Role of the extracellular matrix in COVID-19

Table 1 Dysregulation of the extracellular matrix in coronavirus disease 2019

ECM	Alterations in COVID-19	Suggested ECM role in disease	In other inflammatory and fibrotic lung disorders
MMP-1	Increased MMP-1 levels have been detected in the serum of patients, which correlated with the severity of COVID-19 and early fibrosis with this condition[23]	Drive endothelial cell destruction, such as by over-activating the mmp-1/PAR1 pathway, increasing VEGF-2 receptor expression, and causing endothelial damage. Involved in collagen deposition in IPF	Emphysema, Asthma: MMP-1 levels raised
MMP-2	Increased MMP-2 levels have been detected in the CSF samples of COVID-19 patients with neurological syndrome[30]. Downregulated MMP-2 levels have been detected in the plasma samples with this condition, which correlated with the mortality rate of COVID-19[31]	Involved in disruption of the blood-brain barrier. Being Involved in the regulation of angiogenesis may lead to vascular remodeling. Play an anti-inflammatory effect in the endothelial dysfunction	Asthma, Idiopathic Pneumonia: MMP-2 levels raised. pulmonary fibrosis (IPF): Disproportionate extracellular matrix degradation
MMP-3	Increased MMP-3 levels have been detected in serum of individuals with this condition[37,40]	Associated with activation of MMP-9 and enhanced synthesis of procollagen	Asthma: MMP-3 levels raised
MMP-7	Increased MMP-7 levels have been detected in the serum of obese-diabetic patients with novel coronavirus pneumonia-infected[36]. Elevated in COVID-19 patients with early fibrotic changes[27]	Contribute to airway epithelial damage and inflammation as well as Play a profibrotic effect	Asthma, Cystic fibrosis (CF), ARDS: MMP-7 levels raised
MMP-8	/	/	COPD, Emphysema, Asthma: MMP-8 levels raised
MMP-9	Increased MMP-9 levels have been detected in the circulation of COVID-19 patients with respiratory failure and with obese-diabetic[36]	Associated with respiratory failure. Linked to inflammation-induced tissue remodeling. Contributes to the disruption of alveolar epithelial basement membrane	COPD, Emphysema, Asthma, IPF, UIP, ALI, ARDS: MMP-9 levels raised
MMP-10	The CSF levels of MMP-10 correlated with the degree of neurologic dysfunction exhibited[41]	Associated with neurodegeneration	/
MMP-12	/	/	COPD, Emphysema: MMP-12 levels raised
MMP-14	Increased MMP-14 levels in lung tissue have been detected COVID-19 patients[32]	Implicated in COVID-19 pathogenesis	COPD: MMP-14 levels raised
HA	Increased HA levels have been detected in lungs of deceased COVID-19 patients[13]. HA fragments present at elevated levels in COVID-19 patient plasma[16]	Induce endothelial barrier dysfunction	ARDS: HA levels raised
Proteogly-cans	/	/	COPD, IPF, Asthma, Bronchiolitis obliterans syndrome: Versican levels raised
Collagen	16 collagens are downregulated or diminished in COVID-19[52]. Collagen deposits on Lung Samples of deceased COVID-19 patients[51]	Damage of mechanical characteristics of lungs	Asthma, COPD, IPF: Display differing collagen deposition
ADAMs	Increased ADAM12 and ADAM17 levels have been detected in serum of COVID-19 patients[56-58]	ADAM17 may be associated with viral entry. ADAM12 plays a role in inflammation and endothelial cell permeability	/
ADAMTS	ADAMTS13 decreased significantly with increasing COVID-19 severity[59,60]	Associated with vascular microthrombotic disease	/

COVID-19: Coronavirus disease 2019; ALI: Acute lung injury; ARDS: Adult respiratory distress syndrome; COPD: Chronic obstructive pulmonary disease; ECM: Extracellular matrix; HA: Hyaluronan; MMP: Matrix metalloproteinase; IPF: Idiopathic pulmonary fibrosis; UIP: Usual interstitial pueumonia; VEGF-2: Vascular endothelial growth factor 2.