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

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, China [3][4][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.Coronavirus, including SARS and MERS, has caused two large-scale pandemic in the last two decades 1,2 . Although viral evasion of host immune responses and virus-induced cytopathic effects are believed to be critical in disease severity, studies from humans who died of SARS and animal models suggested that an excessive and aberrant host immune response resulting in an exuberant immunopathology and lethal disease [7][8][9] . Similarly, patients infected with 2019-nCoV, that have been reported recently, have increased plasma concentrations of preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Temporal detection and phylogenetic assessment of SARS-CoV-2 in municipal wastewater

“…Although the pathogenesis of severe COVID-19 remains incompletely understood, emerging data suggests that organ dysfunction and poor outcomes may be mediated by high levels of pro-inflammatory cytokines including IL-6 and dysregulated coagulation and thrombosis. 13,14,19 Continued investigation of these pathological processes and the utility of their biomarkers is needed given recent reports of corticosteroid use and ongoing clinical trials of IL-6-receptor antagonists among COVID-19 inpatients, as well as rapidly evolving guidelines for anti-coagulation in this population. 17,20,21 Consistent with unadjusted data from China, 3 and Italy, 8 hypertension was independently associated with poor in-hospital survival.…”

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.…”

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…Very interestingly, high levels of CD4 + cells expressing both GM-CSF and IL-6 were found in COVID-19 patients, along with GM-CSF-secreting CD14 + CD16 + , compared to healthy controls. Even more intriguingly, Th1 cells expressing both GM-CSF and IFN-γ were detected exclusively in ICU patients, thus suggesting a potential contribution of GM-CSF to CRS [300]. These data are further supported by the evidence that human pulmonary microvascular endothelial cells (HPMEC) are able to secrete GM-CSF following an inflammatory stimulus such as LPS, suggesting a potential important role in the pathogenesis of ARDS, in which increased levels of GM-CSF are present in BAL fluid [301].…”