by Buck Institute
August 6, 2020 . BLOG
What the experts are saying: Part 3 of our biggest takeaways from our COVID-19 webinars
Since the COVID-19 pandemic began, the Buck has been gathering evidence-based opinions and information from top researchers and thinkers about the science aimed at bringing it to an end. What are the biggest takeaways so far? How close are we to getting back to normal? Everyone, from molecular biologists and epidemiologists to clinicians and public health experts, has been remarkably consistent on a few key points. Don’t have time to listen to eleven hour-long conversations? No problem! We’ve assembled the highlights from these webinars in a 4-part series. This is the third in our series. You can access the first, about research into the virus itself, here, and the second, about public health measures, here
Who’s at risk and how should they protect themselves?
It’s not just a flu:
John Newman, Assistant Professor at the Buck and Practicing Geriatrician: A lot of people who get this die and a lot of people who get it who survive will be disabled, and we should talk more about that. So the people who die are just the tip of the iceberg of how this affects us.
Age is just a number, but a really important one:
Matt Willis, Marin County Public Health Officer: The population above age 65 make up about 25% of our population as a whole, but only about 15% of our cases, but they’re about 30% of our hospitalizations. And all of our deaths, of our 17 deaths, are in people above age 65.
Robert Gallo, Co-founder & Director, Institute of Human Virology at the University of Maryland School of Medicine: The average age in Northern Italy was 81, average. So every time somebody 75 died you got some older people dying. Now, you can say there are a lot of old people in Northern Italy, and there are, but I think that’s really a telling thing.
Other numbers matter, too:
Eric Verdin, President and CEO of the Buck Institute: It turns out that obesity is also a really high risk factor for complications. And so are a number of the chronic conditions that we have known for a long time to be associated with aging. And these are heart disease, heart attacks, stroke, cancer survivors, type 2 diabetes, and chronic obstructive pulmonary disease. So this whole group of conditions we know is associated with aging, but some people can actually get them earlier. It turns out that the people who develop these complications early are also at increased risk for COVID-19.
Kevin Tracey, President and CEO, Feinstein Institutes for Medical Research: We showed, clearly, the risk of hypertension, morbid obesity, and diabetes, the risk of age, and we showed the dangers of this disease in a separate study to the kidneys and how important acute kidney injury is to the pathogenesis of this disease
Warner Greene, Director of the Gladstone Center for HIV Cure Research: Hypertension, diabetes, obesity, there are a number of risk factors, as well as lung disease. I think all of this is telling us that there is a significant endothelial function… an endothelial property that all of these diseases damage or affect the endothelium
Melanie Ott, Director of the Gladstone Institute of Virology: Fat is actually a dependency factor, or can be, supporting the virus. It’s also a huge energy bowl, where the virus can access energy for its own replication.
Chromosomes seem to matter, too, but we’re not sure how:
MO: Thinking about the immune system and hormones, we know that women, in general, might have a stronger immune system also because of their pregnancy, you know, and the need to protect the baby. But they, also, we know, have the stronger tendency to have autoimmune diseases, so the tradeoff might be that you have a stronger immune system, but, also, maybe, more propensity for the immune system to overreact.
The river of drug information is fast-moving and turbulent, but there are a few key takeaways:
(1) Don’t doctor yourself
EV: . [Supplements ] at minor doses, they will almost certainly not hurt you. If you’re considering taking them at high doses, I urge caution because at high doses, some of these supplements can have untoward effects. And so you want to make sure that you’re helping yourself, not actually making it worse. And for any of these supplements that emerge as potentially promising, I can guarantee you that clinical trials will be conducted. And, personally, I would resist taking them at high doses until the evidence is there, because we know the potential for harm is truly there, as well.
MO: I would say that it’s very important before stopping any medication because you become concerned or panic, I think the important thing is really to work with your doctor, discuss this with your doctor, and if there is any indication for a switch, do this very slowly.
(2) Some drugs you should avoid
JN: Dextromethorphan is a commonly used cough suppressant. It’s in a lot of over-the-counter medicines. I use it myself when I get sick if I had a cough because it works. It’s not a great drug for older people to take, though. It’s actually a drug that I would generally steer older people away from,
Nevan Krogan, Director of the Quantitative Biosciences Institute at UCSF: There’s other implications here with dextromethorphan. This is a compound of pretty much every cough suppressant that’s out there in the market right now. And, obviously, that’s very ironic because, you know, coughing is one of the major symptoms for COVID-19. We’re not saying that this drug is going to increase infection in people… But we felt the need to try to, as responsibly as possible, report this very interesting connection to the public.
(3) Wait till the dust (and data) settles
MW: Hydroxychloroquine, the medicine that doesn’t do any good at all, it turns out, and for a while it was recommended as something people should use. Ibuprofen. ‘Avoid ibuprofen.’ That was the message. ‘Stay away from ibuprofen.’ That’s changed. So I think we need to take some of these… when we have these early… early suggestions of one thing or another, really, you know, let the dust settle a little bit around that before we get too excited about it.
KT: Dexamethasone or Decadron, it’s a lot more potent than prednisone, it’s one of the more powerful steroids we have in the armamentarium. There’ve been lots of studies of steroids for pulmonary inflammation in the last 30 years, many of which I knew quite well. And, you know, what ends up happening is it seems like one year steroids are the answer for this problem and two years later they’re not, because of secondary infections, immunosuppression, fungal infections, or sepsis, as a complication. And without seeing all the primary data and understanding more about this, it’s very hard to know the risk-benefit ratio.
Doing a clinical trial considering the use of famotidine [Pepcid] in these hospitalized patients. And we said we would be very interested because, remember there were no drugs for this disease, and this is one that many people were taking anyway. So that started a pretty big trial for us that we’ve since enrolled about 230 patients. And as of today, we’re still looking at the data, fingers crossed.
There’s hope on the horizon:
Sue Desmond-Hellmann, Former Chief Executive Officer, Bill & Melinda Gates Foundation: The other thing I’m really positive about is the monoclonal antibodies. Now, we haven’t talked a lot about it, but Operation Warp Speed granted Regeneron, one of the big drug companies, a grant to advance their monoclonal antibody.
WG: I think that if we had combinations of antiviral drugs that acted in a synergistic manner and we could give those drugs early in the course of infection, then such treatments would be highly effective. Indeed, one could even think about using certain types of drugs that were exceedingly safe as prophylactics.
EV: Remdesivir was generated to fight another virus, Ebola.... It turns out that Remdesivir actually works on a key coronavirus protein, the polymerase, which is the enzyme that the virus uses to replicate its own RNA.
MO: Remdesivir is a drug that many have watched very closely to see how it does against the virus.. But at least there is some hope here, and we are… we’re certainly, you know, excited to see the full extent of the… of the clinical data.
KT: With Gilead, we looked at their antiviral drug, Remdesivir. And the question there was does administering this nucleotide-based drug intravenously to patients who are in the hospital, does it shorten the hospital stay or improve mortality?... In those patients receiving Remdesivir, Gilead recently reported that there was benefit in shortening hospital stay, but they had not… the last data I’ve seen, anyways, they had not achieved statistical significance on 30-day, all-cause mortality. But that drug is now recommended by most in the treatment paradigm for COVID. The big question is if we, or anyone, could give the drug earlier to people who were less sick, would it be even more beneficial?
SDH: Remdesivir is made by Gilead, and Gilead is a company that understands how to do what you call tiered pricing. So they, in their HIV and hepatitis drugs, have used this before. So it is possible to go to generic or low-cost manufacturers in India and other countries to have an additional supply made, and to have differential pricing for low income countries.
WG: Remdesivir is only administered intravenously…what you would really like to be doing is getting Remdesivir before people ever come to the hospital in the first place, when the virus is in control of the pathology…if they could come up with an aerosolized form of Remdesivir, or a subcutaneously administered form of Remdesivir, that would be incredibly valuable, because you could use that as an outpatient
Maybe we can cure cancer and the common cold in the meantime?
NK: if you take a bigger step back, we’re also using these approaches on a variety of other diseases, like cancer, and neurodegenerative disease, and heart disease. You actually see amazing commonality there, as well. It’s the same genes being hijacked by HIV that are being mutated in cancer. It’s the same genes being mutated in Parkinson’s that are being hijacked by Zika. Our approach allows us to scan across these diseases and find these commonalities. So then it’s not such a big surprise in my mind, well, an anticancer drug could be used to fight a virus or vice versa.
WG: Once it gets into what’s called the late endosome or lysosome, that’s where it fuses. We’re trying to block that fusion step. And that fusion domain is conserved amongst almost all of the coronaviruses. So if we can come up with a fusion inhibitor against SARS-CoV-2, it should be active against the other coronaviruses, as well.
Our final blog in this series will cover the hot topic of vaccines and immunity. Even with so much still unknown, our experts have a lot of valuable insights into how we can assess immunity and use our understanding to develop one, or many, vaccines quickly.