Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm

Coronavirus disease 2019(COVID-19)is an unprecedented pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).As of 22 February 2021,the worldwide pandemic has resulted in more than 110 million cases and 2.4 million deaths.1 Clinical investigation of COVID-19 patients has shown that a systemic cytokine storm can occur,especially in severe cases.2 Treatment of the SARS-CoV-2-associated cytokine storm with tocilizumab3 or anakinra4 has been shown to immediately improve the clinical outcome in most severe and critical COVID-19 patients.These data highlight the systemic cytokine storm as an important exacerbating event in severe COVID-19;however,our understanding of the molecular mechanisms involved in the initiation of the SARS-CoV-2-associated cytokine storm is limited.In the present study,we uncovered a reasonable explanation for cytokine storm initiation through the analysis of 13 autopsy samples from severe COVID-19 patients.

Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,has become a global public health crisis.Some patients who have recovered from COVID-19 subsequently test positive again for SARS-CoV-2 RNA after discharge from hospital.How such retest-positive(RTP)patients become infected again is not known.In this study,30 RTP patients,20 convalescent patients,and 20 healthy controls were enrolled for the analysis of immunological characteristics of their peripheral blood mononuclear cells.We found that absolute numbers of CD4^(+)T cells,CD8^(+)T cells,and natural killer cells were not substantially decreased in RTP patients,but the expression of activation markers on these cells was significantly reduced.The percentage of granzyme B-producing T cells was also lower in RTP patients than in convalescent patients.Through transcriptome sequencing,we demonstrated that high expression of inhibitor of differentiation 1(ID1)and low expression of interferon-induced transmembrane protein 10(IFITM10)were associated with insufficient activation of immune cells and the occurrence of RTP.These findings provide insight into the impaired immune function associated with COVID-19 and the pathogenesis of RTP,which may contribute to a better understanding of the mechanisms underlying RTP.