Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hydrogen Sulfide Ameliorates SARS-CoV-2–Associated Lung Endothelial Barrier Disruption

Olivier Escaffre
ORCID logo ,
Peter Szaniszlo
,
Gabor Törő
,
Caitlyn L. Villas
,
Brenna J. Servantes
,
Ernesto Lopez
,
Terry L. Juelich
,
Corri B. Levine
ORCID logo ,
Susan L. F. McLellan
,
Jessica C. Cardenas
,
Alexander N. Freiberg
ORCID logo ,
Katalin Módis
*
Version 1 : Received: 23 May 2023 / Approved: 23 May 2023 / Online: 23 May 2023 (10:31:05 CEST)

A peer-reviewed article of this Preprint also exists.

Escaffre, O.; Szaniszlo, P.; Törő, G.; Vilas, C.L.; Servantes, B.J.; Lopez, E.; Juelich, T.L.; Levine, C.B.; McLellan, S.L.F.; Cardenas, J.C.; Freiberg, A.N.; Módis, K. Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption. Biomedicines 2023, 11, 1790. Escaffre, O.; Szaniszlo, P.; Törő, G.; Vilas, C.L.; Servantes, B.J.; Lopez, E.; Juelich, T.L.; Levine, C.B.; McLellan, S.L.F.; Cardenas, J.C.; Freiberg, A.N.; Módis, K. Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption. Biomedicines 2023, 11, 1790.

Abstract

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients’ plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations of barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real-time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H2S-releasing compounds has the potential to ameliorate SARS-CoV-2–associated lung endothelial barrier disruption.

Keywords

endothelial barrier; COVID-19; SARS-CoV-2; hydrogen sulfide; cytokine; TNF-α

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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