Nebulized inhalation of plasma-activated water in the treatment of progressive moderate COVID-19 patients with antiviral treatment failure: a randomized controlled pilot trial
Heng Zhao, Wanting Meng, Xing Lv, Jing Li, Zhigui Cai, Xingxing Guo, Zifeng Wang, Li Guo, Mingzhe Rong, Cong Shen, Dingxin Liu, Liqiang Song
BMC Infectious Diseases, doi:10.1186/s12879-024-09886-w
Background Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. Methods This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. Results A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW.
Declarations Ethics approval and consent to participate The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Medical Ethics Committee of the First Affiliated Hospital of the Air Force Medical University (Approval No.: KY20232004-C-1, January 5, 2023), registered with the Chinese Clinical Trial Registry (Registration No.: ChiCTR2300078706). Informed consent was obtained from all subjects involved in the study.
Consent for publication Not applicable.
Competing interests The authors declare no competing interests.
Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Amini, Hosseini, Fatollah, Mirpour, Ghoranneviss et al., Beneficial effects of cold atmospheric plasma on inflammatory phase of diabetic foot ulcers; a randomized clinical trial, J Diabetes Metabolic Disorders
Anderson, Atkins, Bäckman, Cipolla, Clark et al., Inhaled medicines: past, present, and future, Pharmacol Rev
Azizmohammadi, Azizmohammadi, Dahmardeh, Azargashb, Shokouh et al., Analysis of 239 ordinary and severe cases of COVID-19: clinical features and treatment, Eur J Transl Myol
Bernal, Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients, New Engl J Med
Bisag, Isabelli, Laghi, Laurita, Dirani et al., Cold atmospheric plasma decontamination of SARS-CoV-2 bioaerosols, Plasma Process Polym
Bisag, Isabelli, Laurita, Bucci, Capelli et al., Cold atmospheric plasma inactivation of aerosolized microdroplets containing bacteria and purified SARS-CoV-2 RNA to contrast airborne indoor transmission, Plasma Process Polym
Braman, Postinfectious cough, Chest
Choi, Song, Lee, Hong, Kim, Inhibition of inflammatory reactions in 2,4-dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by nonthermal plasma, Sci Rep-UK
Cortázar, Megía-Macías, Moreno, Brun, Gómez-Casado, Vulnerability of SARS-CoV-2 and PR8 H1N1 virus to cold atmospheric plasma activated media, Sci Rep-UK
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of Coronavirus disease 2019 in China, New Engl J Med
Guo, Lv, Wu, Wang, Wu et al., Safety and efficacy of plasma-activated water on prolonged viral shedding of COVID-19 patients: a randomized controlled trial, Plasma Process Polym
Guo, Xu, Gou, Liu, Zhao et al., Mechanism of virus inactivation by cold atmospheric-pressure plasma and plasmaactivated water, Appl Environ Microb
Guo, Yao, Yang, Zhang, Qi et al., Plasma-activated water: an alternative disinfectant for S protein inactivation to prevent SARS-CoV-2 infection, Chem Eng J
Gül, Gonen, Jones, Taşlı, Zararsız et al., A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™), Front Immunol
Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle et al., Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19, New Engl J Med
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Hwang, Jeon, Wang, Kim, Kim et al., Design and medical effects of a vaginal cleaning device generating plasmaactivated water with antimicrobial activity on bacterial vaginosis, Plasma
Jang, Bok, Ahn, Kim, Kang, Human trial for the effect of plasmaactivated water spray on vaginal cleaning in patients with bacterial vaginosis, Med Sci
Kabinger, Stiller, Schmitzová, Dienemann, Kokic et al., Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis, Nat Struct Mol Biol
Kaushik, Ghimire, Li, Adhikari, Veerana et al., Biological and medical applications of plasma-activated media, water and solutions, Biol Chem
Khanikar, Kalita, Kalita, Kashyap, Das et al., Cold atmospheric pressure plasma for attenuation of SARS-CoV-2 spike protein binding to ACE2 protein and the RNA deactivation, Rsc Adv
Kim, Kim, Applications of plasma-activated liquid in the medical field, Biomedicines
Lee, Lee, Kim, Han, Kang et al., Non-thermal plasma inhibits mast cell activation and ameliorates allergic skin inflammatory diseases in NC/Nga mice, Sci Rep-UK
Lee, Lee, Kim, Won, Kim, Non-thermal atmospheric plasma ameliorates imiquimod-induced psoriasis-like skin inflammation in mice through inhibition of immune responses and up-regulation of PD-L1 expression, Sci Rep-UK
Li, Liu, Liu, Hu, Yang et al., Analysis of risk factors for 24 patients with COVID-19 developing from moderate to severe condition, Front Cell Infect Mi
Li, Zhan, Yang, Tu, Hu et al., Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific singledomain antibody, Cell
Liao, Liu, Yuan, Wen, Xu et al., Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19, Nat Med
Loizou, Kniazeva, Apostolou, Kornev, Kostevitch et al., Effect of cold atmospheric plasma on SARS-CoV-2 inactivation: a pilot study in the hospital environment, COVID
Luo, Yu, Gou, Li, Sun et al., Histopathologic findings in the explant lungs of a patient with COVID-19 treated with bilateral orthotopic lung transplant, Transplantation
Nastasa, Pasca, Malancus, Bostanaru, Ailincai et al., Toxicity assessment of long-term exposure to nonthermal plasma activated water in mice, Int J Mol Sci
Ng, Correia, Seagal, Degoey, Schrimpf et al., Antiviral drug discovery for the treatment of COVID-19 infections, Viruses-Basel
Owen, Allerton, Anderson, Aschenbrenner, Avery et al., An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19, Science
Poulakou, Barakat, Israel, Bacci, Ribavirin aerosol in hospitalized adults with respiratory distress and COVID-19: an open-label trial, Clin Transl Sci
Santi Laurini, Montanaro, Motola, Safety profile of Molnupiravir in the treatment of COVID-19: a descriptive study based on FAERS data, J Clin Med
Seebauer, Freund, Hasse, Miller, Segebarth et al., Effects of cold physical plasma on oral lichen planus: an in vitro study (effects of CAP on OLP), Oral Dis
Shen, Yu, Cai, Zhou, Sheng et al., Quantitative computed tomography analysis for stratifying the severity of Coronavirus disease 2019, J Pharm Anal
Song, Hui, Hull, Birring, Mcgarvey et al., Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses, Lancet Respiratory Med
Tamasauskiene, Sitkauskiene, Immune system in the pathogenesis of chronic cough, Immunol Lett
Wai, Chan, Cheung, Wang, Chan et al., Association of Molnupiravir and Nirmatrelvir-Ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19, Lancet Reg Health -Western Pac
Wang, Zhou, Zhou, Li, Weerasinghe et al., Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry, Theranostics
Xu D, Cui, Xu, Tian, Liu et al., Systemic study on the safety of immuno-deficient nude mice treated by atmospheric plasma-activated water, Plasma Sci Technol
Xu, Shi, Wang, Zhang, Huang et al., Pathological findings of COVID-19 associated with acute respiratory distress syndrome, Lancet Respiratory Med
Zhai, Xu, Li, Guo, Chen et al., Successful treatment of vitiligo with cold atmospheric plasma-activated hydrogel, J Invest Dermatol
Zhang, Chua, Selva, Kedzierski, Ashhurst et al., Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity, Res Sq
Zheng, Zhou, Zhou, Ye, Huang et al., SARS-CoV-2 clearance in COVID-19 patients with Novaferon treatment: a randomized, open-label, parallel-group trial, Int J Infect Dis
Zhou, Guo, Li, Fang, Chen et al., Coronavirus disease 2019: initial chest CT findings, Eur Radiol
Zhou, Zhou, Wang, Xian, Mai-Prochnow et al., Plasma-activated water: generation, origin of reactive species and biological applications, J Phys D
Zhuang, Xu, Wu, Yang, Lin et al., Postmarketing safety concerns with nirmatrelvir: a disproportionality analysis of spontaneous reports submitted to the FDA adverse event reporting system, Brit J Clin Pharmaco
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