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Authors: Ma et al

Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.17.20064907v1

Journal/ Pre-Print: MedRxiv

Tags: Diagnostics, Immunology/Immunity

Research Highlights 

1. Developed a quantitative and sensitive serologic immunoassay for RBD SARS-CoV-2-specific IgA, IgM and IgG for the detection of Covid-19 positive patients.

2. Showed that the inclusion of IgA to the typical IgM and IgG serological test improves the performance.

3. Revealed the kinetics of IgM, IgA, IgG antibody isotypes in Covid-19 patients and suggest a correlation between IgA concentrations and the Covid-19 disease severity.

Summary 

Aims to improve the sensitivity and specificity of COVID-19 serological test by adding detection of SARS-COV2-specific IgA to the classical detection kit. Serum of 87 COVID-19 patients were tested by ELISA between 4-41 days after illness onsets and compared to serum of healthy controls or patients with other infections. Using SARS-COV2 Nucleocapsid (NP) or Receptor-binding-domain (RBD) kits they first concluded that the RBD kit is more reliable. In addition, they compared the detection of IgA, IgM and IgG with the RBD kit at different timepoints after the onset of the symptoms and reported an increased sensitivity and specificity for the detection of COVID19 patients at early stages with the IgA kit in comparison to the IgM or IgG kits while at later stages the detection of IgG was the most powerful. The authors propose to add IgA detection to the serological tests to detect earlier and with more specificity COVID19 patients.

Impact for SARS-CoV2/COVID19 research efforts

· Understand the immune response to SARS-CoV2/COVID19

· Develop diagnostic tools for SARS-CoV2/COVID19

Study Type

· In vitro study

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

Strengths and limitations of the paper

Novelty: The authors propose a serological test including the detection of IgA with the detection of IgG and IgM to increase the sensitivity and specificity of the test.

They provide quantification of IgM, IgA and IgG antibody titers over a period of 40 days after the onset of the symptoms and point out a correlation between the level of IgA in the serum and the severity of the disease.

Standing in the field: There is some supporting literature. The relationship between serum IgA levels and Covid-19 disease severity has been suggested before (https://doi.org/10.1101/2020.04.14.20059733) but looking at only 4 patients.

Appropriate statistics: Accurate and appropriate statistics, non-parametric analyses used appropriately since data non-normally distributed.

Viral model used: SARS-CoV-2 virus model was used as study involved testing serum samples of Covid-19 patients

Translatability: Addition of IgA detection to RBD-based detection kit may increase accuracy of screening people that might have been infected by SARS-CoV-2.

Main limitations:

· Only 17 serum samples collected within the first 10 days of illness onset, therefore accuracy of early diagnosis requires further verification with larger sample numbers.

· RBD expressed in a human cell line but NP antigen expressed in bacteria. Better comparison of serology immunoassay if NP antigen was also expressed in a human cell line.

· Most of the Covid-19 patients enrolled had clinically moderate symptoms (56 of 87), 17 were severe and 5 critical cases. Therefore, IgA level and Covid-19 disease severity positive correlation needs further verification.

· Both IgA and IgG levels correlate with disease severity, but perhaps this simply relates to patient viral load which was not measured.