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Authors: Kuri-Cervantes et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.18.101717v1

Journal/ Pre-Print: bioRxiv

Tags: Immunology/Immunity 

Research Highlights 

1. Expansion of neutrophil and eosinophil and decrease of lymphocyte population frequencies in blood from severe COVID-19 cases compared to moderate or healthy patients.

2. Profound expansion of plasmablasts with oligoclonal expansion and variable level of somatic hypermutations while consistent long CDR3 sequences in severe COVID-19 cases compared to moderate or healthy donors.

3. Heterogeneity of the T cell response amongst the severe cases, with a positive correlation between the increase of activated CD4+ and CD8+ T cells with the frequency of plasmablasts in the patient.

Summary

Kuri-Cervantes et al. conducted a multiparametric flow cytometry analysis of immune cell populations from whole blood of 42 COVID-19 individuals subdivided in moderate, severe and recovered COVID-19 groups, compared to 12 healthy donors. Unbiased analysis of their immunophenotyping reveals selective clustering of severe individuals. While they were able to confirm previous findings in severe cases (e.g. elevated neutrophil/lymphocyte ratio and decreased percentages of all lymphocyte subsets) they also show that the elevated levels of neutrophils and eosinophils were not associated with an increased activation.

In severe cases, an exacerbated plasmablast response and oligoclonal expansion of antibody clones was observed, with the presence of long CDR3 sequences in the largest B cell clones suggesting multi-reactive antibodies.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Study Type

· In vitro study

· Clinical Cohort study (whole blood of 42 COVID-19 donors from mild, to severe to recovered)

Strengths and limitations of the paper

Novelty:

Unbiased analysis of immunophenotyping of blood from a cohort of moderate, severe, recovered COVID-19 donors and healthy control reveals selective clustering of severe individuals.

Severe cases have oligoclonal expansion of antibodies, which have long CDR3s, indicating multi-reactivity, compared to moderate cases that had a more diverse clonal expansion.

The increased frequencies of neutrophil and eosinophil populations were not associated with an activated phenotype.

They highlight a decrease of CD15 expression in neutrophils and CD16 expression in different innate immune cell populations such as NK cells that could be interesting to investigate further.

Standing in the field: They show extensive data on blood immune cell composition between different subgroups of COVID-19 patients that supports other studies, which they always cite.

Appropriate statistics: The statistical tools used are very clear and all listed in the method section of the paper.

Viral model used: SARS-CoV2 from infected patients admitted to the Hospital of the University of Pennsylvania

Translatability: The paper adds to the understanding of the immune response, particularly in severe cases but is not very close to the bedside.

Main limitations:

- The number of patients in each group is very limited, and this type of study would benefit of an increased numbers of donors.

- The median age of the control group is lower than the severe group, which might be an issue for comparison as age alters blood immune cell composition.

- All the data are presented as percentage of live CD45+ population; it would increase our appreciation of the immune landscape modification to include absolute cell numbers.

- This analysis has been conducted on one time point, it would be very interesting to perform similar analysis on longitudinal study, as suggested by the authors.