To the Editor:
Novel coronavirus disease 2019 (COVID-19) is an emerging disease of public health concern, and the current pandemic is having a major global impact. While there is no specific recommended treatment for COVID-19, hydrogen sulfide has the potential to be of therapeutic value for managing acute respiratory illness in patients with COVID-19. However, inhaled hydrogen sulfide has not yet been formally evaluated. Given the extent of the COVID-19 pandemic and the large numbers of hospitalized patients requiring respiratory support, clinical use of inhaled hydrogen sulfide may become an alternate rescue therapy to Suppressing Deterioration in Patients with COVID-19 for the management of acute respiratory distress syndrome (ARDS) in patients with COVID-19.
Increasing attention is being focused on the development of therapeutic strategies against this disease. We read, with great interest, the article by Renieris et al. (1) “Serum hydrogen sulfide and outcome association in pneumonia by the SARS-CoV-2 corona virus” published in this journal. While there is no specific recommended antiviral treatment, and vaccines have yet to be approved, the authors provided a powerful evidence for the connection between hydrogen sulfide concentration in patients serum and outcome survivors of patients from SARS-CoV-2 illness; therefore, hydrogen sulfide (H2S) inhalation therapy may be included in the strategy as a promising therapeutic candidate.
Although H2S is considered a toxic substance at a high concentration, low concentrations are very useful and there are many studies showing its effect on the human body. Hydrogen sulfide is an important gaseous transmitter modulating several biological functions, ranging from lifespan extension to regulation of vascular tone, anti-oxidative and anti-inflammatory effects, nervous, cardiovascular, and immune system, in health and disease (2).
The role of H2S is to assist the defense against coronavirus. This can be achieved by an antiviral property of H2S through two lines, direct and indirect way, the direct way may be due to alterations of the viral membrane or through interfering with ACE2 and transmembrane serine protease 2 (3–6).
Currently, evidence shows that COVID-19 virus requires ACE2 to enter the host cell (7). Beside, the transmembrane serine protease (TMPRSS2) is the main host cell protease which cleaves the S protein of human coronaviruses on the cell membrane, allowing the virus to release fusion peptide for membrane fusion (8). Therefore, co-expression of ACE2 and TMPRSS2 is critical for the cell entry process of COVID-19 (9).
The other line through the contributions of H2S to maintenance of elevated level of glutathione level (GSH), which can itself be another player with antiviral effect, very recently, GSH was also proposed as potentially useful agent against COVID-19 (10).
We advocate for a clinical trial exploring the use of inhaled H2S for the management of COVID-19 ARDS to be conducted as a matter of urgency.
1. Renieris G, Katrini K, Damoulari C, Akinosoglou K, Psarrakis C, Kyriakopoulou M, Dimopoulos G, Lada M, Koufargyris P, Giamarellos-Bourboulis EJ. Serum hydrogen sulfide and outcome association in pneumonia by the SARS-CoV-2 coronavirus. Shock
54 (5):633–637, 2020.
2. Szabó C. Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov
3. Yang G. H2S as a potential defense against COVID-19? Am J Physiol Cell Physiol
319 (2):C244–C249, 2020.
4. Ivanciuc T, Sbrana E, Ansar M, Bazhanov N, Szabo C, Casola A, Garofalo RP. Hydrogen sulfide is an antiviral and antiinflammatory endogenous gasotransmitter in the airways. Role in respiratory syncytial virus infection. Am J Respir Cell Mol Biol
55 (5):684–696, 2016.
5. Bazhanov N, Ivanciuc T, Wu H, Garofalo M, Kang J, Xian M, Casola A. Thiol-activated hydrogen sulfide donors antiviral and anti-inflammatory activity in respiratory syncytial virus infection. Viruses
10 (5):249, 2018.
6. Bazhanov N, Escaffre O, Freiberg AN, Garofalo RP, Casola A. Broad-range antiviral activity of hydrogen sulfide against highly pathogenic RNA viruses. Sci Rep
7 (1):41029, 2017.
7. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huan g CL, et al. Addendum: a pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature
588 (7836):E6, 2020.
8. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell
181 (2):271.e8–280.e8, 2020.
9. Palamara AT, Perno CF, Ciriolo MR, Dini L, Balestra E, D’Agostini C, Di Francesco P, Favalli C, Rotilio G, Garaci E. Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication. Antiviral Res
27 (3):237, 1995.
10. Kim J, Zhang J, Cha Y, Kolitz S, Funt J, Escalante Chong R, Barrett S, Kusko R, Zeskind B, Kaufman H. Advanced bioinformatics rapidly identifies existing therapeutics for patients with coronavirus disease-2019 (COVID-19). J Transl Med
18 (1):257, 2020.