"We can't rely on the summer to stop the spread of the coronavirus, " World Health Organization (WHO) health emergencies program executive director Dr. Michael Ryan said last Friday. "If this happens, it will be wonderful, but no evidence has been found yet that allows us to count on this scenario."
In order to slow the spread of the virus until new drugs and vaccines arrive, private companies, government agencies, and third sector organizations are taking action to promote solutions, somethings together and in cooperation between countries. "Globes" presents you with an up-to-date picture of the situation.
The US testing controversy
Diagnosing carriers and patients is one of the means of managing the crisis. Testing for the virus is essential in order to locate patients who cannot be traced by the health system, release people from isolation, and prevent panic among people who suffer "only" from flu, but who are sure that they are about to die from coronavirus. The US government has been strongly criticized for the small number of tests in the country because it did not create a rapid approval track for tests in addition to those provided by the Centers for Disease Control and Prevention (CDC), and because the existing tests are not accurate enough.
Up until a week ago, tests were administrated in the US only to those who met federal criteria, i.e. who visited countries in which the disease was prevalent or came into contact with patients and exhibited severe symptoms. Following the reports of a patient who waited several days for testing because he had not visited another country and a nurse who treated patients and began to develop symptoms, but was not tested, because she was told that her symptoms were not severe enough, and after evidence began to accumulate that the infrequency of testing had made the US complacent and unaware of the true extent of the coronavirus's prevalence, a dramatic change in testing began. In addition, protests began because the patients tested were required to pay a considerable sum for it.
Even in Israel, only patients who had been in contact with a verified patient and developed symptoms were tested (for free). The approach in the US and Israel is different from the approach in South Korea, where almost no restrictions were imposed on movements of large groups of people, but many tests are conducted, and are made available to everyone. South Korea has even set up drive-through test stations.
Some claim that this policy has resulted in a lower infection rate than in China (excluding damage from the "coronavirus cult" spreading the disease in South Korea deliberately or through negligence). Critics in the US of its testing and detection policy assert that early testing and direction in South Korea has resulted in lower infection and mortality rates in that country. It is hard to know whether this claim is true, because a high level of detection is liable to look like f a low mortality rate.
At any rate, the South Korean response is the result of experience. The country was hit hard by the MERS virus, a previous example of the coronavirus that is less infectious, but more deadly. Patients initially circulated freely within and between hospitals, because no one knew that they had MERS. In order to prevent a recurrence of the same mistake, South Korea developed a fast track for approval of virus diagnosis tests, and commercial companies in the country received approval for producing the systems within a few weeks of the virus being detected - a much shorter approval period than at ordinary times. The South Korean kits are produced at a highly automated plant, as befits a country that is one of the global leaders in sophisticated industrial production. South Korea can now test 10,000 people a day, and receive the test results within a few hours.
The US is not introducing such a track, and its response to date has accordingly been slower. CDC is responsible for developing the test. In earlier epidemics, such as swine flu, CDC did good work, as far as is known, in developing the test and making it available to all those who needed it. This is not true, however, in the current case.
The organization was severely criticized for failing to develop enough tests, despite information from China dating back to December and because the tests developed at the beginning did not give clear cut results. When the tests were improved, few of them were available, and eligibility for a test was greatly restricted. The health organizations of each US state were later given approval to conduct their own tests, followed by universities, but not private companies. The fact that some patients were tested by CDC and others by states also caused confusion in recording how many people had been tested, and it was therefore difficult to calculate the rate of infection among the US population. As a result of CDC's delays, only 1,583 tests were conducted in the first three months of the outbreak. In Israel, where the virus first arrived only a month ago, a much larger number of tests have already been conducted.
As of a week ago, over 100 patients had been found in the US. The number rose to 400 patients and 19 fatalities last Friday.
"This test is neither hard to develop, nor hard to carry out," says Dr. Tal Raveh, an Israeli researcher at Stanford University. "The purpose of this test is to detect and identify the hereditary material of the virus using RT-PCR technology, which many scientists frequently run. I used it when I was a student at the Weizmann Institute." Obviously, when a high degree of accuracy is required even when the test is performed in the field, it becomes a little more complicated, but the obstacle is still only technical, far from the level of scientific complexity involved in development of vaccines.
Stanford developing its own test
As a result of the problems, delays, and lack of availability of the tests developed by CDC, it was decided to allow commercial companies to develop tests and carry them out. Three leading US diagnostic laboratory companies were granted approval: Co-Diagnostics, Quest Diagnostics, and Enzo Biochem, which are currently launching their tests. US company Opko Health, which is also listed on the Tel Aviv Stock Exchange for historic reasons, announced that it would also conduct tests in its chain of laboratories. The US Food and Drug Administration announced that it was granting rapid emergency approvals to companies providing an immediate solution to the great need for tests.
"It is possible that we switched too quickly from over-concentration to a situation in which tests are being developed too quickly, without adequate supervision," Raveh says. "It is a very simple test with unequivocal results, but there are likely to be differences in the sensitivity threshold in tests devised by different companies, resulting in differing capabilities to detect the virus during the incubation period, until uniform technical standards are set by the regulatory authority."
In any case, the Stanford University Medical Center is not waiting for these tests; it has independently developed its own test for the hospital, its community clinics, and the university employees whom it insures, one of whom is already ill. Actually, according to the university's news bulletin, the hospital's researchers, headed by the manager of Stanford's virology laboratory, have been working on this test since January, which means that they saw that there would be a need for tests beside those of CDC, even before CDC itself realized it.
As we have seen in this crisis, when the tests are not sufficiently accurate or sufficiently sensitive, the damage they cause outweighs the benefit that they provide. In Japan, for example, the test used was apparently not sensitive enough. Patients diagnosed as healthy disembarked from the Diamond Princess cruise ship and infected more people on the shore, after a great effort had been made to quarantine the ship and the virus had spread among the passengers. In Wuhan Province in China, where the virus first appeared, an inadequately accurate test was also used initially, which accelerated the spread of the virus.
WHO is now recommending the release of people from hospitals only after two negative results from two tests conducted at a 24-hour interval. Incidentally, tests cannot be used to release people from quarantine before 14 days have passed, because the test is likely to produce a negative result during the incubation period, even if the tested person is a carrier.
The US is promising that by next week, 1.5 million kits will be available, but the need to conduct repeat tests on the same patients means that even after the kits become available, there will not be enough kits to test even one million people in the US, out of a population of 330 million. "Soon, however, every family doctor will be able to test any patient when needed," Raveh says. "I'm afraid that the disease is already here, and when we start extensive testing, we'll find out how many people are really ill, and it will be a great and unpleasant surprise."
"The availability of tests is critical," says former Teva CEO Jeremy Levin, the head of the Biotechnology Innovation Organization (BIO), which coordinates all of the young drug companies in the US that do not come under the heading of big pharma. "It's essential for there to be tests that can be carried out at home, and for the results to be quick, so that people know that they have the virus as soon as they first suspect it. There are now such tests for many diseases. It's completely doable.
"Two weeks ago, we sent a query to all of the companies asking whether they were developing a diagnostic test, drug, or vaccine," Levin adds. "50 companies have already gotten back to us." WHO cites similar numbers: 20 companies worldwide developing vaccines for the disease, and 40 developing tests.
Zvi Marom, CEO of BATM Advanced Communications, which is also about to offer a test based on antibodies for diagnosing coronavirus to the Israeli Ministry of Health, says that the development of these tests takes time, because the antibodies have to be produced. "The only constraint is time," he asserts, "and the medical personnel to administer the test. The dream is to develop a home test, like the test for pregnancy, that can be performed quickly without a doctor, but this will not happen in the coming weeks, and possibly not in the coming months."
The vaccine coalition
BIO has appointed former Biogen CEO Dr. George Scangosto, who now manages vaccines company Vir Biotechnology, to head its coronavirus team. "He will head a coalition of these companies," Levin says, "and he will triumph, there's no doubt of it."
"Globes": What will the coalition do?
Levin: "In addition to having the scientists meet to share their knowledge, we're also working to shape the regulatory tracks for these products, so that they will be fast, but not hasty, and we're looking at the supply chain of raw materials for drugs and vaccines in the pipeline, and for tests. We're trying to make sure that the resources will be available, and will be divided wisely among the companies."
Will you also ask for government incentives for companies developing the vaccine?
"In the past, companies that developed vaccines for epidemics suffered economically, because the epidemic died out before the vaccine reached the market.
"Meanwhile, the response has been strong, and we're not seeing any such problem."
Levin gives a soothing message: "Things have to be taken in proportion. 70,000 people also died of flu last year, even though we had a vaccine. We face viruses constantly. This is not an unknown enemy."
In contrast to the confidence expressed by Levin and leaders of the US health system in the ability to develop additional tests that will be quicker and more accessible, there is no assurance of success in inventing a vaccine.
The conventional vaccine will be a protein identical or similar to a protein from the virus's envelope, which is the protein that the virus needs for infection purposes. In other words, the vaccine protein will stimulate the body to create the right antibody. The companies producing vaccines, however, are not sure that they know which part of the virus is the most important, and what will really delay and paralyze it. Even after a protein is found that will paralyze the virus, it is necessary to make sure that it will not paralyze the cells in a person's body, i.e. does not create side effects. It must also be verified that the immune system responds to this protein strongly enough and generates enough antibodies against it. This game consists of critical information, a bit a of a gamble, and a lot of trial and error. It takes time to devise a vaccine that will stimulate the creation of effective antibodies, and more time to test whether it provides protection against being infected by the virus.
In the war against the coronavirus, not all of the vaccines being proposed are proteins or protein parts. Some companies are proposing to take an RNA sequence from the virus, or DNA based on the RNA sequence, inject it into the body, and allow the body to produce the protein by itself, and then the antibody against the foreign protein. This is a new approach with potential, but it incurs risks. "The concern is that the DNA is liable to be integrated into the genome. It's harder to produce a protein, but it's safer," Raveh says.
If not a vaccine, can a drug against the virus be created? The leading product today, Remdesivir, is in clinical trials. "It mimics a building block that the virus needs in order to duplicate the RNA, its hereditary material, but this is a faulty building block. When the virus tries to reproduce itself, it tries to use Remdesivir, and then the reproduction attempt fails," Raveh says in explaining how the drug works, or so we hope. The drug was administered to a first patient in the US, who recovered, in a compassionate trial. Remdesivir is currently in the midst of clinical trials in China and other countries, and initial results will be published in early April.
Published by Globes, Israel business news - en.globes.co.il - on March 12, 2020
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