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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kerstin Renner ◽  
Tobias Schwittay ◽  
Sophia Chaabane ◽  
Johanna Gottschling ◽  
Christine Müller ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Fresh Blood ◽  
Virus Persistence ◽  
Clinical Recovery ◽  
Immunosuppressive Medication ◽  
Downstream Effects ◽  
Poor Outcomes ◽  
Ventilated Patients

AbstractCoronavirus 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.

scholarly journals T cell anergy in COVID-19 reflects virus persistence and poor outcomes

2020 ◽  
Author(s):  
Kerstin Renner ◽  
Christine Mueller ◽  
Charlotte Tiefenboeck ◽  
Jan-Niklas Salewski ◽  
Frederike Winter ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Severe Pneumonia ◽  
Cell Reactivity ◽  
Virus Persistence ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
T Cell Reactivity ◽  
Poor Outcomes

Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.

scholarly journals T cell anergy in COVID-19 reflects virus persistence and poor outcomes

2020 ◽  
Author(s):  
Kerstin Renner ◽  
Christine Müller ◽  
Charlotte Tiefenböck ◽  
Jan-Niklas Salewski ◽  
Frederike Winter ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Severe Pneumonia ◽  
Cell Reactivity ◽  
Virus Persistence ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
T Cell Reactivity ◽  
Poor Outcomes

Abstract Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.

scholarly journals Case-control, diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

2021 ◽  
Author(s):  
Hellen Hiza ◽  
Jerry Hella ◽  
Ainhoa Arbués ◽  
Beatrice Magani ◽  
Mohamed Sasamalo ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peptide Pool ◽  
Turnaround Time ◽  
Hiv Status ◽  
Operating Characteristics ◽  
Fresh Blood ◽  
Resource Limited ◽  
And Performance

ABSTRACTBackgroundCD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24h turnaround time.MethodsWe recruited 479 GeneXpert® positive cases and 108 symptomatic but GeneXpert® negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert® and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing INF-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus.ResultsSignificantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84-0.91). The assay performance was not significantly affected by HIV status.ConclusionsWe successfully implemented TAM-TB immunoassay routine testing with a 24h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.

scholarly journals Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hellen Hiza ◽  
Jerry Hella ◽  
Ainhoa Arbués ◽  
Beatrice Magani ◽  
Mohamed Sasamalo ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peptide Pool ◽  
Turnaround Time ◽  
Hiv Status ◽  
Operating Characteristics ◽  
Fresh Blood ◽  
Resource Limited ◽  
And Performance

AbstractCD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24 h turnaround time. We recruited 479 GeneXpert positive cases and 108 symptomatic but GeneXpert negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing IFN-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus. Significantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84–0.91). The assay performance was not significantly affected by HIV status. To conclude, we successfully implemented TAM-TB immunoassay routine testing with a 24 h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.

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