Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes

Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.

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