Single-cell landscape of immunological responses in patients with COVID-19

TLDR

The link between COVID‑19 severity and the host immune response remains incompletely defined. We profiled peripheral blood immune cells from 5 healthy donors and 13 COVID‑19 patients (moderate, severe, convalescent) using single‑cell RNA‑seq and paired TCR/BCR sequencing to map transcriptional and functional states. Patients exhibited a robust interferon‑α and inflammatory response, with moderate cases showing expansion of cytotoxic effector T cells linked to recovery, whereas severe cases displayed dysregulated interferon signaling, immune exhaustion, skewed TCR repertoires, and broad T‑cell expansion, underscoring the dynamic immune landscape during disease progression.

Abstract

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.