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【Latest edition March 31】 Medication・Vaccination・medical treatment for COVID-19

2020.04.03

What is coronavirus?
Coronavirus is the cause of common cold with the range of 10% to 35%.
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus by WHO.

How does COVID-19 spread?
People can catch COVID-19 from others who have the virus. The disease can spread from person to person through small droplets from the nose or mouth which are spread when a person with COVID-19 coughs or exhales. These droplets land on objects like door knob or handrail. Other people then catch COVID-19 by touching these objects or surfaces, then touching their eyes, nose or mouth. People can also catch COVID-19 if they breathe in droplets from a person with COVID-19 who coughs out or exhales droplets.

How to treat COVID-19? (medicines and vaccines)
I’ll post information about development of medicines and vaccine in the world.

Avigan Tablet (Generic name: Favipiravir)

Avigan tablet is developed by FUJIFILM Toyama Chemical Co., Ltd in Japan.
The drug is to be considered for use only when there is an outbreak of novel or re-emerging influenza virus infections. Thus avigan tablet has never been distributed in the market but the Japanese government has 2 million stockpile of the drug.

As avigan tablet is a viral RNA polymerase inhibitor with a new mechanism of action, the drug may potentially have an antiviral effect on the novel coronavirus as it is classified into the same type (single-stranded RNA virus) as influenza virus. Efficacy of this drug is already confirmed in animal studies.


On March 13, Gunma University, etc. had started clinical research, and said to clear the drug’s efficacy by administration of this drug to inpatients.

【postscript on March 31】
Prime Minister Shinzo Abe said on March 28 the government will begin clinical trials to formally approve the anti-influenza drug avigan as a treatment for the new coronavirus.

Clinical trials in China showed the drug shortened the recovery time for patients.
The trial also found that X-ray photos confirmed improvements in lung conditions, tested negative in a comparatively short time and  pneumonia symptoms were markedly reduced in case that patients received the drug within 6days from the onset.
Article reporting the lower mortality with avigan tablet is as follows. (written in Japanese)→ 緊急寄稿(2)新型コロナウイルス感染症(COVID-19)治療候補薬アビガンの特徴(白木公康)

Nafamostat mesylate (press on March 19)

The institute of medical science, The University of Tokyo said they have identified nafamostat (trade name: Fusan) as a strong candidate to fight COVID-19.

The research group found that nafamostat inhibited SARS-CoV-2 S protein-initiated fusion at a low concentration (1-10nM range).  

This drug was developed in Japan as treatments for pancreatitis and some other diseases. This drug has been prescribed in Japan for many years and have adequate clinical data with regard to safety. They said they can start clinical trial promptly.

Ciclesonide

The National Institute of Infectious Diseases (NIID) reported that ciclesonide (trade name: Alvesco) was given to 3 patients with the new coronavirus disease, COVID-19. The drug is said to control inflammation and block multiplication of the virus. Ciclesonide, a type of steroid used in inhalers to treat asthma is a safe drug can be used between newborn to aged person. There is currently a lack of pathologic data on COVID-19, but Novel coronavirus (COVID-19) imaging features overlap with SARS and MERS. Virus multiply on alveolar epithelial cells, predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm.
Ciclesonide reaches the lungs where the virus is multiplying so it could be effective in reducing inflammation there.
Article reporting that three patients with pneumonia caused by COVID-19 were given Ciclesonide, and the drug seems effective for COVID-19 is as follows. (written in Japanese)
COVID-19肺炎初期~中期にシクレソニド吸入を使用し改善した3例

Remdesivir

U.S. pharmaceutical firm Gilead Sciences Inc. initially aimed to develop remdesivir as a medication for Ebola. The drug has been reported to be effective in preventing the replication of viruses in previous studies. Wuhan Institute of Virology reported that remdesivir is highly effective in the control of 2019-nCoV infection in vitro. They carried out the essays to measure the effects on the cytotoxicity, virus yield and infection rates, and virus multiplication was inhibited through 48 hours post infection. Researchers in many countries are joining clinical trial on the use of remdesivir. The clinical trial is expected to show the result in April. Remdesivir might be approved as the first drug against COVID-19.

Chloroquine

Chloroquine is a widely-used anti-malarial and autoimmune disease drug. The drug has recently been reported as a potential broad-spectrum antiviral drug. There are some reports showing that chloroquine is effective in the control of COVID-19 in vitro.
In Japan hydroxychloroquine is given to 2 patients with the new coronavirus disease, COVID-19, and both recovered. There’s the possibility of effectiveness to the severe cases, Chloroquine might give treatment option.

Article reporting 2cases recovered after being given hydroxychloroquine is as follows. (written in Japanese)
ヒドロキシクロロキンを使用し症状が改善したCOVID-19の2例はこちら

Lopinavir and ritonavir(trade :name: Kaletra)
 
Kaletra contains two active substances, lopinavir and ritonavir, and is HIV medicine used in combination with other medicines.

Shanghai Public Health Clinical Center reported in hospitalized patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. On the other hand, in Japan 7 patients with severe COVID-19 were treated with this drug by February 21, and some cases are effective. One was discharged from the hospital after 15 days medication, and pneumonia inflammation have disappeared in 2 cases. But 3 patients were on an artificial ventilator after 7days medication.

Article reporting cases revered after being given lopinavir and ritonavir is as follows. (written in Japanese)
新型コロナウイルス肺炎(COVID-19)の症例報告はこちら

TAK-888

On March 4, Takeda Pharmaceutical Company Limited announced the company’s plasma-derived therapy, an anti-Severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) polyclonal hyperimmune globulin (H-IG), to treat high-risk individuals with Covid-19.
H-IGs are created by concentrating the pathogen-specific antibodies from plasma of patients who recovered from COVID-19. By injecting these antibodies to a new confirmed patient, physicians can induce the patient’s immune response and raise the chance of recovery.

Article reporting starting development of COVID-19 plasma therapy is as follows. (written in Japanese)
新型コロナウイルス感染症(COVID-19)治療薬としての血漿分画製剤開発の開始についてはこちら

mRNA-1273
On February 24, 2020, the clinical batch was shipped from Moderna to the NIH for use in their Phase 1 clinical study. This is the first clinical trial of vaccine candidate against the novel coronavirus (SARS-CoV-2).

Instead of using a virus, the vaccine uses genetic material called mRNA to play a role in synthesizing proteins according to genetic information, so that the protein on the surface of the new coronavirus is produced in the administered human body. It is a mechanism that can acquire immunity by producing antibodies against the new coronavirus.

DNAvaccine
Professor Ryuichi Morishita from graduate school of medicine/Faculty of medicine, Osaka University and Osaka-based biotech AnGes said on March 5 that it will develop preventive DNA-based vaccines against the novel coronavirus disease COVID-19. On March 13 another chemical manufacturer, Daicel said to join in their collaboration to develop a DNA vaccine against COVID-19. Daicel provides novel drug delivery device. The production is implemented by Takara Bio that has the plasmid DNA production technology and production facilities.

Since the production of DNA vaccines is made using the bacterium Escherichia coli., DNA vaccines can be delivered at high dosages and cost‐effective. Professor Morishita explains needed period of production is about 2 months.
 
DNA vaccines are safe and can be produced in a short time period without using any dangerous pathogens. By inoculating circular DNA (plasmid) encoding the protein of the target pathogen, the pathogen protein is produced in the body and immunized against the pathogen.

Treatment Report

Infection control and treatment for severe COVID-19 pneumonia that required ventilators.
人工呼吸器装着が必要であった重症COVID-19肺炎の感染対策、治療について

A case of COVID-19 pneumonia in the 70s who improved without treatment
無治療で改善した70歳代のCOVID-19肺炎の1例

Points suspected of COVID-19 infection considered from 6 cases of COVID-19 pneumonia that developed in the community (postscript on March 31)
市中で発症したCOVID-19肺炎の6症例から考察するCOVID-19感染症を疑うポイント(3月31日追記)