Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses

Authors: Zhou et al.

Link to paper: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3614132

Journal/ Pre-Print: Cell Press Sneak Peak

Key Words: Immunology

Research Highlights 

1. SARS-CoV-2 infection results in broad immune cell reduction including T cells, NK cell, monocytes and dendritic cells (DCs)

2. Impaired DC activation, together with weak CD8 T cell responses might contribute to acute COVID-19 pathogenesis

3. Acute SARS-CoV-2 patients showed higher CD4 responses than CD8 responses and these were directed against NP (nucleocapsid) rather than RDP (receptor binding domain) and were of effector memory type.

Summary

The authors investigated the functionality of different innate and adaptive immune cells in both acute (6 severe and 9 mild patients) and convalescent patients (2 severe and 22 mild patients) and observed that acute COVID-19 infection resulted in broad immune cell suppression during the acute phase of infection. Acute patient (AP)-derived plasmacytoid DCs were shown to be reduced in frequency and ability to mature while CD4 and CD8 T cells displayed reduced functionality. Further investigation of the antibody and T cell immune response revealed that while most patients generated neutralizing antibodies, most severe AP developed only weak T cell responses, which was dominated by CD4 T cells.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Study Type

· In vitro study

· Patient Case study

Strengths and limitations of the paper

Novelty: One of the first studies to look more closely at DC numbers and functionality

Standing in the field: Confirms some of the findings of earlier preprints investigating T cell immunity in convalescent patients (Grifoni, 2020; Ni et al., 2020)

Appropriate statistics: Yes, but the sample size of the severely ill patients is quite small

Viral model used: Blood samples of infected COVID-19 confirmed patients

Translatability: The authors suggest that a high ratio of classical DC/pDC at about 50- fold may serve as a potential biomarker for severe sickness

Main limitations: They only look at 8 severe COVID-19 infected patients, of which only 2 are in the convalescent group studied and 6 are in the acute group. They also don’t distinguish within their group between severe and mild patients but just compare healthy, acute and convalescent.