tetano
Editor, Senior Moderator
J Infect Dis
. 2023 Dec 18:jiad536.
doi: 10.1093/infdis/jiad536. Online ahead of print. Severe Acute Respiratory Syndrome Coronavirus 2 Infection Alters Mediators of Lung Tissue Remodeling In Vitro and In Vivo
Michael Wong[SUP] 1 [/SUP], Chandrima Gain[SUP] 1 [/SUP], Madhav B Sharma[SUP] 1 [/SUP], Leila Fotooh Abadi[SUP] 1 2 [/SUP], Cristelle Hugo[SUP] 1 [/SUP], Hariclea Vassilopoulos[SUP] 1 [/SUP], Maria Daskou[SUP] 1 [/SUP], Gregory A Fishbein[SUP] 3 [/SUP], Theodoros Kelesidis[SUP] 1 2 [/SUP]
Affiliations
Background: Altered mediators of airway tissue remodeling such as matrix metalloproteinases (MMPs) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may contribute to morbidity in coronavirus disease 2019 (COVID-19); however, the differential impact of SARS-CoV-2 variants of concern (VOCs) on MMPs is unknown.
Methods: Using both in vitro human airway cell culture model and in vivo transgenic mouse model of SARS-CoV-2 infection, we studied the differential effect of SARS-CoV-2 VOCs on expression of key MMPs and inflammatory mediators in airway cells and tissues.
Results: The most consistent findings with all SARS-CoV-2 variants in infected compared to uninfected human bronchial epithelial cell air-liquid interface cultures were the SARS-CoV-2-induced increases in MMP-12 and tissue inhibitor of MMPs. Infection with both SARS-CoV-2 wild type and SARS-CoV-2 Delta variant over 3 days postinfection (dpi) and with Beta variant over 7 dpi increased lung tissue levels of MMP-9 compared to uninfected mice. Overall, SARS-CoV-2 variants had differential dose-dependent impact on secretion of MMP-1, MMP-2, MMP-9, and MMP-12 that varied at the protein versus the gene level and in the early noninflammatory compared to late inflammatory phase of infection.
Conclusions: We provide novel mechanistic insight that the differential impact of SARS-CoV-2 variants on severity of COVID-19 may partially be attributed to unique changes in MMPs.
Keywords: SARS-CoV-2 infection; lung injury; lung tissue remodeling; matrix metalloproteinases; severe COVID-19.
. 2023 Dec 18:jiad536.
doi: 10.1093/infdis/jiad536. Online ahead of print. Severe Acute Respiratory Syndrome Coronavirus 2 Infection Alters Mediators of Lung Tissue Remodeling In Vitro and In Vivo
Michael Wong[SUP] 1 [/SUP], Chandrima Gain[SUP] 1 [/SUP], Madhav B Sharma[SUP] 1 [/SUP], Leila Fotooh Abadi[SUP] 1 2 [/SUP], Cristelle Hugo[SUP] 1 [/SUP], Hariclea Vassilopoulos[SUP] 1 [/SUP], Maria Daskou[SUP] 1 [/SUP], Gregory A Fishbein[SUP] 3 [/SUP], Theodoros Kelesidis[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38109685
- DOI: 10.1093/infdis/jiad536
Background: Altered mediators of airway tissue remodeling such as matrix metalloproteinases (MMPs) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may contribute to morbidity in coronavirus disease 2019 (COVID-19); however, the differential impact of SARS-CoV-2 variants of concern (VOCs) on MMPs is unknown.
Methods: Using both in vitro human airway cell culture model and in vivo transgenic mouse model of SARS-CoV-2 infection, we studied the differential effect of SARS-CoV-2 VOCs on expression of key MMPs and inflammatory mediators in airway cells and tissues.
Results: The most consistent findings with all SARS-CoV-2 variants in infected compared to uninfected human bronchial epithelial cell air-liquid interface cultures were the SARS-CoV-2-induced increases in MMP-12 and tissue inhibitor of MMPs. Infection with both SARS-CoV-2 wild type and SARS-CoV-2 Delta variant over 3 days postinfection (dpi) and with Beta variant over 7 dpi increased lung tissue levels of MMP-9 compared to uninfected mice. Overall, SARS-CoV-2 variants had differential dose-dependent impact on secretion of MMP-1, MMP-2, MMP-9, and MMP-12 that varied at the protein versus the gene level and in the early noninflammatory compared to late inflammatory phase of infection.
Conclusions: We provide novel mechanistic insight that the differential impact of SARS-CoV-2 variants on severity of COVID-19 may partially be attributed to unique changes in MMPs.
Keywords: SARS-CoV-2 infection; lung injury; lung tissue remodeling; matrix metalloproteinases; severe COVID-19.