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 (p < 0.001), N protein (p < 0.001), and Omicron spike variant (p = 0.01), but not
to Delta spike variant (p = 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 (p < 0.001 and p = 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 SARSCoV-
2 infection to the Delta and Omicron variants.
Keywords: SARS-CoV-2, spike protein, ACE2 receptor, COVID-19, coronavirus, inhibition of binding