ABSTRACT
The different effector functions of human IgG are closely associated with its four subtypes. Class switch towards IgG4 occurs after long-term antigen exposure, downregulates immune responses and is associated with several autoimmune diseases. Interestingly, significantly elevated IgG4 levels have recently been detected after more than two mRNA vaccinations. We here study the distribution of IgG subtypes in the context of Post-COVID syndrome. To this end, we analyzed serum samples from two cohorts of 64 patients after COVID and 64 convalescent COVID-19 patients. We found differences in the absolute levels of Spike protein-specific IgG subtypes for both cohorts. IgG1 was the most abundant subtype, followed by IgG3 and IgG2 and IgG4 in declining order. A significant difference was only detected for IgG2. When further analyzing the IgG4 levels reactive against the Spike protein receptor-binding domain (RBD) and the nucleocapsid-protein of SARS-CoV-2, a small but significant difference was detected for the RBD but not nucleocapsid proteins. Since the total IgG4 levels are very low, we do not expect a biologically relevant role in the development and progression of post-COVID syndrome. However, low IgG2 levels, as seen in the Post-COVID cohort, could contribute to the persistent presence of SARS-CoV-2 antigens, causing chronic inflammation in the setting of post-COVID.
Subject(s)
Autoimmune Diseases , COVID-19 , InflammationABSTRACT
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.
Subject(s)
Pneumonia , Critical Illness , Addison Disease , COVID-19ABSTRACT
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.