Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals
Authors:Zhang et al.
Link to paper:https://doi.org/10.1101/2020.06.12.20129460
Tags: Immunology/Immunity, Clinical
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.
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.
Patients recovered from severe COVID-19 infection have increased CXCR3+ circulating Tfh frequencies compared to non-severe recovered individuals.
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.
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
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.
The MERS-CoV and SARS-CoV antibody titer analysis may not show direct antibody cross-reactivity, and baseline levels are missing (uninfected controls).
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.
More severe patients included in the study would help to make findings more robust
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.