Role of the extracellular matrix in COVID-19

Figure 1 The extracellular matrix of a healthy lung and its remodelling after infection with severe acute respiratory syndrome coronavirus 2. Tenascin C, collagen, elastin, integrins, laminins, perlecan, hyaluronan, aggrecan, and fibronectin are crucial components of the healthy lung matrix structure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the cell via the effects of angiotensin converting enzyme-2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). As a result of identifying the virus, immune cells, specifically macrophages, release proinflammatory mediators that activate more immune cells, creating an uncontrolled cycle of the inflammatory response “cytokine storm”. Extracellular matrix (ECM) remodelling occurs in response to lung injuries, including matrix metalloproteinase (MMP) overexpression and an imbalance between MMPs and tissue inhibitors of MMPs (TIMPs), increased deposition of ECM fragments and collagen, massive formation and deposition of fibronectin, and accumulation of hyaluronan (HA). Moreover, ADAM12, ADAM17, and ADAMTS13 expressions are elevated during SARS-CoV-2 infection. ACE2 angiotensin-converting enzyme 2, TMPRSS2 transmembrane protease serine 2, ADAM17 ADAM metalloprotease domain 17, ADAM12 ADAM metalloprotease domain 12, ADAMTS13 ADAMs with thrombospondin domain 12, HMW-HA high-molecular-weight hyaluronan, MMPs matrix metalloproteinases, TIMPs tissue inhibitors of matrix metalloproteinases. ACE2: Angiotensin converting enzyme-2; ECM: Extracellular matrix; HA: Hyaluronan; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; MMP: Matrix metalloproteinase; TIMP: Tissue inhibitors of MMP; TMPRSS2: Transmembrane serine protease 2; HMW-HA: High-molecular-weight HA.