Authors: Zhou Y, Fu B, Zheng X, Wang D, Zhao C

PMID: 34676125 PMCID: PMC7108005 DOI: 10.1093/nsr/nwaa041


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 mortality [1,2]. Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus (SARS-CoV-2) was reported in December 2019 in the city of Wuhan, Hubei province, China [3–5], 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 24 February 2020, at least 77 779 cases had been reported, with 2666 fatal cases according to the report from China CDC. However, the immune mechanism that potentially orchestrates 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 cytokine environment induces inflammatory CD14+CD16+ monocytes with a high expression of IL-6 and accelerates the inflammation. Given that a large number of inflammatory-cell infiltrations have been observed in lungs from severe COVID-19 patients [7,8], these aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play an immune-damaging role 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 be associated 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 for severe COVID-19 patients.

Keywords: inflammation, COVID-19, SARS-CoV-2

More on: MATH+