Table 4.
Single-cell studies on CAR-T-cell therapy and COVID-19
| Cell type | Sample/Time | Conclusions |
|---|---|---|
| CAR-T-cell therapy | ||
| CAR-T cells | CRS initiation stage | CD8 41-BBz CAR-T enriched in central memory cell phenotype and fatty acid metabolism genes (Boroughs et al., 2020)163 |
| CAR-T cells | CRS initiation stage | CD4 helper and CD8 cytotoxic CAR-T cells are equally effective in directly killing tumor cells (Xhangolli et al., 2019)108 |
| Leukocyte | CRS peak stage | High fever and elevated IL-6 levels are hallmarks of CRS; Human monocytes are the major source of IL-1 and IL-6 during CRS (Norelli et al., 2018)29 |
| CAR-T and endogenous T | CRS peak stage | CAR-T cells in the CRS peak phase transition from a proliferative to a cytotoxic intermediate state; Endogenous T presents an active state in the CRS peak stage (Li et al., 2021)110 |
| CAR-T cells | CRS recovery stage | Clonal diversity of CAR-T cells is highest in products and declines following infusion; Amplified oligoclones at last mainly originate from CAR-T products with high expression of cytotoxicity and proliferation genes (Sheih et al., 2020)109 |
| CAR-T cells | CRS recovery stage | Heterogeneity of CAR-T cells contributes to variations in efficacy and toxicity in LBCL (Deng et al., 2020)164 |
| COVID-19 | ||
| PBMC | 76 COVID-19 patients and 69 healthy donors | Enhanced plasma levels of inflammatory mediators, including EN-RAGE, TNFSF14, and oncostatin M, were correlated with COVID-19 severity (Arunachalam et al., 2020)160 |
| PBMC | 3 COVID-19 patients and 3 healthy donors | Immature neutrophil and nonclassical monocyte pools, with levels of the protein calprotectin linked to disease severity (Silvin et al., 2020)161 |
| PBMC | 9 COVID-19 patients, 5 influenza patients and 4 healthy donors | TNF/IL-1β–driven inflammation was defining characteristics of COVID-19.The type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19 (Lee et al., 2020)129 |
| PBMC | 40 COVID-19 patients and 13 healthy donors | Hospitalization is associated with increased cytotoxic follicular helper cells and cytotoxic T helper cells and a reduction in regulatory T cells (Meckiff et al., 2020)122 |
| BALF | 6 Severe- and 3 mild- COVID-19 patients | Dramatic differences between the mild and severe COVID-19 patients, including an inflammatory signature. SARS-CoV-2 infects epithelial cells and alters immune landscape in severe patients (Bost et al., 2020)123 |
| PBMC | 5 COVID-19 patients, 2 influenza virus patients and 2 healthy donors | COVID-19 patient features XAF1-, TNF-, and FAS-induced T cell apoptosis. COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza, and substantial differences were revealed like expression of interleukin (IL)6R and IL6ST (Zhu L et al., 2020)120 |
| PBMC | 2 COVID-19 patients and 2 healthy donors | A monocyte subpopulation contributes to the inflammatory CRS and tocilizumab treatment can attenuate the CRS in COVID-19 patients (Guo et al., 2020)128 |
| PBMC and whole blood | 53 COVID-19 patients and 56 healthy donors | HLA-DRhiCD11chi inflammatory monocytes with an IFN-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by the occurrence of neutrophil precursors (Schulte-Schrepping et al., 2020)131 |
| PBMC | 13 COVID-19 patients and 5 healthy donors | COVID-19 showed a strong IFN-α response and an overall acute inflammatory response. In severe patients, the immune landscape featured a deranged interferon response (Zhang et al., 2020)133 |
| PBMC | 7 Severe COVID-19 patients and 6 healthy donors | Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines, while peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines (Wilk et al., 2020)162 |
| PBMC, BALF/PFMC, sputum | 196 COVID-19 patients and 25 healthy donors | Systemic upregulation of S100A8/A9, mainly from megakaryocytes and monocytes in the peripheral blood, may contribute to the CRS frequently in severe patients (Ren et al., 2021)136 |