IntroductionThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving, and many mutant variants of the virus are circulating in the world. Recurrent waves of COVID-19 have caused enormous mortality all across the globe. Considering the novelty of the virus, it becomes crucial for healthcare experts and policymakers to understand the demographic and clinical attributes of inpatient deaths in the first and second waves of COVID-19.MethodsThis hospital record-based comparative study was conducted at a tertiary care hospital in Uttarakhand, India. The study included all COVID-19 RT PCR-positive patients admitted to the hospital during the first wave, from 1stApril 2020 to 31stJanuary 2021, and the second wave from 1stMarch 2021 to 30thJune 2021. Comparisons were made with respect to demographic, clinical, laboratory parameters, and course of hospital stay.ResultsThe study exhibited 11.34% more casualties in the second wave, with the number of deaths being 424 and 475 for the first and second waves, respectively. A male preponderance of mortality was evident in both waves with significant differences (p=0.004). There was no significant difference in age between the two waves (p=0.809). The significantly different comorbidities were hypertension (p=0.003) and coronary artery disease (p=0.014). The clinical manifestations demonstrating a significant difference were cough (p=0.000), sore throat (p=0.002), altered mental status (p=0.002), headache (p=0.025), loss of taste and smell (p=0.001), and tachypnea (p=0.000). The lab parameters with a significant difference across both waves were lymphopenia (p=0.000), elevated aspartate aminotransferase (p=0.004), leukocytosis (p=0.008), and thrombocytopenia (p=0.004). During the hospital course of the second wave, in terms of intensive care unit stay, the need for non-invasive ventilation and inotrope support was higher. The complications manifesting in the form of acute respiratory distress syndrome and sepsis were observed more in the second wave. A significant difference was discerned in the median duration of hospital stay in both waves (p=0.000).ConclusionDespite being of shorter duration, the second wave of COVID-19 culminated in more deaths. The study demonstrated that most of the baseline demographic and clinical characteristics attributed to mortality were more common during the second wave of COVID-19, including lab parameters, complications, and duration of hospital stays. The unpredictable nature of COVID-19 waves calls for instituting a well-planned surveillance mechanism in place to identify the surge in cases at the earliest possible time and prompt response, along with developing infrastructure and capacity to manage complications.