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Aim: The aim of the study was to correlate environmental changes with coronavirus disease 2019 (COVID-19) cases in four metropolitan cities. Methodology: Data on monthly cumulative new cases, monthly average temperatures, humidity, precipitation, and average monthly air quality index (AQI) levels for the four Indian cities – Chennai, New Delhi, Mumbai, and Kolkata, and biomedical waste (BMW) quantity at national level were abstracted for the period from March 2020 to December 2020. Results: An inverse correlation was observed between temperature and transmission of the disease in New Delhi and Kolkata which was of fair degree for New Delhi (r = 0.299, P = 0.402) and poor for Kolkata (r = 0.200, P value = 0.579). Positive correlation of fair and poor degrees was observed between temperature and transmission of the disease in Mumbai (r = 0.272, P = 0.448) and Chennai (r = 0.196, P = 0.588), respectively. A positive correlation was observed between the transmission of the disease and humidity in New Delhi, Mumbai, and Kolkata, which was of moderate-to-good degree for Mumbai (r = 0.729, P = 0.017) and poor for New Delhi (r = 0.242, P = 0.501) and Kolkata (r = 0.123, P = 0.735). A significant positive correlation was observed between the rise in COVID-19 cases and the quantity of BMW generated (r = 0.88, P = 0.009). Furthermore, significant improvement in air quality AQI in four metros and water quality biological oxygen demand/chemical oxygen demand of Yamuna river was observed. Conclusions: Understanding of the interplay of environmental meteorological factors on COVID-19 disease transmission and vice versa is necessary for better informed policy framing and future research.