Preprint / Version 1

Protecting Patients from Viral Respiratory Infections

Correspondence Regarding Klompas et al., NEJM June 14, 2023




Correspondence regarding Klompas et al, in NEJM June 14, 2023; titled ''Strategic Masking to Protect Patients from All Respiratory Viral Infections'', a plea for structured use of masks to protect against future CoV2 and other types of viral infections in a hospital setting. We do not disagree with this, but we think that instead of a passive mask barrier, another active way can also achieve this goal, but more broadly.

-The other respiratory viruses that Dr Klampos mentions are almost all of the 'single RNA enveloped' type. This is precisely the starting point of the proposed treatment method with an H2S donor, this has already been described by Dr Casola's group in some top journals (references 5,6,7).

-In addition, NAC (very safe, known for a long time, cheap and available everywhere) has also been designated as an H2S donor. This makes global application possible, especially in low-income countries. [ref 12-18]. NAC effervescent tablets are cheaper than a medically suitable mask. This also invites to include NAC as a comparator in future RC trials.

-This H2S supplementation for the restoration of innate immunity can be applied at different scales (cohorts): e.g. community, hospital, wards, barracks, cruise ships, prison, etc. Then staff and Clients/Patients can be treated combined in such a cohort.


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Bourgonje AR, Offringa AK, van Eijk LE, Abdulle AE, Hillebrands JL, van der Voort PHJ, van Goor H, van Hezik EJ. N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019. Antioxid Redox Signal. 2021 Nov 10;35(14):1207-1225. doi: 10.1089/ars.2020.8247. Epub 2021 Mar 25. PMID: 33607929.

van Hezik E.J. Importance of antiviral H?S in treatment protocols for COVID-19. Pul’monologiya. 2021; 31 (5): 636–644.

Thomas T, Stefanoni D, Reisz JA, Nemkov T, Bertolone L, Francis RO, Hudson KE, Zimring JC, Hansen KC, Hod EA, Spitalnik SL, D'Alessandro A. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI Insight. 2020 Jul 23;5(14):e140327. doi: 10.1172/jci.insight.140327. PMID: 32559180; PMCID: PMC7453907.

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. 2020 Nov;54(5):633-637. doi: 10.1097/SHK.0000000000001562. PMID: 32433216; PMCID: PMC7363385.

Bazhanov N, Ansar M, Ivanciuc T, Garofalo RP, Casola A. Hydrogen Sulfide: A Novel Player in Airway Development, Pathophysiology of Respiratory Diseases, and Antiviral Defenses. Am J Respir Cell Mol Biol. 2017 Oct;57(4):403-410. doi: 10.1165/rcmb.2017-0114TR. PMID: 28481637; PMCID: PMC5650090.

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. 2016 Nov;55(5):684-696. doi: 10.1165/rcmb.2015-0385OC. PMID: 27314446; PMCID: PMC5105180.

Bazhanov N, Escaffre O, Freiberg AN, Garofalo RP, Casola A. Broad-Range Antiviral Activity of Hydrogen Sulfide Against Highly Pathogenic RNA Viruses. Sci Rep. 2017 Jan 20;7:41029. doi: 10.1038/srep41029. PMID: 28106111; PMCID: PMC5247713.

Ma Y, Luo Y, Feng X, Huang C, Shen X. Smartphone-controlled biosensor for viral respiratory infectious diseases: Screening and response. Talanta. 2023 Mar 1;254:124167. doi: 10.1016/j.talanta.2022.124167. Epub 2022 Dec 5. PMID: 36493567; PMCID: PMC9721129.

Desborough MJR, Keeling DM. The aspirin story - from willow to wonder drug. Br J Haematol. 2017 Jun;177(5):674-683. doi: 10.1111/bjh.14520. Epub 2017 Jan 20. PMID: 28106908.

Ezeri?a D, Takano Y, Hanaoka K, Urano Y, Dick TP. N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production. Cell Chem Biol. 2018 Apr 19;25(4):447-459.e4. doi: 10.1016/j.chembiol.2018.01.011. Epub 2018 Feb 8. PMID: 29429900; PMCID: PMC6455997.

Pedre B, Barayeu U, Ezeri?a D, Dick TP. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacol Ther. 2021 Dec;228:107916. doi: 10.1016/j.pharmthera.2021.107916. Epub 2021 Jun 23. PMID: 34171332.

Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020 Nov 2;16:1047-1055. doi: 10.2147/TCRM.S273700. PMID: 33177829; PMCID: PMC7649937.

De Flora S, Balansky R, La Maestra S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J. 2020 Oct;34(10):13185-13193. doi: 10.1096/fj.202001807. Epub 2020 Aug 11. PMID: 32780893; PMCID: PMC7436914.

Yang G. H2S as a potential defense against COVID-19? Am J Physiol Cell Physiol. 2020 Aug 1;319(2):C244-C249. doi: 10.1152/ajpcell.00187.2020. Epub 2020 Jun 9. PMID: 32515982; PMCID: PMC7381713.

Dattilo M. The role of host defences in Covid 19 and treatments thereof. Mol Med. 2020 Sep 29;26(1):90. doi: 10.1186/s10020-020-00216-9. PMID: 32993497; PMCID: PMC7522454.

Ibrahim H, Perl A, Smith D, Lewis T, Kon Z, Goldenberg R, Yarta K, Staniloae C, Williams M. Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine. Clin Immunol. 2020 Oct;219:108544. doi: 10.1016/j.clim.2020.108544. Epub 2020 Jul 22. PMID: 32707089; PMCID: PMC7374140.

Citi V, Martelli A, Brancaleone V, Brogi S, Gojon G, Montanaro R, Morales G, Testai L, Calderone V. Anti-inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H?S donors in COVID-19 therapy. Br J Pharmacol. 2020 Nov;177(21):4931-4941. doi: 10.1111/bph.15230. Epub 2020 Aug 26. PMID: 32783196; PMCID: PMC7436626.

Poe FL, Corn J. N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2. Med Hypotheses. 2020 Oct;143:109862. doi: 10.1016/j.mehy.2020.109862. Epub 2020 May 30. PMID: 32504923; PMCID: PMC7261085.

de Alencar JCG, Moreira CL, Müller AD, Chaves CE, Fukuhara MA, da Silva EA, Miyamoto MFS, Pinto VB, Bueno CG, Lazar Neto F, Gomez Gomez LM, Menezes MCS, Marchini JFM, Marino LO, Brandão Neto RA, Souza HP; COVID Register Group. Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2021 Jun 1;72(11):e736-e741. doi: 10.1093/cid/ciaa1443. PMID: 32964918; PMCID: PMC7543361.

Izquierdo JL, Soriano JB, González Y, Lumbreras S, Ancochea J, Echeverry C, Rodríguez JM. Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19. Sci Prog. 2022 Jan-Mar;105(1):368504221074574. doi: 10.1177/00368504221074574. PMID: 35084258; PMCID: PMC8795755.

Faverio P, Rebora P, Rossi E, Del Giudice S, Montanelli F, Garzillo L, Busnelli S, Luppi F, Valsecchi MG, Pesci A. Impact of N-acetyl-l-cysteine on SARS-CoV-2 pneumonia and its sequelae: results from a large cohort study. ERJ Open Res. 2021 Feb 7;8(1):00542-2021. doi: 10.1183/23120541.00542-2021. PMID: 35136824; PMCID: PMC8646003.

Assimakopoulos SF, Aretha D, Komninos D, Dimitropoulou D, Lagadinou M, Leonidou L, Oikonomou I, Mouzaki A, Marangos M. N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study. Infect Dis (Lond). 2021 Nov;53(11):847-854. doi: 10.1080/23744235.2021.1945675. Epub 2021 Jun 29. PMID: 34182881.

Avdeev SN, Gaynitdinova VV, Merzhoeva ZM, Berikkhanov ZG. N-acetylcysteine for the treatment of COVID-19 among hospitalized patients. J Infect. 2022 Jan;84(1):94-118. doi: 10.1016/j.jinf.2021.07.003. Epub 2021 Jul 10. PMID: 34252497; PMCID: PMC8271031.

Ed J van Hezik MD. N-acetylcysteine-AConvenient Rationale for COVID-19 Consideration of Antiviral H?S for Inclusion in one of the ANTICOV or WHO Master Protocols. AIJR Preprints. Section: Coronavirus Article Id: 296, Version: 1, 2021. URL: