"Years before the coronavirus pandemic, every time I flew, I’d wonder, 'What am I going to get this time,'" admits Dr. Eliav Barr Senior Vice President Global Medical Affairs at MSD (Merck Sharp & Dohme). The last time I met Barr, who is originally from Haifa, in the winter of 2018, I had a cough, and he recoiled and moved away from me. At the time, that seemed rather strange. These days, his reaction is understandable.
During that conversation, Barr predicted that a major epidemic would come. His assessment was that it would probably be another influenza virus, but noted another likely candidate: MERS , also of the coronavirus family, which was transmitted from camels to humans in 2012. If that virus were to mutate, he said, the situation would be cause for alarm.
What we have today is something in the middle: a coronavirus that’s less deadly than MERS but more contagious than the flu. At first Covid-19 seemed like a respiratory illness, but it’s still unclear how it will be defined in the end.
"Globes": How similar is what’s we’re going through now to the scenario you feared?
"Very similar. The transmission dynamics are very similar to what we predicted. The Chinese tried to stop the virus from spreading through various means, but eventually failed to prevent hot spots from forming outside of Wuhan and then outside China. The moment an uncontrolled epicenter like that forms, the infection erupts, just as you’d expect from a contagious disease. Every respiratory virus is different, but the dynamics are similar, especially in viruses where symptoms are mild or nonexistent.
"The only and welcome difference is that it almost never causes damage in children and is apparently less transmitted by them. But that doesn't reassure me very much. In the past 17 years, humanity has dealt with three new coronavirus epidemics: SARS, MERS, and Covid-19. Even if the current pandemic comes to an end, something new may come along."
Chinese bats once again?
"It's definitely possible. Bats, in general, carry a variety of coronaviruses, and that includes bats in China. The MERS virus is circulating among camels in Israel today. Granted, it hasn’t mutated to become adapted to human hosts, and the strain that kills humans is still limited mainly to Saudi Arabia, but in principle, it could happen."
What can be done to prevent SARS-CoV-3?
"Once the SARS epidemic had waned and the MERS epidemic was contained without endangering the West, research in these areas didn’t get enough attention. Now, of course, it’s getting lots of attention; we must not lose momentum.
"The dream vaccine is a pan-corona inoculation that produces antibodies targeting the component common to all coronaviruses that plays an important role in binding the virus to the host cell. There were attempts to do this with the flu, but it turned out to be very difficult and complicated. To be efficient, vaccines, for the most part, must be highly specific. In any case, what we’re learning today about coronaviruses may be applicable to the next epidemic, too."
More contagious and deadlier than the flu
There is a heated debate over whether this virus is ‘like the flu.’ How is it similar and how is it different?
"Covid-19 spreads in aerosol form like the flu. It favors adults, like the flu, but to a greater extent.
"Covid-19 is very dissimilar to the flu in presentation, variety of possible symptoms, and range of damage. It can damage the lungs, heart, cause blood clots, affect the kidneys, and there’s evidence that it can affect the brain. Flu can do non-respiratory damage - to the heart and other organs - but not to this degree.
"Covid-19 is deadlier than the flu. It simply kills more people. It’s more likely to infect you and more likely to kill you, if you’re infected. Additionally, it has a higher rate of people becoming very sick - even if it doesn't kill them - with a serious illness that goes on for weeks."
Some say that, compared with the beginning of the pandemic, we now understand the disease better and therefore treatment is better, so that fatalities are down.
"There’s definitely progress in understanding the disease. One optimistic note from this period is information-sharing among doctors; the online digital era has been extremely useful in this context. MSD and other companies have worked actively to connect doctors, so they can share know-how.
"Another improvement followed from the realization that, for some patients, respirators do more harm than good, and that these machines should be reserved for those who really need them. A respirator can be replaced with a kind of helmet-based oxygen ventilator. It's a far less invasive intervention for the patient. Nevertheless, this is still a very serious illness."
"We must convince the young people"
Barr says that lockdown has proven an unsustainable solution, both economically and socially, and that much should be done before resorting to it. "We haven’t yet realized the maximum potential of masks and social distancing. Older people need to stay at a distance, there’s no two ways about that.
"Young people must be convinced to take social distancing measures, avoid crowding, and wear masks. They’ve got to understand this. They’re not just hurting others but themselves as well. They, or their friends, could get sick with an illness whose effects can be very unpleasant and possibly irreversible. As long as the virus is raging outside, life can’t go back to normal. "
"I don't care who wins, the main thing is getting a vaccine"
So, when will a vaccine actually be available? 120 Covid-19 vaccines are under development. Most of them are in the laboratory phase, some are in animal testing, and a small number are in clinical trials on humans. MSD itself is currently developing two types of vaccines, but Barr is not ready to commit to a timetable.
"Before we started developing the vaccine, we had to understand the level of immune response and the type of response that were needed to prevent the coronavirus from binding to cells," says Barr. "Over time, it became fairly clear that recovering patients do develop antibodies that neutralize the activity of the virus. The neutralizing antibody captures the virus and transfers it to cells that act as a kind of 'garbage disposal', and they destroy the virus.
"Our goal is to generate this sort of antibody, but it won’t be virus-based. Today, we don’t use weakened live viruses or a dead virus. However, the more the vaccine resembles the protein binder - the characteristic coronavirus spike - the greater the chance of creating a neutralizing antibody. It must have the exact outward appearance of its source.
"There are all kinds of approaches but, first of all, it’s important to me to say that I don’t care who wins. The main thing is that it should happen. The more options we have, the faster we can get to as many people as possible. There will be fewer production bottlenecks and fewer people for whom there is no appropriate vaccine.
"So how do you make a vaccine? You can create the protein itself, the spike. But how do you introduce it into the body in all the places where it can stimulate antibody production? It has to be introduced via an agent, a non-infectious organism, let’s say a virus that has been rendered incapable of reproduction. This is done by genetically engineering another virus, one that isn’t SARs-Cov 2.
"Another option is to introduce genetic material into the body, such as RNA, but only disassembled viral RNA, meaning we never introduce the whole virus into the body. This RNA produces the spike protein within the body, after which the body produces an antibody against the spike. This approach is fastest to execute, which is why vaccines using this approach are already being tested, but it is a new approach that hasn’t produced a vaccine to date.
"Apart from efficacy, it’s very important to us that the vaccine should be given in as few doses as possible - if possible, a single dose that’s easy to manufacture, and easy to preserve, in the fridge, not the freezer."
What vaccines is MSD developing and at what stage are they?
"One of the vaccines we’re developing is in partnership with the International AIDS Vaccine Initiative (IAVI). We’re providing a technological basis that’s already used in an Ebola virus vaccine. It is easy to produce, or rather, we’ve already learned how to do it. What we want to do now is to induce expression of the spike protein.
"The second vaccine is based on the measles virus platform developed by Australian company Themis. It’s one of the most infectious pathogens known, so it’s expected to be a highly effective vector."
Did you say the vaccine is based on measles?
"Yes, but as I mentioned before, we never introduce an active measles virus, of course, but disassemble it to prevent it from being able to cause damage, or reproduce. We leave only the outer structure, which the cells recognize, and so it stimulates antibody production. There’s no danger of it causing measles or reproducing in the body. It’s deprived of any such ability. It’s just an agent.
"We’re absolutely certain that it won’t cause measles, but of course there are clinical trials as well. Everything has to be proven and exact, and that’s what we do. That's why things don’t happen so quickly."
What might the timetable be?
"I don't know. I’ve read notices from other companies saying they’ll have a product next year. It's important to be hopeful, but quality and safety requirements are also important. It's clear to us that a defective Covid-19 vaccine would undermine public confidence in the entire concept of inoculation. That’s why we won’t put a product on the market that’s less than excellent, and extremely safe. It’s important as well that the regulators should also consider this point very, very carefully."
Covid-19 accelerates antibiotic crisis
If you found this encouraging, here’s another disquieting prediction from Barr: The corona epidemic is accelerating bacterial resistance of antibiotics, a disaster that infectious disease experts have been warning about for years. What’s the connection? "Covid-19 patients who are hospitalized, especially those who are ventilated, are very susceptible to hospital-acquired infections, particularly pneumonia. To deal with these infections, we need large doses of antibiotics which, in turn, pose the danger of creating antibiotic-resistant strains."
The challenge of managing contamination in hospitals is already in the running with Covid-19 for the title of the world's worst infectious disease problem. See you at the next plague.
Published by Globes, Israel business news - en.globes.co.il - on July 1, 2020
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