Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months, 2023, Santopaolo et al.

[SNT Gatchaman]

Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months
Marianna Santopaolo; Michaela Gregorova; Fergus Hamilton; David Arnold; Anna Long; Aurora Lacey; Alice Halliday; Holly Baum; Kristy Hamilton; Rachel Milligan; Elizabeth Oliver; Olivia Pearce; Lea Knezevic; Begonia Morales Aza; Alice Milne; Emily Milodowski; Eben Jones; Rajeka Lazarus; Anu Goenka; Adam Finn; Nicholas Maskell; Andrew D Davidson; Kathleen Gillespie; Linda Wooldridge; Laura Rivino

COVID-19 causes immune perturbations which may persist long-term, and patients frequently report ongoing symptoms for months after recovery. We assessed immune activation at 3-12 months post hospital admission in 187 samples from 63 patients with mild, moderate or severe disease and investigated whether it associates with long COVID.

At 3 months, patients with severe disease displayed persistent activation of CD4+ and CD8+ T-cells, based on expression of HLA-DR, CD38, Ki67 and granzyme B, and elevated plasma levels of IL-4, IL-7, IL-17 and TNF-α compared to mild and/or moderate patients. Plasma from severe patients at 3 months caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that plasma factors in severe patients may increase T-cell responsiveness to IL-15-driven bystander activation. Patients with severe disease reported a higher number of long COVID symptoms which did not however, correlate with cellular immune activation/pro-inflammatory cytokines after adjusting for age, sex and disease severity.

Our data suggests that long COVID and persistent immune activation may correlate independently with severe disease.

Link | PDF (eLife)

 

[SNT Gatchaman]

Hospitalised: mild, moderate, severe.

In summary, our study highlights a complex recovery of the immune system following severe COVID-19 with evidence of persistent activation of CD4 + and CD8 + T-cells, which may be bystander driven, and elevated levels of T-cell-related cytokines in the plasma of severe patients at 3 months. Our data suggests the lack of a direct association between long COVID and immune activation markers and pro-inflammatory cytokines measured in this study.