Persistent T‐cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID‐19: Results from two Norwegian cohort studies
Marius Trøseid, Tuva B. Dahl, Jan Cato Holter, Anders Benjamin Kildal, Sarah Louise Murphy, Kuan Yang, Ana Quiles‐Jiménez, Lars Heggelund, Karl Erik Müller, Anders Tveita, Annika E. Michelsen, Simen Bøe, Aleksander Rygh Holten, Hedda Hoel, Alexander Mathiessen, Trond Mogens Aaløkken, Børre Fevang, Beathe Kiland Granerud, Kristian Tonby, Kateřina Nezvalová‐Henriksen, Tøri Vigeland Lerum, Fredrik Müller, Ole Henning Skjønsberg, Andreas Barratt‐Due, Anne Ma Dyrhol‐Riise, Pål Aukrust, Bente Halvorsen, Thor Ueland, Norwegian SARS‐CoV‐2 study group
Abstract
BACKGROUND: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. OBJECTIVES: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. METHODS: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. RESULTS: Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. CONCLUSION: Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.