Research progress, current and future course of COVID-19: Revisiting the basics I Part 2
11 May 2020
As we sail through the COVID-19 pandemic, we all would acknowledge the speed with which things are progressing, including the research on COVID19. The onslaught of information – numbers, graphs, predictions and what not – has informed as well as overwhelmed many of us. In such times, what better than having experts answer questions that keep us up at night?! It is with this view that the 'Webinar on COVID-19: Ask The Experts – Part 6’ hosted by DBT/Wellcome Trust India Alliance (India Alliance), THSTI, IAVI and Nature India on 1 May 2020 aimed to take stock of recent scientific advances, public health actions and the future course of this pandemic.
Our expert guests for the webinar were Dr. Gagandeep Kang, Dr. Shahid Jameel and Dr. Jacob John. This is the second part of edited excerpts from the webinar.
On repurposing of drugs
Gagandeep Kang: If you want a drug for an unknown pathogen, the first thing you will go to is available compounds to see whether there is something already available that you can use against a new target. The repurposing of drugs is your fastest way of having a treatment and to be able to do that, people run screens with all available licensed compounds or known compounds and see whether they have an antiviral effect. It's possible now to do very high levels of screening and this allows us to shorten the time to identify what potential treatments might look like. For example, hydroxychloroquine or ivermectin were both identified on such screens. One easy way of starting to do a screen is to look at what worked for related viruses, and then think about applying it to the new virus as well.
Shahid Jameel: There are close to 70 different potential drugs that are being tested. We have also seen how people have jumped the gun, for example with hydroxychloroquine. I just read today that IICT Hyderabad has developed the active pharmaceutical ingredient for the flu medicine for COVID, which is now being transferred to Cipla to scale it up. So, there's a lot of movement both globally as well as in India on drugs. Repurposing of drugs is extremely crucial because that's the fastest you will respond in a growing outbreak. With time we will see more specific drugs, especially since we have a lot of structure-aided drug design and people are able to decipher the structure of key enzymes in this virus.
On convalescent plasma therapy
Gagandeep Kang: This is another one of those where jumping the gun sort of applies. But perhaps we're being a little more cautious here because it's a biological that is coming from patients. There are anecdotal reports that people have done well after convalescent plasma therapy and there is a need to understand that there are actually two ways to do this. One is to take some convalescent plasma and just put it into a person; the other is to do plasmapheresis where you take what you need from a person and put the rest back in to them. So, the ability to treat people with the two different approaches varies. With just doing a standard plasma donation, It's a smaller number.
There are currently ongoing clinical trials in locations around the world that are evaluating the value of plasma therapy. It has been approved for use in India by the Drug Controller General of India and people are being put onto it. The question that I really have about this therapy and how it's being evaluated is, at what point do you want to give somebody plasma? My understanding is that in the Indian context, we are requiring that people be on ventilators and really sick before you give them plasma. Whereas in other countries, the idea is to try and treat people earlier in the illness. When you think rationally about where antibodies are most likely to act, they are most likely to act early in infancy. So, the point about at which point plasma should be given in the clinical course is something that I think needs a little more discussion when clinical trials are designed.
On the use of next generation sequencing to understand epidemiology of COVID-19
Gagandeep Kang: NGS is a very powerful technology and there is a lot you can do with it. If you take a lot of samples together, you could pool them and apply NGS. It would allow you to test a lot of samples really fast and get detailed information on whether the virus is present, and you will get the sequence as well. That makes us a lot of sense in theory, but less sense in practice when you think about how samples are collected from patients, where they are brought to and where they are tested. If I need a thousand samples to be able to do an NGS run, I'll have to wait till I get a thousand and only then start to use this technology. If I'm only testing 10 samples a day, I may have to wait for many days before I get enough samples to be able to do so. I could do fewer samples, but it doesn't make sense to do that in India. I think we need to have a little more thought around the processes by which you will accumulate examples to be able to do this. The Institute for Genomics and Integrative Biology have made a tiny device for doing sequencing for about 15 samples together. It's useful for to get the entire sequence of the virus out. But if you were to use it for testing, you would want a much larger number of samples to be tested in order to justify the time and the expense of such a technology.
On how much we need to test in addition to lockdown
Jacob John: There needs to be an approach very similar to what we did in HIV and otherwise – looking at sentinels or places where you would expect to see a high amount of disease or early indicator. look in populations like frontline workers, healthcare workers and see what's happening among them. It could also be that you have antibody-based assays to help identify when populations can exit lockdowns. The problem is, at this point in time, we are still so early in the outbreak that the prevalence of these conditions is extremely low. So, at different times in the outbreak, we will have different strategies that are important. I think that the early phase would be looking at healthcare workers and other frontline workers, and also doing periodic sero-surveillance studies in the population which are probability-based. Testing high-risk population, contact tracing and testing to control the epidemic is also important, but that's in very specific locations.
On whether the novel coronavirus can really be called ‘deadly’
Shahid Jameel: If you compare it to tuberculosis, childhood diarrhea or malnutrition, it's not; but then all those things don't come concentrated within a few weeks. The way this virus is moving, it can very quickly overwhelm our public health systems. Nobody is saying that you focus only on coronavirus. Many hospitals today are not admitting anyone else other than COVID-19 patients. It's a challenge. When sceptics say that more people are dying because of the lockdown instead of the disease, it may be true to some extent. COVID-19 is an emergency today, so focus on it, but don't let your guard down on other things. In this lockdown, how many people are missing their TB medicines? What effect would that have would the TB bug become more drug resistant because of the lack of attention to it? I would worry about those things.
On the challenges to experimental and clinical research in India, especially after COVID-19
Gagandeep Kang: Challenges of doing research in India were there before the last two months, and I think the only thing that has changed is really logistics in the last couple of months, because it's become very difficult to get reagents to get people into work, etc. Those kinds of things are balanced by the push to have more indigenous research being done. So, there is activity that is trying to promote research, whereas the structures that we have at the moment don't allow us to do the research that we want to be able to do in India.
Jacob John: If you think about research in the context of a public health pandemic like this, the one thing that is clear is the lack of data systems and the lack of an ability to access reliable data that gives us a measure of how big and where the problem is. In public health, you start to address problems appropriately only when you know the scale of the problem, and that allows you to think about what kinds of interventions or what efforts are appropriate here.
We have been relying largely on data that has not come from India. Relying on data and information that has come from outside of India shows the level of sharing that is going on currently around the world, which is something that is truly unprecedented. I hope that this will serve as a model for how research is done in the future globally.
What's really been a problem for us is that we work on assumptions and those assumptions need to be substantiated with data. It becomes extremely useful for us in terms of predicting what's going to happen, as clinicians and as public health people, in looking at what are the risk factors.
Shahid Jameel: The other day, I heard somebody say that there are too many recreational virologists at this time. I take that comment positively in the sense that many more people who are not possibly trained as virologists are attempting to solve the challenges, which is good. While this outbreak has been challenging, it has thrown up many opportunities. One opportunity is how openly data is being shared and how openly people are collaborating, and I do hope that this openness and this collaboration will continue even when the pandemic is long gone.
The second point is that the flurry of activity that you see in a pandemic is good, but you don't prepare for a battle when you're in a war; prepare for a battle before you get into it. That is something we need to start addressing at a research systems level, that funding has to be sustained and not directed always towards asking. The fundamental knowledge that you produce is sometimes a key to solving a problem when you are in a challenging situation like this. So, I do hope that we have learned a lesson from this. I do hope that in future, we will also deal with health security as a matter of national security and spend more on research.
Don't forget that when it came to an outbreak, who mattered most – it's the doctors, the nurses, the delivery people, the scientists who matter most and I hope that lesson is not forgotten once this is over.