Written By: Isaiah Hazelwood, Science Staff Writer

On March 11, 2020, the World Health Organization declared COVID-19 a pandemic, and our lives changed dramatically as we moved to remote work and online classes. Governments declared lockdowns and mandated masks, and the virus continued to spread despite our best efforts. One year later, the pandemic is as large as ever and we continue in protective isolation, though the rollout of new vaccines promises a slow return to safety and normalcy. To mark this date, the Trinity Times presents interviews with University of Toronto’s experts on COVID-19. Dr. Eleanor Fish is a Professor and Associate Chair of International Collaborations & Initiatives in U of T’s Department of Immunology. Her research focuses on broad spectrum antivirals, which are antiviral medications effective against many viruses. She studies cytokines such as interferons and chemokines, biological molecules involved in immune responses. Our interview with her has been edited for clarity and length.

Prior to COVID-19, what were your general areas of research? How did those change in early 2020 when the pandemic began?

My main focus in the past few years has been understanding host-pathogen interactions in viral infections. While each virus has unique characteristics, they all have some common interactions with the organism they infect and common outcomes in terms of the immune response to infection. Instead of focusing on one virus, I’ve worked with many different viruses that threaten global health, like SARS, Ebola, influenza, and now SARS-CoV-2. From these, I consider how broad spectrum antivirals, which disrupt common interactions or elicit common immune responses, may protect against any and all viruses.

Once I learnt of the SARS-CoV-2 outbreak in China, in late December 2019, I contacted colleagues in China and connected with a clinician at a hospital in Wuhan, who was caring for SARS-CoV-2 patients. We established a collaboration to evaluate the therapeutic potential of an inhaled interferon alpha, for the treatment of this infection in hospitalized cases. I have decades of experience conducting research on interferons and consider interferon alpha and beta to be the ideal broad spectrum antivirals. Notably, interferons have been approved for clinical use, just not for acute virus infections.

I saw your collaborative research in Wuhan resulted in papers published in May and December 2020. How has research been since then?

In agreement with our encouraging results from SARS patients in Toronto and Ebola patients in Guinea, we saw that interferon treatment accelerated viral clearance from the airways in COVID-19 cases. This was an exploratory study, not the gold-standard randomized, controlled trial needed to get drug approval, but about 50 other ongoing or completed studies suggest that early treatment with an interferon, either alpha or beta, either nasal drops, inhaled, or subcutaneous injection, have therapeutic benefit. In China, a study of 3,000 healthcare workers found nasal administration of interferon alpha protected them against infection compared to a control cohort. In Cuba, hospitalized COVID-19 patients treated with interferons showed faster viral clearance and they spent less time in the hospital. I’m involved in a study in Santiago, Chile, right now, where we’re looking at using interferon to treat non-hospitalized individuals in the early stages of their infection, to prevent hospitalization, and also to treat post-exposure contacts, who were near someone who tested positive for the virus. With the intent to protect these contacts from infection. All this to say that the Wuhan findings sparked many other trials around the globe examining the therapeutic potential of interferons.

Since last fall, we’ve seen a lot of vaccines for COVID-19 being approved. Is developing treatments for the virus still as important as it was before?

Absolutely. We need to keep in mind this is a global pandemic: while Canada is planning to vaccinate all willing adults by the end of September, there are many countries around the globe where infection will continue unchecked. In resource limited countries, access to vaccines is going to be challenging. Additionally, there will always be those who, for whatever reason, cannot or will not take the vaccine, so we will need therapeutic treatments.

We’ve also seen the virus mutate in the variants of concern. While we hope the current vaccines will still be effective, broad spectrum antivirals will maintain efficacy, as they target essential processes common to all viruses. While we might need to tweak vaccines as the virus changes, broad spectrum antivirals will maintain their therapeutic effectiveness, particularly when the virus becomes more contagious and we need time to vaccinate more people to reach herd immunity.

If you had to guess, when will Canadians see interferons as a treatment?

A colleague of mine, Jordan Feld, recently published stage two clinical trial results that showed interferon lambda treatment in early infection accelerated viral clearance, particularly in those with high viral loads. He’s going to start a phase three clinical trial soon, with the hope that the treatment may be approved if the results are reproducible. There’s a similar phase three clinical trial in Santiago, Chile, I’m involved in, and there’s another phase three study in the UK from the University of Southampton and a company called Synairgen. If outcomes from these trials demonstrate that early treatment with interferons accelerates viral clearance and limits transmission, we might see emergency approval from the FDA and Health Canada, hopefully in 2021.

Until we’re all vaccinated or have good treatments for COVID-19, what would you recommend for people to do to protect themselves?

We all have personal responsibility with limiting the virus’s spread, so as you’ve heard we all should be distancing, masking, and hand-washing. We also need government directed efforts to limit the spread, like widespread random testing, rapid contact tracing, and responsive lockdowns. Australia and New Zealand managed to not only flatten the curve but also bring down case numbers dramatically, and it’s because of how responsive their governments were: as soon as there’s a modest increase in case numbers they declare a short three or five day lockdown, a circuit breaker, trace the outbreak, isolate those cases and contacts, and that stops the spread. Here in Ontario and Canada our testing and contact tracing is not as good as it could be, and perhaps we’ve been too fast to lift restrictions. If we combine our personal responsibilities with responsive government action, then containing the community spread of infection is possible.

How do you expect the new COVID-19 mutants and variants will affect the pandemic?

Let me preface this by saying I don’t have a crystal ball to predict the future, and nobody else has one either! While there are many immunologists and virologists with considerable expertise, it is nigh on impossible to predict how this ongoing pandemic will unfold. Usually, viruses mutate over time to be more contagious and less lethal: viruses spread more if they can access more people, and they spread less if their host dies. In a normal setting, the dominant variant is the one which is more transmissible and less lethal. Of course, this isn’t a normal setting, we have lockdowns so spread happens in hiccups, outbreaks, and waves, but I do suspect that over time COVID-19 will become a less severe disease, like other circulating coronaviruses which generally cause mild, cold-like symptoms that don’t require hospitalization. Vaccines will likely eliminate death and severe disease – again resulting in those that do become infected having a mild respiratory disease that likely will not require hospitalization.

Going beyond the pandemic, how do you expect the last few years are going to change scientists’ jobs, immunology and scientific research as a whole?

I want to switch this question on its head: how has the pandemic changed the public’s interaction with scientists and scientific research? In general, the public are much more appreciative of science and the impact science has had on our rapid understanding of the virus, the development of tests, health recommendations, emerging therapeutics, and the really rapid development of vaccines. Hopefully, the public and governments now have a greater appreciation of the benefits scientific research offers to deal with a pandemic, and this will lead to investment in more resources to support scientific research.

As immunologists, we’ve learned a lot about this pathogen and the clinical disease, and we’re already seeing scientists across Canada committed to continuing to study viral pathogens and host-pathogen interactions. If there is continuing investment in research and infrastructure after the pandemic, we’ll be much better prepared for whatever the next outbreak, epidemic or pandemic is.

What advice would you give to students wanting to pursue a career like yours?

My career’s been an amazing journey; I started with very basic fundamental research and moved all the into clinical trials. In any biomedical research, you need to be creative enough to spot a hidden opportunity, take an idea, and run with it. Take risks. You need to keep a broad perspective and be resilient, because you won’t always succeed. There are always challenges, and if you take each failed grant application or rejected publication personally, you will never move forward. But once you’ve learned to be resilient and be creative, it’s a great career. I’ve travelled the globe, I’ve met colleagues from all around the world who have become friends, and I’ve collaborated on things I never would have dreamed of. Twenty years ago, I couldn’t imagine working in Guinea during an Ebola outbreak, I’ve done that and so much more.

It’s also really important to collaborate and share knowledge or expertise. Knowing that, I co-founded the Beyond Sciences Initiative, a not-for-profit international organization that connects science scholars around the globe. It provides opportunities for mentorship, sharing scientific knowledge, and collaboration across the globe. I would urge any student who’s interested in science worldwide or connecting with other scholars around the globe – Kenya, South Africa, Australia, India, South America, Greece, USA, Italy….among some, to check the website (www.beyondsciences.org) and look at our activities. We have an annual free online, live conference: this year more than 1200 registrants from over 90 countries. You can meet your peers, develop professional networks, and benefit from the many initiatives that will support your career.

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