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

David Setyo Budi, Ihsan Fahmi Rofananda, Nando Reza Pratama, Henry Sutanto, Arisvia Sukma Hariftyani, Saskia Ratna Desita, Aulia Zinedinita Rahmasari, Tri Pudy Asmarawati, Langgeng Agung Waskito, Citrawati Dyah Kencono Wungu*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

3 Citations (Web of Science)


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, 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.

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).

Original languageEnglish
Article number109014
Number of pages13
JournalInternational Immunopharmacology
Early online date4 Jul 2022
Publication statusPublished - Sept 2022


  • Adjuvant therapy
  • COVID-19
  • Integrative medicine
  • Ozone
  • SARS-CoV-2

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