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Introduction: Over the last three years, the world has been battling a long-drawn pandemic resulting from the coronavirus outbreak. Despite the safety measures, there have been multiple pandemic waves happening throughout the world. Therefore, it is necessary to understand the fundamental characteristics of COVID-19 transmission and pathogenesis to overcome the threat of the pandemic. This study focused on hospitalized COVID-19 patients because of their high mortality rate, which indicates the need to improve inpatient management., Methods: Based on the cyclic nature of the pandemic, observations were made to examine the influence of lunar phases on six vital parameters of COVID-19 patients. A multivariate analysis was carried out to study the interactions of lunar phase pairwise on COVID-19 statuses and COVID-19 status pairwise on lunar phases by treating six vital parameters as independent entities., Results: The results of multivariate analysis on the data of 215,220 vital values showed that lunar phases are associated with trends in variations in the vital parameters of COVID-19-infected patients., Conclusion: In summary, our results show that patients infected with COVID-19 appear to be more susceptible to lunar influence compared to non-COVID-19 patients. Furthermore, this study shows a vital parameter destabilization window (DSW) that can help identify which hospitalized COVID-19 patients can recover. Our pilot study forms the basis for future studies to eventually establish the incorporation of variation of vital signs with the lunar cycle into the standard of care for COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Koya et al.)