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Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients.

ABSTRACT:

Background

Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity.

Methods

We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens.

Results

Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81-100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3-4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers.

Conclusions

Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection.

SUBMITTER: Muecksch F

PROVIDER: S-EPMC7665595 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe efficacy of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors.MethodsA cross-sectional study was conducted among 20 prepandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection-based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n = 35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percentage of detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher's exact and Wilcoxon rank-sum tests, respectively.ResultsAmong CCP donors (n = 140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days (interquartile range = 38-50) and 9% (n = 12) were hospitalized due to COVID-19. Compared with healthy blood donor controls, CCP donors had significantly higher plasma levels of interferon (IFN)-γ, interleukin (IL)-10, IL-15, IL-21, and macrophage-inflammatory protein-1, but lower levels of IL-1RA, IL-8, IL-16, and vascular endothelial growth factor-A (P < .0014). The distributions of plasma levels of IL-8, IL-15, and IFN-inducible protein-10 were significantly higher among CCP donors with high (≥160) versus low (<40) anti-SARS-CoV-2 neutralizing antibody titers (P < .0014). The median levels of IL-6 were significantly higher among CCP donors who were hospitalized versus nonhospitalized (P < .0014).ConclusionsHeterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.