Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients

By Yonggang Zhou, Binqing Fu, Xiaohu Zheng, Dongsheng Wang, Changcheng Zhao, Yingjie Qi, R. Sun, Zhigang Tian, Xiaoling Xu, Haiming Wei. National Science Review, 2020

1,065 citations recorded by the source corpus.

Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality1, 2 Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus (SARS-CoV-2) was reported at December 2019 in the city Wuhan, Hubei province, China3, 4, 5, which was also named as pneumonia-associated respiratory syndrome (PARS)6 and can cause coronavirus disease 2019 (COVID-19) to seriously endanger human health Up to 24th of February 2020, at least 77779 cases have been reported with 2666 fatal cases according to the report from China CDC However, the immune mechanism that potential orchestrated acute mortality from COVID-19 patients is still unknown Here we show that after the SARS-CoV-2 infection, CD4+ T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerate the inflammation Given that large amount of inflammatory cells infiltrations have been observed in lungs from severe COVID-19 patients7, 8, these aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology Thus, we suggest that monoclonal antibodies targeting GM-CSF or interleukin 6 may be effective in blocking inflammatory storms and, therefore, be a promising treatment of severe COVID-19 patients

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/ac299584dc3516e0850195df4cc99a650a38df73

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. Nicolas Vabret
2. G. Britton
3. Xiaoling Xu
4. C. Gruber
5. L. Townsend
6. Samarth Hegde
7. Miriam Merad
8. Joel Kim

Citations in the corpus

• Effective treatment of severe COVID-19 patients with tocilizumab (2020, background): “This research has found flow cytometric profiles of increased IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF), and IFN-γ in these severe patients, whereas TNF-α was not significantly up-regulated in CD4 T cells from COVID-19 patients (14).”
• Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection (2020, background): “In severe cases, elevated C-reactive protein (CRP), ferritin, d-dimers in addition to pro-inflammatory factors such as IL-6 and soluble CD25 (sC25), and an increase in intermediate (CD16+ CD14 +) monocytes have been reported [13, 14].”
• Immunology of COVID-19: Current State of the Science (2020, positive): “A caveat, however, pertains to the identification of specific T cells by induced CD69 and CD137 co-expression, since upregulation of CD137 by CD4 T cells, in contrast to CD154, may preferentially capture regulatory T cells (Treg) (Bacher et al., 2016).”