New variants of concerns
New variants of SARS-CoV-2 emerged sequentially, becoming the predominant strains during the pandemic. These variants have distinct ACE2 binding affinity, virulence, transmissibility and host immune responses88-100 (Figure 1). Currently, the most pronounced risk factor for SARS-CoV-2 infection is the emergence of new variants or subvariants that are resistant to neutralizing antibodies and with higher transmissibility101. The subvariants BA.4 and BA.5, most likely stem from Omicron lineage BA.2101, were firstly detected in South Africa99 and are now spreading in Europe and the United States102. BA.4 and BA.5 have become the dominant VOC in many European countries. The hospitalization and death rate of BA.4 and BA.5 were significantly lower compared to previous waves of infection in South Africa99, which may be due to the high population immunity. However, in Portugal, the hospitalization and mortality caused by BA.4/5 were similar to that in the first wave of Omicron infection, which may be due to the higher proportion of elderly individuals in this country101. BA.4 and BA.5 carry additional mutations in the spike proteins assisting the immune escape induced by 3-dose vaccinations and by post-vaccination infection of BA.1103,104. The Omicron variant is continuously evolving escape antibody neutralization resulting in breakthrough infection of SARS-CoV-2 in both vaccinated and in previously infected individuals105. The biological and clinical characteristics of rhinovirus, influenza A, SARS-CoV-2 variants delta, Omicron BA.1 and BA.5 are compared in Table 1.