The Janus‐faced role of interferons and a competition of positive and negative feedback loops determine the course of COVID‐19 infection. After binding to ACE‐2, SARS‐Cov2 is able to enter cells and to replicate. This initiates immune responses via B and T cells and interferon release, thereby reducing the virus load again. However, interferon alpha also stimulates the expression of ACE‐2, which facilitates virus entry and implements a positive feedback loop raising the global virus load.
Higher expression of the transmembrane serine protease 2 (TMPRSS2), as observed, for example, in males, stimulates the binding of SARS‐CoV2 to the ACE receptor and promotes a higher virus load. Simulation of the motif of combined positive and negative feedback loops as outlined in Figure 3 suggests that higher TMPRSS2 expression may also give rise to oscillatory dynamics of the virus load, as previously observed in severe cases of COVID‐19.
Systems modelling explains: A #cybernetic theory of the molecular processes in #COVID-19 predicts oscillatory #inflammation and virus load in severe forms, which result from increased #TMPRSS2 expression.
pubmed.ncbi.nlm.nih.gov/36168893/
doi.org/10.1111/jep....
www.livivo.de/doc/M36168893
