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Development of coronavirus treatment advancing in Japan with existing meds

Ciclesonide (marketed as Alvesco), which has been used as a new treatment against the novel coronavirus, is seen in this photo from the website of Teijin Pharma Ltd.

The development of methods to treat the new coronavirus disease is advancing in Japan, with researchers expected to see the results of clinical research using existing medication as early as the end of April.

One medicine that experts in a government panel have expressed hope in is Ciclesonide (marketed as Alvesco), a type of steroid used in inhalers to treat asthma. A medical team including members of the Kanagawa Prefectural Ashigarakami Hospital administered this drug to three coronavirus disease patients. One of them, a woman in her 70s, saw her fever go down after two days, and her pneumonia symptoms also improved. She later tested negative for the virus and was discharged from hospital after eight days. The other two patients, a man in his 70s and a woman in her 60s, were able to be taken off respirators after receiving the medicine. Currently around 10 people are receiving it.

The National Institute of Infectious Diseases (NIID) reported that Ciclesonide was given to patients with the new coronavirus disease, COVID-19, after being found to have some effect in the treatment of Middle East Respiratory Syndrome (MERS), which is caused by another type of coronavirus. The drug is said to control inflammation and block multiplication of the virus.

Tablets of hydroxychloroquine (marketed as Plaquenil) are seen in this picture from the website of pharmaceutical company Sanofi K.K.

Also being tested is Remdesivir, which was developed as a treatment for the Ebola virus disease. As of March 16, it had been administered to nine patients. Japan's National Center for Global Health and Medicine is participating in international joint clinical trials with the United States and other countries to test the effectiveness of this medicine. Center official Norio Omagari said it had only been used in serious cases in which patients were on artificial respirators or heart-lung machines, but none of them had died.

Hydroxychloroquine (Plaquenil), which was developed to treat malaria, is a similar sort of medicine. When it was given to a male coronavirus disease patient in his 60s who was receiving dialysis treatment due to diabetes, his fever of over 38 degrees Celsius went down after three days, and his symptoms of pneumonia also improved. It is expected he can be released from hospital if he tests negative for the virus.

One more drug in focus is Favipiravir (Avigan), which is used to treat new types of influenza. Japan has a stockpile of about 2 million Avigan pills. Clinical research using the medication on novel coronavirus disease patients with mild to moderate symptoms began in March. The HIV treatment drug Lopinavir/ritonavir (Kaletra) is also being tested, having been administered to 54 patients as of March 1. It is hoped that both of these medications will be effective in preventing the virus from multiplying in patients' bodies. However, an individual related to Japan's Ministry of Health Labor and Welfare pointed out, "We've given Avigan to 70 to 80 people, but it doesn't seem to work that well when the virus has already multiplied. The same goes for Kaletra." Furthermore, care is said to be needed when women who could be pregnant or men who are trying to have children with their partners use Avigan, as it can subsequently cause deformities in fetuses.

This photo from the Fujifilm Corp. website shows the drug Avigan.

None of these medicines was developed for use on patients with the new coronavirus, and government approval would be required for their full-scale use on COVID-19 patients.

A person close to the health ministry commented, "We could see results of clinical research come together in April, and see approval as early as May. But if the results of research are delayed, approval could also be delayed."

Meanwhile Takaji Wakita, director of the NIID, commented, "As we curb the domestic spread of the virus, we'll see prospects for a medical remedy in about half a year."

This photo from the website of AbbVie GK shows the drug Kaletra.

In addition to medicines to treat the disease, there are also hopes for development of a vaccine to prevent infection. But this costs a lot of money, and can take a long time.

"No matter how quickly you do it, it will take a year," said Ken Ishii, a professor at the Institute of Medical Science at the University of Tokyo.

In the meantime, kits to quickly test for the new coronavirus are being developed both in Japan and overseas. Textile and chemical product maker Kurabo Industries Ltd. on March 16 began selling testing kits developed by a Chinese firm that are said to be able to detect the virus in 15 minutes, using a small blood sample. Tests in China showed the kits to be 100% accurate in patients without the virus, and between 76% and 82% accurate when used on patients with the virus, depending on the kit. One kit that can test 10 samples will be sold for 25,000 yen, but the kits are not covered by public health insurance, and will be sold mainly for research and to testing organizations.

This photo shows test kits that can detect the new coronavirus in 15 minutes, which Kurabo Industries Ltd. has started to sell. (Photo courtesy of Kurabo Industries Ltd.)

Separately Akihide Ryo, a microbiology professor at Yokohama City University School of Medicine, has made a prototype kit that is said to be able to quickly detect the new coronavirus, and it was successful when tested on six COVID-19 patients at its hospital. Kanto Chemical Co., a company involved in joint research with the university, is prepared to produce several thousand kits per month.

Up until now, Japan had relied on real-time polymerase chain reaction (PCR) tests based on samples from people's throats or nasal cavities, which require the use of a research lab and take as long as six hours. Japan has not even reached 2,000 tests per day with this method. Test kits, in comparison, speed up the process and can be mass produced.

However, there are downsides in any testing method. With the PCR method, if the virus isn't prevalent in the part of the body from which the sample was taken, the result can falsely come up as negative, so the accuracy rate is said to hover at about 70%. And with the speed testing kits developed at Yokohama City University, for example, it is possible the virus cannot be detected within seven days of being infected due to a lack of antibodies.

To reduce inaccuracies in the test results, there have accordingly been calls for the tests to be restricted to those who have symptoms of pneumonia caused by the coronavirus and other suspected symptoms.

Ichiro Takeuchi, a professor in emergency medicine at the Yokohama City University Medical Center, which is accepting coronavirus patients, pointed out that doctors want to know quickly if there is an infection or not, as this information is helpful when taking measures to prevent the spread of the virus. But the test kits cannot fully replace PCR tests, he says.

"A proper combination of the tests should be carried out depending on the time that has passed since someone developed symptoms and other such factors," Takeuchi says.

(Japanese original by Yuki Ogawa, Sooryeon Kim, Ryosuke Abe and Go Kumagai, Lifestyle and Medical News Department)

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