Clinical, laboratory, and temporal predictors of neutralizing antibodies against SARS-CoV-2 among COVID-19 convalescent plasma donor candidates

Boonyaratanakornkit, Jim; Morishima, Chihiro; Selke, Stacy; Zamora, Danniel; McGuffin, Sarah A.; Shapiro, Adrienne E.; Campbell, Victoria; McClurkan, Christopher L.; Jing, Lichen; Gross, Robin; Liang, Janie; Postnikova, Elena; Mazur, Steven; Lukin, V. V.; Chaudhary, Anu; Das, Marie K.; Fink, Susan L.; Bryan, Andrew; Greninger, Alexander L.; Jerome, Keith R.; Holbrook, Michael R.; Gernsheimer, Terry; Wener, Mark H.; Wald, Anna; Koelle, David M.

doi:10.1172/jci144930

Cited by 78 publications

(105 citation statements)

References 38 publications

(21 reference statements)

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“…When correlating IgG antibody levels and neutralizing titers with clinical picture, our results are consistent with previously published data, observing positive correlation with disease severity [20][21][22][23], age [24][25], and BMI [26][27]. While some reports observed a correlation between antibody levels and male sex [28], we did not observe a statistically significant association in our study.…”

Section: Discussionsupporting

confidence: 92%

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

Giorgi

West

Henning

et al. 2021

Preprint

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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.

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Section: Discussionsupporting

confidence: 92%

“…The lower limit of detection was 1:40. Assays were controlled using a spike protein specific antibody as positive control in addition to virus-only and uninfected cell controls [9]. All data were analyzed using Excel.…”

Section: Methodsmentioning

confidence: 99%

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

Giorgi

West

Henning

et al. 2021

Preprint

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“…Previous analyses involving this cohort revealed significant associations between nAb response and a number of important clinical correlates, including older age, male sex, the presence of fever, difficulty breathing, and hospitalization denoting more severe disease (19). We observed that the clonal breadth of the SARS-CoV-2 T-cell response is significantly correlated (p< 0.05) with each of these variables by both single and multi-variable regression (Figure 2).…”

Section: Resultsmentioning

confidence: 89%

“…The EUROIMMUN assay measures IgG binding to the S1 domain of the SARS-CoV-2 spike protein, and the Abbott Architect assay measures IgG binding to the SARS-CoV-2 nucleocapsid protein. Across the entire cohort and inclusive of all timepoints assessed, these assays had sensitivities significantly lower than TCR-based testing (p=0.01, mid-p McNemar’s test; Table 1, Supplemental Table 2) (19). Notably, when performance was assessed at specific sampling timepoints in the months following initial illness, both serology assays showed steeper declines in quantitative diagnostic scores over time relative to the TCR-based assay (Figure 3C,D), with the greatest differences in sensitivity observed beyond 5 months (>150 days) from initial symptoms (p<0.03 comparing the TCR-based assay to EUROIMMUN and Abbott, mid-p McNemar’s test; Table 1, Supplemental Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…A recent study compared nAb titers with the performance of two SARS-CoV-2 IgG serology tests using blood samples collected up to 6 months after symptom onset as part of a convalescent plasma donor screening program (19). Results from this study demonstrated that these tests correlate with nAb testing, enabling better prioritization of high-titer samples for immunoglobulin donor products.…”

Section: Introductionmentioning

confidence: 99%

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T-cell receptor sequencing identifies prior SARS-CoV-2 infection and correlates with neutralizing antibody titers and disease severity

Elyanow

et al. 2021

Preprint

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Measuring the adaptive immune response to SARS-CoV-2 can enable the assessment of past infection as well as protective immunity and the risk of reinfection. While neutralizing antibody (nAb) titers are one measure of protection, such assays are challenging to perform at a large scale and the longevity of the SARS-CoV-2 nAb response is not fully understood. Here, we apply a T-cell receptor (TCR) sequencing assay that can be performed on a small volume standard blood sample to assess the adaptive T-cell response to SARS-CoV-2 infection. Samples were collected from a cohort of 302 individuals recovered from COVID-19 up to 6 months after infection. Previously published findings in this cohort showed that two commercially available SARS-CoV-2 serologic assays correlate well with nAb testing. We demonstrate that the magnitude of the SARS-CoV-2-specific T-cell response strongly correlates with nAb titer, as well as clinical indicators of disease severity including hospitalization, fever, or difficulty breathing. While the depth and breadth of the T-cell response declines during convalescence, the T-cell signal remains well above background with high sensitivity up to at least 6 months following initial infection. Compared to serology tests detecting binding antibodies to SARS-CoV-2 spike and nucleoprotein, the overall sensitivity of the TCR-based assay across the entire cohort and all timepoints was approximately 5% greater for identifying prior SARS-CoV-2 infection. Notably, the improved performance of T-cell testing compared to serology was most apparent in recovered individuals who were not hospitalized and were sampled beyond 150 days of their initial illness, suggesting that antibody testing may have reduced sensitivity in individuals who experienced less severe COVID-19 illness and at later timepoints. Finally, T-cell testing was able to identify SARS-CoV-2 infection in 68% (55/81) of convalescent samples having nAb titers below the lower limit of detection, as well as 37% (13/35) of samples testing negative by all three antibody assays. These results demonstrate the utility of a TCR-based assay as a scalable, reliable measure of past SARS-CoV-2 infection across a spectrum of disease severity. Additionally, the TCR repertoire may be useful as a surrogate for protective immunity with additive clinical value beyond serologic or nAb testing methods.

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Comparison of Racial, Ethnic, and Geographic Location Diversity of Participants Enrolled in Clinic-Based vs 2 Remote COVID-19 Clinical Trials

et al. 2022

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IMPORTANCERacial and ethnic diversity among study participants is associated with improved generalizability of clinical trial results and may address inequities in evidence that informs public health strategies. Novel strategies are needed for equitable access and recruitment of diverse clinical trial populations. OBJECTIVE To investigate demographic and geographical location data for participants in 2 remote COVID-19 clinical trials with online recruitment and compare with those of a contemporaneous clinic-based COVID-19 study. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted using data from 3 completed, prospective randomized clinical trials conducted at the same time: 2 remotely conducted studies (the Early Treatment Study and Hydroxychloroquine COVID-19 Postexposure Prophylaxis [PEP] Study) and 1 clinic-based study of convalescent plasma (the Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study). Data were collected from March to August 2020 with 1 to 28 days of participant follow-up. All studies had clinical sites in Seattle, Washington; the 2 remote trials also had collaborating sites in New

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Clinical, laboratory, and temporal predictors of neutralizing antibodies against SARS-CoV-2 among COVID-19 convalescent plasma donor candidates

Cited by 78 publications

References 38 publications

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

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

T-cell receptor sequencing identifies prior SARS-CoV-2 infection and correlates with neutralizing antibody titers and disease severity

Comparison of Racial, Ethnic, and Geographic Location Diversity of Participants Enrolled in Clinic-Based vs 2 Remote COVID-19 Clinical Trials

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