Since January 2020, when Coronavirus started spreading in Wuhan, China, and later massively trapped the U.S. and European countries, researchers around the globe, have been racing for an effective cure. By the First week of May 2020, more than 90 vaccines are being developed against COVID-19 by the researchers in pharmaceutical companies and universities across the world. Researchers are trialing different technologies, some of which haven’t been used in a licensed vaccine before. At least six groups have already begun injecting formulations into volunteers in safety trials; others have started testing in animals.
Scientia Pakistan Magazine has interviewed Dr. Michael Gale, Jr., Ph.D. Director of the Centre for Innate Immunity and Immune Disease (C.I.I.I.D.), in the U.S. The C.I.I.I.D. is a research center for immune responses, and viruses and infectious diseases, including coronaviruses. Our senior team member Fawwad Raza and Dr. Micheal discussed how the pandemic has catalyzed the development of novel coronavirus vaccines across the biotech industry, both by pharmaceutical companies and research organizations.
Below are some excerpts of this conversation.
Fawwad: What are the biggest threats of Covid-19 right now?
Dr. Micheal: One of the biggest questions to understand is how the virus is physically recognized by the body and then how it functions to drive the innate and the adaptive immune response in infection.
We found in the patients that they have a very aggressive immune response that is overwhelming and, in the worst cases, debilitating in that the virus turns on immune processes that are actually contributing to disease.
So, we need to know what those processes are, how they are triggered, and how we can intervene with this type of outcome. So I think those are the biggest questions that we are facing right now.
Fawwad: How is Coronavirus different than the other coronaviruses, such as SARS and MERS? How about the flu?
Dr. Micheal: Coronaviruses are physically different from the flu due to the following specific reasons.
- The Coronavirus family consists of viruses that have one long genomic piece of RNA and influenza viruses have multiple parts of nucleic acid, in their genome. That is just one of the significant differences.
- Physiologically, the coronaviruses, as a family, circulate around the globe and typically cause what we consider to be the common cold. In any given year, people get infected with what we will call contemporary coronaviruses that cause a cold, runny nose, maybe a slight fever, and some aches and pains for a few days. But people recover from that.
So, the severe acute respiratory syndrome coronavirus is SARS that spread out in 200-2003, now this new SARS-Cov-2 is different due to some reasons as it causes very severe and fatal respiratory disease. The current Coronavirus differs from all the other coronaviruses genetically, which gives it its own name.
It is different from SARS-1 because there are multiple genetic distinctions across the genome, and importantly, the spike protein, that gives the Coronavirus its name because it sticks out around the edge of the virus, and makes it look like the corona of the sun if you look at it under an electron microscope.
The spike protein is what attaches to cells and the spike protein from Covid-19- versus previous SARS viruses are unique. It is subtly different, in infection properties. It could be physiologically different, so this current virus has a spread much more extensive and disseminates more rapidly. So the infection behavior is quite a bit different from the previous SARS virus.
And then, of course, the syndrome: The respiratory disease syndrome that it is linked to that we now call Covid-19, that syndrome is different because it is slower in progress. Some patients die. Most people recover just fine.
So the previous SARS was a very aggressive acute infection that was not as widely spread and physiologically created an acute and often devastating disease. Therefore, the two viruses are similar, but they have very clinically different behaviors.
Fawwad: What are some misconceptions about this virus and its spread? And how science addresses them?
Dr. Micheal: Well, the biggest misconception, I would say, is that people are safe and the virus can’t be transmitted that easily. But what we are learning is that it is transmitted very effectively. Science has epidemiology. I think we have, in our own experiences, already proven that the virus is very effectively spread among groups of people through social contact.
So, we had some of the behaviors here in the United States where people were not adhering to social distancing and actually facilitated the spread of the virus when these people should have been staying home and containing the virus on their own.
But we must observe social distancing and use it to stop the spread of the virus because it is very efficiently spread.
Science has shown that the virus can persist on surfaces for specific amounts of time. Science has also demonstrated how we can inactivate the virus through sanitizing procedures. Hand washing is mandatory, Social contact control is very crucial.
If we can stick to those protocols for social distancing, and decontamination adherence personally, and on surfaces, it will slow and even contain the spread of the infection in the population.
Fawwad: You study innate immunity. What do you think is the role of innate immunity for this infection? And why is it important to understand the Coronavirus better?
Dr. Micheal: Yes, a good question indeed. Well, innate immunity is a process that protects us daily, we go throughout our lives. Innate immunity can be considered an immune response on the molecular level that can take place inside of any cell of your body.
If you happen to be out in the public one day and you get exposed to influenza virus, or this Coronavirus, or measles, or mumps, or some new virus that is circulating in the environment, the first thing that is going to happen inside the cells that get infected with that virus is that it is going to induce what we call an innate immune response. When this response works appropriately, it will restrict the virus’s replication at that exact site of infection. The virus won’t get a chance to spread throughout the body and to infect the rest of your tissues and your other organs. Innate immunity is vital for daily protection against viral pathogens in addition to protection against bacterial and parasite pathogens.
Without innate immunity, we become very susceptible to virus infection and an innate response plays a crucial role in controlling virus infection at the site of infection and prevents it from being spread throughout the body.
But when the innate immune response gets turned on too much, it can become dangerous and often turned on when it should not be turned on. This also forms the basis of several different auto-immune diseases that we are familiar with, like lupus, probably multiple sclerosis, and other diseases that can be debilitating.
So we know that innate immunity is crucial to control of infections. But innate immunity itself also has to be controlled.
So, what could be happening, we don’t know this yet, because we need to do more research. But the clinical data suggests that what is happening in [the] SARS COV-2 infection, that underlies Covid 19 disease is an innate immune response. In parallel, the inflammatory response triggered by the infection seems to propagate out of control, and it could be contributing to disease and the lethality of the infection.
So, this could be a situation where we may need to find ways to shut down the innate immune response, or a closure to the inflammatory response, to mitigate Covid-19 disease.
Fawwad: Why are certain people at higher risk of developing a worst [case] disease outcome, than others?
Dr. Micheal: What we are learning is that, with SARS COV-2, affected the elderly most, people over 65 years old, is very susceptible to the infection and is an adverse outcome with the Covid-19. Typically, the aged individuals versus young individuals, there are distinct differences in the capacity of immune response to respond to and control infectious disease pathogens.
We understand this process as part of an aging program in the immune system called immune senescence. It is probably more complicated than that. But what we know is that in aged individuals, the immune response is tuned down, or it switches over more to immune regulation response than a response capable of fast response to an infectious disease. Those people end up being much more susceptible to an adverse outcome than youngsters who have a robust immune response capable of swift action against this virus.
Fawwad: How much can this virus travel in [the] air? And for how much time can it be active to infect human beings?
Dr. Micheal: Yes, the aerosols of the virus are a significant concern. It can survive inside the fomites, and saliva droplets elicited from people when they talk. The virus is probably viable, we think, for several hours in fomites. Fomites get deposited on the surfaces of tables, on your hands, on doorknobs, and anything that you touch. And the virus can survive in that environment, for 30 minutes, to 3 hours, maybe even longer.
That is why it is crucial to decontaminate surfaces and to control the aerosol spread of the virus. You see many people walking around with a mask on their face, to control the spread. We think that it is essential that people who are actually known to be infected, if they are around other people, to wear a mask. If you are not infected, the important thing is to make sure the surfaces you touch are clean, or you are maintaining social distancing to reduce exposure to aerosols coming from someone infected.
Fawwad: As some research published in the Journal of the American Medical Association, warns that the current guidelines are based on outdated models from the 1930s. How much distance is safe from one person to another? 3, 6 feet, or 20 feet?
Dr. Micheal: Yes, this is right, it can be risky. So the best data suggests that six feet of distance, or about two meters, is better than three feet. This is the distance by which fomites: again the aerosol droplets that would contain a virus, travel when people talk.
Some people talk louder than others, so when they speak louder, they expel more air. And that is why maintaining a six-foot distance is better than three feet. Now, on the other hand, when people sneeze, or if somebody is talking underneath an airshaft ventilator that pumps air into the room, then that air can spread several feet, much more than six feet. In that case, social distancing beyond six feet, as you mentioned, 20 to 27 feet, is worth considering.
As I sit here today, there is an air vent above me, blowing air into my room. When I talk, somebody who is sitting across the table would be more apt to be exposed to aerosols that I am exuding. If I were infected, this act could be hazardous, and that air vent above me would blow the air past me many feet, greater than six feet.
That is why it is mandatory to maintain a distance, depending on the configuration of your room, six feet or higher.
Fawwad: Some researchers claim that COVID-19 has mutated. And it can mutate from one person to another. Is that true?
Dr. Micheal: Well, there could be some truth to that, so, what happens with viruses that have RNA genomes, when they replicate they don’t proofread their genome, which is very different from viruses with DNA genomes.
The genome of humans is a DNA genome; we make RNA from that DNA genome as we turn our genes on. But these RNA viruses have an RNA genome. When the cells in our body replicate, our DNA genome undergoes proofreading. And if there are mistakes in it, we have repair mechanisms that correct those mistakes, typically.
RNA viruses don’t proofread, they don’t have much proofreading capacity that DNA viruses have. So they make a lot of mistakes when they replicate.
The coronaviruses have other ways to select for maintaining genome integrity. But overall, they don’t proofread when they replicate. So that can lead to the accumulation of mutations that eventually could drive the outgrowth of a new virus strain.
Now there is not a lot of evidence right now; that what is happening in real-time with Coronavirus. Although from patient to patient, there could be new mutations that accumulate to make the virus more fit for that particular patient.
We don’t fully understand that yet because we haven’t done enough experiments to sequence the genome from different patients across this outbreak. But we know from other RNA virus pandemics including HIV, Hepatitis C. virus, for example, that there is a lot of genome mutation that takes place as the virus replicates and adapts to a new person that it infects.
So, we should expect to see some genetic variation in Coronavirus across the globe as it propagates across populations.
Fawwad: Can blood plasma treatment helps to boost the infected patient’s immune system, to fight against Covid-19?
Dr. Micheal: Yes, such treatment is called Passive Antibody therapy, in which we collect blood plasma that contains antibodies from somebody who survived infection and controlled infection eventually with their own antibodies. We transfer that plasma into another infected individual to treat their disease using the previous person’s antibodies.
Passive antibody therapy can be a very effective treatment. It is experimental still. We don’t know how well it works for this SARS-Cov-2. There are clinical studies that are being developed that directly address whether or not passive antibody therapy will be a viable option for treating Covid-19 disease. So, I see this as a potential therapeutic that holds a lot of hope for treating people. But it has yet to be tested.
Fawwad: What are some vaccines and therapies that are being investigated at the University of Washington or other laboratories in the U.S.?
Dr. Micheal: In the University of Washington, several groups focused on developing therapeutic antibodies that are cloning antibodies from patients who have a successful antibody response. They are attempting to produce them in mass quantity for the treatment of infected patients; those are called human monoclonal antibodies.
Besides, the University of Washington is testing two new vaccines. One of them is already in the phase of clinical trials in the local vaccine trial evaluation units. Another one is undergoing testing in a lab. We will soon be requesting approval from the F.D.A. to go into phase one trials. And these are vaccines that can generate rapid antibodies that have the therapeutic benefit of neutralizing the virus upon first exposure. So we are super excited about these.
Across the country, there are also several different vaccines in the pipeline to be tested in humans.
Fawwad: How much time will it take for a vaccine to be approved for mass production?
Dr. Micheal: Unfortunately, it is going to take at least a year or so, and we are probably looking more like at 18 months before it finishes all the trials and gets human approval. Then it has to be mass-produced and shipped around the world. So, it could be 18 months or two years before starting to see a benefit from the vaccine. Let’s hope it comes earlier.
Fawwad: What does the Centre for Innate Immunity and Immune Disease, do?
Dr. Micheal: The Centre for Innate Immunity and Immune Disease, at the University of Washington, is working very closely with a variety of researchers and also our colleagues throughout the world and in the pharmaceutical industries.
One crucial practice we are doing right now is testing drugs that already have clinical approval for other indications. We are testing them for their ability to inhibit virus replication. The center has got active research going on where we are growing the virus in the lab. And we are taking these pre-approved drugs and treating cells with them to identify those pre-approved drugs that can stop the virus.
Once we identify these drugs, the information will be given back to our pharmaceutical partners, and they will rapidly take that information to the U.S. F.D.A. to request fast track approval for treating SARS-Cov-2 infection.
This process will also take time. But it is much faster than getting a vaccine approved. We hope that the work that is going on at our center will facilitate the delivery of anti-viral therapeutics to the population.
Fawwad: What are some of the opportunities provided by the C.I.I.I.D., and how could Pakistani researchers and physicians get benefit from them?
Dr. Micheal: C.I.I.I.D. has several training opportunities. We have over sixty member labs that bring international students, physicians, and post-doctoral scientists onboard for 3 to 6 months, one or two years to work in the labs and conduct clinical research, basic science research, and interactive, collaborative science. We facilitate them with our research agenda for international partners and of the Centre for Innate Immunity and Immune Disease, itself.
In the past, we have had students and post-doctoral scientists, from Taiwan, who studied Entero-virus 71, Entero-virus 68 infection those commonly spread across Asia.
We have had scientists from Brazil, who studied emerging infectious diseases. More recently, we had a scientist from France and joined us for a whole year on a Fulbright fellowship to study the Zika virus’s innate immunity.
This leads to a vibrant interaction which is loaded with training opportunities in infection and immunity, emerging infectious disease, and in translational medicine to identify therapeutics and bring them into the clinic. These opportunities are available through international partnerships in our center.
We are currently working with the Zika virus, Entero-virus 71, SARS-Cov-2, and other contemporary coronaviruses, along with HIV, SIV, Hepatitis B., Hepatitis C., Influenza A virus. We have previously completed some projects on Hantavirus. And we have an ongoing study developing the HIV vaccine that ideally will be in clinical trials soon, with colleagues at Oregon House Sciences University. So these are fascinating studies that are ongoing.
The interview is compiled by Aniqa Mazhar, a team member of Scientia Pakistan magazine.
Fawwad Raza is a Digital Journalist and working as a member Editorial team in ARY News. He is History graduate from University of Karachi, blogger and a passionate traveler. He also conducts various training sessions of digital Journalism for students and working journalists.