In Japan, favipiravir was approved as a stockpile against influenza pandemics and was distributed as an option against for SARS-CoV-2 under government control. Still, the efficacies of antiviral therapies have not been clarified clearly in the course of these patients. However, in the literatüre, there is a case report that emphasize recovery two days after favipiravir treatment. This case suggest that favipiravir may be contributed to the amelioration of the lung lesion in Covid-19 (13).
In a large scale study, among the 1,023 deaths, the majority were among patients of ≥ 60 years of age. The ≥ 80 age group was characterized by the highest fatality rate (20.3%) among all age groups (14). Relatively fewer cases were reported among young children (0–9 years-old). While more males were affected by the disease, the male-to-female ratio varies between different populations. As the pathogen has been extraordinarily contagious, no deaths have occurred in mild or even severe cases; but the fatality rate reached 49% among patients that were classified as critical cases (14). These findings are compatible with the presented study.
In a prospective, multicenter, open-label, randomized superiority trial examined the efficacy of favipiravir versus arbidol for treating COVID-19 (15). There was no difference in the 7-day clinical recovery rate for favipiravir versus arbidol in the overall population. However, this difference existed for a subgroup of non-critical patients without hypertension or diabetes (15). Three registered clinical trials are planned regarding the use of favipiravir against COVID-19 (16, 17, 18). The presented study was performed in an intensive care unit and parallel to the mentioned studies; 42.5% of the patients (n:76) had hypertension and 29.1% (n:52) had diabetes mellitus.
In the presented study, the most common symptom was "fever" (57.5%, n:103) and second symptom was dispnea (42.5%, n:76). In a similar study; major symptom at the onset of illness was again fever (88.7%) (5). The other symptoms were cough (67.8%), fatigue (38.1%), dyspnea (18.7%), and myalgia (14.9%). Additionaly; these symptoms could be followed by sputum production, dizziness, headache, vomiting, abdominal pain, diarrhea, sore throat, nasal congestion and rhinorrhoea (5). Differently; in a small study two patients reported diarrhea, one had liver injury and one had poor diet (19). The recent study from China reported favipiravir had fewer side effects such as diarrhea and transaminitis in non-transplant COVID‐19 (20).
There are some studies about the heart related disorders during medical treatment combined with favipravir. A study that reports prolonged QT interval due to favipiravir has been encountered (19). In another study; two patients who were followed-up in the Intensive Care Unit (ICU) with favipiravir combined treatment developed ventricular tachycardia; both had increased T peak to T end (Tp-e) interval and Tp-e/QTc ratio despite normal QTc intervals before treatment (21). In the presented study 23.5% (n:42) of the patients had heart disease during the hospitalization but no heart related problem was detected during follow-up.
In the presented study; no significant adverse ractions were noted related with favipravir combined treatment group. In another study, favipiravir had significantly fewer adverse effects than the lopinavir/ritonavir group (22). Similarly; in the trial conducted on patients with COVİD-19 indicated better results in patients treated with favipiravir than the group treated with lopinavir/ritonavir. Additionally, less side effects were noted in the treatment group (20).
Studies have reported that lymphocytopenia occurs in severe types of Covid-19 (23). Again; lymphocytopenia and hyponatremia were detected in a patient who recovered after treatment for Covid-19 pneumonia (24). In a Japanese clinical trial with 501 patients, the main adverse reactions were detected as rising uric acid (n:24, 4.79%), diarrhea (n:24, 4.79%), neutropenia (n:9, 1.80%), increased AST (n:9, 1.80%) and increased ALT (n:8, 1.60%) (25). In a trial of favipiravir with patients with COVID-19, the most common adverse events were liver enzyme abnormalities, psychiatric, gastrointestinal symptoms and serum uric acid elevations (26). The overall adverse reactions were mild symptoms, but pregnant woman should not be treated with favipiravir (25). In the presented study, serum uric acid levels were not evaluated but liver enzyme abnormalities were detected parallel to the literature.