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

Chen, Zigui; Chong, Ka Chun; Wong, Martin C.S.; Boon, Siaw S.; Huang, Junjie; Wang, Maggie H.; Ng, Rita W.Y.; Lai, Christopher K.C.; Chan, Paul K.S.

OBJECTIVES: To examine SARS-CoV-2 variant replacement in association with containment capacity and changes in case-fatality at country level. METHODS: Altogether, 69,571 SARS-CoV-2 full genomes collected globally within the first six months of 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; whereas 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 group to reach 50% increment of G*, whereas only Singapore and South Korea had non-G* persisted throughout the first six months. Countries with higher IHR scores (β-coefficient: -0.001, 95% C.I. [-0.016, -0.001], p=0.034) and higher stringency indexes (OxCGRT) (β-coefficient: -0.011, 95% C.I. [-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% C.I. [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% C.I. [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 investigations.