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

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.

SUBMITTER: Renner K

PROVIDER: S-EPMC8140132 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Renner Kerstin K Schwittay Tobias T Chaabane Sophia S Gottschling Johanna J Müller Christine C Tiefenböck Charlotte C Salewski Jan-Niklas JN Winter Frederike F Buchtler Simone S Balam Saidou S Malfertheiner Maximilian V MV Lubnow Matthias M Lunz Dirk D Graf Bernhard B Hitzenbichler Florian F Hanses Frank F Poeck Hendrik H Kreutz Marina M Orsó Evelyn E Burkhardt Ralph R Niedermair Tanja T Brochhausen Christoph C Gessner André A Salzberger Bernd B Mack Matthias M

Nature communications 20210521 1

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 ...[more]

PMID: 34021143

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Project description:ObjectivesBronchiolitis is a common indication for mechanical ventilation in the PICU. Both bronchiolitis and invasive mechanical ventilation may cause adverse long-term pulmonary outcomes. This study investigates children with a history of invasive mechanical ventilation for bronchiolitis, addressing: 1) the extent, 2) potential explanatory factors, and 3) possible impact on daily life activities of adverse long-term pulmonary outcomes.DesignSingle-center cohort study.SettingOutpatient PICU follow-up clinic.PatientsChildren 6-12 years old with a history of invasive mechanical ventilation for bronchiolitis (age < 2 yr).InterventionsNone.Measurements and main resultsLong-term pulmonary outcomes were assessed by a standardized questionnaire and by spirometry. Nineteen out of 74 included children (26%) had adverse long-term pulmonary outcomes, of whom the majority had asthma (14/74, 19%). By logistic regression analysis, we assessed whether background characteristics and PICU-related variables were associated with long-term pulmonary outcomes. In general, we failed to identify any explanatory factors associated with adverse long-term pulmonary outcomes. Nonetheless, atopic disease in family and longer duration of invasive mechanical ventilation (days) were associated with greater odds of having asthma at follow-up (odds ratio, 6.4 [95% CI, 1.2-36.0] and 1.3 [95% CI, 1.0-1.7], respectively). Adverse pulmonary outcome at follow-up was associated with more frequent use of pulmonary medication after PICU discharge. In comparison with those without adverse pulmonary outcomes, we did not identify any difference in frequency of sports performance or school absenteeism.ConclusionsIn this single-center cohort, one-quarter of the children attending follow-up with a history of invasive mechanical ventilation for bronchiolitis had adverse, mostly previously undetected, long-term pulmonary outcomes at 6-12 years. Atopic disease in family and longer duration of invasive mechanical ventilation were associated with presence of asthma. The presence of adverse pulmonary outcomes was associated with more frequent use of pulmonary medication after PICU discharge.

Dataset Information

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

Publications

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

Similar Datasets

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