Cell death and pathological findings of the spleen in COVID-19 patients

Pathol Res Pract. 2021 Nov:227:153610. doi: 10.1016/j.prp.2021.153610. Epub 2021 Sep 8.

Abstract

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.

Keywords: Apoptosis; Autophagy; COVID-19; Cytokines; Spleen.

MeSH terms

  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Apoptosis*
  • Autophagy*
  • Autopsy
  • Biomarkers / analysis
  • CD11b Antigen / analysis
  • COVID-19 / immunology
  • COVID-19 / mortality
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Case-Control Studies
  • Caspase 3 / analysis
  • Host-Pathogen Interactions
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Sequestosome-1 Protein / analysis
  • Spike Glycoprotein, Coronavirus / analysis
  • Spleen / immunology
  • Spleen / pathology*
  • Spleen / virology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • BCL2 protein, human
  • Biomarkers
  • CD11b Antigen
  • CD68 antigen, human
  • ITGAM protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3