Evolutionary Dynamics of SARS-CoV-2 Variants under Strict Non-Pharmaceutical Interventions - a Population-Based Study.

Introduction: China implemented a dynamic zero-COVID strategy to curb viral transmission in response to the coronavirus disease 2019 (COVID-19) pandemic. This strategy was designed to inhibit mutation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. This study explores the dynamics of viral evolution under stringent non-pharmaceutical interventions (NPIs) through real-world observations. Methodology: Our analysis encompassed all polymerase chain reaction (PCR)-confirmed COVID-19 cases (n = 780) from two consecutive outbreaks occurring in July to August 2021. Epidemiological investigations and in-depth viral genome analyses were conducted to determine the sources of infection and the inter-outbreak linkages. Results: The outbreaks likely originated via contaminated objects from an imported COVID-19 case to local airport cleaners. Most patients presented clinically mild symptoms. All viral genomes clustered into a single clade, with genomes from the subsequent Yangzhou outbreak forming a distinct branch, diverging from those of the initial Nanjing outbreak. Compared to the Wuhan-Hu-1 strain, the Delta variants isolated from the imported case and early local cases in Nanjing had 35 nucleotide mutations and three deletions. Various single nucleotide variant (SNV) combinations were observed in subsequent transmissions, with NPIs accounting for the termination of 67.2% (92/137) of SNV combinations. Stringent implementation of NPIs resulted in a greater number of terminated SNV combinations than emerging ones. Additionally, vaccination of cases was associated with SNV combination termination. Conclusions: This study underscores the significant role of NPIs in preventing the accumulation of SARS-CoV-2 mutations.