Evaluating Therapies for COVID-19 and Staying Engaged During a Pandemic

Segment description: Erin K. McCreary, PharmD, BCPS, BCIDP, infectious diseases clinical pharmacist at the University of Pittsburgh Medical Center, discusses emerging literature on potential therapies COVID-19 and how the infectious disease community can work together during this pandemic.

Interview transcript: modified slightly for readability

Contagion®: Thanks for joining us for another Contagion® coronavirus video. Today I'm joined by Dr. Erin McCreary who collaborated with Dr. Jason Pogue on behalf of the Society of infectious Diseases Pharmacists to put together a review of early and emerging options for treating COVID-10. The review was published in Open Forum Infectious Diseases and will be summarized in an article on Contagion®. Dr. McCreary, thanks for joining me. Why don't we just jump right in and talk about what we know about appropriate management of treating patients with COVID-19?

McCreary: Thanks, Michaela, thanks for having me. And thanks for everything honestly, that the Contagion® team is doing. You guys are doing an exceptional job keeping up with all this. We know that it's a lot and that is partially what motivated us to start writing this article. You guys actually reached out and said we need to start making sense of all the data out there and we couldn't have agreed more.

I think the most important thing to emphasize is that there is no antiviral agent proven effective for the treatment of COVID-19. Supportive care remains our standard of care, and that includes oxygenation most importantly, and then everything else involved. For appropriate management of patients right now, one of the best things to emphasize is just clear team communication and protecting your healthcare workers as well as taking care of your patient.

So take the time to put on your PPE. Over communicate with who's doing what on the team to manage these patients and throughout your health systems or your institutions. This is a time more than ever, to appreciate your laboratory team and your infection preventionist; they are just doing amazing work around the clock as is everyone. Aside from all of that though, the best way we can treat patients with COVID-19—both now and what we need to learn for the future— is to enroll them in randomized controlled trials. The control piece is critical because we have no idea if any of these therapies help. The worst-case scenario is that some of these therapies that we're experimenting with may hurt the patient.

It's our responsibility to our patients—and honestly to the scientific community—to answer those questions of what might hurt, what might help as robustly as possible. We also appreciate, though that not every patient is able to be enrolled in a clinical trial. If that's the case, we understand that there's this overwhelming human desire to do something. That's why people are trying experimental therapies. But none of these agents have been proven effective. We must critically evaluate literature as it emerges and make the safest decisions possible for our patients.

Contagion®: While none of the therapies are approved for treating COVID-19. I know that there are a lot of therapies that are being reported to show promise in treating these patients. So what are some of these therapies that you feature in your article?

McCreary: Yeah, that's a great question. That's where we were kind of teasing into how do we cipher through all the data that's available and, and make the safest possible decision for our patients? I think the most important thing to anchor on right now is what you said. We have no approved therapy; we don't know that any of these drugs work. None of them are proven to be effective for COVID-19. The second thing we need to remember is that throwing the kitchen sink at patients really hinders our ability to tease out on the back end what may or may not have been effective. More importantly what may have caused patients harm.

So caution in moving forward with this, but of all of the proposed antivirals and immunotherapies that are out there right now, No. 1, enrolling a patient in a remdesivir trial, if possible. They just switched from a compassionate use program to an expanded access program. As data comes out, and as we learn how to enroll patients in the expanded access, that's prudent; that makes sense to try to get that patient in that trial or get remdesivir expanded access, speaking just to the United States.

The possible benefit, and again, I'm not saying there's a benefit, but with what we know about hydroxychloroquine, the potential antiviral activity for a short course of therapy at this time that may outweigh the risks. But that's a discussion for each patient and for each treatment team.

The toxicities and the drug interactions of chloroquine, lopinavir-ritonavir, ribavirin, and other agents that have been suggested at this time. The toxicities of those agents seem to outweigh any possible benefit and we don't know that those can be recommended. Then finally, oseltamivir should be used for patients with influenza.

Oseltamivir should not be used for the treatment of COVID-19. All of these drugs are not benign. They all have side effects which include QTc prolongation, cardiac toxicities outside of QTc prolongation, hepatic toxicity, and then gastrointestinal toxicities like diarrhea. Those are all also manifestations of COVID-19 disease. So, again, it's very important to tease these things out and take a lot of thought and pause before giving your patients potential antivirals. The other thing that has a lot of discussion right now is long term consequences of IL-6 inhibitors, and/or use of corticosteroids. Those are unknown. I believe the role for using those agents right now is in the context of a clinical trial.

Contagion®: Thanks so much for summarizing all of that for us. It seems like this situation is ever evolving. Information is coming out left and right day and night. What is your advice for how infectious diseases clinicians can keep up with all the news and the developments while responding to a pandemic?

McCreary: Like and follow Contagion®. I promise they didn't plug me to say that, but you guys really are amazing. Your email announcements and everything you're posting on your website is credible. It's resourceful. Contagion® is a great resource for people.

Twitter. Obviously, I love Twitter, but it's a constant news feed full of really amazing people. It's full of people who are trying to help and who are citing articles. I scroll through Twitter every day and then and email myself articles and read them when I have time throughout the day and try to try to carve out, time to evaluate COVID-19 literature every day. Every day you fall a day behind because so many things are coming out so quickly. I've never seen anything like it.

One of my attending physicians worked with a librarian to come up with a PubMed search, which now that I'm thinking about this we should include that search criteria, because people can copy and paste that into PubMed, and sign up for daily alerts for any article published that falls within that search context. I'm happy to share that out. Thanks to Ghady Haidar who's one of my attendings who actually thought of doing that.

I've been getting that report every day to stay up to literature that's published. Back to Twitter a bit though... there's a lot of amazing people putting out a lot of helpful things. But there are also a lot of people who put inaccurate information on social media.

So please take what you see on the internet with a grain of salt and validate anything you read with the data. Know where that statement came from. Don't just repeat a statement that you hear. SIDP, the Society of Infectious Diseases Pharmacists is working on drug literature review and updates as a pertinent chunk of information comes out. We released YouTube videos earlier this week that address the pharmacotherapy options out there right now that have reasonable discussion around them. The people who made those videos are absolutely incredible. They turn that around very quickly, and they're staying on top of it. Check out those videos. They're a great resource.

I know we're all absolutely overloaded with emails right now. But clinicians and researchers should carefully read any COVID-19 related email that are coming in from your institution, so you are aware of your local policies and procedures and protocols. Because again, we don't know. We are doing the best we can, and you need to know what your institution is saying so that you follow those guidelines and work on your team at your institution. I'll say group texts are saving my life right now as we all keep up with each other and try to keep each other up to date try and share ideas. Reach out to your colleagues. Joining professional organizations would be a last thing I think ID clinicians could consider during this time, if you're not involved in IDSA, SHEA, PIDS, SIDP, and others right now, it might be a good time to join. There's a lot of community information sharing; a lot of email, listservs, websites, email blasts, those are good ways to stay up to date as well.

Contagion®: So in addition to just staying up to date, how can infectious disease clinicians work together within the community in order to stay strong and work through these difficult times together?

McCreary: Yeah, Michaela, I think that's the most important question you've asked. Honestly, this is the most important thing we can we can continue to focus on other than taking care of our patients right now. Be kind to one another. It's easy. It's simple. Just be kind to people right now. Everyone's doing a lot.

The New England Journal of Medicine published a paper a few days ago, and it discusses fair allocation of medical resources. So what would you have to do if you had to decide between 2 patients to get a ventilator if you only had 1? I'll say reading that paper is the second thing that brought me to tears during this.

The first thing was when I started having colleagues across the country, tell me about the young, healthy patients with no comorbidities. We're learning a lot about this disease as it progresses. And we know that some of percentage of patients get critically ill and that includes young patients, which I think was underappreciated at the beginning of this pandemic. It's tough. And so those are the 2 things that really hit me hard this week.

A week ago, one of my mentors sent me this really amazing article that a business had put out about leadership during crisis situations. There were 2 phrases in there that really resonated with me. I just want to share them kind of with the scientific community as well. The first one was a phrase of deliberate calm. Leaders and health care workers and families and anyone in this right now... deliberate calm is essentially the ability to detach from a fraught situation, or a really reactive situation, and then think clearly about how you're going to navigate your way through it. So I think everyone in the ID community needs to display a sense of deliberate calm to help each other make the best decisions we can as safe as we possibly can.

But different things are hitting different people hard every day. We all went into this business to take care of patients. When that's what gets you going in the morning and your sole purpose and then you have to make a decision on who gets a ventilator. I really can't even imagine being in that position. So demonstrate empathy to your family right now, to your friends, to your colleagues, to people you don't even know but that are in the medical community doing the best they can. I think a simple "how are you doing?" text goes a really long way and is getting a lot of us through.

The second one was a concept of bounded optimism. That is essentially confidence and enjoy but with realism, right? Pause, assess, and then act on things. Use your teams like you've never used them before. Collaborate, be transparent with people about what's happening as much as you can share information out as possible. And overall, effectively communicate. I think that's been a theme throughout this.

Then the last thing that ID community can do is share what you're learning with the world. We need to know. We need to learn from each other like we never have before. But share what you're doing and what you're learning in a peer reviewed and critically analyzed fashion. Like when Jason and I wrote that article we sent it to 6 or 7 people to peer review and they were incredible, and they turned around thoughtful, intentional comments for us very, very quickly. But as quickly as that paper got out, it was thoroughly peer reviewed.

Social media has united the world like never before. Information spreads very quickly. One wrong message here could literally cost people their lives. We are all trying to do everything we can to stop this and cure this. But we owe it to our patients and to each other to be intentional, and to take care of each other too.

Contagion®: Thanks so much for those helpful tips and for sharing your thoughts with my audience and me. It's always a pleasure to speak with you, Dr. McCreary. You're doing great work, so keep it up. You can keep up with SIDP on their website. Thanks so much to everyone, and especially to Dr. McCreary for this great interview.

Thanks, Michaela. Thank you for your time.

>>Read: COVID-19 Treatment: Updates March 19-24, 2020 by Erin K. McCreary, PharmD, BCPS, BCIDP, and Jason M. Pogue, PharmD, BCPS, BCIDP

PubMed resources provided by Ghady Haidar:

PubMed search string (copy and paste into PubMed basic search)

"severe acute respiratory syndrome coronavirus 2"[Supplementary Concept] OR "severe acute respiratory syndrome coronavirus 2"[All Fields] OR "2019 ncov"[All Fields] OR (wuhan[tiab] AND coronavirus[tiab] OR corona virus[tiab]) OR “Covid 19”[all fields] OR "sars cov 2"[All Fields] OR 2019nCoV[All Fields] OR "coronavirus disease 2019"[tiab] OR "corona virus disease 2019"[tiab] OR “ncov 2019”[tiab]

LITCOVID: curated literature hub maintained by the National Library of Medicine

https://www.ncbi.nlm.nih.gov/research/coronavirus/

To create an auto-alert:

https://www.nihlibrary.nih.gov/resources/subject-guides/keeping-current/creating-alerts-pubmed