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

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

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-23334-2

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