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 GMCSF or interleukin 6 may be effective in blocking inflammatory storms and, therefore, be a promising treatment for severe COVID-19 patients.

Coronavirus, including SARS and MERS, has caused two large-scale pandemics 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 have suggested that an excessive and aberrant host-cytokine storm results in an exuberant immunopathology and lethal disease [9–11]. Inflammatory cytokine storm refers to the immune system gone awry and an excessive inflammatory response flaring out of control. Cytokine storms are associated with a wide variety of infectious and non-infectious diseases including graft-versus-host disease, autoimmune disease, severe virus infection, multiple organ dysfunction syndromes and chimeric antigen receptor (CAR) T-cell therapy [12, 13]. It has been reported that, following SARS-CoV infection, dysregulated cytokine/chemokine responses and higher virus titers cause an inflammatory cytokine storm with lung immunopathological injury [12, 14]. Such inflammation associated with the cytokine storm may begin at one local site but spread farther throughout the body via the systemic circulation [12, 14]. Similarly, patients infected with SARS-CoV-2 who have been reported recently have had increased plasma concentrations of inflammation-related cytokines, including interleukins (IL) 2, 7 and 10, granulocyte-colony-stimulating factor (G-CSF), interferon-γ-inducible