Association analysis of long-term surveillance data for COVID-19 globally in 2020-2023: The relationship between COVID-19 infection, mortality, virus mutation and vaccination and natural immunity

Objective The Corona virus disease 2019(COVID-19) rapidly spread across the world after its emergence in 2019 and is still ongoing. The epidemic are closely related to virus mutation, vaccination, and natural immunity, but there is still a lack of long-term surveillance data analysis to quantify their interaction. Methods We downloaded the data on the number of new COVID-19 cases, new deaths and vaccination doses globally from January 2020 to September 2023 from the OWID database. Representative countries with complete information collection were selected to analyze the correlation between the monthly vaccination population, the naturally infected population,new cases, and new deaths of COVID-19, respectively, quantified by Pearson partial correlation coefficient r value. Stratified analysis was performed according to the SARS-COV-2 variants and vaccine types. Results In the early stage of the COVID-19 epidemic, the global total data showed a weak correlation between COVID-19 vaccination and the number of new cases (r=-0.357, P=0.386), and a significant association with deaths (r=-0.894, P=0.003), and differentiation among six typical countries, but all were negative. There was a significant negative association between natural immunity to COVID-19 and new cases (r=-0.795, P=0.018), and a moderate association with COVID-19 deaths (r=-0.614, P=0.270). Again, the strength of the association varied across countries, but all were negative. In the late stage of the COVID-19 pandemic, global data showed a positive correlation between COVID-19 vaccination and new infections and deaths (r=0.715; r=0.865), stratified analysis showed that except for the weak negative association in China, the other 5 countries showed moderate/strong positive association. There was a moderate negative correlation between global natural immunity to COVID-19 and new infections and deaths (r=-0.627; r=-0.669), but there are differences between countries. Conclusions In the early stages of the pandemic, vaccination reduces the risk of death from COVID-19, and natural immunization reduces the risk of both infection and death. In the late stage of the epidemic, vaccines against the previous strains have no significant protective effect, but sustained natural immunity can still reduce the risk of infection and death to a certain extent, playing a major role in protecting the population. Besides, the regional differences should be considered in the evaluation of the effect.