Multimodal single-cell analyses of peripheral blood mononuclear cells of COVID-19 patients in Japan

SARS-CoV-2 continues to spread worldwide. Patients with COVID-19 show distinct clinical symptoms. Although many studies have reported various causes for the diversity of symptoms, the underlying mechanisms are not fully understood. Peripheral blood mononuclear cells from COVID-19 patients were collected longitudinally, and single-cell transcriptome and T cell receptor repertoire analysis was performed. Comparison of molecular features and patients' clinical information revealed that the proportions of cells present, and gene expression profiles differed significantly between mild and severe cases; although even among severe cases, substantial differences were observed among the patients. In one severely-infected elderly patient, an effective antibody response seemed to have failed, which may have caused prolonged viral clearance. Naive T cell depletion, low T cell receptor repertoire diversity, and aberrant hyperactivation of most immune cell subsets were observed during the acute phase in this patient. Through this study, we provided a better understanding of the diversity of immune landscapes and responses. The information obtained from this study can help medical professionals develop personalized optimal clinical treatment strategies for COVID-19.

Automated summary

Through the analysis of single-cell transcriptome and T cell receptor repertoire, differences in cell proportions and gene expression profiles were found between mild and severe cases of COVID-19, as well as among severe cases. In a severely infected elderly patient, characteristics such as depletion of naive T cells, low T cell receptor repertoire diversity, and aberrant hyperactivation of immune cell subsets were observed. This study provides valuable insights into the diversity of immune landscapes and responses.