SARS-CoV-2 antibody response and serum neutralizing capacity of early unvaccinated COVID-19 patients in the Philippines

• Critical understanding of the natural infection-induced protective antibody response and the extent of the interindividual variation therein has fundamental bearing in dealing with emerging infectious diseases, including those caused by coronavirus. • Early COVID-19 patients having high binding antibodies against SARS-CoV-2 but low neutralizing capacity to the virus found in this study might be one of the contributory factors to disease pathogenesis, severity and mortality outcomes . • Following future resurgence of related viral infections, treatment strategies involving passive antibody therapies should be recommended and deployed with caution. The immune response to SARS-CoV-2 infection, particularly the dynamics of antigen-specific and isotype-specific antibodies, is critical for understanding disease progression and outcomes. This study characterizes the antibody profiles and serum neutralizing capacity as well as its relationship with disease severity among COVID-19 patients from the Philippines, prior to the national COVID-19 vaccination rollout. A total of 177 serum samples from 67 hospitalized patients with RT-PCR-confirmed COVID-19 were analyzed during the first wave of the pandemic between October 2020 to April 2021. Various antibody isotypes (IgG, IgM, and IgA) against SARS-CoV-2 S1, S2, RBD, and N proteins, as well as IgG antibodies against human ACE2, were quantified by enzyme-linked immunosorbent assay (ELISA). Serum neutralizing capacity was assessed by ACE2-RBD binding inhibition assay and pseudovirus neutralization assays. The relationship of the binding antibodies with various clinical parameters was also determined. IgG, IgM, and IgA antibody responses were associated with disease severity within two weeks of symptom onset. Notably, IgM responses positively correlated with elevated inflammatory markers, including ferritin and C-reactive protein, while IgM-N predicted in-hospital mortality. However, patient sera lacked neutralizing activity against the SARS-CoV-2 Wuhan strain. While the ACE2 IgG antibodies were detected, their presence was not associated with disease severity or inflammatory responses. These findings suggest that while binding antibodies are prevalent early in infection among COVID-19 patients early in the pandemic, serum neutralizing capacity remains low in the absence of vaccination. The clinical significance of detectable anit-ACE2 antibodies in COVID-19 warrants further investigation.