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

• Published in: International immunopharmacology 2022-09, Vol.110, p.109014-109014, Article 109014
• Main Authors: Setyo Budi, David, Fahmi Rofananda, Ihsan, Reza Pratama, Nando, Sutanto, Henry, Sukma Hariftyani, Arisvia, Ratna Desita, Saskia, Zinedinita Rahmasari, Aulia, Pudy Asmarawati, Tri, Agung Waskito, Langgeng, Dyah Kencono Wungu, Citrawati
• Format: Article
• Language: English
• Subjects: Adjuvant therapy; COVID-19; COVID-19 Drug Treatment; Hospitalization; Humans; Integrative medicine; Intensive Care Units; Length of Stay; Ozone; Ozone - therapeutic use; SARS-CoV-2
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.109014

•Ozone may have therapeutic benefits, especially in severe COVID-19 infection.•Ozone can improve inflammatory markers, such as IL-6, LDH, D-Dimer, and CRP in severe COVID-19.•Ozone was not associated with major safety concerns compared to standard therapy. 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. 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. 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, I2 = 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, I2 = 84%, random-effects) and ICU admission (RR = 0.57 (95 %CI [0.05–6.71]), I2 = 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. 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)