In the Cancer and COVID-19 CME event hosted by Penn Medicine and featuring Dr. Anthony Fauci, Dr. Kathleen Murphy, MD, Associate Hospital Epidemiologist, discusses infection, testing, treatment and vaccines for COVID-19. She provides a clinical overview of COVID-19 infection and a summary of the pandemic’s epidemiology.
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Twitter @PennMDForum Dr. Murphy’s physician profile
hi, everyone, and it's a pleasure to be speaking with you this evening. Over the next 15 minutes, I will be giving a brief overview of the pandemic epidemiology, a clinical review of Kobe 19 infection, as well as some additional updates on testing, treatment and vaccination that hopefully will complement the information presented by others already including Dr Fauci. So to start, I would just like to again comment on sort of the global scale of the pandemic at this time, and it's really staggering to review these numbers. I know we've discussed them already, but we are now at the point of over 33 million confirmed cases of Cupid Worldwide and specifically here in the United States. We have over seven million confirmed cases and have just reached the sobering milestone of over 200,000 deaths since our first case diagnosed in January. This graphic is from a resource at Johns Hopkins University. The websites below I encourage you to explore it. It's really an excellent compilation of data. This graph is also from the Johns Hopkins Covert Resource Center, and I'll just highlight here. This is a timeline of the pandemic, as depicted by a seven day moving average of daily confirmed cases, which has led right now, as you can see in the graphic by India, the U. S. And Brazil and the US depicted in Orange here, we've had very fairly limited success, um, in decreasing our case count. Despite initial efforts in March of shutting down our communities and acting social distancing. And as states began to reopen in May, you can see we had quite a second surge over the course of this summer on I really think the trajectory of our curve from here on out is going to depend on a couple of different factors. We see schools and communities continuing to reopen. We anticipate challenges over the winter months with social distancing. As more time is spent indoors, we're upcoming into the flu season on how we can continue to encourage social distancing, masking testing and contact tracing eyes all dependent as well as a safe and effective vaccine. So there's a lot of ah, lot of things in play to where we go from here. So now I just want to talk a little bit about some of the clinical aspects of Cove in 19 that I think are important to review a doctor, Fauci touched on one of the challenges of the stars. Kobe to virus is that a patient's peak infectivity may actually be within the 24 hours prior to symptom onset or write it symptom onset, which is really important in terms of mitigating transmission and creates quite a challenge. And, as was mentioned, up to 30 40% of people are asymptomatic or have very minimal symptoms, yet can still be significant vectors of transmission. I agree with Dr Fauci that there's likely a spectrum of transmission, and as you probably have read in the scientific literature and in the media, there is quite a debate right now over transmission dynamics between droplet and airborne spread. But I agree that the most prominent form of spread appears to be via droplet transmission, although we do worry about airborne transmission, particularly in very close confined spaces with poor ventilation on, I think that's a particular concern in some situations where we've seen some outbreaks stem from. But one thing that does reassure me about the motive transmission. Predominantly being droplet is the efficacy that we've seen with universal masking. And that's particularly been prominent in my role is the hospital epidemiologist. Here is pen where when we enacted universal masking in March, we saw a significant decline to essentially no staff to staff and staff to patient transmission with Universal Masking Onda. We've been very, very encouraged by that data and our personal experience here, as was mentioned, We have a better understanding now about the spectrum of clinical presentations of coded 19, which I put some CBC data from their surveillance, um, network here on the right, similar to mention by Dr Fauci. We know about 20% of patients will require hospitalization and about 5% I see level care, and our overall mortality rate right now in the U. S. Is about 3% since the start of the pandemic. But we've made significant strides within our critically ill population relative to how we ventilate patients, anti coagulation and some treatment strategies, including steroids that will touch on in a little bit. We know about risk factors for severe illness which were already been highlighted, including a amazing review by Dr Aggarwal of what's known in the oncology population. Although we need more data, including an organ transplant and other immune compromised groups. Onda We really do need more studies about long term sick. Well, a Here it pen. We have a Post Cove ID clinic run by our rehab clinic and are pulmonary doctors. And we're seeing a lot of chronic respiratory complaints, fatigue and cognitive impairment and patients that we need to understand and look into further. And I'll also comment that we have seen an incredible, disproportionate impact on our black, Hispanic and Native American communities, as was mentioned by Dr Fauci and it's really highlighted. The urgent and important efforts need to address longstanding systemic health and social inequities. So I wanted to go a little bit more in detail into testing. AST has been asked in our question and answer session. Already, we have three general types of tests for SARS. Kobe to at this time on bears multiple platforms that have been designated on granted approval by the FDA for emergency use authorization. Molecular testing has by far and large been the most common tests performed. Luther Porn over 90 million of these tests in the US to date, the most commonly used in the health care setting. Andi, This test uses reverse transcription PCR testing to essentially detect stars Kobe to RNA from respiratory tract specimens. They're very analytically sensitive and very useful in high risk settings such as hospitals or nursing facilities. Dialysis units where it's really important. Thio have a very sensitive tests so you can contact trace and isolate people appropriately. Um, these tests of a very low positive rates. We have seen challenges with false negatives, even though this is a highly sensitive test if patients are tested too early in their course related to specimen quality. And we do think there's some discrepancy between upper respiratory tract and lower respiratory tract shedding, and it's not always feasible or safe to get a bronchoscopy, for example, or an induced sputum sample for diagnostics, one of the biggest challenges with molecular testing that I get asked about a lot is just a reminder that it doesn't differentiate between live or infectious virus um, or continued shedding of sort of dead viral genetic fragments. So it's really not a test of infectivity, and patients can continue to shed virus for weeks to even many months after their initial diagnosis on, we still have a very limited capacity of rapid molecular ass A's, which impacts us on a daily basis in the hospital. Anti gene based tests, which detect viral protein, are also increasingly available and these air attractive because their rapid tests they have results in minutes. They don't need extensive lab equipment to perform them, and they are less sensitive than molecular tests. But I do think they have a role because of their low cost and ease of administration, particularly in low risk settings where you're doing surveillance, for example, in school or university settings or for other population based screening efforts. Antibody testing is now available, which most often detects I, G, M and I gig to the stars Kobe to surface spike protein, which has been described by Dr Fauci. And people develop antibodies, usually between one and three weeks after symptom onset. The sensitivity and specificity can vary based on essay on. We need more data about the duration, um, and actually role of antibody mediated immunity. Some studies have shown that antibody levels start to wane even within a few months after infection, and we need more information on that. I'll just highlight here on by. Someone had submitted a question actually about saliva based testing. But I'll highlight this study from Yale, where researchers actually validated saliva based molecular testing and found actually higher amounts of stars Kobe to our DNA in saliva specimens and less variation over time than compared to the traditional nasal fringe. I'll swab. And so this technology was actually used by the MBA this year for surveillance. Testing on Gail's Protocol now has been granted an FDA EU a, um, advantages of saliva based testing, which are very attractive to me, is that people can self collect samples. We don't need to rely on swabs or other transport media, which has had shortages already in the pandemic. Onda, for all these reasons, were also currently validating a saliva based test here at Penn, in line with discussing testing strategies. I think it's important because we've also struggled with this during the pandemic just to comment on the challenges of using testing to determine when a patient is no longer infectious and recovered from Kobe, 19 could come out of isolation and in general, at the beginning of the pandemic, we were using mostly a test based strategy where we needed to see to negative tests to clear people from isolation to now more of a time based strategy where we wait for a duration of time after people develop symptoms to clear them in terms of from isolation and either in the hospital or at home. Ondas I mentioned the challenges that molecular PCR tests can again remain positive for weeks to months after initial diagnosis. Andi just reflect dead viral genetic material that's still in the respiratory epithelial cells on, def. We wait for these tests based clearance. This has resulted additionally in delays in care on gets really challenging logistically to coordinate multiple repeat tests. So the CDC guidance has now shifted to for most patients, except for severely immuno compromised patients to move towards a time based strategy. And the data we currently have looking at actual cultural virus, um, from respiratory samples indicates that there is no cultural virus between 10 and 20 days, depending on illness severity after symptom onset. Andi, I think relative to the oncology population at Penn, we've really worked closely between infectious disease infection control, andare oncology providers on how to navigate individual decisions for cancer patients, for example, when to return to treatment or start other immuno suppressive agents very similar in the solid organ transplant world. And we need more data on duration of infectivity in immune compromised patients so that we can more accurately rely on time or or really use a test based strategy in this setting. I'll comment now just about briefly on some treatment options. Some of these studies were already mentioned by Dr Fauci, so I'll leave the information here and just touch briefly. Um, but one of our most promising treatments is Dixon Method Zone. And we really think, hopefully this mortality, um, is related Thio inflammation mediated lung injury that occurs a little bit later in illness course. But this is data on the recovery trial that doctor found she mentioned, and as as was discussed, it showed a significant 28 day all cause mortality benefit for patients who were on oxygen, particularly in ventilated patients, with the caveat that patients with a longer duration of symptoms had the greatest mortality benefit. So we do think that there can be harm to giving steroids too early. Um de Severe, which Dr Fauci also discussed, is a viral RNA polymerase inhibitor, which has good in vitro activity against SARS. Kobe, too, so has been promising. Now has FDA You? A approval is well for all hospitalized patients on din May the ACT One study, which was the adaptive Kobe treatment trial, was published in the New England Journal that showed a faster median recovery time by about four days for patients receiving room de severe. Although no significant mortality benefit at 14 days on, we also have a better understanding now about duration of treatment therapy for non ventilated patients. There seems to be not a benefit to using longer therapy between five and 10 days, and so from de severe, particularly in the past, has been a limited resource, and so that's helped us navigate our dozing strategies. I'll speak a little bit about convalescent plasma, which has received a lot of media attention recently and is now also now also has FDA. You a approval? Um, unfortunately, we need more data. The current randomized control trials that we have have not shown a mortality benefit, two of which I've listed here, um, by Leah, all published in JAMA, which was an RCT in Wuhan, China. And then the plastic trial just recently pre print revealed their data. This was done in India again with no mortality benefit but but still in pre print and needs to be peer reviewed. Um, the Mayo Clinic has published information on their experience with convalescent plasma. Um, they were originally providing plasma through an expanded access protocol. So have ah, cohort of about 30,000 patients who received plasma and just looking at their cohort of people who received plasma. They did see a mortality benefit to people who received it earlier in Disease Course and who received higher, tighter. But again, this was all compared within their group of patients who had received plasma. So we need more randomized control. Trial data. Eso at Penn We've worked with our antimicrobial stewardship team to really come up with a guideline for our patients, which follows a lot of the N H guidelines as well. We use from D severe for hospitalized patients with moderate or severe illness, um, decks, methods own based on again oxygen requirement. We have a trial that we can enroll convalescent plasma on. We're looking into other immuno module Torrey agents, um, in the trial setting were enrolling patients in the trial, looking at various sitting up here, but we need more data on immune compromised patients for sure. And then finally, I'll just speak to vaccine. So this is a website by the, uh, New York Times that has a really great up to date review of vaccines and where they are in development that I encourage you to look at further. Um, I think that the question of when we have will have the vaccine is difficult to answer. Is Dr Fauci alluded Thio? And we really need a commitment to a transparent evaluation of safety and efficacy, you know, as health care providers were going thio need to be comfortable being advocates for our vaccination. And a lot of this depends on how and how transparent the data is onda and really to generate public trust in the vaccine. Um, here's a list of what I think are four of the most promising vaccine candidates in phase three trials. Um, two of them are mRNA vaccines. Madonna and Pfizer on the other two are at a no viral vector vaccine, all in currently in phase three trials at this time. And the interesting thing about the vaccines is that in sort of an unusual move, thes four manufacturers have actually published their Phase three trial protocols, so that's given us a little bit of insight into the data we can expect. So all are enrolling tens of the target, enrolling tens of thousands of patients. Um, three of the vaccines all but Johnson and Johnson require two doses, which is sort of important to think about broad scale operas. Operational izing of this on Ben two of the vaccine. The MMR vaccines require storage and ultra low temperature, which has also led to some consideration of challenges of how we would coordinate and transport thes from mass scale vaccination. But I'll just leave with a comment that, interestingly, the primary endpoint of these vaccine studies is important to understand because they're all looking at prevention of symptomatic Kobe 19 infection, which can be mild disease on Lee. The Johnson and Johnson primary endpoint includes severe critical illness, so we just need to take this into account because ideally, the vaccine would do more than prevent mild disease. Ideally, we would have time and data to really show prevention of moderate and severe illness on, I think, when the state is available on how the FDA will navigate their criteria for expedited approval is still to be determined, and I'm also eagerly awaiting this data
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