In a bid to find a new way to treat COVID-19 patients, the leading national center for medicine is turning to a funnyman to bring in donations.
But as Japanese doctors gear up for clinical trials that they hope will give hospitals a new type of treatment for the new coronavirus, some institutes overseas have already moved on to new remedies.
Comedian Yoshiaki Yoza features prominently on the website of the National Center for Global Health and Medicine (NCGM), where he asks COVID-19 survivors, like himself, to donate their blood plasma for a trial that doctors hope will prove to be a life-saver.
“Perhaps my blood could be of a little help, and that’s why I joined the study and provided my blood plasma,” he says on the website. “If we could get cooperation from a lot more people, we could conquer coronavirus!”
The NCGM’s Center Hospital and several other hospitals in Tokyo, Osaka and Nagoya have been asking recovered patients to donate their plasma samples if an initial blood test confirms the presence of high levels of antibodies. The hope is that high antibody levels in the blood of a survivor can save others.
That level of enthusiasm is no longer felt overseas, where many doctors have already judged that convalescent plasma therapy, as the treatment is known, is ineffective against COVID-19.
Whether or not a certain treatment may be effective against a new disease can only be known after it’s tested with patients. But Japan’s slow move toward plasma treatment has once again highlighted the nation’s lack of agility in a public health crisis.
The Center Hospital has tested around 700 recovered patients and gathered plasma from nearly 200 of them, said Dr. Satoshi Kutsuna, chief physician at the NCGM’s Disease Control and Prevention Center.
Using donated plasma, Kutsuna has been leading a randomized clinical trial of 200 COVID-19 patients since February to ascertain efficacy in treating others in the first five days after the onset of symptoms. The treatment’s safety was confirmed during a previous trial conducted from October to February in which 11 COVID-19 patients with moderate symptoms were injected with plasma. Ten of them have recovered but a woman in her 90s died.
In the latest trial, the Center Hospital is administering the transfusion of convalescent plasma containing high antibody levels to patients in the first five days after the confirmation of the disease.
“This will likely not be effective for patients with severe symptoms,” Kutsuna said. “We’ve been gathering reports that it’s effective to use it on patients in the early stages after the onset of symptoms, so I think it’s important to inject it” even earlier rather than later.
If the trial proves successful, the therapy may be granted approval in Japan for treatment of the disease. But securing abundant supplies of plasma could present a challenge as a donor’s blood type must match that of the recipient.
Often called “liquid gold” due to its color, convalescent plasma typically contains powerful antibodies for fighting COVID-19. A tried and tested therapy, the treatment — for which Shibasaburo Kitasato (1853-1931), a bacteriologist who helped build the foundation for modern medical science, was an early pioneer — has been used effectively against diphtheria, the Ebola virus and during the 1918 flu pandemic, among other instances, saving countless lives.
Early on in the pandemic when there were not many options for treating the disease and vaccines remained a distant goal, doctors worldwide experimented with the technique. In the U.S., the Mayo Clinic led an expanded access program beginning in April last year, with more than 70,000 American patients receiving convalescent plasma by late August.
Dr. Kazuhiro Yamaguchi, a guest professor at Tokyo Medical University, said initial indications from its use at the Mayo Clinic and in India, as well as a double-blind randomized clinical trial in Argentina, have pointed to signs of efficacy and lower mortality rates, especially when the transfusion was given within three days of a COVID-19 diagnosis.
Following the clinical trials, the U.S. Food and Drug Administration (FDA) last August granted an emergency-use authorization to the plasma treatment, saying it may be effective in lessening the severity of symptoms and quickening recovery in some hospitalized patients.
But clinical trial data on plasma therapy has also shown mixed results.
The U.K.’s Recovery Trial, a large-scale trial that sought to identify effective treatments for COVID-19, found no significant difference in 28-day mortality rates or in the proportion of patients discharged from hospitals within 28 days, Yamaguchi said.
“The study was conducted in a proper double-blind randomized clinical trial, and the results were all negative,” Yamaguchi said, adding that the meta-analysis of 10 randomized clinical trials worldwide has also shown no significant difference in mortality rates or in improvements for people with severe symptoms.
Many hospitals in the U.S. have abandoned plasma therapy, except for a small number of clinical trials. The FDA also revised its emergency authorization in February, restricting it to the use of high titer plasma therapy, which involves higher levels of antibodies, for hospitalized patients early in the course of their illness and only to those who have impaired immunity and cannot generate an adequate antibody response themselves.
Like vaccines, Japan moved on plasma therapy much later than some other countries, experts say, with the first vaccines having been almost developed overseas even before the therapy program got started in Japan.
Dr. Joe Chiba, a professor emeritus at the Tokyo University of Science, said Japan could have proactively pursued serum therapy using convalescent plasma from infected passengers and crew on board the quarantined Diamond Princess cruise ship in Yokohama in February last year, before the virus began spreading more rapidly inside the country.
“The critical role (of plasma therapy) is mainly to prevent or treat COVID-19 in the very early stage of the pandemic when there are only a small number of patients,” he said.
Takeda Pharmaceutical Co. co-founded the CoVIg-19 Plasma Alliance in April last year to help develop a potential plasma-derived therapy called hyperimmune intravenous immunoglobulin medicine, which is made by condensing antibodies in plasma. But the alliance last month ended their one-year collaboration after a large-scale clinical trial of nearly 600 adult patients in the U.S. and 10 other countries across five continents failed to reach its targets.
Overseas, the focus has turned to monoclonal antibodies as a potential COVID-19 treatment. Some drugmakers have produced monoclonal antibodies, which are laboratory-made proteins that mimic the way the immune system fights off the virus and are thought to be more potent than convalescent plasma or immunoglobulin.
The FDA gave emergency use authorization to two monoclonal antibodies made by U.S. firm Regeneron Pharmaceuticals Inc. last November that are to be administered together for the treatment of mild to moderate COVID-19 cases. The cocktail was used to treat then-U.S. President Donald Trump when he contracted the disease in October and is said to have helped him recover faster.
The monoclonal antibodies treatment, which experts say would cost thousands of dollars per intravenous transfusion, has not been approved for use in Japan. But the government has reached an agreement with Chugai Pharmaceutical Co. to have the firm secure Regeneron’s cocktail supplies if it clears regulatory approval.
With monoclonal antibodies on the horizon, experts say Japan may be better off if it moves on from convalescent plasma.
“Now that the vaccines have been released as well as monoclonal antibodies, it seems as though plasma therapy no longer has a role to play, except that it would be worthwhile to introduce optimized plasma therapy in countries that are facing delays in vaccine supplies,” Chiba said.
In a time of both misinformation and too much information, quality journalism is more crucial than ever.
By subscribing, you can help us get the story right.