Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

Authors: Cervia and Nilsson et al

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.21.108308v1

Journal/ Pre-Print: bioRxiv

Tags: Cell Biology, Clinical, Diagnostics, Immunology/Immunity

Research Highlights 

1. Characterisation of SARS-CoV-2 antibody response in relation to disease severity

2. Analysis of mucosal antibody titers in exposed healthcare workers revealed detectable SARS-CoV-2 IgA in nasal fluids in some cases where serum IgA/IgG levels remained undetectable

3. Identification of serum IgA levels as potential prognostic biomarker for disease severity

Summary 

Cervia, Nilsson et al aimed to characterise the determinants of SARS-CoV-2-specific antibody responses in two different cohorts, patients with mild versus severe COVID-19 and SARS-CoV-2 exposed healthcare workers. Serum IgG levels were negative or increased slightly late after symptom onset in mild COVID-19 patients, whereas serum IgG and IgA increased significantly in severe COVID-19 patients. High serum IgA levels correlated with severe acute respiratory distress syndrome (ARDS). Analysis of nasal fluids and tears of healthcare workers alongside serum levels suggested that high nasal IgA correlated with a more mild course, whereas high serum IgA correlated with a more severe disease course, however serum and mucosal antibody levels were not directly compared.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19: analysis of IgA/IgG humoral response in relation to severity of disease, measurement of antibodies in mucosal fluids

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19: correlation of disease severity and symptoms with disease progression, exposure, sex, and age

Develop diagnostic tools for SARS-CoV2/COVID19: proposal of serum IgA as prognostic biomarker of disease severity

Study Type

· Clinical Cohort study

Strengths and limitations of the paper

Novelty: Correlation of antibody response with COVID-19 severity, IgA serum levels as biomarkers, mucosal SARS-CoV-2 specific antibodies in exposed healthcare workers

Standing in the field: SARS-CoV-2 specific IgA as prognostic marker for disease severity has been proposed in an earlier longitudinal study

Appropriate statistics: Statistics seem well thought-through

Viral model used: Immunoassays using SARS-CoV-2 spike protein, cohort with patients infected with SARS-CoV-2

Translatability: Low antigen exposure will elicit mucosal IgA-mediated response, which could be protective for health care workers (also inversely correlated with age)

Main limitations: longitudinal study underpowered (n=2) and shows huge variation is IgA responses within mild cases, making conclusions difficult. Serum and mucosal antibody level correlation was not investigated but would have been important to validate their hypothesis regarding site specific IgA and disease course.

The antibody response should have been tested against additional antigens other than S1