Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

Combined Therapy of Ciclosporin Plus Favipiravir in the Management of Patients with Severe COVID-19, not Responding to Dexamethasone: A non-Controlled Prospective Trial.

BACKGROUND: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.

Evaluation of adalimumab effects in managing severe cases of COVID-19: A randomized controlled trial.

BACKGROUND: COVID-19, which is a disease caused by the SARS-CoV-2 virus, has spread around the world since late 2019. Studies have found associations between the rising levels of TNF-α and severe COVID-19 cases. Hence, TNF-α blocking can possibly be a favorable intervention in modifying COVID-19. To this end, in order to manage pneumonia caused by COVID-19, adalimumab may potentially be considered as a potential therapeutic agent. The present study aimed to investigate the potential therapeutic role of adalimumab in treating COVID-19 cases in combination therapy with remdesivir and dexamethasone. METHODS: Among the 68 patients who were included in the current randomized controlled trial, 34 were assigned to the adalimumab group and the remaining 34 were assigned to the control group. Adalimumab at a dose of 40 mg, subcutaneous for once, was used for the intervention group. Both the intervention and control groups received remdesivir, dexamethasone, and supportive care. The data gathered to make comparisons of the groups included demographic information, the rate of mortality, mechanical ventilation requirement, length of stay in hospital and Intensive Care Unit (ICU), and imaging findings. RESULTS: There was no significant difference between the two groups in the terms of mortality rate (P-value = 1) and mechanical ventilation requirement (P-value = 1). The length of hospital and ICU stay as well as radiologic changes were not affected either (P-value = 1, 0.27, and 0.53, respectively). CONCLUSIONS: Our findings did not support the use of adalimumab in combination with remdesivir and dexamethasone in the treatment of severe COVID-19 cases.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial.

BACKGROUND: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. METHODS: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. RESULTS: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively). CONCLUSIONS: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.

Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial.

BACKGROUND: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. METHODS: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. RESULTS: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. CONCLUSIONS: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.