves. Methods: We conducted an observational study at five hospitals in Dhaka, Bangladesh, with at least one dedicated COVID-19 unit for treating patients that followed national guidelines between November 2020 and February 2022. We collected data prospectively between 1 July 2021 and 30 September 2021 (delta) and retrospectively from 1 November 2020 to 4 March 2021 (ancestral), 5 March 2021 to 30 May 2021 (alpha/beta), and 1 January 2022 to 28 February 2022 (omicron), with the periods representing distinct waves of COVID-19. The primary outcome was 30-day case fatality across the waves. We used multivariable robust Poisson regression models with robust variance to estimate the 30-day case fatality risk ratio during various waves. Results: Among 966 participants, the rate of 30-day case fatality was comparable across different variants. However, the proportions of patients with fever (P < 0.001), cough (P < 0.001), breathing difficulty (P < 0.001), nausea (P < 0.001), fatigue (P < 0.001), headache (P < 0.001), diarrhoea (P < 0.001), loss of smell (P < 0.001), runny nose (P < 0.001), and chest pain (P = 0.001) were smaller during the omicron wave than the other three waves. After adjusting for potential confounders, the multivariable model showed that the likelihood of case fatality was significantly associated with age (adjusted risk ratio (aRR) = 1.05; 95% confidence interval (CI) = 1.04-1.07); hypoxaemia (aRR = 5.29; 95% CI = 1.58-17.7); critical disease (aRR = 6.45; 95% CI = 1.89-21.99), and modified early warning score ≥4 (aRR = 2.58; 95% CI = 1.71-3.88). We observed an 85% (aRR = 0.15; 95% CI = 0.03-0.72) reduction in case fatality among patients with any oxygen (L/min) compared to those without oxygen. However, individuals requiring ≥15 L/min of oxygen showed a significantly higher case fatality compared to those needing <15 L/min oxygen (aRR = 5.63; 95% CI = 2.68-11.81 for ancestral variant, aRR = 2.83; 95% CI = 1.25-6.41 for alpha/beta variant, aRR = 2.73; 95% CI = 1.56-4.77 for delta variant, aRR = 2.84; 95% CI = 1.56-5.16 for omicron variant). Remdesivir was associated with an increased case fatality during alpha/beta (aRR = 6.96; 95% CI = 1.54-31.43), delta (aRR = 4.13; 95% CI = 1.17-14.58), and omicron waves (aRR = 8.89; 95% CI = 2.46-32.13) compared to the ancestral wave. Dexamethasone administered during admission did not have any significant association with death (P = 0.239) in the entire cohort. However, dexamethasone reduced case fatality by 78% among the moderate to severe COVID-19 subgroup. We observed a 37% reduction in case fatality among vaccinated participants compared to those without vaccination (aRR = 0.63; 95% CI = 0.40-0.99). Conclusions: Our study provides insights into the clinical patterns, treatment impact, and case fatality across various SARS-CoV-2 variants in resource-limited settings. The findings underscored the crucial role of oxygen therapy and vaccination in reducing COVID-19 case fatality. They also emphasise the necessity for continuous disease surveillance and highlight the importance of close monitoring of patients with higher oxygen requirements (≥15 L/min) due to their association with fatal outcomes, as well as the significance of sustaining vaccination efforts and the need for clinical trials of newer antivirals in the ongoing battle against COVID-19.