＜prologue＞
I started a blog called “The Baby Boomer Generation’s Miscellaneous Blog”（Dankai-sedai no garakutatyou:団塊世代の我楽多（がらくた）帳） in July 2018, about a year before I fully retired. More than six years have passed since then, and the number of articles has increased considerably.
So, in order to make them accessible to people who don’t understand Japanese, I decided to translate my past articles into English and publish them.
It may sound a bit exaggerated, but I would like to make this my life’s work.
It should be noted that haiku and waka （Japanese short fixed form poems） are quite difficult to translate into English, so some parts are written in Japanese.
If you are interested in haiku or waka and would like to know more, please read introductory or specialized books on haiku or waka written in English.
I also write many articles about the Japanese language. I would be happy if these inspire more people to want to learn Japanese.
my blog’s URL:団塊世代の我楽多（がらくた）帳 | 団塊世代が雑学や面白い話を発信しています
my X’s URL:団塊世代の我楽多帳（@historia49）さん / X
Since January 2020, we have been fully engaged in efforts to prevent the global spread of COVID-19, leaving no time for Ebola countermeasures. While developing an Ebola vaccine is certainly important, I believe that developing a vaccine for COVID-19 is currently the top priority.
1. Development Status of Treatments and Vaccines for COVID-19
The biggest reason for the fear of COVID-19, which has now become a pandemic, is not that it is transmitted through the air or droplets, but rather that effective treatments and vaccines have not yet been developed.
According to the March 6, 2020 issue of Answers News, the current situation is as follows:
(1) Treatments
According to the US clinical trial registry website ClinicalTrials.gov, clinical trials currently underway for COVID-19 include the antiviral drug remdesivir (Gilead Sciences, USA), the anti-HIV drug lopinavir/ritonavir combination (AbbVie’s Kaletra, USA), and the anti-influenza drug favipiravir (Fujifilm Toyama Chemical’s Avigan). In Japan, these three drugs are being administered as part of an observational study conducted by a research team at the National Center for Global Health and Medicine.
On February 26, the Japanese Association of Infectious Diseases published interim guidelines outlining points to note when using Kaletra and Avigan, two of the three drugs approved in Japan, for COVID-19. According to the guidelines, antiviral drugs should be administered to patients aged 50 or older, those with diabetes, cardiovascular disease, chronic lung disease, chronic obstructive pulmonary disease, and those in an immunosuppressed state. In all cases, administration should be considered once hypoxemia develops and oxygen administration is required.
＜Remdesivir (Gilead, USA)＞
On February 26, Gilead announced the initiation of a Phase 3 (P3) clinical trial of remdesivir for COVID-19. The trials will consist of two phases: one involving 400 severely ill patients and the other involving 600 moderately ill patients. Participants will be medical institutions around the world, primarily in Asia, where many cases are diagnosed. In both trials, remdesivir will be administered intravenously for five or 10 days, and efficacy will be assessed using fever and oxygen saturation as indicators.
Clinical trials of remdesivir have already begun in China (led by the China-Japan Friendship Hospital) and the United States (led by the National Institute of Allergy and Infectious Diseases, or NIAID). Gilead’s clinical trial is expected to complement these trial data. Results from the Chinese trial are expected in April.
Remdesivir is a nucleotide analog originally developed as a treatment for Ebola hemorrhagic fever. Previous research has suggested that the drug may be effective against coronaviruses such as MERS (Middle East Respiratory Syndrome) and SARS (Severe Acute Respiratory Syndrome), and in a statement released on February 3, Gilead said, “The data emerging from coronaviruses other than the current COVID-19 virus are encouraging.”
＜Lopinavir/ritonavir combination drug (AbbVie’s Kaletra)＞
Lopinavir is a protease inhibitor that inhibits viral replication, while ritonavir maintains its blood concentration and enhances its effectiveness. Kaletra, a combination drug containing these drugs, was approved in Japan in 2000 as a treatment for HIV infection.
In vitro and animal model studies have demonstrated its effectiveness against MERS, and virtual screening suggests its potential for COVID-19. According to CrinicalTrials.gov, several clinical trials administering lopinavir/ritonavir to COVID-19 patients are currently underway in China.
＜Favipiravir (Fujifilm Toyama Chemical’s Avigan)＞
Avigan is an anti-influenza drug approved in Japan in 2014. It is not available commercially because it can only be used in the event of a new influenza outbreak, but the government has stockpiled enough for 2 million people in preparation for a new influenza outbreak.
Avigan suppresses viral replication by inhibiting RNA polymerase, the genetic replicating enzyme of influenza viruses. Since the novel coronavirus that causes COVID-19 is also an RNA virus, like the influenza virus, it is expected to be effective. However, because animal testing has confirmed teratogenicity, it cannot be used by pregnant women or those who may be pregnant. Both men and women who may be pregnant should use contraception.
＜Other＞
According to ChiCTR, in addition to these three drugs, clinical trials are currently underway in China using the following: the anti-HIV drug darunavir/cobicistat; the antimalarial drug chloroquine; the antiviral drug interferon; the anti-influenza virus drugs oseltamivir and baloxavir; the steroid drug methylprednidrone; and the anti-IL-6 receptor antibody tocilizumab.
On March 4, Takeda Pharmaceutical announced that it would begin development of TAK-888, a hyperimmune globulin preparation against the causative virus SARS-CoV-2, as a treatment for COVID-19. TAK-888 is a concentrated form of pathogen-specific antibodies extracted from the plasma of recovered patients. Administration of this preparation is expected to enhance the activity of the patient’s immune system and increase the chances of recovery.
Takeda is in discussions with regulatory authorities around the world to develop TAK-888, and is also exploring its existing products and drug candidate library for other drugs effective against COVID-19.
Pfizer also appears to be developing a new antiviral drug. Reuters reported on March 2 that Pfizer has identified a compound that exhibits antiviral activity against SARS-CoV-2 and is currently evaluating the compound with a third-party organization. Elsewhere, Regeneron Pharmaceuticals has partnered with the U.S. Department of Health and Human Services (HHS) to develop an antibody drug for COVID-19. Alnylam Pharmaceuticals also announced on March 4 that it will develop an siRNA targeting SARS-CoV-2 with Bir Biotechnology.
According to the Chinese Clinical Trial Registry (ChiCTR), several clinical trials of favipiravir for COVID-19 are currently underway in China.
(2) Vaccine
Clinical trials for a vaccine to prevent COVID-19 are expected to begin soon. On February 24, the US biotech company Moderna announced the first shipment of its investigational coronavirus vaccine, mRNA-1273. The US National Institute of Advanced Industrial Science and Technology (NIAID), plans to begin Phase 1 trials soon.
According to information registered on ClinicalTrials.gov, the Phase 1 trial of mRNA-1237 will be conducted on 45 healthy men and women aged 18 to 55. The vaccine will be administered twice, four weeks apart, to evaluate safety and immunogenicity.
Regarding the development of a COVID-19 vaccine, the Coalition for Epidemic Preparedness Innovations (CEPI), headquartered in Norway, has partnered with Inovio (USA), the University of Queensland (Australia), Moderna/NIADI, and CureVac (Germany). GlaxoSmithKline (GSK) of the UK is collaborating with CEPI’s development program by providing adjuvant technology. GSK has also agreed to a research collaboration with China’s Clover Biopharmaceuticals. GSK will also provide Clover with adjuvant technology and support the mass production of the vaccine it develops.
Other companies that have announced their intention to develop a COVID-19 vaccine include France’s Sanofi and the US’s Johnson & Johnson. On March 5, Reuters reported that Pfizer is considering joint vaccine development with Germany’s BioNTech.
Among Japanese companies, Anges announced on March 5 that it would jointly develop a DNA vaccine with Osaka University. Takara Bio will also cooperate in manufacturing. ID Pharma, a member of the I’rom Group, has agreed to jointly develop a vaccine with the Shanghai Public Health Clinical Center affiliated with Fudan University in China. The two companies are jointly developing a tuberculosis vaccine using the Sendai virus vector, and they aim to leverage that experience to develop a vaccine against the new coronavirus.
2. Ebola Hemorrhagic Fever Vaccine Development Status
(1) Ministry of Health, Labour and Welfare and National Institute of Infectious Diseases (NIID) Decide to Import Pathogens
According to a May 30, 2019, Sankei Shimbun report, the Ministry of Health, Labour and Welfare and National Institute of Infectious Diseases (NIID) officially announced their intention to import the Ebola pathogen. They stated that they would import the pathogen as early as summer 2019.
On the 30th, the Ministry of Health, Labour and Welfare and National Institute of Infectious Diseases (NIID) officially announced their policy on importing highly fatal Category 1 infectious disease pathogens, such as Ebola hemorrhagic fever, at a meeting of stakeholders held at the NIID Murayama Building (Musashimurayama City, Tokyo), where the pathogens will be stored. They are expected to be brought into Japan as early as this summer, but the import route and date will not be announced in advance.
The pathogens targeted for import are those of five infectious diseases that have been reported overseas: Ebola hemorrhagic fever, South American hemorrhagic fever, Lassa fever, Crimean-Congo hemorrhagic fever, and Marburg virus disease. With the 2020 Tokyo Olympic and Paralympic Games approaching, the government is strengthening its testing capabilities in the event of a domestic outbreak.
Until now, Japan has used artificially synthesized pathogens, but using actual pathogens will make it possible to establish testing methods to determine the state of recovery.
The BSL-4 facility at the NIID Murayama Building, where the samples will be stored, is equipped with high-performance filters and other measures to ensure high safety. The Ministry of Health, Labor and Welfare and the NIID presented their idea for importing the samples to Musashimurayama City in November of last year. They have held information sessions and tours for residents to date, and believe they have gained a certain level of understanding.
The stakeholder meeting was attended by representatives from the Ministry of Health, Labor and Welfare, the NIID, and local residents. Local residents reportedly requested that the government “continue to increase transparency.” The Ministry of Health, Labor and Welfare intends to begin preparations for actual importation in the future, but stated, “If there is demand, we would like to continue holding information sessions and other events.”
In December 2019, the Japan Agency for Medical Research and Development (AMED), a national research and development agency, announced the start of Phase I clinical trials of an Ebola vaccine developed by the University of Tokyo. Has the vaccine already been imported?
The Ebola outbreak that broke out in the Democratic Republic of the Congo in August 2018 appears to still be ongoing, even 18 months later. Organizations such as Doctors Without Borders are treating the disease, continuing to administer vaccines and other treatments. The mortality rate for Ebola is said to be 60% to 70%.
However, since Ebola is not transmitted through the air or droplets, there is no risk of infection unless one comes into contact with the blood or bodily fluids of an infected person. This means that there is a high risk of infection among medical teams and volunteers treating Ebola. Unlike COVID-19 pneumonia, which is not transmitted through the air or droplets, there is no need to worry about a major outbreak in Japan.
(2) Was there a need to import the Ebola pathogen?
I’m not an expert, so I don’t have any scientific evidence, but would it be impossible to respond if Ebola and other pathogens were not imported?
Wouldn’t it be enough for doctors to gain a detailed understanding of the symptoms of Ebola and then import currently available treatments?
If there are currently no cases in Japan, wouldn’t it be possible to prevent it at the border by thoroughly strengthening the quarantine system at the borders of entry and exit?
(3) Are safety measures in place for the Ebola pathogen adequate?
According to a July 1, 2019, Sankei Shimbun report, “Health, Labor and Welfare Minister Takumi Nemoto met with the Mayor of Musashimurayama and reached a certain level of understanding.”
This is said to be a measure for the 2020 Tokyo Olympics and Paralympics, but the risk of terrorism and the possibility of a major earthquake cannot be ruled out.
If that were to happen, wouldn’t there be a risk that terrorists would steal the pathogen and use it as a biological or chemical weapon, leaving us powerless to do anything about it?
In fact, in the Democratic Republic of the Congo in Africa, the death toll from Ebola hemorrhagic fever has exceeded 2,000, and the infection is spreading. Furthermore, there are reports that doctors and medical facilities treating patients have come under attack, making containment measures difficult.
Also, if a natural disaster on the same level as the Great East Japan Earthquake or worse were to occur, is there a risk that the pathogen could escape and cause widespread damage?
(4) Shouldn’t the priority be to tighten quarantine screening for people returning from or entering the country from endemic areas?
I believe that the first priority should be to conduct extremely strict quarantine screening for people returning from or entering areas where Ebola hemorrhagic fever is prevalent, such as the Democratic Republic of the Congo, in order to prevent the spread of Ebola hemorrhagic fever at the border. Since the incubation period is usually around seven days, careful attention will be needed to assess people who have a fever or are feeling unwell, especially those with a fever.