Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors

Abstract

Background: Characterizing the kinetics of the antibody response to SARS-CoV-2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection. Methods/Materials: We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA). Results: From April to November 2020 we enrolled 202 donors, mean age 47.3 +/- 14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12 -163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA50 were positively associated with mean IgG levels (p = <0.0001). Mean IgG levels and neutralizing titers were positively associated with COVID-19 severity, increased donor age and BMI (p=0.0006 and p=0.0028, p=0.0083 and p=0.0363, (p=0.0008 and p=0.0018, respectively). Over the course of repeat visits, IgG decreased in 74.1% of donors; FRNA50 decreased in 44.4% and remained unchanged in 33.3% of repeat donors. A weak negative correlation was observed between total Ab levels and number of days post-symptom recovery (r = 0.09). Conclusion: Anti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.

Persistence of Anti-SARS-CoV-2 Antibodies Six Months after Infection in an Outbreak with Five Hundred COVID-19 Cases in Borriana (Spain): A Prospective Cohort Study

“…However, in obese COVID-19 patients, a reverse association has been observed between high BMI and lower SARS-CoV-2 antibodies [41]. In addition, the increase of SARS-CoV-2 antibodies in the second survey was associated with age older, higher BMI, more severe disease [42] and low current smoke. A hypothesis was suggested that a tobacco mosaic RNA virus, presented in the respiratory tract of smokers, could have some protection against the SARS-COV-2 virus [43].…”

Persistence of Anti-SARS-CoV-2 Antibodies Six Months After Infection in an Outbreak With Five Hundred COVID-19 Cases in Borriana (Spain): A Prospective Cohort Study

“…However, in obese COVID-19 patients, a reverse association has been observed between high BMI and lower SARS-CoV-2 antibodies [41]. In addition, the increase of SARS-CoV-2 antibodies in the second survey was associated with age older, higher BMI, more severe disease (42) and low current smoke. A hypothesis was suggested that a tobacco mosaic RNA virus, presented in the respiratory tract of smokers, could have some protection against SARS-COV-2 virus (43).…”

COVID-19 antibody detection and assay performance using red cell agglutination

“…The surface-exposed location of the spike glycoprotein makes it a major target of neutralizing antibodies [16]. An in-house developed fluorescence reduction neutralizing assay (FRNA; not authorized by FDA; sensitivity and specificity data not available) [17] was performed to detect neutralizing antibodies against the SARS-CoV-2 virus (NT50) in all 140 CCP samples [14].…”

“…These C19-kodecytes are agglutinated in the presence of SARS-CoV-2 antibodies using routine serologic platforms. We perform a clinical evaluation of this C19-kodecyte assay in CCP donors previously assessed with 2 commercial immunoassays and a virus neutralizing assay [14]. Amendments of 1988 (CLIA), were used to detect total binding antibodies against the SARS-CoV-2 virus in all 140 CCP donors [14,15].…”

“…We perform a clinical evaluation of this C19-kodecyte assay in CCP donors previously assessed with 2 commercial immunoassays and a virus neutralizing assay [14]. Amendments of 1988 (CLIA), were used to detect total binding antibodies against the SARS-CoV-2 virus in all 140 CCP donors [14,15]. The 125 healthy volunteer donors were only tested with the Ortho Total assay.…”