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.
ABSTRACT
Background: Despite numerous outbreaks, antibody responses to SARS-CoV-2 in residents of skilled nursing facilities (SNF) are not well described. We reviewed serological test results in a cohort of SNF residents who had been repetitively screened for SARS-CoV-2 infection by nasopharyngeal swab PCR. Methods: In late March 2019, we identified symptomatic SARS-CoV-2 PCR positive residents at a SNF. In response, all remaining SNF patients were serially screened, and all SARS-CoV-2 PCR positive patients were transferred to the acute care hospital or cohorted in a separate COVID Recovery Unit (CRU) in the SNF. In early June, all SNF residents (SARS-CoV-2 PCR positive and negative) underwent serologic testing for SARS-CoV-2 Spike (S1/S2) IgG (DiaSorin). DiaSorin IgG-positive results for patients that were SARS-CoV-2 PCR-negative were reflexed to nucleocapsid IgG (Abbott). Antibody testing occurred a median of 69 days (63-70 IQR) after PCR positivity. Results: Nineteen SARS-CoV-2 PCR positive residents were identified from the outbreak and an additional 9 were transferred from the acute care hospital to the CRU;1 died and 1 received convalescent plasma leaving 26 SARS-CoV-2 PCR positive residents, including 6 who were asymptomatic, that were eligible for serologic testing. Twenty-four of the 26 were positive for IgG by the DiaSorin assay;one seronegative resident was one of the asymptomatic residents. There were an additional 121 residents in the SNF whose SARS-CoV-2 PCR was negative at least once. Among these 121 SNF residents with negative SARS-CoV-2 RT-PCR, all but two were seronegative by the Diasorin assay. The two seropositive residents had no nucleocapsid antibodies when reflex tested by the Abbott assay. Conclusion: In a limited sample of SNF residents with SARS-CoV-2 PCR positivity, the sensitivity of the Diasorin assay was 92% (24/26) and the specificity was 98% (119/121). None of the residents with negative SARS-CoV-2 PCR had confirmed positive antibody results using reflex testing (DiaSorin/Abbott). Despite high risk exposure in congregate living facilities, we found no evidence of additional SARS-CoV-2 exposure, reinforcing the importance of serial surveillance SARS-CoV-2 testing and early cohorting in SNF settings. (Table Presented).