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Authors: Sterlin et al. 

Journal/ Pre-PrintmedRxiv 

TagsDiagnosticsImmunology/ImmunityTherapeuticsVaccines 

Research Highlights 

  1. Longitudinal analysis of phenotypic changes in B cells and their antibody secretion 

  1. Photonic ring immunoassay to test purified antibodies against various viral antigens revealed potent IgA neutralisation targeting the RBD region of SARS-CoV-2 

  1. Early SARS-CoV-2-specific humoral responses are dominated by IgA-producing plasmablasts, but IgG antibody titers are prevalent in the serum at later stages 

Summary 

Sterlin et al aimed to characterise the humoral immune response following SARS-CoV-2 infection. They performed a longitudinal serum analysis in 38 infected patients with differing severities of COVID-19 disease course. Phenotyping the immune compartment revealed a majority of CCR10-expressing plasmablast at the onset of disease. The early humoral response is dominated by IgA-secreting plasmablasts, whose antibodies were more efficient at neutralising SARS-CoV-2. Late stages of COVID-19 revealed a predominance of IgG in the serum. They also assessed local immunity using bronchoalveolar lavage (BAL) of severe patients harvested at different timepoints, which showed a predominance of IgG. Therefore, mucosal and systemic response against SARS-CoV-2 may differ and needs to be taken into account regarding vaccine design and antibody tests. 

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19: analysing the humoral immune response over time 

Develop a vaccine for SARS-CoV-2: looking at humoral antibody responses over time is important for shaping vaccine design 

Study Type  

  • Patient Case study 

Strengths and limitations of the paper 

Novelty: Longitudinal phenotyping of humoral response including B cells, Tfh and antibody responses; testing antibodies in serum for neutralising activity, IgA antibodies have greater neutralising potential 

Standing in the field: IgA responses suggested as early biomarker in several studies, contradicts another study regarding Tfh cell numbers over time 

Appropriate statistics:Statistics seem appropriate to our knowledge and are described in methods. 

Viral model used: Original SARS-CoV-2 infected patients, pseudovirus used for neutralisation assays 

Translatability: Assessing humoral response and its protectivity over time is important for successful vaccine design, potential application for antibody test design 

Main limitations: Limitations described in discussion, antibody responses not stratified based on severity of COVID-19 infection, BAL samples obtained only from severe patients, longitudinal studies should compare various sites (mucosal vs systemic), IgG antibodies protectivity wasn’t assessed in healthy donors