Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus.
Zhou, Y. et al.
bioRxiv 2020.02.12.945576 (2020) doi:10.1101/2020.02.12.945576.
Peripheral blood samples from patients infected by Covid-19 show a decrease in lymphocytes, specifically CD8+T cells in ICU-patients. However, the lymphocytes show a more activated phenotype especially viral exhausted T-cells subsets co-expressing Tim-3 and PD-1. Covid-19 patients show an increase of activated GM-CSF CD4+Th1 cells and inflammatory CD14+CD16+ monocytes with high IL-6 expression. Reported immunological changes are more pronounced in ICU-admitted COVID-19 patients versus non-ICU patients. Data suggests that excessive and aberrant immune cell infiltration as part of an exaggerated immune response results in severe lung pathology. Monoclonal antibodies targeting GM-CSF or IL6 receptor may be viable strategies to curb immunopathology.
- Increase of CD4+Th1 cells producing GM-CSF and IL-6 in patients infected with Covid-19
- Increase of CD14+CD16+ monocytes with high IL6 expression. Activated immune cells play immune damaging role.
- ICU vs non-ICU cases distinguished by high GM-CSF from CD4+ T cells and high IL6 from CD14+ CD16+ monocytes
For serological detection of SARS-COV-2
Yes, they show an increase of cytokines (IL-2, IL-7, IL-10, G-CSF, IP10, MCP-1, MIP1A, TNF-a), an increase in C-reactive protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase. A decrease of haemoglobin and albumin.
For treatment of SARS-COV-2 positive individuals
Yes, targeted immunomodulation which reduces the cytokine storm such as monoclonal antibodies that target GM-CSF or IL6 receptor may help ameliorate pulmonary inflammation.
Strengths and weaknesses of the paper
Work carried out on hospitalised patients with confirmed infection of Covid-19. Patients infected with Covid-19 stratified according to ICU vs non-ICU and compared to healthy controls. Appropriate statistics used and high n numbers (n=10-21). Comparison of cytokine markers from SARS and MERS to Covid-19.
Study compares ICU vs non-ICU cases but doesn’t present data representing the majority of COVID19 infections which is asymptomatic or mild.