Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes.
Kerstin RennerTobias SchwittaySophia ChaabaneJohanna GottschlingChristine MüllerCharlotte TiefenböckJan-Niklas SalewskiFrederike WinterSimone BuchtlerSaidou BalamMaximilian Valentin MalfertheinerMatthias LubnowDirk LunzBernhard GrafFlorian HitzenbichlerFrank HansesHendrik PoeckMarina KreutzEvelyn OrsóRalph BurkhardtTanja NiedermairChristoph BrochhausenAndré GessnerBernd SalzbergerMatthias MackPublished in: Nature communications (2021)
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.
Keyphrases
- dendritic cells
- coronavirus disease
- end stage renal disease
- ejection fraction
- sars cov
- newly diagnosed
- chronic kidney disease
- intensive care unit
- prognostic factors
- type diabetes
- machine learning
- emergency department
- metabolic syndrome
- immune response
- cell proliferation
- big data
- induced apoptosis
- oxidative stress
- deep learning
- peripheral blood
- early onset
- artificial intelligence
- weight loss