Delaware going to approve our rotations and then also approval from your affiliates as walking in to your institution as well. So I want to thank you for persevering through. I also want to thank you for always responding to all of my many requests to I feel like every time I email you asking for something, but we truly do appreciate it. Our students really appreciate it. I know in the beginning and I really didn't have any answers for them. The students would ask me, are these rotations going to happen? And, you know, I tried to be optimistic, but I truly did not know. And again, thank you for letting this happen. And hopefully this will be, things will be getting better. And teaching through a pandemic has really been a challenge. Next slide, please. So discussion of the 2021 clinical practicums. It's been like a little bit of a mixed bag. Of course, we had to have snow on top of everything else. So we did have some snowy days. Unfortunately, a few students had car accidents. There are some car trouble. Back one, please. Sorry. Our students stayed in Airbnb ease. So they were really truly thankful. They're always thankful for clinical practice. But they really were truly thankful this year for the opportunity to go. So a lot of them did step forward and volunteer to travel or to get an Airbnb. And then this is the part he had a little bit challenging for me and for everybody. So I had all these different COVID scenarios. So he was like Mrs. Monson, I had an exposure but I don't have symptoms. Have symptoms but I have no exposure. I got the COVID shot, so I have immunity, but I got a COVID test. So that could be like a whole case study. It's like what do you do there, but we always have side on err, on the side of caution and be conservative. And we have to take into account the university roles and then also your institution's roles. Also, I had students that had symptoms but had a negative COVID test. So you still have allergies, you still have the common cold. So it was things and so on. You need a little bit more flexible with the attendance. We really do strive for 20 days. But this year was definitely a little bit more challenging. And trying to all of the makeup days. Next slide, please. So an update on the 2020 2021 clinical practicums. At the beginning in January. We were really fortunate that our analysts students and our Biotech students to or offered the COVID vaccine in January, January 2021. So that was awesome. And a lot of your institutions also offered it to our students as well. So I thank you for that. So moving forward, the University of Delaware Oh, it's requiring all students to be vaccinated by mid August to return to campus for fall semester. So hopefully this time next year, there won't be a question of, is the student vaccinated or not? They should all be fascinated. New requirements for your institutions. So please keep me up to date. I know some of our institutions they require and N95 masks. So our students have to go get a fit test. Also, we got an e-mail recently saying bad eyewear. Moving forward that the student's going to need osha approved eyewear, glasses, face shield or goggles. And again, let me know of any other requirements. Next slide please. So trudge axis. It's, you know, it's time just keeps moving forward. It's hard to believe. We're in the fourth year of use. So we started in 2018 with Karen Brinker. So she set the stage and initially we had a few Biotech students in it. And I did like a little tally the other day, I have a 124 users just in my MLS platform. So there are 97 supervisors, which are the clinical instructors. I have 27 students. So we've been utilizing it for the time. Logs, skill logs, lab practicals, student evaluations, and a written assessments. And you guys are doing a great job. As a GAN I knew I realized that you had been having turnovers with your staffing retirements or a staffing shortages. It whenever you get somebody knew, just let me know and I will send out an email with instructions. It's really straight forward. The person just registers, sets up a username, password, and then they can have full access to judge axis. And as you all know, it is free for all of you. Next slide, please. So this year has been a little bit different. I when I first took this job, I traveled traveled quite a bit. And then last year we were we were a little bit we were, I had of things we were thinking about doing Zoom. Nobody really knew that much about Zoom. And so I was traveling and doing Zoom meetings. So this year because of restrictions, you really can't have visitors to hospitals. All of my all of my meetings with you have been through Zoom. I think they've been pretty successful. You can let me know if you think a little bit differently. But generally how I do it is I need ten or 15 minutes with the student. Then I meet with you as well. So you can see my tally. I've had quite a few Zoom meetings this year. I really have not traveled. And then moving forward for next year, we'll see if things get lifted and maybe I can travel a little bit more to come and visit you. Also. I'm always available by available by phone call, so please feel free to either e-mail me or give me a call. Next slide, please. So problems, concerns, and issues. So again, I kinda address that about the absences. A lot of them were due to COVID. Initially. Beginning of all of this, we did have students that had to quarantine. So that was a little bit of a challenge. And then students trying to do makeup days, we did the best that we can and I think we did a pretty good job of it. Another concern that I had somebody had voiced was using a laptop in the laboratory and an unclean area. So if you have a student or students to want to study for the BOC and they are trying to do like assignments from the University of Delaware on Media Lab. So let's say that you have a really busy morning, maybe busy afternoon, but the last hour or two of the day is kinda quieter in the lab. Please feel free to let the students know that. And they can go on their laptop in a clean area. If you have another room or somewhere, or they could go and let them know. Our students, although they're very tech savvy and they text and they, they can email. They're very they feel very awkward and coming forward and asking you if they could have that opportunity. So please let them know. And a porous if you see somebody bring out a lap laptop or cell phone in the laboratory, please let them know that that is not acceptable. And you can email me as well. Another issue that I had with our students, not retaining instructions. So again, we can talk about this a little bit more in the breakout session. These students were definitely affected by the limited amount of face-to-face time in the laboratory. So they may have you can let us know during that time what you feel that the students were deficient on and just the instrumentation. And I do encourage the students to take notes. And you could do that as well. Even though they're always high-tech, they don't always take notes like with a little notebook. And I think that would be very helpful for them as well. Another issue or concern that I had or that you have had a lot of Ernst Young, a lot of our instructors in the hospital are very young. So our students may start to feel a little more comfortable with them or little too casual with. So they have to recognize that, you know, that they are the student and then the person in the hospital as an instructor. So I've had issues with the student being a little bit too talkative or that type of thing. But please let them know that you are the student and the other person as the instructor. Next slide, please. So the highlights I was talking about the highlights. Pretend the concerns. I'll say we successfully are graduating 20 to MLS students and we will have one in the fall 2021. We're going to have to master students actually start on June first. And I just met with him this morning at eight AM and we were going, uh, Richard, Texas, they're a little bit nervous. So they're going to be graduating at the end of August. Although there are master students, they are entry level master students. So I know a lot of you are concerned. You may feel a little intimidated that the student is a master's level, more so than an undergrad. But basically the rotation is the same and instead of a four week commitment, be a three-week commitment. The other positive things that I got, although there's been a very challenging year, several of the instructors have said that the student is the best student ever that they had. So I thought that was, I love to hear that. It's always very encouraging. And, and although it's been a very challenging year, our students are young and they're very adaptable. So one of the things that I thought that I would go phew that's a little bit different that I don't normally do, is each time the student goes on rotation, they have to breakthrough me a journal. So they have to kind of bright what they've done through the day. Then we have like a talking point like let me know something about your experience at the hospital. So the first journal assignment was what are your initial impressions of the clinical laboratory science profession? So I'll just read a little bit to you what some of the students had written. The student is in need of texts. So many opportunities to learn. There are various departments that have many job opportunities. I was learning something new every day. I realized how important technique an organization is when dealing with specimens. Because you can potentially put someone's life at risk when something is missed. Another student wrote overall, I did not realize how much instrument maintenance goes into one day, but that was kind of funny. One student wrote, I was told if I ever apply that they would hire me and not to forget about them once I graduated. How exciting another student said, everyone is so dedicated and passionate about there. How about their job and finding a diagnosis for the patient. And another student had written, I never realized how important multitasking is. So I thought that was pretty good too. Another question prompt is, what is a work ethic? Well, what is a reliable, accountable, and diligent employee? Describe one such employee that you've met on rotation. So I won't say who the name is, but I'll just tell you a little bit about this. The student wrote The Tech I shadowed who displayed the clearest meaning of work ethic, played a delicate balancing game, performing both LID tech and her new manager responsibilities. Despite how stressful the job was, she always worked hard and was reliable member of the team. At a moment's notice to drop what she was doing to help her colleagues or myself if they had a problem. If something went wrong or wasn't completed, she held herself accountable and did not point fingers. And again, they mentioned how important being able to multitask is. So I just want you to realize that, you know, all the students get all of the theory and the initial hands on from us here at Willard hall. They really do learn a lot from you and they're watching and they're taking all of that in. And that's why it's so important for them to have that clinical experience. And then the last writing prompt, what have you learned clinically and how has your experience affected your professional development? And student wrote my contribution to quality health care. It is ensuring errors in healthcare are kept at a minimum in any line of work, errors can spell disaster. For healthcare workers like ourselves, that disaster can come at the cost of patient lives. And learning the job over the course of these rotations has been one thing. But the learning implication, if we become lazy or complacent in our line of work has major takeaway from the top my time that they got from rotation. So they did realize that. So I just wanted to share that with you. I get like, I get so many journals and so many different writing prompts and some of them are really, really great. So I hope you enjoyed that. Next slide, please. All right. So I am ahead of schedule TO, but I think I think Dr. Flynn is here. So I'm going to introduce Dr. Flynn, so we're a little bit ahead schedule o and then one last thing. Why heavier your attention. So when we have our breakout sessions today, just some ideas of what we would like to go over with you. But I'm like, let us know our students strengths. Let us know our students weaknesses. Also let us know if you have noticed a major difference with this group of students versus others? If you have, what would you recommend that we do moving forward? But things should get fatter. Alright. Now on to our continuing education session. It is my pleasure to introduce to you Dr. Cynthia Flynn. Dr. Cynthia Flynn attended medical school at Albany Medical College and completed residency and fellowship at Massachusetts General Hospital. And as a board certified, she has been a staff pathologists, section chief of microbiology and molecular diagnostic laboratories, and a member of infection prevention committee that Christianity care for 23 years. For 15 years she has been in the, in the course coordinator of the EEG Scott microbiology symposium, presentations at Christiana infectious disease conference, Morbidity and Mortality Conferences, and state laboratory preparedness advisory community. Dr. Flynn is a member of Christianity cares COVID-19 task force. She has been fortunate to work with a great team of medical laboratory scientist and his shoe technologists. And thank them for their support. And it is my pleasure to introduce to you Dr. plan. Please join me in welcoming her. Thank you very much for that kind introduction. Are you hearing me okay. Is my face up on the screen or not? Yes. Okay. Just making sure hopefully I don't look too bad, but I can't see myself anyway. Uh-huh. Hi. I'm on. Nice to see you. So I'll be talking about what we've all been dealing with. This. Here are sars, CoV-2, COVID-19 pandemic. All that we've dealt with here at Christianity care and throughout the state and the world. So I'll go on to the next slide, please. So for first started about coronaviruses in general, there are important human and animal pathogens. There are a large family of envelope 8220 nanometer meter single-stranded RNA viruses. The distinct morphology of the corona is caused by the petal. I'll flub shake spikes that cause that show up as a crown around the virus on electron microscopy. And the RNA genome codes for two non-structural open reading frame, our genes as well as the spike protein, the, the envelope, the membrane and the nuclear capsid genes. And these are all important for both our testing and for monoclonal antibody therapies and vaccines that we're so fortunate to now have. So next slide, please. So I'll go over the epidemiology of coronaviruses. They infect the respiratory and GI tracts. They're widespread throughout the animal kingdom, infecting mammals and birds, including cats, dogs, pigs, mice, worst as wells and God knows what else. But bats are the largest host and had the largest variety of Coronavirus genomes. And as we well know from other coronaviruses, they can cross-species barriers. In Christ, disease in humans. We've got a new one in Malaysia That's crossover from dogs to humans. Seems to be a small thing, but something, yeah, we may be dealing with these types of things for entire careers now. Anyway, for years we've known about the coronavirus, is that cost and holds the two 29 e, The OC 43, et cetera. From now on I just call these the pre 2019 coronaviruses and they've just cause like lower pathogenicity than sars CoV-2, they account for ten to 30% of just the common cold we deal with every year. They're endemic there year round, but mostly we see them in the, in the fall and the spring and we started to see some of these pop up. Now that sars CoV-2 is decreasing. Like rhinoviruses, they can cause some more severe lower respiratory track infections in both children and adults. And sometimes they cause GI hepatic or neurologic disease as well. In the past two decades, we've dealt with these three new novel coronaviruses. First sars CoV-2, which mostly hit Canada and Toronto in, in the in North America, but also obviously was very severe and Asia, mers COBie, which was mostly dealt with in the Middle East, but also somewhat in Europe and sars CoV-2, which we've all dealt with. So please next slide. So to deal with just to talk about what's been going on with sars CoV-2 and COVID-19. And although sars CoV-2 is the name of the virus and COVID-19, the name of the disease. I'll use them interchangeably in this presentation as most people do. So COVID-19 spent reported on every continent, including our researchers in Antarctica, they experienced COVID-19. Governments worldwide have responded with various degrees of public health measures to curb the spread. Obviously, New Zealand, Stan, great and other places, not so much. So globally we've from last week when I last updated these slides, over a 164 million cases and over 3 million deaths with an overall global case fatality rate of 2.1%. Mean United States. We've had 32 over 32 or 33 million now cases and we're getting close to the 600000 deaths. Thank our we haven't gotten there yet. Um, so in, in the US, our case fatality rate is 1.8%. The last time US healthcare worker data has been presented at span, 3600 deaths, but that was last reported in April. And, you know, a very small percent of our health care workers or people of color, two-thirds of the people who had died at US healthcare workers have been people of color, which is so sad. In Delaware, We've had over a 100 thousand cases with 1641 deaths. Our case fatality rate gladly is less than the global or the US. It's 1.5%. So it continues to be a major worldwide pandemic. We all know what's going on in India. So US is still number one in cases and deaths, followed by India in cases in Brazil and deaths. And even though children have a less severe form of the disease in most cases, they're still in the new US has been that we've reported 3 million, over 3 million cases and at least 296 deaths. So obviously a much lace in this case fatality rate. But there, they are in more and more children are becoming the major or a major part of the infection on the variant seem to be creating a easier ability to infect children and they continue in, That's something we're really worried about. So next slide. So I'm going to talk about the different types of coronavirus testing because that's mostly what I'm involved with and this is mostly a testing talk. So nucleic acid tests are the gold standard test for detecting coronavirus. And it measures the, the are the, the RNA by reverse transcriptase PCR. The antigen tests detect viral antigen proteins and serology tests detect past infections by detecting our IgG or IgM are rare. Rare case it VHS detect IgA, but that's not really recommended by the FDA. Next slide. So the utility of sars CoV-2 tests. So the reason why that PCR-based tests are considered the most useful. I can see that it's over a long span of time from one week before symptom onset up to four to six weeks, you can catch a patient's infection with a PCR-based tests. The rapid antigen tests only are from one week before to one week after. So they're good for outpatient and physician offices or potentially other areas, but, but not as good as a PCR test and antibody tests. As you can see, because the PCR tests become positive and stay positive during the time of IgM and IgG, they're not really useful for acute diagnostics, except in some very rare instances. I'll talk about later, next slide. So there's an emergency use authorization by the FDA. I declared by the US health and Service Health and Human Services Secretary. And they did was this was declared in early February and it triggers the FDA to grant this emergency use authorization to improve diagnostics and expedients. Access for diagnostic tests enables them to be developed within weeks and months instead of years and more on more. And so it helped to this whole process along. And as of last week, there were 272 EUA for molecular tests and sample detection, 24 antigen test and 78 anybody tests. So we have it, we have so many more tests where sars CoV-2 than we have for most other disease processes or viruses. This off. So at home, testing available with 50 molecular and one anybody tests to be collected that can be collected at home. One molecular prescription at home tests that you can buy a molecular little kit that you can actually just do at home to see whether you have sars CoV-2. There's two antigen prescription at-home tests for over the counter I antigen tests that you can just go into Walgreens or Cvs and buy these tests now and to over-the-counter molecular tests. And there are nine antigen and three molecular tests that are used for serial screening programs in various sports or schools or other institutions. Next slide, please. So to go over, what are saga was at Christianity care for setting up testing and doing testing. We, we first set up our first test, the Cepheid GeneXpert. We set up an a day. Usually validations take a month or at least a couple of weeks to kick out all the tires. But We were so desperate from having said I'm tests to DPH L or viral core plaster male, whoever had capacity and whoever to turn the tests around fastest that we needed. We needed in-house testing. So we set the gene, we validated the Cepheid gene expert in a day, had it up and running, but had very limited testing. Later, we had the Fed gene expert four plex which allowed for influenza a BRS, RSV, as well as sars CoV-2. And by that point, CEF had had more capacity and we could provide this at Christiana well-maintained Middletown labs. Now we're back to Sir Toby two only, but we still have now we have Burt very much improved capacity and they're done at all three setups. And we have the Roche, KOBAS 60 and 100, and the Christiania molecular lab. We started off with just one instrument, which occasionally would decided it had enough of sars CoV-2 testing and collapse on us. But now we have two instruments and that's making life better too. In order to provide a little bit more data than just sars CoV-2. We decided to bring on to what we decided that we wanted a multiplex panel to provide more targets. And cryogen and cryostat were first FDA EUA approval. So we bought a new instrument, we validated that. And then they were very unreliable with their supplies. So we had a bio fire and so we bombed by a fire, got their FDA approval. We validated that test as well. And between those two instruments, NAS to test kits, we provide one test and we go back and forth and Moab depending upon what what supplies we have and how many modules we have, et cetera. The diet Sorenson plaza is now in use at the Cecil County Union hospital. That's part of the Christianity care system. And in Maryland, we have instruments at Wilmington and Christianity, but we're having trouble with validation and having it be reliable for us. But we had been excited because it was allowed us to do batches of 12, eight samples and it allowed us to lower respiratory samples such as BAL. So we're still working on it, but it's not as reliable as we wanted it to be. Our microbiology team has provided daily support for the molecular lab, an IC sectioning URL. For most of the pandemic. They actually did the first step of the molecular tests, pipetting samples for the assay, and then handing off the pipetted samples that are in the Roche collection device into the to the molecular lab to finish up the tests. But they're still running the tests to get the molecular on team a hand. Next slide please. So this is what this effort cartridges look like if you have a seam, I'm sure this team, this mostly see them and this is R infinity instrument here, and this is our great microbiology team. Some of them are retired and some of them are about to retire, but many of them are still pumping out sars, CoV-2 and other results and I'm very grateful for them off Next slide, please. This is a cryogen tias that instrument if you haven't seen that yet. The ties x, the cartridges, very simple to use and load. But again, we had some supply issues and there are some failures of the test. Occasionally. We've had to replace the modules, all that fun stuff. But it's when it's working, it's a powerful instrument. Next slide. The bio fire film erase. A little bit more difficult to set up, yeah, like two little biles to put your master mix in your sample in and then put them together and then load them, et cetera. But it's been, it's been a workhorse, although we only have two modules and that's been a problem. Hopefully we'll, we'll put more modules in that tower by bio fire is still the only tests to get its full FDA approval for sars CoV-2. Got it. March. So it's in its on this It's in this game for the long haul. Next slide, please. And this is what the dinosaur and some flexor looks like. It looks like a, basically a coffee maker on the lab shelf. And then you use these like eight well plates. And you can ill the the tinfoil by keeps the ones that you haven't used available for using again, on some lamps on discard the get to disk if your CT value is below 25 or if you have a high amount of virus, I'll talk about CT values later. But anyway, it's hello labs around the country use this instrument and early in the pandemic, it had a really great reputation, but we're, we're seeing some flaws right now. Next slide, please. So this is the Roche 6800. We now have another one in another room and the molecular lab. But this it has, it has automated pipetting steps, can do 92 samples in a batch. For things that are fully FDA approved, it's great. Or you can do C, T and G, and HPV and HIV and hep, C, et cetera, all in one run. It can be fully automated that way. But sars CoV-2 is not automated that way. So you have to do for sars CoV-2 runs, and that's it. But anyway, next slide. So about our Roche instrument. So at the beginning of the pandemic, Roche wasn't supporting us getting the the testing because we weren't put a hotspot, even though we're very close to New York and we all know that. But anyway, so first, Roche, because we were contacted all our senators and representatives and Governor et cetera, complained about the fact that we had the sweatshirts, your mat and we can be frightening testing for Delaware, but we can't. They, they supported letting us develop an EUA test. I gave us a paper about how to do it and figured we'd never get there, but we did we actually validated it in a week or two and they provided us the reagents to do that. But then after we decided we were doing too much testing and decided, well, they'll just let us do the EUA. So he had to go back to doing the EUA. But anyway, we got there, we did it microbiology assisted throughout. We did the 92 samples per run. The general lab assistant with evening reporting. We had challenges with all the different supplies and staffing challenges. People just couldn't take the workload that we were we were, we had to go through and the molecular lab and human issues that I talked with, especially about, especially with mucoid specimens. But we got through it. And it's, you know, it's, it's been quite a challenge. But anyway, Next slide please. So anyway with the molecular labs in the micro lab had where I've not the only lab set or challenge during the pandemic, the general lab did, you know despite having a decreased number of patients in the hospital, the inflammatory marker testing went through the roof with C-reactive protein procalcitonin lactate dehydrogenase ferritin D-dimer increase in quite a bit that D-dimer we had to increase the reporting range because of just how much clotting these COVID patients have. We we went to like the absolute upper limit that we could do for reporting on the general lab supported the COVID send out. So we had to do early in the pandemic and continue to have to do because of some lower respiratory samples. We brought on interleukin-6 testing on the erosions, the Rocher general lab instrument. And in four months did over a year almost 2500 tests. And we had a way to tweak a lot of that reporting and make sure people understood that doing multiple tests with the interleukin-6 doesn't work on because the levels don't go down quickly upon testing and it binds with drugs that you would have fake wood work against interleukin six and still it's detectable in the blood, et cetera. So there's a lot of education that we had to do about this type of new test, our next slide. So about these assays that we use for molecular detection of sars CoV-2. Most of them, like all the ones I showed that we use and Christiania are real-time PCR assays. But other labs use loop mediated isothermal amplification or lamp or a trance transcription mediated amplification or TMA. That's the whole logic instrument. And down that's used at TPA shell. That is CRISPR technology is I use that Sherlock instrument and may someday be a very important point of care test or lab tests in our general labs. But the other, a lot of people have the multiplex amplification with microarray detection. Digital PCR is the is also used in next-generation sequencing by alumina is very important, but the different assays amplifying detect different genes on the sars CoV-2 genome and most have two or more genes. In order to still be detected, even if you have different variance mutations. And some assays patients can collect at home and send to the laboratory next slide. Okay, So the test, because we have so many tests to over 250 different tests being used in different labs. Always test to detect different as differ in many aspects and not all are created equal. We tried to use the best, most sensitive test in our lab, but not everybody's been able to do that. And different specimen types and different collection methods make for more sensitive or less sensitive tests. Different methods, so use different reagents and instruments, different performance characteristics, limits of detection, et cetera, at different time to results. But I do now and some antigen tests or 15 minutes, it's four hours on the instrument for the Roche, it can be a whole day for some of these are half a day for some of these sequence analysis. It's always different turnaround times and also depends on laboratory capacity and staffing. So all this is like comparing apples to oranges and this is just with molecular assays. Next slide. We aim. We all know about how that we've had so much supply chain disruption. We had was a critical factor. We were always allocation early on for 3-SAT Fed supplies, Roche supplies, everything and and so, and, and just supplies for culture started to become an issue. And because it's a global than everybody wants the same supplies. Yeah. And yeah, it was it was definitely definitely a lot of stress there. We were senior leadership where we had meetings three times a week with with our with our supply chain people to make sure that we had enough collection kips, reagents, consumables, PPE, etc. And of course, pre-existing says staffing shortages just became worse. Next slide. So just to discuss what the testing strategies are for sars CoV-2. So there's three different categories. Diagnosis is just people that have symptoms on individual level diagnosing them with COVID-19. Either they're asymptomatic and exposed or they have symptomatic screening is you don't have symptoms. I are asymptomatic. You don't have suspected exposure, but you're being screened on a regular basis to make sure you don't have COVID and you're not spreading it to others. And surveillance is monitoring the whole community or population level. And usually that those results de-identified and don't come back to individual patients. But can be used for they don't use by individuals, but they can be used by the government or the school or wherever to make changes to screen more patients, etc. Next slide. So the type of specimen collection, nasal pharyngeal swab, so usually considered most sensitive. And anterior in areas in mid turbinate. The next most sensitive with wall pharyngeal swabs consider at the least sensitive. But we do do occasional all pharyngeal swab testing on patients that can't tolerate for some reason or other something in their nose. We've used viral transport media, universal transport media. Liquid means E swabs and sailing. We had not used the inactivated media because of the cyanide gas danger. But some labs have used it and certain, certain assays. Next slide. So the NAT test performance by specimen type, the data comparing the accuracy of testing from various sites is limited, but we get more and more every day. Test sensitivity does vary by specimen type. Upper respiratory samples are the most practical. Lower respiratory samples do have higher viral loads and can more likely reveal positive results. Then upper respiratory tract specimens in some very sick patients. But we have to send those tests out to Mayo. We have not about none of our FDA approved test your validated. At this point. The viral RNA levels are higher and more frequently detected in a nasal pharynx compared to the oral pharynx in most studies. Next slide. So the collection, specimen collection and handling is critical to any respiratory virus testing. And if, if it's a poor collection, it's going to have an end points. The testing results, so improperly collected in an appropriately timed or indirectly handled are more likely to yield false negative tests results, and collecting these respiratory specimens is close to clinical onset as possible. It normally within three days of illness is most likely to give a true positive result. And the amount of virus present in the duration of viral shedding varies. The patient anatomic site and the and the specimen collection and on more than one specimen over time can enhance recovery. Testing and multiple specimen types can be advantageous and access solution of specimens should be minimized to avoid making a false negative sample. So very important to have proper transport handling, storage. Because RNA can be very unstable, easily degraded. There's RNAs is everywhere, but then the sample within that environment, etc. Next slide. So these are some of the kits for the self collected specimens that can we release. It can reduce the need for PPE. Some studies have shown that the anterior near a self Kohut did, or the midterm at eight specimens can be almost as good as a nasal pharyngeal swab collected by a healthcare professional provider. And the FDA is approved, has approved self collected for the Roche cobalts. And they've also lets me know self caught this slide, the specimens that many of us have had this curative tests. But our labs at Christiania are not approved for saliva testing. On and down. Anyway, there are multiple FDA you a home collection kits next slide. So as far as the predictive values of the sars CoV-2 chess, you know, the sensitivity and low numbers of false negatives, increased negative predictive value, and then specificity of Blessed be now low numbers of false positives. We have an increased positive predicted I meant up, comes down at prevalence. I mean during that the height of the pandemic that we had a very high prevalence and some days of 20 percent positives, etc. A patient had a positive result at a positive result. Now we're having a lot, a much, much less positive results. So our positive predictive values are going to be going down, but our negative predictive values are going up. So you all know this. I'm preaching to the choir here. Okay, Next slide. So what does a positive NAT test for COVID really mean? Generally, it confirms the diagnosis of COVID-19 and ill patient. And normally you don't need to do any additional testing. Patients with COVID-19 no. Can have detectable sars CoV-2 RNA and their upper airways for weeks after onset of symptoms. And so there can be prolonged viral RNA detecting, detected, detected by these tests. And it doesn't necessarily indicate ongoing infectious nest in the patient if their, if their symptoms have improved. And there had, we had plenty of positive NAT tests following documented viral RNA clearance. And it doesn't necessarily suggest that there's relapse, that they could be reinfected by a barrier. Next slide. So the significance of prolonged viral shedding. So per the CDC, patients can continue to have detectable RNA in the upper airways following clinical recovery for three days after recovery. In generally, the RNA concentrations are below levels which in which the virus can be replicated or isolated. And also isolation. Infectious virus from upper airway specimens greater than 10 days after illness onset. It's only rarely been documented in patients with a non-severe infection whose symptoms have resolved. Infectious virus has also been isolated from respiratory samples of patients who have a good Pete. Positive RNA tests. Flourine clinical improvement. And with initial viral player, clearance is not been isolated. And this severe, clinical, severe or critically ill patients though, can shed virus longer, especially if they're immunosuppressed, organ donors, etc. Next slide. So as far as negative NAT test, usually it means that the patient's not infected with virus. Annex, it excludes COVID-19. However, we do have false negative test. And that means either the patient or it could be a poor quality specimen. It could be grilled too early or late in the disease. The specimen could have been not handled properly without virus, could not be might not be present at that site at that time of the collection for technical reasons because of PCR innovation or virus mutation. So hey, Christianity patients admitted and they have a negative tests and they're highly clinically suspected. They do have a second test. When they're up on the floor, they repeat that test. And if they're very highly suspicious to made into a lower respiratory sputum or BAL and send it to Mayo Clinic. So therefore, the negative result doesn't rule out infection and repeat testing is recommended if there's a suspicious for the high suspicion for COVID-19. So it's up, the optimal timing for the repeat testing isn't known. We usually do is that you do at 24 hours or 48 hours after the initial tests. Next slide. So here's just another graph showing you the timing of the symptom onset and when RT-PCR is apt to be positive are apt to have false negatives. So early on, before symptoms are really there and late in the disease, you know, 20 days into the disease or so, the patient could still have COVID pneumonia, but you would get a negative result next slide. So that's where serology can come in and be useful on for that patient at 20 plus who is in the ICU, the IgG and IgM, this will still be positive and can be a useful test. I'll see, you can see here that the BAL continues to be positive after the nasal pharyngeal PCR, it goes towards negative and also the stool PCR continues. That's why China has stool PPAD or rectal swabs for screening. Next slide. So talk about cycle thresholds and should cycle threshold to be reported and how should they be used, etc. Ct value refers to the number of cycles in RT-PCR needed to amplify viral RNA to a detectable level. And they can be such as subjective indicator to the relative viral RNA level at a specimen. Lower CT values tend to reflect higher viral loads and vice versa. But we don't normally don't report this because these are qualitative tests. They're not designed to be quantitative. There is no In a way to really make these completely a quantitative test the way they're designed. And so some laboratories do provide these values upon request and we do it to infection prevention and some other places as necessary. But how some of our tests such as bio fire, don't have cycle threshold. And so the clinical application of cycle threshold is, is uncertain because it's not standardized. And if they can't be considered the same across platforms, the selfed CT value can't be equated to a dinosaur and, or a Roche or a et cetera. So that's also another problem. Next slide. So here's a temporal profile of the different CTE values and viral loads in different patients in between and an endotracheal aspects and saliva, you can tell that they tend to decrease over time, but not quite. So viral loads tend to be higher during the first week of symptom onset. And pneumonia can develop late when the upper respiratory PCR is negative. Next slide. So the clinical utility of CT values for COVID, lower CT values may be associated with worse course of illness and outcome. Mortality tends to be worse. Disease progression tends to be worse with a lower CT. Disease. Fifth is, disease severity tends to be worse in activity tends to be worse. But next slide. But at the same time, we can't really depend on CT base. So there has been some surveillance of sars CoV-2 in wastewater. I knew I know New Castle County does do this and send this to an outside lab. Significant portions of individuals with sars COVID-2 infections can shed virus to species. And so you can monitor the wastewater to see if where having COVID outbreaks if even when patients aren't coming forward to be tested. And so this has been useful to tell when the COVID rates are going up and down, even when patients are being tested, it can be used even look for variance. Next slide about COVID antigen testing platforms. There's multiple EU ways. They can be formed rapidly and at point of care. They can have, they have faster turnaround time and they can be useful during early stages when the viral loads are at their highest, but they are less sensitive than most snap tests. And a negative antigen test does not rule out sars COVID-2 infection. If clinical suspicion is high, they have to get an AB test and false positive results are less likely, but they have occurred. Especially the triage and tests has shown some false positives or some, as we know, some of those from other EA, EIA tests, etc. We see false positives with different UTMs can create a lie and et cetera, that's been, that's happened with these antigen tests. Next slide. The only real, as far as COVID serology is concerned. The IgM and IgG antibodies developed along that same timeframe. I've shown you that in a couple of graphs now. And so there's really no great utility for testing IgM versus IgG in, in sars CoV-2. The disease severity likely affects the magnitude of the antibody test response. And the anti-bias decline over time in three to four months. The anybody decline may not mean lack of protect, protection because of memory B cells. And neutralizing antibodies are detected in the majority of symptomatic patients. But titers and durations may vary and we don't have many neutralizing antibody tests available to general laboratory. Next slide. So as far as the utility of sars CoV-2, the antibody tests are not useful for diagnosis. They really lack sensitivity. There also, the FDA recently came out with a statement saying they should not be used to, To, to tell whether patients responded to their vaccine. They are useful for epidemiological and service seroprevalence studies. They useful too for accessing exposure if used after 14 days post symptom onset. So we do use them in our ICUs when a patient's had a negative RT-PCR and they're wondering whether they really have COVID. They're very useful in children's hospitals for the multi-organ system inflammatory syndrome because those patients usually present with that syndrome after having maybe not even known they've had COVID. And it's useful for identifying and manufacturing COVID-19 convalescent plasma. Not that we do that anymore, but when we did do that, it was useful and they're using it to monitor vaccine trials, ongoing trials. Next slide. So next generation sequencing for sars CoV-2 played a major role in identifying the virus at first, and it's bad now and now it's very important again as to understand the dynamics of our outbreak, the mutation analysis to detect the variance that we're seeing now. And DPH has done an amazing job of now doing all are positive tests that are CT values under 35. This where it's the cutoff that they can, that they can actually amplify. And so the mutations of concern in the various areas that we've seen. The most important in the spike proteins are these. 484 K and L. Four to five are, are seen in most of these important bear action. Then there's these other mutations that I've shown are also things that are considered important mutations that, that they look for next slide. So there are various levels here for variance. The variance of interest for sars CoV-2 have specific genetic markers that change receptor binding and reduced neutralization antibodies or reduce our treatment episode. Many of them have been found in New York. This B11, 26 to be 12, 5. There's the P2 in Brazil and these various IT in India that we're hearing about on the news that be 1617 lineage where there's been 23. So the CDC still calls them variance of interests, the WHO as we categorize them into variance of concern. Next slide. Variance of concern or another level of worrisome for these. For these variants, increased transmissibility, more severe disease increase deaths, significant reduction in efficacy of neutralization antibodies and previous infections are not making. I'm not helping to provide immunity for these various, somewhat of a decrease in vaccination efficacy depending upon which, which vaccine you've received, reduce effectiveness of treatment and possible detection, diagnostic failure. But anyway, so P11 seven assemble one. We have the UK, that's the UK variant, is 50 percent more likely to be transmitted compared to the original sars CoV-2. That P1, which was first identified in Japan from a patient from Brazil, has a moderate impact and neutralization of monoclonal antibodies and reduce treatment efficacy. The South African variant B 1315, very important variant, 50 percent increased in transmission, reduced reduction and trends in treatment as well as vaccine. And then there's two that's of concern from California that also increase transmission by 20 percent. Next slide. So this is our data from a week ago in, from Delaware and Christiana for variance of interests. So as you can see that New York is number one. And this B1 26 is the most important. For a while, I thought the B12 six lineage was very similar base. You can see they have very different mutations and that I'm not very happy about what that nomenclature. Last week, we did confirm that we have one Indian variant, B 1.2617, but I didn't get a chance to run this list because it I got the information too late, but we have identified one patient that we knew had traveled from India and developed her disease. Next slide. So our variance of concern and Delaware that B11 seven is our number one and continues to be our number one. For scene in the United Kingdom. We have seen one South African variant and we knew that that patient was likely to have the South African variant when we sent it for sequencing. The California variance we identified early and say that around those levels, the Brazilian invariant, the P1, has continued to increase over time. Next slide. So variance of high consequence. Luckily, we have not seen this yet and we do not want to see this. This will mean more in another new pandemic. It'll mean that our prevention measures that we're using now and our medical measures are not working anymore. And it'll demonstrate failure of our diagnostics. Failure of our vaccines significantly reduce susceptibility to multiple therapeutics and more severe clinical disease and increased hospitalizations and deaths, et cetera. We don't want to ever see a variance of high consequence next slide. So to go over a couple cases that we've seen here at Christiana. We had this 142 year old male who had a chronic lymphocytic leukemia lymphoma and had Rikers transformation to diffuse large B-cell lymphoma. And he'd gone through five cycles of chemotherapy and it was admitted for cycle sex and had a screening NP swab that was positive for sars CoV-2. However, this patient was asymptomatic and was discharged on six chase after admission. So even though he was a immunocompromised patient, this patient did not develop true COVID disease. Next slide. And so this case is a 58 year old male who is admitted to the ED with shortness of breath, cough and diarrhea for one to two weeks. And outside lab had diagnosed him with sars CoV-2. And we knew we had COVID pneumonia. But the patient had traveled to Kenya and was clinically suspected of having possible South African variant. His pulse ox was very low in the seventies. I was hypoxic, required high-flow nasal cannula. Was it needed to them? To the medical ICU, acute hypoxic respiratory failure and acute renal failure. And we repeat is COVID test in order to send it to DPH all for sequencing. And we did identify the South African burying it next slide. So as admissions labs, his D-dimer is elevated, we have seen higher levels and that in COVID patients, but definitely a significant elevation. His IL-6 was elevated. Anything over 35 is shows your risk for B have been on a ventilator. You can see is of the age was elevated procalcitonin of this elevated that I saw. I saw nothing in the chart to say that he was ever treated with antibiotics. Ever suspected of having an antibiotic is CRP was elevated, fibrinogen was elevated and his transamination, as you can see, we're also abated. Next slide. Here you can see it's chest X-ray with showing obvious signs of pneumonia with the with the infiltrates in both and both upper lobe, so pretty much white out a blue lobes next slide. So it was treated with IV steroids in a five-day course, different depths of air, which is our kind of our usual for patients in medical ICU. He he didn't receive tools to mode, which is which is a specific IL-6 inhibitor which we've been using. Although not all studies have shown that TOC is useful. But this patient didn't receive it because of the Internet in place, trams and an ace is, and that's a counter productive thing for some of the liver issue. But he did he did actually get to walk or get mold out of this hospital after a 10-day hospital an issue. So successful discharge for COVID. Next slide, please. I just want to show you a few pictures. We we we at Christiana Care decided in order to conserve PPE and protect the pathology department to not perform autopsies on COVID patients, but some academic centers DID. And these are some pictures from COVID autopsy, pathology. You can see most severe COVID patients do have diffuse alveolar damage with fibrin at those black arrows lining the airspaces. There's also fibrin thrombi within the vessels and interstitial chronic inflammation is shown on the lower slide, next slide. And a very important part of of COVID is increase thrombosis. Why the D-dimer tests have been so important and they can have deep vein thrombosis and their legs and other organs. They could have microthrombi and our lungs. Study is 68 autopsies. They showed DAG and diffuse alveolar damage in 87% of the autopsies, acute inflammation in 43%, large thrombi and 32 percent and microthrombi and 65 percent. And this long none the lower picture showed with the with the orange arrow shows Obstructive microthrombi and those small vessels. So the upper picture shove a large macro thrown by next slide. So the happy news vaccination. Many of us have received the Pfizer or Madonna mRNA vaccines. You can see that this definitely advocate because I've been personally vaccinating a lot of these younger, 12, 15-year-old snap were approved for the Pfizer. And Madonna has also submitted that data to the FDA and hopefully with the approved soon. So you can see the mRNA is somewhat different in both the Madonna and the Pfizer. Mrna is full link spike protein mRNA in the Pfizer and it's somewhat modified in the Madonna. And the timing is, we know it's somewhat different. Day 121 pfizer gave 129. In Madonna. They both had large numbers of patients in the clinical trials and small numbers of positive cases of patients who got there who actually contracted COVID. And so both had the 94% efficacy and small numbers of positive cases in the J and J is a viral vector vaccine using at an add new virus vector in once in a spike protein. And though it's a one dose vaccine, I mean the good news about the J&J's it was tested against solve these circulating variance and performed very well against the variance. But we do know now that it causes these rare blood clots and especially the CNS blood clots young women, There's recently been a death in Brussels. And so, yeah, definitely a major, a major factor against the J and J vaccine along with some problems with with getting enough J and J produced, which is unfortunately cut back on and they use this vaccine next slide. So the good news for all of us who received mRNA vaccines is they're very effective. Again, all the variants that we're seeing, the B11, 17, which is our dominant variant in the US. There's no difference between the the, the wild-type virus and to be 1 17 as far as how well our vaccines work. The other variants have concern that P1, as well as the California variance and the Indian variant ID, there is a slight decrease, but not so much that we would even know. We will still, we are still protected against those with our vaccines. We won't be in the hospital, we won't be in the ICU, et cetera. We probably won't even captured at all if we did catch it. As long as our immune systems are good, we're good. The South African variant is more of a concern. It is a six-fold reduction in insensitivity to the viruses, however, do the vaccines rather. However, that still means that we're not going to be in the ICU and we're not going to die. As long as we have good immune systems, we are protected against severe disease with the South African variant, which is great. Next slide. So there had been breakthrough cases as expected, 95%, it's not a 100 percent. Their overall, there's over 10 thousand, but the CDC has stopped collecting the data for just break through and you don't need to be hospitalized. They are continuing to collect data if you're hospitalized or fatal breakthrough cases in the US. So the latest data is one that's in 339 hospitalized are fatal but two cases. And we vaccinated over a 115 million. So it's a very, it's an incredibly small number. And one in one out of 36 if required hospitalization, but 21% of those were asymptomatic. They were screened upon admission or before surgery, etc. So you've been even up that number. It's not all that number. Really on the data showed that more, there were more brac breakthrough cases in women. But overall, when you look at the hospital numbers, it's evening out. Mostly it's over 65. And unfortunately for those of us, yeah, for the patients who are immuno-suppressed to solid organ transplants or other severe immunosuppression. The vaccines aren't really working for them. Johns Hopkins has shown that in multiple studies. Now, I mean, we may be able to find a way that multiple vaccines give them more, more. But right now, unfortunately, those patients, we know they're not protected and they need to continue to mask next slide. So there have been some studies that show that sent dogs can be trained to detect sars CoV-2. Eight dogs were trained for a week to, to, to, to, and they, they show a sensitivity of 82% and a specificity of 96.4%, which is better than the antigen testing. That's for sure. Randomized sample say they did great. And you can see that they are used in some airports. Next slide. So can I answer any questions? Thanks. Great to give this talk to you and, and thank you very much for inviting me. Thank you so much, Dr. Flynn. And that was just wonderful. Thank you. Yeah, I'm good. And I do want everybody to know Dr. blends on vacation right now through presentation on that. So j.com and beyond. Thank you. Yep. It's been like to get a vacation this year. Does anyone have any questions? I have a quick question. So the gripper invariance that you're talking about variance have Concern course. The tests that we have now that are currently in play and Christianity, for example. A will those be detected by the current tests or yes, Emily, we keep we keep track of that belief. Everybody will always be detected. We really can't tell the difference between them. They're starting to come out with some PCR tests to tell the difference, but you're never going to find a new variant that way. So and at this point we do know that with our Cepheid test, there is one target that might get knocked out that may tell us that we're more likely to have a variant. And we've put a comment in our report for that, that it's called we're supposed to call the test presumptive positive and some Pysch. Early in the pandemic, the dark started using presumptive positive to mean low positive. Yeah. So when we knew that this was going to happen, we change our reporting to put a comment in presumptive positive. This may slightly means you have a variant. Okay. Something like that. I'm curious about can a patient be infected with more than one variant? Probably not. At the same time. We have seen very few patients was co-infections with sars CoV-2, we saw some early on. But now we're really not seeing that. I mean, over time, yes. I mean, you can have regular I mean, that's the whole Brazil problem. They had. They had COVID to begin with. And they kind of were very lack statistical about it. We're all like we've got natural immunity now. And the P0, P2 variant took over and like wiped out a whole big city in on the Amazon. Yeah. So that's why the, the, the mRNA vaccines are so amazing and so important that they are giving us immunity to these variants that natural immunity does not give us at all. Thank you. Nice talk. I was very, very covered everything from soup to nuts. Yeah. Pretty much had to deal with. Perfect. But I really appreciate you all being here and I so appreciate all that you do on I couldn't do anything that I do if I don't have the people that work in these labs and you really produce some amazing, amazing that text. So, so thank you again. Thank you. Any other questions? I have a question. Like, you know, when you watch when you watch the news, you hear so many different experts talking about where we're at with this pandemic and different views like whether it's national or global. I'd like your opinion. Where do you where do you think were out on this are clear, right? Yeah. Different scenarios? Yeah. I mean, I worry I worry that we're not vaccinated or not. You know, where yeah, we've gotten has 65 percent of Delaware has gotten one-shot. That's not good enough. I want to be we're Vermont is in Massachusetts in Hawaii. I don't want, you know, when I complained that highest, you know, doing their their lottery system and everything and Delaware has put in a small lottery system. But we need to do more. We need to be out in the, you know, do and mobile bands going through Wilmington because we all know what respiratory viruses do. And this summer maybe okay. But this way or may not. Especially if more people don't get vaccinated. And you know, what's, what's going on. India and Brazil isn't going to always stay in India and Brazil. So we will, we will hope for the best, but we'll plan for the worst. We stock up test kits, we stop, wait, stock up supplies. We, you know, even if the US gets back to normal, It's going to take five years at best a decade, even at best, to get the rest of them vaccinated. And in the meantime, we have enough people in our country that are not just vaccine hesitant or vaccine. God knows what. Thank you. Yeah. Sorry to be a downer. How you're being audited, who enact and everybody who's on this call, if you have anymore questions, are anymore anything else that you wanted discussed? My email is Cynthia, FCY, anti-HIV a dot Flynn, FL, Y and N at Christianity Care.org. And so just please drop me an email anytime I'm happy to discuss anything. Kim. Thank you so much. Any other questions? Yeah. Do you have a timeline of when the FDA my lower the vaccine vaccinate to nature. I would say it's a way they haven't submitted yet to the FDA. The studies are definitely going on. I mean, they've been quick to do it with this 12 to 15 age. I think they might be a little more cautious with the younger ones, but they are doing it all the way down to like, I mean, this the studies are ongoing. It's going to be hard. It could be within a month, it could be longer. I can't really say on that. But they are definitely excited about doing it. I know that. I know at least the studies are ongoing, so that's good. I mean, Pfizer and Moderna are definitely wanting to do it for everyone. I think there'll be a lump. And there is, of course, I mean, all all children are at risk for the multi organ inflammatory syndrome. So it's not that children aren't at risk. Nsa said before children are becoming a bigger percentage as more adults get pushed to detected of the disease. So even though there are people who believe that children are just not affected by this, it's not true. Yeah. And there are plenty of children that know that they don't want to infect their grandparents or their parents. When I did my last vaccine clinic and was injecting that 12, 15-year-old say we're so stoic and so brave. We're tougher than the guys with the tattoos. And screen. If I need to see more vaccines going to Canada, I have a son living up there right now. Gotten one plus 16 weeks for the next one? No. I I I when I have a lot of friends in Canada, I went to college at McGill. And so they're, they're good people either. They have a big place in my heart. Here. It sounds like no other questions. Well, thank you again so much. We appreciate it so much. That was wonderful. Okay. You have a great meeting paying tuition right here. So Paul is going to share the pace information and then we're going to take a five-minute break so everybody can run terrestrial or anything you need to do for go get a drink, coffee before we jump right into our breakout session. So Paula, I'll pull up the screen again and I'll thank you. Thank you. I think it's back at the beginning. So many hop through here real quick. Sorry. Way down here. How has, as Leslie does that secret. I have always wanted to do this secret session code where this continuing head is 0, 5, 2 line. And then there's a link here on the screen. If you have any issues with getting your continuing ed, you can email me. Also. These are the instructions are included as well. Again, the session code is 200, five to one. And we can put that in the chat as well. Yeah. Yeah. Be careful what you wish for Paula. Looking for you to help volunteer at the next meeting is to be a moderator. Always a way. It's like, what is the K for everybody's waiting. Thank you. So let's take a five minute break and we'll resume at my clock says 1048. So 1033, give or take. And then we'll jump right into our breakout sessions. Thank you. Thanks. The police power. 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00. 0 0. 0. Okay. Okay. Well, I think we're nearing the end of our break and give everybody another sec here. Has a great session. Leslie, It was really nice. I was she did a fantastic job. I heard it once before, but I was like, Okay, I just learned a lot more. Again. Sam is listening and he said we should invite her to as a speaker to like our seminar series that we have with the graduate students. I think people would find it very interesting.
Affiliates Meeting May 28, 2021
From Jodi Allen May 28, 2021
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