Investigation of SARS-CoV-2 IgG Binding Capability to Variants of the SARS-CoV-2 Virus

The SARS-CoV-2 pandemic has confirmed that the ability to rapidly mutate may be extremely beneficial for a virus. Not long after the first wave, new variants emerged with altered infectivity, disease severity, and mortality. These new strains most notably had numerous mutations of the spike (S) protein, a surface protein responsible for binding to and entering the host cell. The Delta and Omicron strains demonstrated increased immune evasion and improved binding affinity to the host cell receptor, angiotensin-converting enzyme 2 (ACE2). This study examines the ability of wild-type SARS-CoV-2 IgG to bind Delta and Omicron antigens, as well as their functional binding capabilities to two different S-ACE2 complexes. Twenty SARS-CoV-2 positive samples from patients who had recovered from infection with ancestral SARS-CoV-2 in the first wave of COVID-19 and 10 pre-pandemic control samples were studied. SARS-CoV-2 exposed patients showed significantly higher levels of IgG to SARS-CoV-2 S1/RBD (<i>p</i> < 0.001), N protein (<i>p</i> < 0.001), and Omicron spike variant (<i>p</i> = 0.01), but not to Delta spike variant (<i>p</i> = 0.966) when compared with controls. Furthermore, patient samples showed significantly greater inhibition of SARS-CoV-2 S1/RBD and E484K spike to ACE2 binding (<i>p</i> < 0.001 and <i>p</i> = 0.015, respectively). Conversely, there was no correlation between the binding inhibition of S1/RBD and E484K spike to ACE2 receptor. This study shows there is considerable cross-reactivity of IgG generated by wild-type SARS-CoV-2 infection to the Delta and Omicron variants.