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Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series

Authors: Dahlke et al Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.14.20059733v1

Journal/ Pre-Print: bioRxiv

Key Words: antibody response, peptide array, longitudinal, B cells

Research Highlights 

1. Longitudinal sample analysis of individual B cell epitope development

2. Usage of full-proteome peptide microarray to identify specific epitopes

3. Identification of IgA response as potential biomarker for disease progression

Summary 

Dahlke et al employed the use of high-density peptide microarrays to analyse antibody development and epitope kinetics during SARS-CoV-2 infection. They compared a patient exhibiting moderate/severe symptoms to one with a mild disease course (household control). Extraction of blood at different timepoints allowed them to follow the development of specific B-cell epitopes, which evolved over time. Over time the antibody response became more diverse in the severe patient, but was diverse earlier on in disease in the mild patient. Usage of full-proteome peptide microarrays was crucial for identification of antibodies and antigens.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19: they performed a longitudinal analysis of the antibody response of two patients along the course of the disease

Develop diagnostic tools for SARS-CoV2/COVID19: they propose the kinetics and strength of the SARS-CoV-2-specific IgA response to be potential prognostic markers of disease course

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: Development of B cell clonality against SARS-CoV-2 over time, and generation of peptide microarray for further antibody studies

Standing in the field: B cell clones identified previously (BCR-seq), but not longitudinally so far

Appropriate statistics: no statistics applied

Viral model used: Original Wuhan strain of SARS-CoV-2 used for alignment

Translatability: kinetics and strengths of IgA response could be used as biomarker (but what would the standard be?)

Main limitations: very low number of patients analysed making any conclusions relating severity to antibody response impossible, collection dates not

corresponding, control not shown, control patients had same disease as patient 2, no discontinuous or conformational epitopes can be detected. Analysis of B cell response is also very superficial.

· Patients at different stages of disease