Immunological characterization of COVID-19 endotypes of critically ill patients
Anasthesiologie und Intensivmedizin
; 63:S226-S227, 2022.
Article
in English
| EMBASE | ID: covidwho-1965402
ABSTRACT
Introduction Over the last 20 months Sars-CoV-2 research revealed tremendous insights into the pathophysiology resulting in vaccines and first immunomodulatory therapies in an unprecedented short time [1]. However, the patient's individual clinical course is remarkably heterogenous and the effectivity of immunomo-dulatory therapies especially in critically ill patients is still very variable [2]. Therefore,a better understanding of the patients' individual immune response is needed [3]. Methods Unbiased machine learning grouped 323 Covid-19 patients treated at the Klinikum Rechts der Isar ICU into 3 different clusters. For this we queried the ICU electronic files and analyzed relevant clinical features (Fig. 1+2). To delineate biological differences within these clusters, we applied a 14 parameter flow cytometric panel to PBMCs from 27 of these CoV2 ICU patients. Flow data was analyzed using FlowJo and the FlowSOM package for unsupervised clustering (Fig. 3+4). Written informed consent was obtained from all patients and healthy controls. The study was approved by the local ethical review board (Az249/20 S-EB). Results Patients from cluster 1 had above ICU average respiratory function (Fig. 2), reduced liver function and received lower dose catecholamines. Immunologically these patients had significantly higher amount of CD3+CD4+ T helper cells (Fig. 5). Whilst B cell numbers were reduced, they were highly activated (HLA-DR-ordf). Activated monocytes produced high amounts of TNFa. Interestingly, proinflammatory CD14+ HLA-DRlow monocytes were not increased. Cluster 2 contains patients with renal impairment, an increased tendency for bacterial infection and elevated blood lactate levels. Cluster 3 is made up of long-term ICU patients with severely reduced respiratory function and high ECMO-dependency (Fig. 1). These patients had significantly increased ratios of activated innate immune cells. We have detected elevated levels of an interesting population of CD14+ HLA-DRlow monocytes, a well-established player of immune suppression [4], while cytotoxic T cells and B cells were found to be significantly reduced. Conclusion These data provided evidence that clinically defined endotypes of critically ill Covid-19 patients exhibit a distinct immune profile. The immunological differences support our theory that these endotypes might require personalized immunomodulatory therapies to restore the pro-regenerative cell function in ICU Covid-19 populations and improve patient outcome in the future.
catecholamine; CD3 antigen; CD4 antigen; endogenous compound; HLA DR antigen; tumor necrosis factor; adult; B lymphocyte; bacterial infection; cell count; cell function; clinical feature; conference abstract; controlled study; coronavirus disease 2019; critically ill patient; cytotoxic T lymphocyte; data analysis software; drug therapy; ethics; female; helper cell; human; human cell; human tissue; immunocompetent cell; immunosuppressive treatment; immunotherapy; informed consent; kidney disease; lactate blood level; liver function; low drug dose; machine learning; major clinical study; male; monocyte; outcome assessment; peripheral blood mononuclear cell; respiratory function
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Anasthesiologie und Intensivmedizin
Year:
2022
Document Type:
Article
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