[Involvement of the complement cascade in severe forms of COVID-19].

The complement system is an essential component of the innate immune system. Its excessive activation during COVID-19 contributes to cytokine storm, disease-specific endothelial inflammation (endotheliitis) and thrombosis that comes with the disease. Targeted therapies of complement inhibition in COVID-19, in particular blocking the C5a-C5aR1 axis have to be taken into account in the establishment of potential biomarkers and development of therapeutic strategies in the most severe forms of the disease.

Complement cascade in severe forms of COVID-19: Recent advances in therapy.

The complement system is an essential component of the innate immune system. The three complement pathways (classical, lectin, alternative) are directly or indirectly activated by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). In the most severe forms of COVID-19, overactivation of the complement system may contribute to the cytokine storm, endothelial inflammation (endotheliitis) and thrombosis.

Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome.

Phosphoinositides regulate the TCR/CD3 complex membrane dynamics and activation.

Phosphoinositides (PIs) play important roles in numerous membrane-based cellular activities. However, their involvement in the mechanism of T cell receptor (TCR) signal transduction across the plasma membrane (PM) is poorly defined. Here, we investigate their role, and in particular that of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in TCR PM dynamics and activity in a mouse T-cell hybridoma upon ectopic expression of a PM-localized inositol polyphosphate-5-phosphatase (Inp54p).