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The Viral Infection and Respiratory Illness Universal Study (VIRUS) is a prospective, cross-sectional, observational study and registry of all eligible adult and pediatric patients who are admitted to a hospital. Marilyn N. Bulloch, PharmD, BCPS, FCCM, was joined by Rahul Kashyap, MD, MBA, at the 2023 Critical Care Congress to discuss the Discovery VIRUS COVID-19 Registry. Dr. Kashyap is an assistant professor and clinical research scientist at Mayo Clinic in Rochester, Minnesota, USA.
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Dr. Bulloch: Hello and welcome to the 2023 Critical Care Congress Edition of the Society of Critical Care Medicine Podcast. I’m your host, Marilyn Bulloch. Today, I am pleased to be joined by Rahul Kashyap, MD, MBA, to discuss the COVID-19 VIRUS Registry. Dr. Kashyap is an assistant professor and clinical research scientist at the Mayo Clinic in Rochester, Minnesota. He’s also the medical director of research at WellSpan Health York Hospital in York, Pennsylvania. Welcome, Dr. Kashyap. Before we start, do you have any disclosures to report?
Dr. Kashyap: I’m happy to be here. VIRUS Registry was funded by a couple of entities, but it was paid through the institution so there are no personal disclosures there.
Dr. Bulloch: Thank you for that. Let’s get started. This is a personal love of mine because I love respiratory viral infections. I think anyone who’s been in healthcare, especially critical care in the last three years, has just been inundated with COVID. Tell us about the background of the VIRUS Registry. Where did it get started? How did it get organized?
Dr. Kashyap: Sure. How much time do we have? The VIRUS Registry, I would say one tweet sent by somebody on the East coast, my mentor and colleague at Mayo Clinic looked at that tweet and said, “Dr. Kashyap, you’re working on something like that. Let’s get together.” That was Dr. Allan Walkey. He sent a tweet that if anybody’s looking for observational studies to initiate nonrandomized clinical trials. That’s it, that changed everything. In the background, we were working on some global common data elements project within SCCM Discovery, it was a little frustrating that we were not ready to launch it and then the virus was coming, so it was a little bit sad. But we had a few things done in the past. Then we just got together, SCCM, Dr. Vishakha Kumar, co-PI Dr. Walkey, and myself. Thanks to SCCM’s Discovery infrastructure, we were able to launch this study in three weeks in March 2020. We have published about it. Dr. Walkey has published it in Critical Care Explorations. I would say: full of passion, hard work, and collaboration, those were three key points for this to be launched in March 2020.
Dr. Bulloch: Three weeks, that sounds impressive. I bet there’s a lot of work that went into those three weeks. How much has it grown since then?
Dr. Kashyap: Since then, I think in the first day or two we had roughly 12 sites signed up, and then we had 10 patient data on day 1. Everybody pitched in and helped from legal, R&D, and so on and so forth. This registry has become the second largest registry of this kind in the world, the largest in North America, more than 326 hospitals from 26 countries, including both adult and pediatric. It’s grown to now enroll 88,000 unique patients, both adult and pediatric. More than that, it’s a story of thousands of people during the time of the pandemic working to do manual data collection, data automation, and many different things. Academically, productively, roughly 35 or 36 publications have been published in the last 37 months.
Dr. Bulloch: Wow. Tell me about some of these publications. What are some of the things that your group is looking at with the registry?
Dr. Kashyap: The registry was designed that, can we look at the operational data, can we look at these data to answer some of the pressing questions? The first few papers were just talking about the guiding principles of how to establish a registry. Dr. Walkey is the primary author on that. We looked at multiple different things. What is a practice variation across the hospital? Then we found that it made it a huge splash at the time, Dr. Domecq wrote that paper as a first author, that everything, keeping aside which hospital you go to, and we didn’t reveal any hospital’s name and so on and so forth, that may determine your outcome of COVID-19.
When we are talking about early days, no vaccine, we did not know what worked, what didn’t work, many different variants and things like that as well, so it should be taken with a grain of salt. Then everything under the sun, I’m looking at treating its manifestations, looking at the readmission rates, looking at the project management of the registry. We had our hub-and-spoke model, how things could look from a leadership angle. If you go down all the different things like what sort of the oxygenation they required, we looked into pediatric parts, we looked into MIS-C and the patients who come into the ICU, how they’re dealing with it as well. Dr. Denson published on metabolic syndrome that made it to a JAMA Network paper as well, so, anything that we could answer from the limited dataset we had, it was looked and asked for.
We are very, very proud of the fact that, out of these 37 or 38 publications, except the first two papers, each paper is written by a different coauthor. There’s a lot of collaboration and a reward built in for people, and it was truly multiprofessional. We have authors who are not only MDs, but RNs, medical students, PharmDs, and so on and so forth. We are very proud that we were able to live through SCCM’s expectations of being diverse as well. It’s one of our discoveries or flagship projects through those years.
Dr. Bulloch: It sounds like the registry has managed to look into a lot of the pathophysiology and everything like that. One of the things that I know early on you said, we don’t know what to do, we don’t know how to treat these. Has that been something that you’ve been able to capture in your limited dataset?
Dr. Kashyap: Yeah. The registry, if we go into detail on that, we had the buckets of data of demographics of all these patients, chronic medical conditions, other processes of care, what kind of medication they required, what happened with them, organ failure, and so on and so forth, and some vitals as well, lab values and outcomes, ICU and hospital length of the stay, mechanical ventilation duration, discharge disposition, and so on and so forth. What we did is we had a few core ideas where the core team wanted to answer those questions, I would say six or seven. Then, I think, at one point, we had roughly 120 ancillary ideas submitted by the investigators from these 300 hospitals. Out of them, I think 65 got approved. We are still in the process of sending the data and having them work through those things. It gives you the idea that if people joined hands together, even dealing with crisis, and especially during crisis, you can do quite a bit with zero funding in the beginning and then it got funded. It helped the infrastructure at SCCM Discovery and Mayo Clinic and Boston University as well.
Dr. Bulloch: I think you bring up a good point. We faced a time where we couldn’t be like, Oh, this is my research, I’m going to be the star on it. We had to work together. It’s nice to see that that seems to be one of the positive things that has come out of the pandemic that hopefully will continue to remain true. How do people get involved with this, if they haven’t heard about this registry up until now, what do they do? And they said, This is great. I want to participate.
Dr. Kashyap: Absolutely. If you’re listening to this podcast in your car, once you park and go to the hospital or work, check it out. If you just type in SCCM Discovery VIRUS COVID-19 Registry; VIRUS stands for Viral Infection and Respiratory Illness Universal Study. When we designed it, we kept it a little bit timeless, that lets us capture the COVID-19, but it could be open for other viral infections as well. You can very well get involved. We’ll reach out. You can say, Contact us, or if you’re listening to me, you can email me, Dr. Kumar, Dr. Walkey, or just the journal CCM saying, Hey, we’d like to see who can we get in touch with for SCCM Discovery VIRUS Registry. It’s not too late. It’s never too late, it stays open for the existing participating sites. We’re telling them, Hey, can you enroll as many new patients until March 2023? We’ll keep the registry open for a couple of years, then people can still continue to contribute data until December. But any new site is welcome to include data any time. They can do manual data collection. We can provide some automatic data collection opportunities as well. We may talk about what is next after the registry where there’s some opportunity to be part of infrastructure building project, which we are doing now with the collaboration with CURE ID, with the FDA, which we’ll talk about today or maybe in a subsequent version.
Dr. Bulloch: That sounds wonderful. Now, you mentioned before you had over 100 ideas that were submitted but 65 were accepted. It seems like a very difficult job narrowing that down because I’m sure they were all really good ideas. How did you triage or prioritize what you had the bandwidth or just the manpower to be able to look into?
Dr. Kashyap: That’s where SCCM and Discovery come in the picture. Discovery has experience through their projects like CERTAIN, HEMAIR, SARI-PREP, and things like that, where a large number of investigators contribute to data. There are reward systems for people. You’re contributing the data, you always own your own data, you can always get it back and then do whatever you want to do with it. Two, if your data are being used for a collaborative publication and you made it through certain rules, we had the top 5% sites and top 10% sites, you’ll be a main author in the author list as well. You’ll get a chance to add it and then review and approve it. Anybody else’s data, I think we had a rule of 10 minimum, 10 good patients, means a complete dataset, you’ll be a collaborative coauthor. Every single institution can have up to five coauthors from each institution if the data are less. If an institution has 1500 patients, but somebody only has 50, they will still get a coauthorship as well.
In that process, and Discovery has done it for many years now, there was a form they could submit that, I want to seek the data, again, they can seek whole data to ask a primary question. They could submit a nicely designed PICO question, maybe a page-long proposal. Then it went through the core team to review it. Then, what we found, which was sound as well as structurally needed, those proposals got approved quickly. Then we started sending them all de-identified data with all the DUAs and all legal paperwork, without revealing any hospital’s name, for them to utilize it. In some cases, we were able to provide them the statistical support as well. But in most cases, institutions that had resources or investigators were able to analyze the data and write it up, and then managed to get reviewed and approved by the core team or the core members, who got approved by Discovery’s leadership to make sure that we have a good quality check as well as some sort of internal peer review before the manuscript goes up.
Dr. Bulloch: Interesting. Now, a lot has changed in three years. I feel like the COVID that we were dealing with in February, March, April 2020 is very different than the COVID we’re seeing now in a lot of ways. Are there any plans to go back and maybe revisit any of those original questions that you looked into in the early parts of the project?
Dr. Kashyap: One thing is: Is it a good registry? Absolutely. Is it a perfect registry? Probably not. We learn a lot through this process. We learn many things. We learn that, yes, if there are a few committed people and largely motivated people across the world, you can do these things with no funding or zero funding or very minimal funding. Two is that there are limitations for that. Automated data collection would have increased the process. Now, we are much better at manual data collection, prioritizing the data, which we did early enough that we want to have a minimum dataset that we can answer some of these questions as well. We are building capacities through the CURE ID project to see how we can have automatic data collection, we can have the large sum of data dump from vitals, labs, and medications. Nobody’s going in and collecting them manually, they adjust for error and of course it takes a lot of manpower as well. There are some questions we could not answer. First question is early versus late intubation. Our registry was not designed to capture the date and time of intubation. Because of IRB things and de-identification and all, we could not have dates in the registry, so that question could not be answered. But we are looking for ways to see how we can enhance the database with maybe only some few selected sites or dedicated to provide the current data.
Dr. Bulloch: It sounds like you’re making the best of what you have. As someone who loves viral infections, it sounds great. In my own head, I can think of a million different things you could do with it. What have been the implications of it so far?
Dr. Kashyap: That’s a broad question.
Dr. Bulloch: Intentionally so.
Dr. Kashyap: Absolutely. Yeah. I could take it any direction, but let me put it this way: It has some viral panels, BioFire and other panels’ data as well. I don’t think some questions have been asked specifically from that angle. There’s, I think, one question, working on coinfection, I was aware of in its final stages, looking into those things. We are living in a triple pandemic, so to speak, with COVID-19, then monkeypox, then our usual influenza and RSV in this regard as well.
Dr. Bulloch: Both of those have made big comebacks this year.
Dr. Kashyap: Exactly. I think one of the largest societies, SCCM, as well as through Discovery, has shown that, yes, there are people with their expertise and there’s willingness to collaborate with anybody around the world as well. Now we are collaborating with FDA and WHO and a few others as well, even the Radiological Society of North America is the imaging partner for the registry. We thought we would have it in REDCap, but then we realized that they do it much better than us. It’s all de-identified images and all, American College of Radiology. Implications are that their infrastructure, which is going to get better, we’re working on it, the data coming out of it was able to answer some high-value questions, and there are still many questions unanswered.
We don’t know what happened, what caused and what worked, what did not work properly. We had some idea. Infrastructure like this and a registry like this have created the second layer of investigators who are not just MDs working in the same area. Now, we have seen a crop of young, new, or even any-age investigators, both male and female, and any of the genders, for that matter, across specialties who were able to step up, contribute, and drive the registries field. It was pragmatic. We kept updating and adding things, and that was the beauty of it. That was pretty flexible. So, that is the biggest implication I would see that we have created a next gen of investigators across the spectrum, within the country and outside. That success story needs to go out and be told, and I’m glad that we are doing it today.
Dr. Bulloch: That sounds like it was really both personally and professionally fulfilling for some of those young investigators because when you’re young and you’re just trying to feel your way through, you don’t know how to get started. Then, here you have this major global pandemic, big public health crisis, and you want to contribute that way. It’s almost like this gave them the opportunity to fulfill two big opportunities at once.
Dr. Kashyap: True enough. I will tell you that one of the medical students, she’s a coauthor on 16 or 17 of the manuscripts from the VIRUS COVID-19 registry, she’s a lead and first author of cutaneous manifestation of COVID-19, who was the part of the registry when she was onboarding the sites on REDCap. Onboarding 300 sites in three, four months with 3000-plus people is not an easy task. She contributed what she could at the time. But as she learned PICO, she was able to write it and then get it published as well. There are tons of stories like that. A medical student or nonmedical person able to write a project management paper on the VIRUS COVID Registry, a pharmacist, RN, PhD, MD, and whatnot.
Those are the stories that are personally fulfilling for me and our leadership team as well. I think collaboration is the one thing that made it possible, that everybody says, What can I do to help? Then people pitched in their time. If you imagine that you have 10 patients the first few months in your ICU or hospital, you can’t do much with those 10 patients. The best you can do is write case studies to see what happened with them. But if 100 institution had just 10 patients, now we’re talking about 1000 patients, you can have quite a few hypotheses with PICO questions to answer some of the burning questions during the early phase of the pandemic when we did not know what was happening.
Dr. Bulloch: That’s very true, especially for hospitals with staffing loads and their resources are limited. What impact on clinical care have you seen come out of the registry’s work?
Dr. Kashyap: A couple of things is that, of the data, the evidence is low compared to a randomized controlled trial. But these data and hypotheses gave you an idea to design what it is. I’ll give another example: Now we’re in the process of, and leaders are looking at, drug repurposing, saying, How can we look into these operational data to design pragmatic trials within the U.S. and outside, that any existing treatment that worked really well, can we study it a little bit more in detail? CURE ID and drug repurposing collaboratives are fantastic examples of that, we are looking to have data automation and pragmatic trials like platform-based trials that you can randomize a whole hospital. Data get pulled out automatically and see what worked for them, what did not work for them in this regard. Those implications are huge. It’ll take time for those who come in. We are hoping we could do these things in a timely fashion and be ready for the next pandemic, which is going to happen in our lifetime sooner than we think. I think the implications are to look at data and then design an infrastructure that could be activated in weeks and months.
Dr. Bulloch: I think that’s really important because, as we’ve discussed here at Congress this year, the next pandemic is not a matter of if, but when. If you look at history, they happen quite more often than I think most people realize. To be able to have this structure already in place, we may be able to get boots on the ground and going a lot faster than maybe we were able to with this past pandemic. What do you want to see as your next steps with the registry?
Dr. Kashyap: Our next steps are very clear. We want to make sure what we started with ended on a high note, at least from the COVID-19 perspective. We want to make sure that data collection, which is ongoing, is complete and try to get it as complete as possible. The infrastructure building for data automation, utilizing the queries edge tool through CURE ID, and so on and so forth. Creating awareness among institutions who could not join when, it’s totally understandable, the hospitals were understaffed to take care of patients, forget about research. So, those who could not and think that now that we might be out of the acute crisis can join as well and become the node of this network to get reactivated if and when needed. That’s one side of the approach.
Two is, now participating institutions and other investigators know that now they could submit their idea and others could work on those ideas, utilize the infrastructure, the platforms, and things like that. The VIRUS Registry is one example of collaboration but, God forbid, the next flu pandemic or flu emergency comes, the infrastructure could be utilized, the legal paperwork, DUAs, and all those things. Of course, you have to do those things, new proposals and things like that, but it should not take us years now. It could be done within days and weeks as well. I would say that that is something those who are listening to this podcast today should look out for. You can work on ideas we already have and you can present your ideas so others could work on them and we’ll be happy with that.
Dr. Bulloch: Right. It sounds like this is something that is not going to go away. It’s going to be here for a long time to come, and it’s a great thing to hear.
Dr. Kashyap: Yeah. I would add, so far the registry was open for participating institutions and investigators. We do have plans to open it up for anybody with appropriate ideas, submissions, and approvals. Then legal paperwork, maybe a DUA signed as well could be utilized because we like to see different questions being asked and answered by smart people like those listening to this podcast today.
Dr. Bulloch: You heard him. If any of you are interested, please look at the VIRUS Registry on Discovery’s website. I think we’re about out of time, but before I close, I want to give you an opportunity to talk about anything we didn’t discuss today.
Dr. Kashyap: I think we pretty much covered it. I would just say that if you’re holding back that, I have never done research, or I don’t know, I’ve never been part of any big collaboration like that, if you’re a member or not a member of SCCM, I would invite you to join a Discovery group. It’s a fantastic group, reach out, I’m on LinkedIn, I’m on Twitter. Email me or anybody in SCCM at this time to reach out. If you have not done this before, or if you think you don’t have enough skills, worry not. We have enough tools for you to get started and we’d like to see if we can work on your ideas and take it further.
Dr. Bulloch: Well, that’s wonderful and thank you so much for joining us today. This concludes another edition of the Society of Critical Care Medicine podcast. For the Society of Critical Care Medicine podcast, I’m Marilyn Bulloch and thank you for joining us.
Marilyn N. Bulloch, PharmD, BCPS, FCCM, is an associate clinical professor and Director of Strategic Operations at Auburn University Harrison School of Pharmacy. She is also an adjunct associate professor in the Department of Family, internal and Rural Medicine at the University of Alabama in Tuscaloosa, Alabama, USA, and the University of Alabama Birmingham School of Medicine.
This podcast was recorded during the Society of Critical Care Medicine’s 2023 Critical Care Congress. Access essential education online through Congress Digital. More than 120 sessions are available on an easy-to-use platform. Continuing education credit is also available. Some SCCM members receive complimentary access to Congress Digital. To learn more, visit sccm.org/congressdigital.
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