Aberrant pathogenic GM-CSF⁺T cells and inflammatory CD14⁺CD16⁺monocytes in severe pulmonary syndrome patients of a new coronavirus

Abstract

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 was reported at December 2019 (2019-nCoV) in the city Wuhan, Hubei province, China3–5, which was also named as pneumonia-associated respiratory syndrome (PARS)6. Up to 9th of February 2020, at least 37, 251 cases have been reported with 812 fatal cases according to the report from China CDC. However, the immune mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still unknown. Here we show that after the 2019-nCoV 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 accelerates the inflammation. These aberrant and excessive immune cells 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. Therefore, we suggest that monoclonal antibody that targets the GM-CSF or interleukin 6 receptor may potentially curb immunopathology caused by 2019-nCoV and consequently win more time for virus clearance.

A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

“…These findings supported a hypothesis that rapid production of IL-6 might be a possible mechanism leading to the deleterious clinical manifestations in viral pathogenesis [24]. Recently published researches on the clinical characteristics of severe patients with SARS-CoV-2 infection showed that IL-6 was significantly elevated especially in those ICU patients, which caused excessive activated immune response [25,26,27,28,29]. The pathological role of IL-6 in SARS-CoV-2 infection indicated that IL-6 blockade may provide a feasible therapy for the treatment of COVID-19.…”

“…Notably, current pathological studies have shown that the severe patients infected by SARS-CoV-2 generally have higher plasma levels of IL-2, IL-6, IL-10, TNFα, IFN-γ [25,27,28,29], implying a high risk of the inflammatory-associated cytokine storm after viral infection. In addition, reduction and functional exhaustion of T cells have also been observed in COVID-19 patients [27].…”

COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome

“…Similar to our findings, Zhou and colleagues recently reported on the presence of a significantly higher percentage of CD14 + CD16 + inflammatory monocytes in the peripheral blood of COVID-19 patients compared to normal healthy controls. 17,18 They also reported that the percentage of CD14 + CD16 + monocytes was much higher in severe pulmonary syndrome patients from ICU. They also showed that these monocytes had the capability of secreting GM-CSF and similar to our findings could also secrete IL-6, which was higher in ICU patients, in association with cytokine storm.…”

Analysis of coagulation parameters in patients with COVID-19 in Shanghai, China

“…Current research suggests that cytokine release syndrome (CRS) caused by immune imbalance following SARS-CoV-2 infection may be an important cause of diffuse microvascular injury. Researchers analyzed 30 immunological parameters in the blood of 33 COVID-19 patients and speculated that the mechanism of inflammatory damage may be T cell activation following SARS-CoV-2 infection and production of a large amount of granulocyte-macrophage colony-stimulating factor and IL-6, which induces a cascade of inflammatory factors (11). IL-6 can cause coagulopathies through many pathways.…”