Experimental Treatment with Favipiravir for COVID-19 from wisepowder's blog
An outbreak of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) infection and its caused coronavirus disease 2019
(COVID-19) have been reported in China since December 2019. More than
16% of patients developed acute respiratory distress syndrome, and the
fatality ratio was about 1%–2%. No specific treatment has been reported.
Herein, we examined the effects of Favipiravir (FPV) versus Lopinavir
(LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with
laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg
twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by
aerosol inhalation (5 million U twice daily) were included in the FPV
arm of this study, whereas patients who were treated with LPV/RTV (Days
1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5
million U twice daily) were included in the control arm. To get more
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Changes in chest computed tomography (CT), viral clearance, and drug
safety were compared between the two groups. For the 35 patients
enrolled in the FPV arm and the 45 patients in the control arm, all
baseline characteristics were comparable between the two arms. A shorter
viral clearance time was found for the FPV arm versus the control arm
(median (interquartile range, IQR), 4 (2.5–9) d versus 11 . The FPV arm
also showed significant improvement in chest imaging compared with the
control arm, with an improvement rate of 91.43% versus 62.22% . After
adjustment for potential confounders, the FPV arm also showed a
significantly higher improvement rate in chest imaging. Multivariable
Cox regression showed that FPV was independently associated with faster
viral clearance. In addition, fewer adverse events were found in the FPV
arm than in the control arm. In this open-label before-after controlled
study, FPV showed better therapeutic responses on COVID-19 in terms of
disease progression and viral clearance. These preliminary clinical
results provide useful information of treatments for SARS-CoV-2
infection.
A recent outbreak of coronavirus disease 2019 (COVID-19)
caused by the novel coronavirus designated as severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) started in Wuhan, China, at the end
of 2019. The clinical characteristics of COVID-19 include respiratory
symptoms, fever, cough, dyspnea, and pneumonia [1], [2], [3], [4]. As of
25 February 2020, at least 77 785 cases and 2666 deaths had been
identified across China [5] and in other countries; in particular, 977
and 861 cases were identified in South Korea and Japan, respectively.
The outbreak has already caused global alarm. On 30 January 2020, the
World Health Organization (WHO) declared that the outbreak of SARS-CoV-2
constituted a Public Health Emergency of International Concern (PHEIC),
and issued advice in the form of temporary recommendations under the
International Health Regulations (IHR).
It has been revealed that SARS-CoV-2 has a genome sequence that is 75%–80% identical to that of SARS-CoV, and has more similarities to several bat coronaviruses [6]. SARS-CoV-2 is the seventh reported human-infecting member of the family Coronaviridae, which also includes SARS-CoV and the Middle East respiratory syndrome (MERS)-CoV. It has been identified as the causative agent of COVID-19. Both the clinical and the epidemiological features of COVID-19 patients demonstrate that SARS-CoV-2 infection can lead to intensive care unit (ICU) admission and high mortality. About 16%–21% of people with the virus in China have become severely ill, with a 2%–3% mortality rate [1], [4]. However, there is no specific treatment against the new virus. Therefore, it is urgently necessary to identify effective antiviral agents to combat the disease and explore the clinical effect of antiviral drugs.
One efficient approach to discover effective drugs is to test whether the existing antiviral drugs are effective in treating other related viral infections. Several drugs, such as ribavirin, interferon (IFN), Favipiravir (FPV), and Lopinavir (LPV)/ritonavir (RTV), have been used in patients with SARS or MERS, although the efficacy of some drugs remains controversial. It has recently been demonstrated that, as a prodrug, FPV (half maximal effective concentration (EC50) = 61.88 μmol·L−1, half-maximal cytotoxic concentration (CC50) > 400 μmol·L−1, selectivity index (SI) > 6.46) effectively inhibits the SARS-CoV-2 infection in Vero E6 cells (ATCC-1586) [7]. Furthermore, other reports show that FPV is effective in protecting mice against Ebola virus challenge, although its EC50 value in Vero E6 cells was as high as 67 μmol·L−1 [8]. Therefore, clinical studies are urgently needed to evaluate the efficacy and safety of this antiviral nucleoside for COVID-19 treatment.
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