This study investigates T cell hyporeactivity in hospitalized COVID-19 patients, particularly those requiring ventilation. A sensitive method measuring polyclonal T cell activation via downstream effects on responder cells (basophils, pDCs, monocytes, neutrophils) revealed pronounced T cell hyporeactivity in ventilated patients, linked to prolonged viral persistence and poor outcomes. This hyporeactivity was found to be T cell extrinsic, caused by plasma components, and reversible upon clinical recovery. Gender differences in monocyte responses were observed, and IL-2 partially restored T cell activation. A predictive score, based on immunological markers, was developed to forecast fatal outcomes and identify patients who might benefit from interventions aimed at boosting T cell activity.

Kerstin Renner, Tobias Schiwitty, Sophia Chaabane, Johanna Gottschling, Christine Müller, Charlotte Tiefenböck, Jan-Niklas Salewski, Frederike Winter, Simone Buchtler, Saidou Balam, Maximilian V. Malferthener, Matthias Lubnow, Dirk Lunz, Bernhard Graf, Florian Hitzenbichler, Frank Hanses, Hendrik Poeck, Marina Kreutz, Evelyn Orsó, Ralph Burkhardt, Tanja Niedermair, Christoph Brochhausen, André Gessner, Bernd Salzberger, Matthias Mack