“If all this new data isn’t understood and interpreted in context, it could lead to some really harmful public policy decisions"

US virologist Dr Angela Rasmussen talks to Tom Ireland about how COVID-19 differs to previous outbreaks she has studied, the danger of press releases and pre-prints being used as data, and the ‘incoherent’ response at the federal level.

Dr Angela Rasmussen is a virologist and associate research scientist at Columbia University's Centre for Infection and Immunity. Her research explores the relationship between host response to infection and disease outcome, a relationship she is now studying in an animal model of COVID-19.

Tell me about some of the COVID projects that you've been involved with or that you're collaborating on.

I just found out I got funding to look at host responses in a rhesus monkey model experimentally infected with this coronavirus. The goal is to look at gene expression over the course of the infection, and identify specific host responses to both the infection and the disease that they develop.

For me, some of the most interesting questions are about the types of disease that this causes – why does one person have very mild disease where they may not even notice symptoms of it, and another gets this very distinctive pneumonia, with these unusual symptoms, like the ‘ground-glass’ opacity that people have observed in the lungs of severe COVID patients? Even some of the mild symptoms are very unusual compared to a lot of other respiratory diseases, like the loss of sense of smell. I think those questions are incredibly interesting from a host response perspective.

I think long term, research is going to try to look at the effects of host genetics and host environment in determining how severe the disease is.

Can you explain what how things have changed for you since the pandemic began?

I did work on emerging diseases prior to this, primarily on Ebola. I've also studied MERS coronavirus, H7N9 influenza and other types of emerging influenzas. What's very unusual about this is trying to do the type of research that I do from home, not from a lab.

The good news is that because of most of it has to be done in a high containment lab by collaborators, I'm used to having other people do a lot of the lab work. But working completely from home, and not being able to go in and talk to my university administrators about getting grants and things like that has proved to be pretty challenging.

Are those who study disease outbreaks always primed to change their research focus very quickly when a new disease emerges?

Not really – I've never been in a situation like this one where all of my non-SARS-CoV-2 work has taken a backseat. With MERS coronavirus we did put some other work on hold to pivot our efforts towards getting animal studies out as quickly as possible, but that was over a period of about a year and the rest of our work didn't have to completely stop.

I think one of the biggest challenges for everybody in science is that the only work that anybody can access a lab for right now is SARS-CoV-2 work. All other work has been deemed non-necessary.

Why do you think this virus has become so widespread and deadly compared to MERS and SARS?

This one really seems to be a lot more transmissible from person to person, and I've seen several hypotheses. For example, the spike protein seems to be very good at finding ways to bind to the cellular receptor for the virus, and people have proposed that this higher binding affinity could make the virus more capable of infecting cells.

There is another feature in the spike protein called the furin cleavage site that was present in MERS but not SARS which has also been associated with pathogenicity. It's possible that it allows the virus to spread from cell to cell or to infect different types of cells in the body more easily. So that's another hypothesis that has been offered and it could be a combination of those two things.

I've seen that you've been very active online and in the press trying to make sense of other data that is coming out. Why do you feel that’s important to do alongside your research?

What is unusual in this situation is that the data is coming out so much faster than it did for any virus emergencies I’ve seen before in my career. One reason is widespread and affordable sequencing, and the other is the existence of pre-print servers. Thousands of viral genomes have been uploaded to online strain databases and pre-prints are coming out so fast that I can't keep up with all of them.

The pace at which data is coming out is fantastic but there have also been some studies that have either been just not great, or misinterpreted. And I see a lot of problems with press reports and press releases being treated as if they are data.

I don't want this information not to come out – but it needs to be interpreted very carefully within context. We can’t make assumptions, for example, that people are having reactivations of their viral infections because we don't have any good data that says that they do.

We certainly can’t say based on preliminary serology results that a lot more people have been exposed than we think and therefore it's not as big of a risk to open up society. If these things aren't understood in their proper context, they could form the basis for some really harmful public policy decisions.

Do you feel the research sector as a whole is responding well?

Normally because of the funding climate, science can be extremely competitive. Collaboration is essential to what I do and always has been, but there's certainly much more of a community spirit among scientists – it's been great to see how many of my colleagues are banding together.

That said, I think everybody is getting real sick of Zoom and Skype meetings and being on the phone all day and I don't know that I appreciated before how exhausting that is. I think that we still have a way to go to figure that side out.

In terms of funding agencies, it’s been sort of chaotic as they understandably are already depleted in our current administration.

I think a lot of scientists who are not in the infectious diseases space are now pivoting their research to COVID research, which is fine. But I'm very curious to see how this this first series of grant submissions is going to go, because all the people who are working on COVID don't really have time to sit down and write a big grant application. The people who don't have anything to do because their research programmes have been shut down, do.

A couple of other very interesting observations have emerged from this that I think really highlight persistent inequities and problems within our biomedical research in the United States. One of them is that a few different journal editors have now observed that the vast majority of submissions they are receiving about COVID are authored primarily by men. Which could be likely to do with the fact that women, when working from home, are often disproportionately tasked with a lot of domestic jobs, home-schooling their kids, keeping their kids out of trouble, cleaning, and so forth.

And I'd be very curious to see if that is also reflected in the grants that are funded. And I would imagine that those types of inequities are also in place for people who are from different socioeconomic backgrounds, and people who are disabled, and so forth.

And at the federal level?

I'm not a policy person, but my opinion is that the president has not led a coherent or evidence based-response on behalf of our larger federal Government. While there are certainly highly qualified very effective experts like Dr Fauci involved in the response, the overall federal response has been, in my opinion – just as an American citizen and a voter – disastrous, and complete chaos. I am not shy about saying that I do think that the delay in response, as still delays in getting testing capacity getting up to where it's needed, I think overall it's really going to be detrimental to public health overall in the United States as well as abroad.

Dr Angela Rasmussen is an associate research scientist at Columbia University's Centre for Infection and Immunity. Her research explores the relationship between host response to infection and disease outcome, and she is currently studying this in an animal model of COVID-19.