A global analysis of replacement of genetic variants of SARS-CoV-2 in association with containment capacity and changes in disease severity

OBJECTIVES: To examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant replacement in association with containment capacity and changes in case fatality at country level. METHODS: Altogether, 69 571 full SARS-CoV-2 genomes collected globally within the first 6 months of the pandemic were examined. The correlation between variant replacement and containment capacity was examined by logistic regression models using the WHO International Health Regulation (IHR) score, the Oxford COVID-19 Government Response Tracker (OxCGRT) and the vulnerability index INFORM as proxies, while correlation with changes in monthly crude case fatality ratios was examined by a mixed effect model. RESULTS: At the global level, variant lineage G∗, characterized by the S-D614G mutation, replaced the older lineages L and S in March 2020. European countries—including Finland, France and Italy—were the first to reach a 50% increment of G∗, whereas only Singapore and South Korea had non-G∗ persisting throughout the first 6 months. Countries with higher IHR scores (β-coefficient –0.001, 95%CI –0.016, –0.001; p 0.034) and higher stringency indexes (OxCGRT) (β-coefficient –0.011, 95%CI –0.020, –0.001; p 0.035) were associated with lower levels of G∗ replacement, whereas higher vulnerability indexes (INFORM) (β-coefficient 0.049, 95%CI 0.001, 0.097; p 0.044) were associated with higher replacement levels. Crude case fatality ratio showed a positive correlation with G∗ replacement (β-coefficient: 0.034, 95%CI 0.011, 0.058; p 0.004), even after adjusting for testing capacity and other country-specific characteristics. CONCLUSIONS: SARS-CoV-2 variant lineage G∗ (S-D614G) replaced older lineages more efficiently in countries with lower containment capacity, and its possible association with increased disease severity deserves further investigation.