COVID Rounds: Inpatient Management of Patients With Mild or Moderate COVID-19

Raj Gandhi: Welcome everyone to today's Covid rounds. We're going to be talking about inpatient covid-nineteen management of people with mild covid-nineteen.

Raj Gandhi: I'd like to introduce myself and my co-panelists. My name is Raj Gandhi. I'm at Massachusetts General Hospital and Harvard Medical School in Boston, Mass. And I'm going to turn next to Dr. Cantrell, and ask him to introduce himself.

Steve Cantrill: Thanks, Raj. I'm Steve Cantrell. I live in Denver. I was the Associate Director Medical Director of Department of Emergency Medicine at Denver Health Medical Center and Associate Professor of Emergency Medicine at the University of Colorado, Health Sciences Center.

Raj Gandhi: I'm also delighted to be joined by our next panelist, Dr. Patel.

Payal Patel: Yeah. Hi, my name is Payal Patel. I'm an infectious diseases physician. I've also worked as a hospitalist, and I work as the system-wide Director of Antimicrobial stewardship at Intermountain Healthcare.

Raj Gandhi: Wonderful. So let's go ahead and launch right in. I'm going to start us off with a poll and ask you participants how many adult people with covid-nineteen do you provide care for in a typical week, one to 4, 5 to 10,

Raj Gandhi: 11 to 1516 to 20, or more than 20 or finally, not applicable. Please go ahead and let us know your your practice.

Raj Gandhi: So now let's turn to a case. This is, as we mentioned, a person with COVID-19, with mild to moderate disease. But who's hospitalized? So this is a person who's 78 years old. They have a history of lymphoma. They've received rituximab

Raj Gandhi: as well as other chemotherapy for their lymphoma

Raj Gandhi: in the past 3 months, and this individual presents to the emergency department with right hip pain. After a fall.

Raj Gandhi: They also report fevers, myalgias, cough, and some other upper respiratory symptoms that started 2 days prior to this fall.

Raj Gandhi: and when you see this individual. The blood pressure is 1 40, over 85. The heart rate is 96. Respiratory rate is normal at 14, temperature is 38.2, and importantly, the oxygen saturation on room air on ambient air is 95%. So normal

Raj Gandhi: physical exam is notable for a right leg with external, significant external rotation and shortening.

Raj Gandhi: and in terms of vaccination and prior covid status. This person had 2 Mrna covid vaccines. 3 years ago, I should say 2 doses of the Mrna vaccines 3 years ago, but has not had any boosters since.

Raj Gandhi: Did have COVID-19. About 2 years prior to this admission you do a Covid test, and the Antigen test is positive.

Raj Gandhi: So the person admitted for their their broken leg, but also has signs and symptoms of Covid, and is testing positive for Covid.

Raj Gandhi: So our 1st pretest question for you is, is this patient eligible for antiviral therapy and go ahead and vote? And a no. Only recommend antiretroviral therapy. If the person is requiring supplemental oxygen, which they're not.

Raj Gandhi: B. No, not eligible, because they don't have

Raj Gandhi: additional risk factors for progression.

Raj Gandhi: c no not eligible for antiretroviral therapy, because they neither are requiring supplemental oxygen, nor do they have additional risk factors

Raj Gandhi: or D yes.

Raj Gandhi: antiviral therapy. I'm sorry antiviral therapy. Is recommended because of their age and immunocompromising conditions, both of which are significant risk factors for progression and as a reminder, the person is 78 years old, and also has lymphoma, and is receiving chemotherapy containing, with a regimen containing Rituximab. Go ahead and vote.

Raj Gandhi: Now we're going to take a poll. This is to understand what your approach would be, so which therapy, if any, would you recommend a Remdesivir? Only

Raj Gandhi: B. Namactivir Ritonavir? Only

Raj Gandhi: see either Remdesivir or Nomatrovir Retinovir

Raj Gandhi: d.

Raj Gandhi: Remdesivir, or nomatrovirtonavir, but this time adding dexamethasone or E. No treatment is warranted.

Raj Gandhi: Please vote.

Raj Gandhi: And now over to my colleague. Over to you.

Payal Patel: Yeah, thank you. Yeah, I'm Gonna go through some current trends in in Sars-cov-two.

Payal Patel: This is a most recent capture. But you know if you're interested, the Cdc. Covid tracker is still live, and they're updating that twice a week.

Payal Patel: One thing that I would really highlight, as you know, this. This chart can be confusing. But I think one thing that I would highlight from the infectious disease background is

Payal Patel: that all current variants that are really in play. Here are omicron related. And so the vaccines that have been updated have been in terms of the omicron. And so I think that's really important. We were seeing a lot more changes early when Covid had 1st come out. And so that's something to think about. The media often talks about this, too. But

Payal Patel: deep in those newspaper articles are that these are all omicron subvariants. I think that's really important to keep in mind.

Payal Patel: This is just noting what has been happening with hospitalizations. And actually, along with this, mortality, trends are very similar as well. Those are also continually being updated on the Cdc Covid tracker website. If you want to see latest trends on those.

Payal Patel: If you take a look at this graphic, you know, thinking back t020-19-2020, that's the yellow line. And then again, looking at 2021 and those hospitalizations and then bringing us to where we are now, the red line. That's basically the lowest amongst the hospitalizations, and so we've definitely seen an improvement in hospitalizations

Payal Patel: and mortality associated with Covid-nineteen.

Payal Patel: I'll hand it over to Dr. Cantrell.

Steve Cantrill: Thank you very much. We're going to discuss now the initial workup in the emergency department when presented with a patient who may have

Steve Cantrill: covid-nineteen. This is the case that we've already been discussing. Obviously, in this case, in reality, the patient usually comes in without having a test that's positive.

Steve Cantrill: and our goal is to determine which patients are going to require hospitalization, and those that we can treat in the Ed and then release with follow-up follow-up was extremely important, especially during the initial onslaught of covid-nineteen, because we weren't really sure what we were dealing with.

Steve Cantrill: So we have that information. We're going to do a standard hmp. In this patient, including the risk factors for progression to severe covid-nineteen, then laboratory testing. We've touched on briefly, certainly an antigen test or the nucleic acid amplification test.

Steve Cantrill: And it's important as seeing this patient initially, that we realize there's a 5 day window in which the actual test can be negative. But the

Steve Cantrill: patient can, in fact, have covid-nineteen. So a negative test means it's negative only at that instant, and does not mean the patient does not have Covid. Very important to remember. We'll do a Cbc kind of standard and a complete metabolic panel, and then any other labs as indicated by other comorbidities. The patient may have

Steve Cantrill: in terms of imaging. Not everyone would get a chest X-ray if it was truly a very mild case. But if you're concerned, or if the patient has risk factors. Go ahead and get a chest. X-ray, or if there's severe or critical, you may want to get a chest ct, an Ekg. If indicated, and then any other studies that may be indicated

Steve Cantrill: in terms of the Nih severity classification. You see the classifications here mild, moderate, severe, and critical, and our patient falls into the mild. She has a fever, she has cough, she has muscle pain, and her O 2 sat importantly, is 95.

Steve Cantrill: It would be fall into the moderate classification based on clinical assessment and imaging, or but with a normal, essentially normal. O 2 set 95, or or 94 or above

Steve Cantrill: severe would be an O. 2 sat less than 94, or their pao, 2 fio, 2 ratio was less than 300 of Mercury or their Tachypneic to a rate of greater than 30, or their long X-ray showed infiltrates in more than 50%. And then, obviously the critical anyone who's in septic shock, respiratory, failure, or multi-organ dysfunction.

Steve Cantrill: Now, just a note about pulse, oximetry. It can be a little misleading. It can be offset by skin pigmentation skin, thickness and skin temperature. And it's also important to note that many of the

Steve Cantrill: portable single digit pulse oxes that you can buy, you know.

Steve Cantrill: in a drugstore or

Steve Cantrill: through mail order have not been FDA approved. And even though some of them have been cited because they state they're FDA approved or they're not so. You should certainly calibrate any

Steve Cantrill: any pulse ox that you you use at home

Steve Cantrill: in terms of death, risk ratio. This is a combined graph by age and by Comorbid conditions. And what this points out is how age is the strongest risk factor you're dealing with. If you are 65 to 74, you have 6.7 times the risk of death from covid-nineteen

Steve Cantrill: less so with some of the other comorbidities. Here's top is obesity. 1.3 times chronic kidney disease and on down to

Steve Cantrill: heart disease and other comorbidities. But you can see the slope of that curve based on age. So we pay a lot of attention to age in terms of assessing what the patient's risk for further development of the disease process.

Steve Cantrill: Now this patient, again, has hematologic malignancy, and she's on immunosuppressive medications. Those are also indications of higher risk. And then you have some with the suggested higher risk and some with mixed evidence. This was put together by the Cdc. And it's actually quite helpful

Steve Cantrill: in the Ed. Some places have used something called the Priest score pandemic, respiratory infection, emergency system, triage or priest.

Steve Cantrill: And it's very nice because it doesn't require any lab test. It requires some historical data and

Steve Cantrill: vital signs. And that's really it. And this has been validated. Now one caveat. This was developed and validated before we had good treatments for covid-nineteen. So in the patient that we presented, she'd get 1 point for her respiratory rate. 1 point for her. O 2 sat

Steve Cantrill: 1 point for her heart rate, one for her temperature and 3 points for her age. So this would give her a total score of 7. And based on this, it would be an 18% chance of disease progression in this lady.

Steve Cantrill: So again, it's

Steve Cantrill: it's can be very helpful, especially if you don't have rapid access to to testing.

Steve Cantrill: So what we've got in this lady, her Antigen test is positive. Cbc and Cmp. Were unremarkable. Chest X-ray was clear, and her X-ray of her pelvis and right hip shows a greater trochanter fracture on the right, so certainly she'll be admitted to the hospital. And then

Steve Cantrill: what are we going to do?

Steve Cantrill: Raj, do you want to want to take this.

Raj Gandhi: Yeah, I mean, I'd like to pick up where you left off on the risk factors for progression.

Raj Gandhi: certainly. The Graphic you just showed us around age is very, very

Raj Gandhi: dramatic. A lot of that data did come from the 1st year of COVID-19. I think the cutoff for that particular study was March 2021. So it was even before we had widespread vaccination.

Raj Gandhi: That being said, the part that really impresses me is that even today, in 2024,

Raj Gandhi: the majority of people who end up in the hospital are people over the age of 60 or 65. And so, even though the risk has fallen, as Dr. Patel showed us substantially. Nevertheless, age continues to be a large contributor to our hospitalized as a risk factor for hospitalization.

Raj Gandhi: I do wanna also

Raj Gandhi: say that

Raj Gandhi: covid vaccine status, if there's no doubt that vaccination prevents progression to to

Raj Gandhi: severe disease. And that's true across the board, whether you're younger or older.

Raj Gandhi: but immunocompromised people still, I think, and and this patient will certainly counted that

Raj Gandhi: don't always mount an adequate, immune response. This patient has 2 strikes against them. One is the last. Vaccination

Raj Gandhi: was well over 2 years ago, so certainly antibodies wane t cells, perhaps not as much, but antibodies wane, and then the other strike is the rituximab really makes the antibody response. As Dr. Patel highlighted, you know, suboptimal. So maybe I'll see how Dr. Patel thinks about this person.

Payal Patel: Yeah, I think I will shout out to antimicrobial stewardship programs throughout. Wherever the person watching this is working, this is something that has come up in the last few years where they're admitted for something else, completely unrelated to covid-nineteen in this case for a fall, and then they're found to have Covid-nineteen, and I think this is a place where you might want to look at whether your institution has outpatient

Payal Patel: guidelines versus inpatient guidelines for covid-nineteen when those are being formulated. We think about the patient in the ambulatory setting versus the inpatient setting, and if they're admitted for covid-nineteen, it's kind of a different case.

Payal Patel: In this case, I think I would kind of put those 2 together. One thing that we've talked about before is logistics. So there hasn't been necessarily head-to-head Remdesivir versus the oral options antivirals. But logistically Remdesivir can be challenging in the outpatient space, but easier to do inpatient. So that would be something

Payal Patel: I would be thinking about. But this would be a really good time really to think about what your institution is offering for the outpatient and inpatient, and then kind of combine them together. In this case.

Raj Gandhi: Yeah. And in that regard you reminded me of a really important point when these trials were done, and we're going to talk about the trials that lead to our current approach. When they were done they were either done in the outpatient setting or

Raj Gandhi: in the hospital. And yet this particular patient that we're talking about. Had she not had a trochanteric fracture, her covid is probably such that she would be treated as an outpatient, so we have to in some ways extrapolate

Raj Gandhi: data from the outpatient trials that we'll talk about to this person. So that that's just something to keep clear that there

Raj Gandhi: It's really an interesting

Raj Gandhi: situation we're in where we're.

Raj Gandhi: It's fair to say that being in the hospital versus not being in hospital, if you're not in the hospital for a particular Covid related condition shouldn't matter, and that's why we do these extrapolations.

Raj Gandhi: But but the studies don't they weren't divided that way. And and that's why you'll sometimes see people. And you know, sometimes it's called expert opinion, because we're we're extrapolating from certain circumstances. So.

Steve Cantrill: Let me just say 1 point about starting patients on antivirals in the Ed. We feel pretty strongly about that, and the sicker the patient the more strongly I feel sometimes the Ed is very, very busy, and we just we can't get to that. But I feel it's quite important, especially in the severely ill patient.

Steve Cantrill: because there's so many delays built in to most institutions, unfortunately getting the big patient up on the floor.

Steve Cantrill: getting orders, written, getting the drug from pharmacy, and if we can get the 1st dose going with the patient in the Ed, I think that's a big plus for the patient.

Raj Gandhi: Yeah. And I think that really touches on the importance of multidisciplinary care. The Ed will stabilize the patient antiviral therapy as we're about to talk about works best if you started early, and then they'll hand off that care of that patient to either the surgeon who might be fixing the fracture or to an internal medicine physician depending on what the primary service is. So yeah, I totally agree.

Raj Gandhi: maybe I'll

Raj Gandhi: shift this now to kind of. We're doing this kind of like a.

Jacqueline Meredith: So I'm gonna interrupt. I forgot I in there. But you can ignore it. I was just trying to like, see what it? Yeah, sorry.

Raj Gandhi: Yeah, you you tripped me up because I have my other slides on my right hand side. So who.

Jacqueline Meredith: No, that was.

Jacqueline Meredith: I was just trying to.

Raj Gandhi: Yeah, okay, yep, you keeping us on our toes. Thank you, Jake.

Raj Gandhi: So okay, maybe I'll recalibrate here. And you can edit this out.

Raj Gandhi: so

Raj Gandhi: Dr. Patel and Dr. Cantrell have talked a lot about the risk factors. Let's put this all together on a single slide. And so we've already mentioned and talked a bit about age. And so age, certainly, as we heard, is perhaps the most important risk factor. And when we mean age, as you get into your seventies and eighties and nineties. That's really when age becomes an important risk factor.

Raj Gandhi: Chronic medical conditions also play a role. And so we want to know if our patients have diabetes, do they have obesity? Do they have other

Raj Gandhi: conditions, heart and lung disease? I would really put up there if they have severe chronic, obstructive, pulmonary disease, if they have severe cardiac disease that's going to increase the risk of a

Raj Gandhi: a progression.

Raj Gandhi: We've mentioned rituximab several times immunosuppressive conditions or medications is a 3rd dimension in terms of your patient's risk with

Raj Gandhi: lymphodepletion, rituximab being prominent, but also stem cell transplants and hematologic malignancies there are a couple of conditions that we sometimes think about as immunosuppressive that are less impactful. So, for example.

Raj Gandhi: Tnf inhibitors in the big scheme of things are less likely to lead to

Raj Gandhi: progression than than some of the other immunosuppressants we we give, and so that's been learned over the course of Covid. And then

Raj Gandhi: in our patient we talked about vaccination. But yes, there's no doubt that full vaccination plus boosting

Raj Gandhi: is going to put someone at the lowest risk, and so keep that into account, as you're as you're trying to decide whether to give antiviral therapy.

Raj Gandhi: Okay, so we're going to now delve into the treatment recommendations. And we'll do this kind of as you would if you were seeing this patient on rounds. And what we will do next is we'll talk some about our guidelines for treating a patient such as this, and then we'll delve into some of the evidence. So here I'm showing

Raj Gandhi: the Infectious Diseases Society of America. COVID-19 guidelines, recommendations for hospitalized patients. And I'd like to focus on the mild to moderate category because

Raj Gandhi: Dr. Cantrell and Dr. Pyle have shown us that this is a person with mild to moderate disease. The person has a saturation of oxygen. Over 94% does not require oxygen.

Raj Gandhi: so let me underline here from the poll questions. This patient should not get steroids for the treatment of of the COVID-19. There are strong data now.

Raj Gandhi: finding that

Raj Gandhi: that steroid use in mild to moderate covid-nineteen makes things worse, makes people develop more severe disease. It's a lifesaver for people who are on oxygen, and that's where dexamethasone should be used. And in part 2 of this series we'll talk about that. But not for this patient.

Raj Gandhi: This patient, I think, convinced everyone has a high risk for progression to severe disease, and is within 7 days of symptom onset. She's about 2 days in so Remdesivir certainly would be where I would go next, and that's what the Idsa guidelines recommend. Is

Raj Gandhi: Dr. Patel mentioned. Remdesivir is quite feasible in the inpatient setting, where where this patient is harder to do in the outpatient setting

Raj Gandhi: that Esa guidelines allow us to consider Nemativir Rotennavir an oral drug. If within 5 days of symptom, onset.

Raj Gandhi: bandage guidelines which have recently been sunsetted are largely concordant. Let's draw our attention to the very top box as we were alluding to in the kind of the discussion in the ambulatory setting, or if a person's hospitalized for a non-covid reason.

Raj Gandhi: not on oxygen. And so this patient's hospitalized for her her hip fracture, then steroids are not recommended, and again.

Raj Gandhi: Namactivir, Ritonavir, or Remdesivir rise to the top of the list with Molnupiravir given as an alternative. If you can't use one of the preferred options.

Raj Gandhi: So this is just a summary of where our patient is. As we've heard.

Raj Gandhi: She has the background already mentioned, and is covid antigen test positive.

Raj Gandhi: So let's

Raj Gandhi: Ask the question again that we that we started with near the outset

Raj Gandhi: is this patient eligible for antiviral therapy? And you've got the 3 choices that the no choices.

Raj Gandhi: and then the Yes choice

Raj Gandhi: and the yes, choice clearly is correct because she has. She's age 78 years old. We've talked about that, and she's immunocompromised.

Raj Gandhi: And I think this is really a summation of what we've already talked about. I think everyone here I'm looking around at my colleagues, and they're all giving me by their body language the green light that this is someone that they would treat.

Raj Gandhi: I'm going to turn things over to Dr. Cantrell to talk a little bit about anticoagulation, not, of course, an antiviral, but very important, for people like this.

Steve Cantrill: Thank you, Dr. Ghani. Yes, just a couple comments about that. That, as with, we're now anticoagulating at least at a prophylactic dose level. Many of the patients that we admit for different reasons. But and that would be true for a non covid-nineteen

Steve Cantrill: admission, even though they do have covid-nineteen as long as they don't require any oxygen

Steve Cantrill: and that would just be the prophylactic dose. Now, if they need oxygen. And, in fact, if their d-dimer levels are above the normal range.

Steve Cantrill: and if they don't have any contraindications, then you would want to consider a therapeutic dose of heparin. All others would get the prophylactic dose. Again, unless there are contraindications.

Steve Cantrill: High flow. O 2 or non-invasive ventilation.

Steve Cantrill: they would get the prophylactic dose, and those in an icu would also get the prophylactic dose. Many of these patients sometimes have already been started on a therapeutic dose before they're transferred to the Icu, and those would be moved to the prophylactic dosage.

Raj Gandhi: Perfect. Thank you for that. And now let's we mentioned that on rounds, if we were seeing this patient we would be talking not only about what we're going to do. But we'll talk about. We would talk about why we want to do something. So let's now review the evidence that lead us to some of the recommendations that the Idsa and Nih have come up with. So let's start with the drug. Remdesivir.

Raj Gandhi: Remdesivir, of course, was the 1st antiviral that was really endorsed by both of these guidelines, and that

Raj Gandhi: endorsement was really based on the seminal act. One study. This was done by the national institutes of allergy and infectious diseases. Just as a brief reminder, this was a randomized double, blind, placebo-controlled phase, 3. Trial. It was done in adults. They all were hospitalized with covid-nineteen.

Raj Gandhi: and they all had in this case evidence of lower respiratory tract infection. And that's important.

Raj Gandhi: They were randomized to placebo or remdesivir, and in this instance the Remdesivir was given for as long as 10 days.

Raj Gandhi: The primary outcome is shown here, the rate of

Raj Gandhi: The recovery time was lower, shorter in the Remdesivir arm than in the placebo arm, and there was also a reduction in mortality, although that was not statistically significant. The relative risk of mortality was substantially lower. Now that was really to be augmented by some of the subgroup analyses. And this is how these guidelines really ended up where they are.

Raj Gandhi: The benefit of Remdesivir was most apparent in those participants who had a symptom duration of 10 days or less. And so, if you look at this forest plot. What you're seeing is that the recovery rate ratio

Raj Gandhi: is is favoring Remdesivir in people who had a shorter duration of symptoms, and that supports Dr. Cantrell's

Raj Gandhi: approach of starting antiviral therapy soon after contact with the patient, and not waiting.

Raj Gandhi: For the person to progress.

Raj Gandhi: The other important part here is that the

Raj Gandhi: benefit was most obvious, for in this early study in people who were receiving oxygen, but who had not yet gotten to the point of needing mechanical ventilation.

Raj Gandhi: Now we've said before, Dr. Patel pointed out that this patient might actually, had she not, had the broken femur might have been treated as an outpatient. So let's

Raj Gandhi: reflect on what are the data for outpatient treatment with Remdesivir. So this is the well-known pine tree study. This was done in non-hospitalized high risk. Individuals with covid-nineteen let me underline that term high risk. So all of these individuals

Raj Gandhi: had some condition that placed them at high risk for progression.

Raj Gandhi: They all had COVID-19 for less than or equal to, 7 days, and it was a large study, 584 individuals.

Raj Gandhi: I'm going to draw your attention. People were randomized to Remdesivir this time for 3 days, or placebo for 3 days I'm going to draw your attention to the

Raj Gandhi: to the hospitalization or death part of this table, an 87% reduction in hospitalization and death or death in people who got Remdesivir as compared to placebo. And so that's really the evidence that we would apply to the patient

Raj Gandhi: we're discussing.

Raj Gandhi: I'm going to turn things over to

Raj Gandhi: to Dr. Patel for a discussion of the other option. Here Nomactivir Ritonavir.

Payal Patel: Yeah, thank you. So I'll go through some of the work that's been done on this Med, and you'll be familiar with some of these studies you may not know if one thing that you can take away today you'll know what epic Hr. And Epic. Sr. Stands for. And so this was the 1st study that was done on Nirmatrovir Ritonavir, and it was. This is really important to note that this was done on unvaccinated adults.

Payal Patel: And so, if you were to do this study today you would probably have a really different study, because at this point it's really hard to find someone who hasn't been vaccinated or been infected at this point. So I think that's a really key thing to think about in this work. These patients also had often more than one risk factor or one risk factor for progression to severe Covid. We've been talking a lot about that

Payal Patel: during this presentation, so that included age above 60. It included things like obesity, smoking, immune suppression, cancer as well. And so when they did this study, they did again. It was a double, blinded, randomized trial with Placebo versus this medication.

Payal Patel: it had really significant results, and it showed that taking near Ritonavir reduced risk of hospitalization or death by 88%. So this is, you know, the basis of

Payal Patel: how a lot of these recommendation for this drug was made. But you know, as people thought about this, a lot of questions that came up definitely on rounds were often seeing patients who have been vaccinated or don't have these risk factors. This came up all the time in the outpatient setting. I must have fielded hundreds of calls just asking that question. So the second study

Payal Patel: is Sr. Standard risk. So Hr. High risk, Sr. Standard risk. So this study epic, Sr. Was published actually, just this year. And it looked at that question of folks who either have been vaccinated or don't have those risk factors. Even in this group there were a number of participants that did have risk factors for severe disease, which include again age

Payal Patel: or one of those other risk factors that we talked about before. This was important because, as potentially suspected by many who had been using this medication in the outpatient setting. This did not show a large benefit when again looking at the double blinded placebo versus taking this medication, there was only one day of difference in symptoms.

Payal Patel: And so I think that's really important to think about. And it's changed the way that different hospitals have really talked about their outpatient guidelines for use of this medication.

Payal Patel: And then we wanted to highlight some work that was actually just presented at Id Week. It's important to think that this is a pooled analysis. So this is almost like a sub analysis of the work that has been done, not necessarily a new trial.

Payal Patel: and the same authors looked at the results from Epic Hr. And Sr. So, looking at that initial work from where a number of patients were unvaccinated and had severe risk factors for progression of Covid-nineteen in the 2021 era again. So that's really important to think about when that was happening. And then.

Payal Patel: looking at that standard risk, epic. Sr. They put that together, and found that looking at

Payal Patel: risk of, or how many days you had symptom onset. The difference was 12 days to 14 days when you compare that to the results from epic. Sr. Which was one day difference, and was thought to be largely a negative study. I think I would take that into mind. The difference here between is 2 days, so would really have to think about what you think is important in terms of symptom alleviation.

Payal Patel: and whether to you that would be a positive or negative, or maybe somewhat in the middle kind of study.

Payal Patel: I just wanted to highlight. Here we heard about the guidelines from Dr. Gandhi. I think it's important to think about if you're thinking about treating someone with one of these medications, particularly Nirmatrovir Ritonavir, there's a number of really great resources online that you can look through to see if the patient is taking something that may be

Payal Patel: contraindicated. I want to highlight here that there are some medications which you really would try to avoid, and they're listed on the left here. And then there's some other medications where the patient could potentially hold

Payal Patel: that medication or use with caution. So if you do have a question, and you have an id pharmacist or someone or an er pharmacist available to talk this through. I think that's really important to think about, because

Payal Patel: that may actually help you decide whether you need to use this medication or not, and we have some resources here that you can you can use. But it's quite easy to find on the web.

Payal Patel: Okay, I will hand it over to you. Dr. Gottlieb.

Raj Gandhi: Thank you. And and maybe before we leave the drug interaction issue, since that is a very common question.

Raj Gandhi: this Liverpool site that Dr. Patel, highlighted as my go-to site, and I want to just call out HIV for a moment, since I mainly take care of people with HIV,

Raj Gandhi: even though. The Ritonavir part of numatrovir Ritonavir

Raj Gandhi: is in some of our HIV regimens. The protease inhibitor based regimens. The FDA. After careful consideration, feel like we can continue our

Raj Gandhi: our patients with HIV on their

Raj Gandhi: protease inhibitor container regimen, because the nemativir Rotonavir, of course, is so short. It's only 5 days, and so that's short enough a time that people can tolerate, even having a little bit extra.

Raj Gandhi: Ritonavir. But but do as Dr. Patel said. Take take that use that Liverpool site, because it's really

Raj Gandhi: incredibly useful.

Raj Gandhi: All right. So this is the same slide that we talked about before, and I think we're in firmly in the mild to moderate camp. We're going to give either Remdesivir, or perhaps, since the logistics do favor, Remdesivir would probably

Raj Gandhi: move right ahead and and give Remdesivir

Raj Gandhi: and and we already talked about this, and and this really accords both with the Idsa guidelines as well as with the Nih guidelines.

Raj Gandhi: So for the final part, I think.

Raj Gandhi: you know I'm curious, Dr. Cantrell, if you were in, since you're in the Ed, would you start this patient on? Sounds like you would treat Remdesivir. No matter depends on the drug other drugs that they might be taking. You know, how would you apply this evidence that we've just reviewed to the care of this particular patient.

Steve Cantrill: For this patient. I think we would start her on Remdesivir.

Steve Cantrill: and again, as I mentioned, try to get that done expeditiously.

Raj Gandhi: That would agree. And in part, even though I think it's okay to extrapolate from outpatient trials for Nomactivir Ritonavir.

Raj Gandhi: there are. We talked about the Pine Tree study, which was done in outpatients with Remdesivir. But the very 1st study that we started with Act one

Raj Gandhi: that had a range of people from quite severe disease, but also to milder disease. And there were other studies that we didn't review, also done in the hospitalized setting with Remdesivir that included people who were not on oxygen. So I think there's even more clinical trials, data for hospitalized patients with Remdesivir than there is for Nemactivir Tynavir. That being said, if there's a person

Raj Gandhi: recovered quickly or wasn't going to be in the hospital for very long, I would have no hesitation about using the Macrotonavir. There's no reason to keep the person in the hospital for an intravenous infusion. We all know that we don't want to unnecessarily prolong hospitalizations, but Dr. Patel, do you work on stewardship? Maybe you can tell us how in your institution this patient would be treated.

Payal Patel: Yeah, I agree. And our institutional guidelines would also recommend Remdesivir. I think this is a great time to think about. Dr. Cantrell is very familiar with the evidence. And so that's very helpful. And we've talked about the earlier the better in starting something like this in many hospitals. If you have a broken hip. You're probably not going anywhere for a little while, but in other situations you may be in and out.

Payal Patel: So I think, thinking about getting that 1st dose, and quickly, before you potentially even had to talk to Id or the id pharmacist getting the 1st dose is really helpful, and I would agree, I think, looking at the summary of evidence that before we had this talk today, and then, I think, even more, after looking at the evidence today. I think the evidence would likely favor

Payal Patel: using Remdesivir in this patient, and I wouldn't necessarily think about her almost as an outpatient who happens to be in the hospital.

Raj Gandhi: Maybe I can.

Raj Gandhi: Also reflect for a moment on some gaps in COVID-19 management.

Raj Gandhi: you know, one striking figure that I read recently that was published by the Cdc. In 2024 looked at the outpatient use of nemativir Ritonavir.

Raj Gandhi: and what it found is that among people over the age of 90 people who, none of us would doubt, are at high risk for progression. Only 33% or so, a 3rd were prescribed nematrovir, Ritonavir, and I think that's too low. That's way too low. And I think in some ways there's confusion arisen somehow about the benefits of these therapy.

Raj Gandhi: and I think we should be. We don't want to overtreat. We don't want to treat a 25 year old marathoner that they don't fit the guidelines for treatment but a 90 year old, every guideline that I'm aware of, and every clinician, I think, really should be using Namactivir Ritonavir.

Raj Gandhi: The other last

Raj Gandhi: thing that I want to say is, sometimes people feel like the rebound syndrome with the Matributonivir is somehow

Raj Gandhi: you know, excludes people, or is a consideration against Imativir Ritonavir. I don't think that's the case when I've seen rebound, and I have seen plenty of rebound. It does occur, for sure

Raj Gandhi: it doesn't tend to be severe, and it really should not be a reason to avoid using pneumatrovirotonavir in someone who, like this patient, has a lot of risk factors for progression.

Payal Patel: Yeah, I agree. I would think that that may have been, and and continues to be, a barrier in

Payal Patel: primary care and ambulatory prescribing for this medication. From what I have experienced, I think that the rebound phenomenon has gained a lot of without necessarily a lot of literature associated with it. And so I think one takeaway for this, especially if anyone's in practicing in the outpatient setting, is thinking again about those risk factors, and who would actually benefit

Payal Patel: from some of these medications.

Raj Gandhi: You want the last word before I bring home our take-home points and and and begin to to wrap.

Steve Cantrill: No, I think this is a very good discussion, Dr. Gianni, and do you think it's an educational problem in terms of the use in the elderly.

Raj Gandhi: Good question. I think we really need to understand better why people who are at high risk aren't receiving therapy. I don't know if it's an access to care and education problem, or in some ways just sadly covid fatigue where people really aren't, you know, reflecting on the evidence that they would ordinarily bring to the

Raj Gandhi: to the care. And so I think we all have a role to try to, you know. Use the evidence we have, and treat those patients at highest risk, understanding that not everyone is at the same risk. And so this is not a drug that everyone uses. Same with Remdesivir. It's for the people who are at the highest risk, and that's where I would put my efforts.

Raj Gandhi: So with that Dr. Patel mentioned, take home. Let's do a few take home points. Treatment of covid-nineteen and hospitalized patients depends on the severity of disease and risk factors for progression. And I know we're all convinced that advanced age and being immunocompromised, are important risk factors for developing severe covid-nineteen

Raj Gandhi: and people with mild to moderate COVID-19 who have risk factors for progression to severe disease. The pine tree population, Remdesivir is recommended.

Raj Gandhi: and in people who develop severe covid-nineteen and require supplemental oxygen. Immunomodulators as well as antivirals are recommended, and please join us for Part 2 of these covid rounds, where we'll really delve into the treatment of a severely ill patient with covid-nineteen. Thank you for joining, and look forward to seeing you again.

Jacqueline Meredith: Great job. Thank you.