Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences.

Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits efficacy against coronavirus disease 2019 (COVID-19) pneumonia. Although high doses of favipiravir are required due to the molecule being a purine analog, its conversion into the active form in infected cells with active viral RNA synthesis enhances the antiviral specificity and selectivity as a chain terminator with lethal mutagenesis. Another characteristic feature is the lack of generation of favipiravir-resistant virus. COVID-19 pneumonia is caused by strong cell-mediated immunity against virus-infected cells, and the inflammatory response induced by adaptive immunity continues to peak for 3 to 5 days despite antiviral treatment. This has also been observed in herpes zoster (HZ) and cytomegalovirus (CMV) pneumonia. Inflammation due to an immune response may mask the effectiveness of favipiravir against COVID-19 pneumonia. Favipiravir significantly shortened the recovery time in patients with mild COVID-19 pneumonia by 3 days with the start of treatment by the 5th day of symptom onset. Since both CMV and COVID-19 pneumonia are caused by adaptive immunity and prevention of cytomegalovirus pneumonia is the standard treatment due to difficulties in treating refractory CMV pneumonia, COVID-19 pneumonia should be prevented with early treatment as well. In the present study, we have comprehensively reviewed the optimal antiviral therapy for COVID-19 based on clinical trials of favipiravir for the treatment of COVID-19 pneumonia and the concurrently established therapies for other viral infections, particularly HZ and CMV pneumonia. Optimally, antivirals should be administered immediately after COVID-19 diagnosis, similar to that after influenza diagnosis, to prevent COVID-19 pneumonia and complications resulting from microangiopathy.

Effect of universal varicella vaccination and behavioral changes against coronavirus disease 2019 pandemic on the incidence of herpes zoster.

BACKGROUND: Since 2014, universal varicella vaccination has reduced the varicella and herpes zoster (HZ) incidence in vaccine recipients and increased the incidence in the child-rearing generation until 2017. OBJECTIVE: This study aimed to understand the future epidemiologic trends of HZ after the disappearance of varicella epidemics and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The Miyazaki Dermatologist Society has been monitoring and analyzing the incidence of HZ patients after universal vaccination since 1997. RESULTS: The HZ incidence in Oka varicella vaccine recipients aged 0-4 years decreased with the reduction in chickenpox incidence. The HZ incidence among those aged 5-9 years increased between 2015 and 2017 and decreased thereafter. From 2014-2020, the HZ incidence continued to increase to 36.6%, 51.3%, 70.2%, 56.7%, and 27.3% among those aged 10-19, 20-29, 30-39, 40-49, and 50-59 years, respectively. The HZ incidence in patients aged ≥ 60 years increased by 2.3% annually from 2014 to 2020, corresponding to an annual 2% increase since 1997, and was unaffected by varicella epidemics. COVID-19 infection control measures, lifestyle changes and the resulting stress did not affect the HZ incidence in 2020. CONCLUSION: Universal varicella vaccination eliminated varicella epidemics, and HZ was reduced in vaccine recipients. The HZ incidence for those aged 10-59 years increased from 2014 to 2020, in contrast to those aged ≥ 60 years, which is attributable to booster immunity expiration due to varicella contact in this age group.

Favipiravir, an anti-influenza drug against life-threatening RNA virus infections.

Favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in Japan. Additionally, favipiravir is being stockpiled for 2 million people as a countermeasure for novel influenza strains. This drug functions as a chain terminator at the site of incorporation of the viral RNA and reduces the viral load. Favipiravir cures all mice in a lethal influenza infection model, while oseltamivir fails to cure the animals. Thus, favipiravir contributes to curing animals with lethal infection. In addition to influenza, favipiravir has a broad spectrum of anti-RNA virus activities in vitro and efficacies in animal models with lethal RNA viruses and has been used for treatment of human infection with life-threatening Ebola virus, Lassa virus, rabies, and severe fever with thrombocytopenia syndrome. The best feature of favipiravir as an antiviral agent is the apparent lack of generation of favipiravir-resistant viruses. Favipiravir alone maintains its therapeutic efficacy from the first to the last patient in an influenza pandemic or an epidemic lethal RNA virus infection. Favipiravir is expected to be an important therapeutic agent for severe influenza, the next pandemic influenza strain, and other severe RNA virus infections for which standard treatments are not available.

Characteristics of viral infections including novel coronavirus (COVID-19) and the effects of antiviral drugs

In the previous manuscript (No.5005) and the previous manuscript (No.5004), the virological characteristics of the novel coronavirus were inferred, and the development process of the antiviral drug favipiravir (trade name: Avigan) and COVID-19 pneumonia The therapeutic effect was introduced. This article describes the differences between viral and bacterial infections and the characteristics of the action of various antiviral drugs.