Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals
clinical immunology/immunity
Authors:Zhang et al.
Link to paper:https://doi.org/10.1101/2020.06.12.20129460
Journal/ Pre-Print:MedRxiv
Tags: Immunology/Immunity, Clinical
Research Highlights
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The majority (3/4) of the Covid-19 recovered patient sera had neutralizing properties against SARS-CoV, but only a fraction (17.9%) contained neutralizing antibodies againstMERS-CoV proteins, suggesting variable degree of cross-reactivity.
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Individuals recovered from severe Covid-19 were observed to have neutralising antibodies with higher binding and neutralization titers compared to those recovered from non-severe Covid-19.
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Patients recovered from severe COVID-19 infection have increased CXCR3+ circulating Tfh frequencies compared to non-severe recovered individuals.
Summary
This study examines the antibody repertoire and PBMCs of 67 recovered COVID-19 patients (17 severe, 50 non-severe). Consistent with previous studies, individuals had detectable SARS-CoV-2 S1 and S2-specific antibody titers which correlated with serum neutralising activity. In addition, the authors found a small, but significant increase of SARS-CoV-2-specific antibody titers and neutralisation activity as well as increase of CXCR3+ circulatingTfh frequencies in severe compared to non-severe individuals, which suggests that in these individuals a stronger immune response was likely induced. Furthermore, a significant portion (¾) of the patients displayed detectable levels of reactive antibodies against SARS-CoV. A notable, but less frequent reactivity was also detected against MERS-CoV or against both SARS-CoV and MERS-CoV (17.9% and 10.45% of the patients, respectively), suggesting possible various degrees of cross-reactivity.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Clinical symptoms and pathogenesis of SARS-Cov2/COVID19
Treatment of SARS-CoV2/COVID19 positive individuals: This data could have implications for the treatment with convalescent plasma, by prioritizing serum from individuals recovered from severe COVID-19 infection.
Study Type
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Clinical Cohort study (e.g. drug trials)
Strengths and limitations of the paper
Novelty: A novel observation in this paper is the increase of SARS-CoV-2 antibody titers,serum neutralisation capacity and CXC3R+ Tfh frequencies in severe compared to non-severe patients.
Standing in the field: Most findings are previously published, including the presence of SARS-CoV-2-specific circulating Tfh cells
Appropriate statistics: Accurate and appropriate statistics
Viral model used: SARS-CoV-2, SARS-CoV, MERS-CoV antigens and pseudoviruses
Translatability: If individuals recovered from severe SARS-CoV-2 infection have higher antibody titers and neutralisation capacity, serum from such patients could potentially be prioritized for the treatment with convalescent plasma
Main limitations:
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There was no uninfected control group to compare base-line levels of SARS-CoV-2, MERS-CoV and SARS-CoV-specific antibodies in these assays.
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The MERS-CoV and SARS-CoV antibody titer analysis may not show direct antibody cross-reactivity, and baseline levels are missing (uninfected controls).
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They do not cite or describe what pseudovirus(es) they use for the neutralisation assay, the legend for Extended Data Figure 2 c-e, describing the neutralisation results for the three viruses is not clear.
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More severe patients included in the study would help to make findings more robust
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Authors suggest that CXC3R+ Tfh cells are essential for producing nAbs. While they showpositive correlation between neutralisation activity and CXC3R+ Tfh frequencies, which supports similar observations published previously on HCV-infected patients, more functional studies are needed to establish the causal link between neutralisation activity and circulating Tfh.