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Nebulized inhalation of plasma-activated water in the treatment of progressive moderate COVID-19 patients with antiviral treatment failure: a randomized controlled pilot trial

Zhao et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09886-w, ChiCTR2300078706
Sep 2024  
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Progression -9% Improvement Relative Risk CT improvement 73% Hospitalization time 28% Time to discharge 30% Plasma-activated water  Zhao et al.  LATE TREATMENT  RCT Is late treatment with plasma-activated water beneficial for COVID-19? RCT 23 patients in China (January - July 2023) Greater improvement with plasma-activated water (p=0.036) c19early.org Zhao et al., BMC Infectious Diseases, Sep 2024 Favorsplasma-activated water Favorscontrol 0 0.5 1 1.5 2+
RCT 23 moderate COVID-19 patients with antiviral treatment failure, showing nebulized plasma-activated water (PAW) improved chest CT and accelerated cough resolution compared to saline control, however there was no significant difference in progression. No adverse reactions were reported. Authors suggest that PAW may disrupt SARS-CoV-2 binding and replication and have anti-inflammatory effects in the lungs.
risk of progression, 9.1% higher, RR 1.09, p = 1.00, treatment 4 of 11 (36.4%), control 4 of 12 (33.3%).
no CT improvement, 72.7% lower, RR 0.27, p = 0.04, treatment 2 of 11 (18.2%), control 8 of 12 (66.7%), NNT 2.1.
hospitalization time, 27.8% lower, relative time 0.72, p = 0.16, treatment 11, control 12.
time to discharge, 30.0% lower, relative time 0.70, p = 0.24, treatment 11, control 12.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Zhao et al., 12 Sep 2024, Single Blind Randomized Controlled Trial, China, peer-reviewed, 12 authors, study period January 2023 - July 2023, trial ChiCTR2300078706. Contact: liudingxin@mail.xjtu.edu.cn, songlq@fmmu.edu.cn.
This PaperPlasma-activ..All
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.
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Cell. 2022;185(8):1389–401.', 'journal-title': 'Cell'}, { 'issue': '1', 'key': '9886_CR24', 'doi-asserted-by': 'publisher', 'first-page': '165', 'DOI': '10.1111/cts.13436', 'volume': '16', 'author': 'G Poulakou', 'year': '2023', 'unstructured': 'Poulakou G, Barakat M, Israel RJ, Bacci MR. Ribavirin aerosol in ' 'hospitalized adults with respiratory distress and COVID-19: an ' 'open‐label trial. Clin Transl Sci. 2023;16(1):165–74.', 'journal-title': 'Clin Transl Sci'}, { 'key': '9886_CR25', 'doi-asserted-by': 'publisher', 'first-page': '84', 'DOI': '10.1016/j.ijid.2020.07.053', 'volume': '99', 'author': 'F Zheng', 'year': '2020', 'unstructured': 'Zheng F, Zhou Y, Zhou Z, Ye F, Huang B, Huang Y, Ma J, Zuo Q, Tan X, Xie ' 'J, et al. SARS-CoV-2 clearance in COVID-19 patients with Novaferon ' 'treatment: a randomized, open-label, parallel-group trial. Int J Infect ' 'Dis. 2020;99:84–91.', 'journal-title': 'INT J INFECT DIS'}, { 'key': '9886_CR26', 'doi-asserted-by': 'crossref', 'unstructured': 'Cortázar OD, Megía-Macías A, Moreno S, Brun A, Gómez-Casado E. ' 'Vulnerability of SARS-CoV-2 and PR8 H1N1 virus to cold atmospheric ' 'plasma activated media. Sci Rep-UK. 2022;12(1).', 'DOI': '10.1038/s41598-021-04360-y'}, { 'issue': '2', 'key': '9886_CR27', 'doi-asserted-by': 'publisher', 'first-page': '123', 'DOI': '10.1016/j.jpha.2020.03.004', 'volume': '10', 'author': 'C Shen', 'year': '2020', 'unstructured': 'Shen C, Yu N, Cai S, Zhou J, Sheng J, Liu K, Zhou H, Guo Y, Niu G. ' 'Quantitative computed tomography analysis for stratifying the severity ' 'of Coronavirus disease 2019. J Pharm Anal. 2020;10(2):123–9.', 'journal-title': 'J PHARM ANAL'}, { 'key': '9886_CR28', 'unstructured': 'Assessing COVID-19-related symptoms in outpatient adult and adolescent ' 'subjects in clinical trials of drugs and biological products for ' 'COVID-19 prevention or treatment. ' 'https://www.fda.gov/media/142143/download. Accessed 13 August 2024.'}, { 'key': '9886_CR29', 'doi-asserted-by': 'crossref', 'unstructured': 'Azizmohammadi S, Azizmohammadi S, Dahmardeh S, Azargashb H, Shokouh SJH, ' 'Mohajeri-Iravani M, Mobasher M, Soleiman-Meigooni S, Zabihi M. Analysis ' 'of 239 ordinary and severe cases of COVID-19: clinical features and ' 'treatment. Eur J Transl Myol. 2021;31(3).', 'DOI': '10.4081/ejtm.2021.9579'}, { 'key': '9886_CR30', 'doi-asserted-by': 'crossref', 'unstructured': 'Li D, Liu C, Liu J, Hu J, Yang Y, Zhou Y. Analysis of risk factors for ' '24 patients with COVID-19 developing from moderate to severe condition. ' 'Front Cell Infect Mi. 2020;10.', 'DOI': '10.3389/fcimb.2020.548582'}, { 'issue': '8', 'key': '9886_CR31', 'doi-asserted-by': 'publisher', 'first-page': '4398', 'DOI': '10.1007/s00330-020-06816-7', 'volume': '30', 'author': 'Z Zhou', 'year': '2020', 'unstructured': 'Zhou Z, Guo D, Li C, Fang Z, Chen L, Yang R, Li X, Zeng W. Coronavirus ' 'disease 2019: initial chest CT findings. Eur Radiol. ' '2020;30(8):4398–406.', 'journal-title': 'EUR RADIOL'}, { 'key': '9886_CR32', 'doi-asserted-by': 'crossref', 'unstructured': 'Guo L, Xu R, Gou L, Liu Z, Zhao Y, Liu D, Zhang L, Chen H, Kong MG. ' 'Mechanism of virus inactivation by cold atmospheric-pressure plasma and ' 'plasma-activated water. Appl Environ Microb. 2018;84(17).', 'DOI': '10.1128/AEM.00726-18'}, { 'issue': '6', 'key': '9886_CR33', 'doi-asserted-by': 'publisher', 'first-page': '2811', 'DOI': '10.7150/thno.70098', 'volume': '12', 'author': 'P Wang', 'year': '2022', 'unstructured': 'Wang P, Zhou R, Zhou R, Li W, Weerasinghe J, Chen S, Rehm BHA, Zhao L, ' 'Frentiu FD, Zhang Z, et al. Cold atmospheric plasma for preventing ' 'infection of viruses that use ACE2 for entry. Theranostics. ' '2022;12(6):2811–32.', 'journal-title': 'THERANOSTICS'}, { 'issue': '15', 'key': '9886_CR34', 'doi-asserted-by': 'publisher', 'first-page': '9466', 'DOI': '10.1039/D2RA00009A', 'volume': '12', 'author': 'RR Khanikar', 'year': '2022', 'unstructured': 'Khanikar RR, Kalita M, Kalita P, Kashyap B, Das S, Khan MR, Bailung H, ' 'Sankaranarayanan K. Cold atmospheric pressure plasma for attenuation of ' 'SARS-CoV-2 spike protein binding to ACE2 protein and the RNA ' 'deactivation. Rsc Adv. 2022;12(15):9466–72.', 'journal-title': 'RSC ADV'}, { 'issue': '11', 'key': '9886_CR35', 'doi-asserted-by': 'publisher', 'first-page': 'e329', 'DOI': '10.1097/TP.0000000000003412', 'volume': '104', 'author': 'W Luo', 'year': '2020', 'unstructured': 'Luo W, Yu H, Gou J, Li X, Sun Y, Li J, He J, Liu L. Histopathologic ' 'findings in the explant lungs of a patient with COVID-19 treated with ' 'bilateral orthotopic lung transplant. Transplantation. ' '2020;104(11):e329–31.', 'journal-title': 'Transplantation'}, { 'issue': '4', 'key': '9886_CR36', 'doi-asserted-by': 'publisher', 'first-page': '420', 'DOI': '10.1016/S2213-2600(20)30076-X', 'volume': '8', 'author': 'Z Xu', 'year': '2020', 'unstructured': 'Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, ' 'Zhu L, et al. Pathological findings of COVID-19 associated with acute ' 'respiratory distress syndrome. Lancet Respiratory Med. 2020;8(4):420–2.', 'journal-title': 'Lancet Respiratory Med'}, { 'issue': '6', 'key': '9886_CR37', 'doi-asserted-by': 'publisher', 'first-page': '842', 'DOI': '10.1038/s41591-020-0901-9', 'volume': '26', 'author': 'M Liao', 'year': '2020', 'unstructured': 'Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, Cheng L, Li J, Wang X, Wang ' 'F, et al. Single-cell landscape of bronchoalveolar immune cells in ' 'patients with COVID-19. Nat Med. 2020;26(6):842–4.', 'journal-title': 'NAT MED'}, { 'issue': '2', 'key': '9886_CR38', 'doi-asserted-by': 'publisher', 'first-page': '895', 'DOI': '10.1007/s40200-020-00577-2', 'volume': '19', 'author': 'MR Amini', 'year': '2020', 'unstructured': 'Amini MR, Sheikh Hosseini M, Fatollah S, Mirpour S, Ghoranneviss M, ' 'Larijani B, Mohajeri-Tehrani MR, Khorramizadeh MR. Beneficial effects of ' 'cold atmospheric plasma on inflammatory phase of diabetic foot ulcers; a ' 'randomized clinical trial. J Diabetes Metabolic Disorders. ' '2020;19(2):895–905.', 'journal-title': 'J Diabetes Metabolic Disorders'}, { 'issue': '1', 'key': '9886_CR39', 'doi-asserted-by': 'publisher', 'first-page': '15564', 'DOI': '10.1038/s41598-017-15725-7', 'volume': '7', 'author': 'YS Lee', 'year': '2017', 'unstructured': 'Lee YS, Lee M, Kim H, Won H, Kim C. 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. 2017;7(1):15564.', 'journal-title': 'SCI REP-UK'}, { 'issue': '7', 'key': '9886_CR40', 'doi-asserted-by': 'publisher', 'first-page': '1728', 'DOI': '10.1111/odi.13697', 'volume': '27', 'author': 'C Seebauer', 'year': '2021', 'unstructured': 'Seebauer C, Freund E, Hasse S, Miller V, Segebarth M, Lucas C, Kindler ' 'S, Dieke T, Metelmann HR, Daeschlein G, et al. Effects of cold physical ' 'plasma on oral lichen planus: an in vitro study (effects of CAP on OLP). ' 'Oral Dis. 2021;27(7):1728–37.', 'journal-title': 'ORAL DIS'}, { 'issue': '11', 'key': '9886_CR41', 'doi-asserted-by': 'publisher', 'first-page': '2710', 'DOI': '10.1016/j.jid.2021.04.019', 'volume': '141', 'author': 'S Zhai', 'year': '2021', 'unstructured': 'Zhai S, Xu M, Li Q, Guo K, Chen H, Kong MG, Xia Y. Successful treatment ' 'of vitiligo with cold atmospheric plasma–activated hydrogel. J Invest ' 'Dermatol. 2021;141(11):2710–9.', 'journal-title': 'J INVEST DERMATOL'}, { 'key': '9886_CR42', 'doi-asserted-by': 'crossref', 'unstructured': 'Zhang W, Chua B, Selva K, Kedzierski L, Ashhurst T, Haycroft E, Shoffner ' 'S, Hensen L, Boyd D, James F et al. Immune responses in COVID-19 ' 'respiratory tract and blood reveal mechanisms of disease severity. Res ' 'Sq. 2021.', 'DOI': '10.21203/rs.3.rs-802084/v1'}, { 'issue': '18', 'key': '9886_CR43', 'doi-asserted-by': 'publisher', 'first-page': '1708', 'DOI': '10.1056/NEJMoa2002032', 'volume': '382', 'author': 'W Guan', 'year': '2020', 'unstructured': 'Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L, Shan H, Lei C, Hui DSC, ' 'et al. Clinical characteristics of Coronavirus disease 2019 in China. ' 'New Engl J Med. 2020;382(18):1708–20.', 'journal-title': 'NEW ENGL J MED'}, { 'issue': '10223', 'key': '9886_CR44', 'doi-asserted-by': 'publisher', 'first-page': '497', 'DOI': '10.1016/S0140-6736(20)30183-5', 'volume': '395', 'author': 'C Huang', 'year': '2020', 'unstructured': 'Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, ' 'et al. Clinical features of patients infected with 2019 novel ' 'coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.', 'journal-title': 'Lancet'}, { 'issue': '1', 'key': '9886_CR45', 'doi-asserted-by': 'publisher', 'first-page': 'S138', 'DOI': '10.1378/chest.129.1_suppl.138S', 'volume': '129', 'author': 'SS Braman', 'year': '2006', 'unstructured': 'Braman SS. Postinfectious cough. Chest. 2006;129(1):S138–46.', 'journal-title': 'Chest'}, { 'issue': '5', 'key': '9886_CR46', 'doi-asserted-by': 'publisher', 'first-page': '533', 'DOI': '10.1016/S2213-2600(21)00125-9', 'volume': '9', 'author': 'W Song', 'year': '2021', 'unstructured': 'Song W, Hui CKM, Hull JH, Birring SS, McGarvey L, Mazzone SB, Chung KF. ' 'Confronting COVID-19-associated cough and the post-COVID syndrome: role ' 'of viral neurotropism, neuroinflammation, and neuroimmune responses. ' 'Lancet Respiratory Med. 2021;9(5):533–44.', 'journal-title': 'Lancet Respiratory Med'}, { 'key': '9886_CR47', 'doi-asserted-by': 'publisher', 'first-page': '40', 'DOI': '10.1016/j.imlet.2019.12.013', 'volume': '218', 'author': 'L Tamasauskiene', 'year': '2020', 'unstructured': 'Tamasauskiene L, Sitkauskiene B. Immune system in the pathogenesis of ' 'chronic cough. Immunol Lett. 2020;218:40–3.', 'journal-title': 'IMMUNOL LETT'}, { 'key': '9886_CR48', 'doi-asserted-by': 'crossref', 'unstructured': 'Lee M, Lee YS, Kim HJ, Han CH, Kang SU, Kim C. Non-thermal plasma ' 'inhibits mast cell activation and ameliorates allergic skin inflammatory ' 'diseases in NC/Nga mice. Sci Rep-UK. 2019;9(1).', 'DOI': '10.1038/s41598-019-49938-9'}, { 'key': '9886_CR49', 'doi-asserted-by': 'crossref', 'unstructured': 'Choi J, Song Y, Lee H, Hong J, Kim G. Inhibition of inflammatory ' 'reactions in 2,4-dinitrochlorobenzene induced Nc/Nga atopic dermatitis ' 'mice by non-thermal plasma. Sci Rep-UK. 2016;6(1).', 'DOI': '10.1038/srep27376'}], 'container-title': 'BMC Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-024-09886-w.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12879-024-09886-w/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-024-09886-w.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 9, 12]], 'date-time': '2024-09-12T09:05:33Z', 'timestamp': 1726131933000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09886-w'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 9, 12]]}, 'references-count': 49, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['9886'], 'URL': 'http://dx.doi.org/10.1186/s12879-024-09886-w', 'relation': {}, 'ISSN': ['1471-2334'], 'subject': [], 'container-title-short': 'BMC Infect Dis', 'published': {'date-parts': [[2024, 9, 12]]}, 'assertion': [ { 'value': '12 April 2024', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '5 September 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '12 September 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': '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.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare no competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '960'}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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