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

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

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.