Characteristics of COVID-19 and possibilities of early causal therapy. Results of favipiravir use in clinical practice

Abstract

This paper provides the results of a study evaluating the efficacy and safety of etiotropic therapy in patients hospitalized with SARS-CoV-2 infection. Objective. Тo evaluate the efficacy and safety of favipiravir (Areplivir) in patients with coronavirus disease 2019 (COVID-19) and compare it with recommended standard therapy. Patients and methods. Two hundred men and women aged between 18 and 80 years with COVID-19 were randomized into this study. The experimental group included patients who received favipiravir, whereas the control group comprised patients who received causal therapy in accordance with the latest version of the temporary methodical recommendations of the Ministry of Health of Russia ‘Prevention, diagnosis, and treatment of coronavirus infection (COVID-19).’ The efficacy and safety of therapy were evaluated by assessing clinical improvement using the WHO Ordinal Scale for Clinical Improvement, clinical and laboratory parameters, findings of chest computed tomography (CT), and elimination of SARS-CoV-2. We also analyzed the frequency and type of adverse events, need for invasive and non-invasive ventilation, and death rates. Results. Our analysis has demonstrated significant benefits of favipiravir over standard therapy in terms of the time to clinical improvement (in the experimental group it was 4 days shorter on average), time to recovery, frequency of recovery after 10 days (44% of patients from the experimental group and 10% of patients from the control group had no clinical signs of the disease at this time-point), and frequency of virus elimination by day 10 of therapy. Treatment with favipiravir was associated with a significant improvement in the lung condition (according to CT), normalization of laboratory parameters, and saturation level. Favipiravir has demonstrated a good safety profile similar to that of standard therapy. There was no difference in the frequency of adverse events between the experimental and control groups. Conclusion. The use of favipiravir for the treatment of SARS-CoV-2 infection reduced the time to clinical improvement by 4 days on average compared to standard therapy, ensured improvement of the lung condition (according to CT scans), and facilitated virus elimination in more than 90% of patients, thereby promoting faster recovery. Favipiravir had a good safety profile and was well tolerated by patients. This treatment regimen was shown to be effective, sufficient, and clinically reasonable to achieve good outcomes. Timely initiation of therapy with favipiravir (Areplivir) improves disease prognosis and reduces the global socioeconomic burden of the current pandemic. Key words: COVID-19, Areplivir, coronavirus, causal therapy, favipiravir

The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies

“…We performed meta-analysis for 16 RCTs ( Balykova et al, 2020a ;Balykova et al, 2020b ;Balykova et al, 2020c ;Bosaeed et al, 2021 ;Chen et al, 2020a ;Chuah et al, 2021 ;Doi et al, 2020 ;Finberg et al, 2021 ;Ivashchenko et al, 2021 ;Pushkar, 2020 ;Ruzhentsova et al, 2021 ;Shenoy et al, 2021 ;Shinkai et al, 2021 ;Solaymani-Dodaran et al, 2021 ;Tabarsi et al, 2021 ;Udwadia et al, 2021 ) and 1 non-RCTs ( Cai et al, 2020 ), which studied the effect of favipiravir on hospitalized patients. The baseline characteristics of the controlled trials can be found in Supplemental Table 3.…”

Favipiravir does not improve viral clearance in mild to moderate COVID-19 – A systematic review and meta-analysis of randomized controlled trials

“…These results are also supported by the analysis of the proportion of patients who achieved viral clearance rather than the time to viral clearance. There were 13 studies that contained information on RR for viral clearance [ 10 , 12 , 13 , [15] , [16] , [17] , [19] , [20] , [21] , [22] , [23] , [24] , [25] ] ( Table S1 ). Viral clearance was significantly higher in the groups treated with favipiravir with moderate severity (RR = 1.16 [95 % CI: 1.02–1.32, p < 0.01], I 2 = 0 %) and in those who were treated in the hospital (RR = 1.17 [95 % CI: 1.06–1.28, p < 0.01], I 2 = 18.9 %) than in the case of the comparators ( Fig.…”

Evaluation of favipiravir in the treatment of COVID-19 based on the real-world

“…A total of 324 studies were excluded after title and abstract screening, and the full texts of 60 studies were then evaluated for eligibility. Finally, 13 studies were included in this meta-analysis, and a total of 47 articles were excluded for definite reasons ( Figure 1 ) [ 33–45 ]. It is important to mention that two of the studies marked by a and b are different studies with the same first author and published in the same year, such as Dabbous et al (2021a) and Dabbous et al (2021b) [ 37 , 38 ].…”

“…After seven days of treatment with FVP, the researchers decide whether to continue to use FVP according to the specific conditions of the subjects Patients assigned to the control group received drugs other than favipiravir and treatment according to the needs of the disease. [ 44 ] Ivashchenko et al (Russia) RCT 40/20 Unclear (>18) Unclear Moderate AVIFAVIR 1600 mg BID on Day 1 followed by 600 mg BID on Days 2–14 (1600/600 mg), or AVIFAVIR 1800 mg BID on Day 1 followed by 800 mg BID on Days 2–14 (1800/800 mg) SOC according to the Russian guidelines for treatment of COVID-19 [ 39 ] Balykova et al (Russia) RCT 100/100 I:49.7 C:49.7 (18–80) I:51.0 C:51.0 Moderate FVP was 1600 mg twice a day on the 1st day and 600 mg twice a day on days 2–14 Standard of Care will be prescribed in accordance with the recommended treatment regimens presented in the Russian guidelines for the prevention, diagnosis and treatment of COVID-19 according to the decision of the Investigator [ 33 ] Balykova et al (Russia) RCT 17/22 I:47.2 C:47.5 (21–73) Unclear Moderate FVP was 1600 mg twice a day on the 1st day and 600 mg twice a day on days 2–14 Twelve patients (54.5%) received a combination of HCQ and Azithromycin as an antiviral therapy, 8 patients (36.4%) – HCQ (monotherapy),2 patients (9.1%) -LPV/RTV. The dosage regimen was the following: for HCQ, it was 800 mg on the first day (400 mg twice a day); then, 400 mg/day (200 mg twice a day) for 2–7 days; for Azithromycin, 500 mg once a day for 5 days; for LPV/RTV, 400 mg+100 mg orally every 12 hours for 14 days.…”

“…Our meta-analysis found that mild-to-moderate patients taking FVP had significantly shorter hospital stays than patients taking other drugs. Balykova et al reported a 4-day reduction in the mean length of hospital stay for patients taking FVP compared to patients in the control group but did not include this meta-analysis of the length of hospital stay because the study did not report a corresponding standard deviation [ 33 ]. Hassanipour et al, in a recently published meta-analysis, showed that patients in the FVP group had a significant clinical improvement compared to the control group at 7 days after initiation of treatment, and within 14 days, the clinical improvement rate in the FVP group was 10% higher than that in the control group, but it was not statistically significant [ 48 ].…”