Targeted Immunosuppression Distinguishes COVID-19 from Influenza in Moderate and Severe Disease
bioinformatics cell biology immunology/immunity
Authors: Mudd et al
Journal/ Pre-Print: medRxiv
Tags: Bioinformatics, Cell Biology, Immunology/Immunity
1. COVID-19 patients had significantly reduced circulating monocytes and increased early antibody-secreting B cells compared to healthy controls and influenza patients.
2. Plasma levels of IL-6 and IL-8 were upregulated, and GM-CSF, IFN-g and IL-9 were downregulated in COVID-19 patients compared to influenza patients.
3. Single cell transcriptional profiling of patient PBMCs revealed downregulation of IFN-g and IFN-a responses and an upregulation in metabolism, proliferation, stress and apoptosis-related genes in immune cells of COVID-19 compared to influenza patients.
The authors immune profiled blood of individuals with COVID19, Influenza or neither. PBMC profiling showed that COVID-19 patients had significantly reduced circulating monocytes and increased early antibody-secreting B cells compared to healthy controls and influenza patients. Cytokine profiling revealed distinct immune profiles between COVID-19 and influenza patients, with higher IL-6 and IL-8 in COVID-19. Severe COVID-19 patients were mostly not observed to have a cytokine storm phenotype. Single-cell RNA sequencing of patient PBMCs found suppression of type I and type II interferon signalling and an increase in metabolic, stress and apoptosis-related pathways. Inflammatory mediators including IL-6 were identified as strongly correlated with acute respiratory failure in both influenza and COVID-19.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Understand the virology and/or cell biology of SARS-CoV2/COVID19
- prospective observational cohort
Strengths and limitations of the paper
Novelty: This study identified cytokine and single-cell signatures that differentiate COVID-19 infection from influenza infection in circulating immune cells. The authors find that cytokine storm phenotype is less common in severe COVID-19 than severe influenza patients.
Standing in the field: This study contradicts current idea that ‘cytokine storm’ is associated with acute respiratory distress/failure as the authors did not observe any cytokine storm phenotype in COVID-19 patients with acute respiratory failure in this cohort. It does support current evidence of suppressed IFN type I response in severely affected COVID-19 patients and animal models.
Appropriate statistics: Yes
Viral model used: n.a.
· The cohort of 79 only contained 7 patients with influenza and acute respiratory failure
· Low sample sizes for single cell analysis – only one healthy control analysed
· The three COVID-19 patients displaying cytokine storm phenotype were excluded from comparative analysis