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. 2021 Sep 8;11:666987. doi: 10.3389/fcimb.2021.666987

Figure 2.

Figure 2

The potential role of SARS-CoV-2 infection in the reduction of testosterone and associated COVID-19 severity. SARS-CoV-2 induces oxidative stress, activation of nod-like receptor pyrin-3 (NLRP3) inflammasome and abnormal immune activation, downregulation of angiotensin converting enzyme 2 (ACE2), and activation of receptor for advanced glycation end-product (mRAGE). Downregulation of ACE2 with activation of mRAGE increases angiotensin II (AngII) and reduces Mas receptor (MasR). Activation of NLRP3 inflammasome triggers release of nuclear factor kappa B (NF-κB) and together with cyclooxegenase-2 (COX-2) and p38 mitogen-activated protein kinase (p38MAPK) stimulate release of pro-inflammatory cytokines, which cause testicular injury. These pathophysiological changes reduce production and release of testosterone from injured testes. Reduction in the level of testosterone provokes releases of pro-inflammatory cytokines and reduces anti-inflammatory cytokines with immune deregulation. These changes lead to induction of cytokine storm with consequent augmentation of COVID-19 severity.