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Authors:Zhang et al. 

Journal/ Pre-Print:MedRxiv 

Tags: Immunology/Immunity, Clinical 

Research Highlights

  1. 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. 

  1. 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. 

  1. 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  

  • 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: 

  • 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 nAbsWhile 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.