Pre-Existing Immunity to Beta-Coronaviruses HKU1 and OC43 May Affect Susceptibility to SARS-CoV-2 Infection

Non-SARS coronaviruses (HCoVs) contribute substantially to seasonal common colds. Their struc¬tural homology with SARS-CoV-2 suggests a possible cross-reactivity and cross-protection. The presence of IgG to the most common HCoVs (NL63, 229E, OC43, HKU1) in correlation with RBD-specific IgG and IgA, and the susceptibility to SARS-CoV-2 infection was evaluated in 48 individuals with recently diagnosed moderate SARS-CoV-2 infection (A, n=24) or intensive exposure to SARS-CoV-2 (B, n=24). Anti-S1 IgG for each of the four HCoVs, alongside with RBD-IgG and RBD-IgA were evaluated using ELISA (Creative Diagnostics, USA; Euroimmune, Germany). RBD-specific IgG and IgA were detected in 37% and 71% of group A (average levels 8.5 and 6.8) and 42% and 29% of group B (average levels 3.4 and 4.6 respectively, p<0.05). IgG specific for NL63, 229E, and OC43 was present in 100.0%, and for HKU-1 - in 94% of tested samples (average index 7.4, 3.9, 4.1, and 2.6, respectively). The levels of IgG to NL63 and 229E did not differ significantly between the groups (7.6 vs.7.2; 3.7 vs. 4.1, p>0.05), nor did correlate with anti-SARS-CoV-2 response. HKU-1-specific IgG was significantly decreased in COVID-19 patients (A) as compared to SARS-CoV-2 resistant donors (B): 1.98vs.3.2, p<0.01. Curiously, OC43-spe¬cific IgG was lower in the group with intensive exposure to SARS-CoV-2 (3.5vs.4.7, p<0.01), and correlat-ed with RBD-specific IgA (R=0.42, p<0.05). IgG to seasonal coronaviruses is commonly detected, but only HKU-1-specific IgG was associated with resistance to SARS-CoV-2 infection. OC43-specific IgG may be induced simultaneously with RBD-specific IgA and interfere with SARS-CoV-2 neutralization.