Preprint Club
A cross-institutional Journal Club Initiative

Keywords

• Human Lymphoid tissue

• SARS-CoV-2

• Interferon alpha response

Main Findings

Lymphoid tissues are crucial to generate long-term immunity but their study in human has mostly been limited to post-mortem samples of adults or children’s tonsils. Here the authors used post-nasal space biopsies of living individuals during acute COVID-19 disease, in convalescent individuals or healthy controls. Using droplet-based single-cell RNA sequencing, flow cytometry and confocal microscopy of nasal-associated lymphoid tissue (NALT) and blood, the authors assess how the lymphoid tissues defend themselves from viral challenge.

The authors show that in acute infection, infiltrating monocytes form a shield beneath the epithelium and around lymphoid follicles, recruiting neutrophils that can form neutrophil extracellular traps (NETs). During convalescence, tissue macrophages express molecules that promote repair and restoration of tissue integrity. While memory B cells are expended in acute COVID-19, the germinal center (GC) B cell made the majority of B cells in convalescent individuals. Interestingly, the authors observed that germinal center B cells express anti-viral transcripts (interferon-alpha response) that inversely correlate with the transcription factor Bcl-6. Among T cells, only tissue-resident memory CD8 T cells undergo clonal expansion and maintain cytotoxic transcriptional programs into convalescence.

Limitations

• The correlation with viral load or Spike tissue staining might be interesting to investigate.

• The measure of SARS-CoV-2 Ab titers and isotypes in relation to memory B cells and GC formation would also be great.

• The impact of age / disease severity on both IFN-alpha response and GC formation would be important.

Significance/Novelty

The authors showed that type I interferon responses are central following viral challenge and that they shape the adaptive immunity, confirming results from experimental models. This data obtained from lymphoid tissues of living individual are an really valuable resource for the community.

Credit

Reviewed by Nicolas Ruffin as part of a cross-institutional journal club between the Icahn School of Medicine at Mount Sinai, the University of Oxford, the Karolinska Institute and the University of Toronto.

The author declares no conflict of interests in relation to their involvement in the review.