Influence of Environmental Factors and Genome Diversity on Cumulative COVID-19 Cases in the Highland Region of China: Comparative Correlational Study

BackgroundThe novel coronavirus SARS-CoV-2 caused the global COVID-19 pandemic. Emerging reports support lower mortality and reduced case numbers in highland areas; however, comparative studies on the cumulative impact of environmental factors and viral genetic diversity on COVID-19 infection rates have not been performed to date. ObjectiveThe aims of this study were to determine the difference in COVID-19 infection rates between high and low altitudes, and to explore whether the difference in the pandemic trend in the high-altitude region of China compared to that of the lowlands is influenced by environmental factors, population density, and biological mechanisms. MethodsWe examined the correlation between population density and COVID-19 cases through linear regression. A zero-shot model was applied to identify possible factors correlated to COVID-19 infection. We further analyzed the correlation of meteorological and air quality factors with infection cases using the Spearman correlation coefficient. Mixed-effects multiple linear regression was applied to evaluate the associations between selected factors and COVID-19 cases adjusting for covariates. Lastly, the relationship between environmental factors and mutation frequency was evaluated using the same correlation techniques mentioned above. ResultsAmong the 24,826 confirmed COVID-19 cases reported from 40 cities in China from January 23, 2020, to July 7, 2022, 98.4% (n=24,430) were found in the lowlands. Population density was positively correlated with COVID-19 cases in all regions (ρ=0.641, P=.003). In high-altitude areas, the number of COVID-19 cases was negatively associated with temperature, sunlight hours, and UV index (P=.003, P=.001, and P=.009, respectively) and was positively associated with wind speed (ρ=0.388, P0.1). Key nonsynonymous mutations showed positive correlations with altitude, wind speed, and air pressure and showed negative correlations with temperature, UV index, and sunlight hours. ConclusionsBy comparison with the lowlands, the number of confirmed COVID-19 cases was substantially lower in high-altitude regions of China, and the population density, temperature, sunlight hours, UV index, wind speed, PM2.5, and CO influenced the cumulative pandemic trend in the highlands. The identified influence of environmental factors on SARS-CoV-2 sequence variants adds knowledge of the impact of altitude on COVID-19 infection, offering novel suggestions for preventive intervention.