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Authors: Chen et al 

Journal/ Pre-Print:MedRxiv 

Tags: Clinical/ Diagnostics 

Research Highlights 

  1. Severe COVID-19 patients have the highest levels of S1 and RBD-specific antibodies 

  1. RBD-ACE2 binding was disrupted by serum from patients with severe COVID-19 

  1. Sera from severe COVID-19 were the most able to neutralize SARS-CoV-2 

Summary 

The study by Chen et al investigates the correlation between neutralizing antibodies and disease severity in COVID-19. The authors recruited 59 patients in total and specifically: 10 severe, 34 moderate, 4 mild and 11 asymptomatic individuals. Severe patients had the highest levels of specific antibodies, while the RBD-ACE2 binding was interrupted by the addition of serum from severe COVID-19, but not by moderate or mild. Finally, in apseudotype or SARS-CoV-2 neutralization assay, severe sera neutralized the virus and deletion of RBD-specific antibodies reduced this effectThese results suggest that disease severity may determine both antibody levels and their neutralizing capacity.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to  SARS-CoV2/COVID19: the study interrogates the correlation between disease severity and neutralizing antibodies 

Study Type  

  • Clinical Cohort study (e.g. drug trials) 

  • Patient Case study 

Strengths and limitations of the paper 

Novelty: Previous studies have shown that severe patients have higher levels of anti-S1 and anti-RBD-specific SARS-CoV-2 antibodies (Okba et al, MedRxiv, 2020). Similarly, the correlation of higher antibody titers of IgA, IgM and IgG with disease severity has also been shown (Hansen, MedRxiv, 2020). On the other hand, the correlation with neutralization and depletion of different antibody specificities is novel. 

Standing in the field: The study fits well with previous research in the field, showing that disease severity correlates with high antibody titers and neutralization. However, key aspects still need to be investigated. For instance, having specific antibody responses against S1 epitopes other than RBD may be detrimental and lead to antibody-dependent enhancement as has been suggested previously (Iwasaki and Yang, Nature Reviews Immunology, 2020). This study has important implications for vaccination, suggesting that patients who hadasymptomatic, mild and moderate disease might require vaccinationAdditionally, more investigations are required to determine whether convalescent plasma for antibody therapy should only be taken from patients with severe COVID-19. 

Appropriate statistics: Yes, the authors used a one-way ANOVA and Pearson’s correlation 

Viral model used: EPI_ISL_444969 

Translatability: Far from bedside, but provides important information for convalescent plasma donation and vaccination strategies 

Main limitations:  

  1. Why is the moderate disease neutralization so variable? There is a large spread (and in some cases looks like two groups) – is there a hypothesis for that? Were there any significant clinical differences? 

  1. Given that anti-N antibodies or certain S1 epitopes might mediate ADE, it would be interesting to investigate these in terms of their levels and subsequent neutralization. 

  1. Do the high antibody titers correlate with T cell responses? 

  1. It would be important to account for time-dependent variables of sample collection.