Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months
- University of Bristol, United Kingdom
- North Bristol NHS Trust, United Kingdom
- University Hospitals Bristol and Weston NHS Foundation Trust, United Kingdom
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript files or supplementary files. Raw file (FCS files) for all flow cytometry data have been deposited in the FlowRepository, the link for access to the data is provided in the Material and Methods, Flow cytometry data analysis section.The code script and data for the analysis in Figure 6 are publicly available here: https://github.com/gushamilton/discover_long_covid. The link is provided in the Material and Methods, statistical analysis section.
Article and author information
Author details
Michaela Gregorova
Funding
Wellcome Trust (Elizabeth Blackwell Institute (EBI) with funding from the University's alumni and friends)
- Anu Goenka
- Linda Wooldridge
- Laura Rivino
Southmead Hospital Charity (DISCOVER)
- Fergus Hamilton
- David Arnold
- Laura Rivino
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
Ethics
Human subjects: Information regarding our ethics approval and consent process is provided in the Materials and Methods section and copied below.Patients hospitalized with COVID-19 ({greater than or equal to}18 years of age) were recruited between 30th March and 3rd June 2020 into the observational study DIagnostic and Severity markers of COVID-19 to Enable Rapid triage (DISCOVER), a single-centre prospective study based in Bristol (UK). Research Ethics Committee (REC) approval: REC:20/YH/1021. Survivors were invited at 3, 8 and 12 months post admission to attend outpatient follow up clinics for a systematic clinical assessment (Arnold et al 2020). For those patients attending a face-to-face follow-up, consent was taken to collect samples for research purposes (blood for PBMC isolation, plasma and serum). When available serum collected from patients at admission was made available to the research team.
Version history
- Received: November 18, 2022
- Preprint posted: November 27, 2022 (view preprint)
- Accepted: June 11, 2023
- Accepted Manuscript published: June 13, 2023 (version 1)
- Version of Record published: July 4, 2023 (version 2)
Copyright
© 2023, Santopaolo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months
eLife 12:e85009.
https://doi.org/10.7554/eLife.85009
