Abstract Background The kinetics of antibody responses to SARS-CoV-2 infection are not fully understood. We analyzed IgG responses to the SARS-CoV-2 Spike protein receptor binding domain (RBD) in COVID-19 patients admitted to VA Greater Los Angeles (VAGLA) and correlated with clinical outcomes. Methods Serially admitted patients from March 20-May 10, 2020 with at least one available residual serum specimen were included in this analysis. Serum samples selected for analysis included first, last, and intermediaries spaced ≥ 5 days apart, as available. Anti-RBD IgG was detected with an enzyme immunoassay (EIA) using recombinant RBD protein. Serum from an uninfected individual collected April 2019 was used as control. The average optical density of the control in triplicate plus 3 standard deviations was considered the threshold positive/negative value. The highest dilution above the threshold value was considered the IgG titer. Clinical groups were defined as asymptomatic, moderate/severe (no ICU) or critical (mechanical ventilation, cytokine storm and/or death). Results Of the 43 consecutive patients admitted to VAGLA with COVID-19 in this analysis, 40 developed detectable RBD IgG responses with maximum inverse titers (MIT) ranging 100-819,200, geometric mean 12,152. Five patients remained asymptomatic but had positive EIAs with median MIT 3200 (IQR 800–3200). Twenty-five had moderate-severe illness with median MIT 25600 (IQR 6400–102400). Ten patients with critical disease had median MIT 38400 (IQR 8800–51200). The median time to positive IgG was 10 days for asymptomatic (IQR 10,10), 4 days for moderate-severe (IQR 3,15), and 7 days for critical (IQR 3.5,14.5). The figure depicts RBD IgG titers over time after onset of symptoms. Asymptomatic patients had a more gradual rate of increase and lower peak titers, while critical patients had the fastest rate of rise and the highest peak titers. Of the 21 patients with samples > 30 days after symptom onset (range 31–67 days), there was no evidence for decrease in anti-RBD IgG. Kinetics of IgG to SARS-CoV-2 receptor binding domain by clinical severity Conclusion Following infection with SARS-CoV-2, disease severity correlates with both the rate of increase and peak in antibody titers. Anti-RBD IgG titers did not decrease over the observation period. Disclosures All Authors: No reported disclosures