Infectious disease expert warns it is ‘really serious’

MNT: What lessons have you learned from your work on other viruses that might help with the current pandemic?

Prof. Paul Kellam: I think there are a number of things. One, and probably the most important one, is speed.

What infectious disease virologists and epidemiologists know and relearn is: Whatever you’re doing, do it faster.

That’s always the tempo through virus outbreaks, and because the data that you have are always behind where the epidemic is, you always need to be mindful of speed to try to catch up.

That has been something that’s come out through this pandemic. It is speed. Speed to identify the case clusters right back at the beginning in China. Speed to identify the infectious agent in the first cases.

Speed to get the virus genome sequenced and made publicly available, and an incredible amount of speed then to generate RT-PCR diagnostics so that we can start to identify infected individuals to try to control the early epidemic by contact tracing.

The distancing and then eventual shutdown we are now in is what eventually happens with a pandemic when we are always running to catch up.

We are, however, able to bring this epidemic under control, at least for a period of time. We can see this in China and in South Korea. To do this, we need Herculean efforts of social distancing and the quarantining of individuals when they’re infected — on their own or in a family unit — for 7–14 days to break transmission chains so that you don’t get as much transmission in the community and, therefore, directly affect the proportion of people that can become seriously ill so this is in a range that’s manageable by healthcare systems.

So we know that we what we’re doing in Europe, the U.K., and across much of the world has the potential to turn our epidemics into where China and South Korea and southeast Asia have successfully — for now — got to.

Now, however, we need to start thinking about maintaining the speed of thinking and action into what we do next.

The sharing of data is absolutely important, as well.

Normally, the publication process in science is very slow. In this pandemic, we’ve noticed, probably for the first time ever in an outbreak, that sharing happens through these sorts of interviews, through social media, such as Twitter, and through using scientific preprint servers.

So people, this time, have really led by example. When they have new data, they have, clearly, to submit it to the scientific peer review process because that’s the accepted way to assess the science, but while that’s going on, they also deposit the papers, unreviewed, on preprint service for rapid and free access. You need to be careful to distill these rapid publications, using your judgment to distinguish the good from the bad, though.

The sharing of clinical information and sharing of epidemiological information are also crucial, and the use of these to synthesize a decision-making and policy framework is important at the national and international levels.

MNT: We have covered quite a few things on MNT that have come from preprint servers. Under normal circumstances, we would only cover peer reviewed research. As an expert, do you think it is okay for people to look at studies on preprint servers when they are published?

Prof. Paul Kellam: It absolutely is.

You’re right that you need to think that this is unfiltered, non-peer reviewed, and, therefore, it’s just put out exactly as it is. I also realize that all my papers have been improved during the peer review process, as well.

What is important is that scientists who are consuming the data — junior and senior scientists alike — are all producers of papers and, in some cases, peer reviewers themselves. So when I read a preprint server paper, I tend to read them from the point of view of: Well, as this is not peer reviewed, if I were reviewing it, what would I be happy about, and what would I be unhappy about?

In a rapidly growing pandemic and with a new virus pathogen, I will look to see if I can cross-validate new preprint information with other information that comes out. And so, you end up making your own synthesis of the information, knowing that it has the potential to have some errors in it.

Generally, you try to look at the quality of the science and the quality of the labs and the people who are doing it and make a judgment call.

MNT: Do you think that most of the studies that have been coming out live as the pandemic unfolds are very good quality?

Prof. Paul Kellam: Perhaps, but I’ve got a selective reading list in that I know what I’m looking for, and I know the sort of groups that I’m looking to be publishing, and I go to their publications. There are some fantastic coronavirus groups in the world, some fantastic vaccine and antibody groups, fantastic structural biology groups, and epidemiology and modeling groups.

They are high quality because they’re on the cutting edge, they have all the reagents, they have deep experience and understanding, and they are of the mindset to put their papers on preprint servers first.

So in a way, it’s a very self-selecting group, which is, I guess, the right way to operate in a crisis to get timely information out publicly.

And one way to judge and filter that I use is study size. If you’re doing a clinical study, or if you’re reporting on clinical parameters and outcomes, and you only report on two individuals in the study, then it is interesting, but I worry about small numbers. In contrast, when you have a detailed clinical study of 79,000 individuals, such as the Chinese CDC [Center for Disease Control and Prevention] description of COVID-19, then you are on safer ground.

“But the most overriding feeling is one I would call fear. It is not a paralyzing fear but the knowledge that this is really serious because of the extent of the infection and because of the amount of serious illness and deaths.”

Of course, there is a danger that you miss important information that is there in a smaller study, but if it is solid, it should reappear in bigger studies.

MNT: And as a scientist, how are you finding the situation? How’s your team dealing with it?

Prof. Paul Kellam: It is exhausting, but fortunately, my team and family are so far well. But the most overriding feeling is one I would call fear.

It is not a paralyzing fear but the knowledge that this is really serious because of the extent of the infection and because of the amount of serious illness and deaths.

Because the virus is a pandemic, infecting all of the world, probably in multiple waves, even a small percent or fraction of a percent of deaths per infection ends up growing to a very big number of people. And that is the most sad and worrying thing to me.

It is a sense of foreboding of just how bad this is, balanced against the fact that we can do things to slow it down, but they have profound effects on people’s lives and countries’ economies, as we are seeing.

The fear is tempered by the fact that there are logical things that we are and should be doing. These include vaccines, prophylaxis with antibodies, developing antiviral drugs, and understanding how we can use existing medicines to help people who are seriously ill have a better chance of survival.

But all of those things take time, and the process of clinical development — normally very careful, linear, risk averse, and regulated for safety as you would expect — is slow when there’s this magnitude of human disease.

So now, back to speed again. We need to be really nimble, do the things that are necessary to have, but not do all of the things that are nice to have in order to make effective treatments and preventives available to large numbers of people quickly and safely, wherever they are in the world.

Read the rest of our interview with Prof. Kellam in Part 2.

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