Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity

Abstract

Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

Robust diagnosis of infectious disease, autoimmunity and cancer from the paratope networks of adaptive immune receptors

“…Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially targets the epithelial tissue of the nasal cavity and spreads to the upper respiratory tract, lung, and other organs. Here, we utilized BCR heavy chain data from a single cell sequencing study of primary blood mononuclear cells (PBMCs) of 44 COVID-19 patients (106,640 BCRs) and 58 healthy donors (174,139 BCRs), all of whom were unvaccinated 31 . After splitting the randomly, 71 donors were used for training and 31 were held out for testing.…”

“…1A ) and paratope ( Fig. 1B ) networks using the BCRs of ten COVID-19 from a previous study 30 . Notably, none of the clonotype networks connected different donors, consistent with the previously reported low sharing of BCR clones 9, 22 .…”

“…Diagnosis is usually confirmed by polymerase chain reaction (PCR), which can detect the presence of viral nucleic acids 32 . To evaluate the performance of a theoretical AIR-based diagnostic system, we utilized BCR heavy chain data from a single-cell sequencing study of peripheral blood mononuclear cells (PBMCs) from 44 COVID-19 patients (106,640 BCRs) and 58 healthy donors (174,139 BCRs), all of whom were unvaccinated 30 . After splitting the data randomly, 71 donor datasets were used for training, and 31 were used for testing.…”

Systems-wide view of host-pathogen interactions across COVID-19 severities using integrated omics analysis

“…Studies have identified specific genetic variants associated with increased risk, highlighting the importance of genetic predisposition. 49 , 50 …”

Adaptive best subset selection algorithm and genetic algorithm aided ensemble learning method identified a robust severity score of COVID‐19 patients

“…Given that patients with severe COVID-19 exhibit substantial immune changes including lymphopenia [16][17][18], we also explored the components of the different S8A). The previous study has shown that the severe/ critical patients' antigen processing and presentation ability was significantly reduced [19], which was consistent with our result (Figure S8A).…”