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      Ozone as an adjuvant therapy for COVID-19: A systematic review and meta-analysis

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          Abstract

          Objective

          Ozone adjuvant in COVID-19 management showed conflicting results in prior studies. Here, we aimed to comprehensively evaluate benefits and side effects of ozone as adjuvant therapy in COVID-19 patients.

          Methods

          Systematic searches were conducted in MEDLINE, ScienceDirect, Cochrane Library, Springer, medRxiv, and ProQuest for articles investigating ozone as adjuvant therapy in COVID-19. Clinical and laboratory outcomes, mortality, length of hospital stay, intensive care unit (ICU) admission, and adverse events were assessed.

          Results

          Thirteen studies were included in this review. Case-control studies, but not randomized controlled trials (RCTs), showed a decrease in mortality following ozone therapy (OR = 0.24 (95% CI [0.07–0.76]), p = 0.02, I 2  = 0%, fixed-effect). However, ozone therapy did not improve the length of hospital stay (SMD = -0.99 (95 %CI −2.44 to 0.45), p = 0.18, I 2  = 84%, random-effects) and ICU admission (RR = 0.57 (95 %CI [0.05–6.71]), I 2  = 73%, p = 0.65, random-effects). Consecutive case control studies suggested that ozone therapy significantly improved levels of D-dimer (p = 0.0060), lactate dehydrogenase (LDH; p = 0.0209), C-reactive protein (CRP; p = 0.0040) and interleukin (IL)-6 (p = 0.0048) as compared to standard therapy alone.

          Conclusions

          The beneficial effect of ozone in COVID-19 management seems to be limited to the improvements of laboratory parameters among severe patients, including the reduction of IL-6, LDH, CRP, and D-dimer levels. Meanwhile, other study endpoints, such as mortality, length of stay and ICU admission, were not improved following ozone therapy, although it may partly be due to a shorter duration of viral clearance. Furthermore, no serious adverse event was reported following ozone therapy, suggesting its high safety profile. (PROSPERO ID: CRD42021278018)

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          Most cited references36

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

            Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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              RoB 2: a revised tool for assessing risk of bias in randomised trials

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                Author and article information

                Journal
                Int Immunopharmacol
                Int Immunopharmacol
                International Immunopharmacology
                Elsevier B.V.
                1567-5769
                1878-1705
                4 July 2022
                September 2022
                4 July 2022
                : 110
                : 109014
                Affiliations
                [a ]Faculty of Medicine, Universitas Airlangga, Indonesia
                [b ]Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, the Netherlands
                [c ]Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Health Sciences University, NY, USA
                [d ]Department of Internal medicine, Faculty of Medicine, Universitas Airlangga, Indonesia
                [e ]Institute of Tropical Disease, Universitas Airlangga, Indonesia
                [f ]Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Indonesia
                Author notes
                [* ]Corresponding author at: Department of Physiology and Medical Biochemistry, Airlangga University, Jalan Mayjen Prof. Dr. Moestopo No.47, Surabaya, Indonesia.
                [1]

                These authors contributed equally to this work.

                Article
                S1567-5769(22)00498-2 109014
                10.1016/j.intimp.2022.109014
                9250927
                72b14e4a-976b-4479-b29a-898d47862850
                © 2022 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 5 April 2022
                : 31 May 2022
                : 28 June 2022
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                covid-19,sars-cov-2,ozone,adjuvant therapy,integrative medicine

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