Atmospheric ozone is produced when nitrogen oxides react with volatile organic compounds. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome contains a unique N-terminal fragment in the Spike protein, which allows it to bind to air pollutants in the environment. ‘Our approach in this review is to study ozone and its effect on the SARS-CoV-2 virus and patients with coronavirus disease 2019 (COVID-19). Article data were collected from PubMed, Scopus, and Google Scholar databases. Ozone therapy has antiviral properties, improves blood flow, facilitates the transfer of oxygen in hypoxemic tissues, and reduces blood coagulation phenomena in COVID-19 patients. Ozone has immunomodulatory effects by modulating cytokines (reduction of interleukin-1, interleukin-6, tumor necrosis factor-α, and interleukin-10), induction of interferon-γ, anti-inflammatory properties by modulating NOD-, LRR- and pyrin domain-containing protein 3, inhibition of cytokine storm (blocking nuclear factor-κB and stimulating nuclear factor erythroid 2-related factor 2 pathway), stimulates cellular/humoral immunity/phagocytic function and blocks angiotensin-converting enzyme 2. In direct oxygen-ozone injection, oxygen reacts with several biological molecules such as thiol groups in albumin to form ozonoids. Intravenous injection of ozonated saline significantly increases the length of time a person can remain hypoxic. The rectal ozone protocol is rectal ozone insufflation, resulting in clinical improvement in oxygen saturation and biochemical improvement (fibrinogen, D-dimer, urea, ferritin, LDH, interleukin-6, and C-reactive protein). In general, many studies have shown the positive effect of ozone therapy as a complementary therapy in the recovery of COVID-19 patients. All the findings indicate that systemic ozone therapy is nontoxic and has no side effects in these patients.

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The objective of this study was to provide lung disinfection by nebulizing ozone gas with distilled water and olive oil for patients who have clinical symptoms due to coronavirus disease 2019 (COVID-19). The study attempted to reduce the viral load of COVID-19 in the lungs of patients, to provide a faster response to medical treatment. Between August 2020 and September 2020, 30 patients who met the study criteria were prospectively evaluated. There were 2 groups with 15 patients in each group: patients in control group were not treated with ozone and only received standard COVID-19 treatment; patients in ozone group received lung disinfection technique with ozone and standard COVID-19 treatment. A statistically significant difference was found in the length of stay in hospital, change in C-reactive protein, polymerase chain reaction results after 5 days, and computed tomography scores between two groups. There was no statistically significant difference in D-dimer, urea, lactate dehydrogenase, lymphocyte, leukocyte, and platelet between two groups. According to the data, we think that the lung disinfection technique applied with ozone inhalation reduces the rate of pneumonia in COVID-19 patients and makes the patients respond faster to the treatment and become negative according to the polymerase chain reaction tests. The study was approved by the Ethical Committee of the Istanbul Medipol University Clinical Trials (approval No. 0011) on July 2, 2020.

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Cytokine storm in coronavirus disease 2019 (COVID-19) patients leads to acute lung injury, acute respiratory distress syndrome, multiorgan dysfunction, shock, and thrombosis thus contributing to significant morbidity and mortality. Several agents like steroids, ascorbic acid, vitamins (C, D, E), glutathione, N-acetylcysteine have been used and several studies are underway to identify its efficacy in addressing undesirable effects due to COVID-19 illness. Among several experimental modalities based on expert opinion and anecdotal data, melatonin is one molecule that appears promising. Owing to its anti-inflammatory, anti-oxidant, and immunomodulatory properties, melatonin can be an important agent used as a component of multimodal analgesia in COVID-19 patients, suspected patients, and patients with exposure to positive patients undergoing emergency or urgent surgeries. Further research is required to know the optimal time of initiation, dose, and duration of melatonin as an adjunct.

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Coronavirus disease 2019 (COVID-19) pandemic has caused an urgent need for investigating potential treatments. Traditional medicine offers many potential remedies that have been historically used and have the advantage of bypassing the cultural obstacles in the practice of medicine. We aimed to investigate the efficacy of Zufa syrup in the treatment of suspected patients with mild to moderate symptoms of COVID-19. This triple-blind randomized controlled trial recruited patients with evidence of COVID-19 on chest computed tomography without an indication of hospital admission from March 2020 until April 2020. Participants were assessed by a physician and completed a pre-specified form to assess the duration and severity of symptoms. Patients were randomized to receive Zufa syrup (a combination of herbal medicines: Nepetabracteata, Ziziphus jujube, Glycyrrhizaglabra, Ficuscarica, Cordia myxa, Papaver somniferum, Fennel, Adiantumcapillus-veneris, Viola, Viper‘s-buglosses, Lavender, Iris, and sugar) or identical-looking placebo syrup at a dose of 7.5 mL (one tablespoon) every 4 hours for 10 days. After applying the eligibility criteria, 116 patients (49.1% male) were randomized to trial arms with a mean age of 44.3. During the follow-up, Cough, dyspnea, headache, myalgia, anorexia, anxiety, and insomnia improved gradually in both groups, and showed no difference between Zufa syrup and placebo. Oxygen saturation and pulse rate had stable trends throughout the follow-up and were similar between study arms. No patient required hospital admission or supplemental oxygen therapy during the study period. To conclude, in patients with mild to moderate symptoms of COVID-19, Zufa syrup did not show any difference in symptomatology over a 10 days’ period when compared with placebo. Due to potential effects of medicinal plants in the treatment of respiratory infections, further studies are warranted to clarify their role in COVID-19. The study was approved by the Ethics Committee of the Qom University of Medical Science (Ethics committee reference number IR.MUQ.REC.1398.165) on March 10, 2020 and was registered in Iranian Clinical Trial Center (approval ID: IRCT20200404046934N1) on April 13, 2020.

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The coronavirus disease 2019 (COVID-19) epidemic went down in history as a pandemic caused by corona-viruses that emerged in 2019 and spread rapidly around the world. The different symptoms of COVID-19 made it difficult to understand which variables were more influential on the diagnosis, course and mortality of the disease. Machine learning models can accurately assess hidden patterns among risk factors by analyzing large-datasets to quickly predict diagnosis, prognosis and mortality of diseases. Because of this advantage, the use of machine learning models as decision support systems in health services is increasing. The aim of this study is to determine the diagnosis and prognosis of COVID-19 disease with blood-gas data using the Chi-squared Automatic Interaction Detector (CHAID) decision-tree-model, one of the machine learning methods, which is a subfield of artificial intelligence. This study was carried out on a total of 686 patients with COVID-19 (n = 343) and non-COVID-19 (n = 343) treated at Erzincan-Mengücek-Gazi-Training and Research-Hospital between April 1, 2020 and March 1, 2021. Arterial blood gas values of all patients were obtained from the hospital registry system. While the total-accuracyratio of the decision-tree-model was 65.0% in predicting the prognosis of the disease, it was 68.2% in the diagnosis of the disease. According to the results obtained, the low ionized-calcium value (< 1.10 mM) significantly predicted the need for intensive care of COVID-19 patients. At admission, low-carboxyhemoglobin (< 1.00%), high-pH (> 7.43), low-sodium (< 135.0 mM), hematocrit (< 40.0%), and methemoglobin (< 1.30%) values are important biomarkers in the diagnosis of COVID-19 and the results were promising. The findings in the study may aid in the early-diagnosis of the disease and the intensive-care treatment of patients who are severe. The study was approved by the Ministry of Health and Erzincan University Faculty of Medicine Clinical Research Ethics Committee.

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Coronavirus disease 2019 (COVID-19) triggers important changes in routine blood tests. In this retrospective case-control study, biochemical, hematological and inflammatory biomarkers between March 10, 2020, and November 30, 2020 from 3969 COVID-19 patients (3746 in the non-intensive care unit (non-ICU) group and 223 in the ICU group) were analyzed by dividing into three groups as spring, summer and autumn. In the non-ICU group, lymphocyte to monocyte ratio was lower in autumn than the other two seasons and neutrophil to lymphocyte ratio was higher in autumn than the other two seasons. Also, monocyte and platelet were higher in spring than autumn; and eosinophil, hematocrit, hemoglobin, lymphocyte, and red blood cells decreased from spring to autumn. In the non-ICU group, alanine aminotransferase and gamma-glutamyltransferase gradually increased from spring to autumn, while albumin, alkaline phosphatase, calcium, total bilirubin and total protein gradually decreased. Additionally, C-reactive protein was higher in autumn than the other seasons, erythrocyte sedimentation rate was higher in autumn than summer. The changes in routine blood biomarkers in COVID-19 varied from the emergence of the disease until now. Also, the timely changes of blood biomarkers were mostly more negative, indicating that the disease progresses severely. The study was approved by the Erzincan Binali Yildirim University Non-interventional Clinical Trials Ethic Committee (approval No. 86041) on June 21, 2021.

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A 76-year-old female received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac, Sinovac^®, Beijing, China) and subsequently experienced chest discomfort. A computed tomography performed 1 day after vaccination showed multiple infiltrations in both lungs and ground-glass shadows in both lung fields. Her fingertip oxygen saturation was 81% and there was widespread wheezing on physical examination. Based on these findings, the patient was hospitalized with a preliminary diagnosis of drug-induced pneumonitis and acute asthma exacerbation due to a SARS-CoV-2 vaccine. During her hospitalization, 40 mg/d systemic steroid, 4 times a day salbutamol nebulized, 2 L/min inhaled oxygen therapy and 400 mg/d moxifloxacin intravenous were administered for 5 days. One month later, the thorax computed tomography scan revealed that the previous findings were almost completely regressed.

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