Mayo Clinic experts provide the latest information on various aspects of the COVID-19 pandemic including the state of the pandemic; the delta, lambda and other variants; and progress in the prevention and management of COVID-19 disease.
Zelalem Temesgen, M.D., consultant, Division of Infectious Diseases; professor of medicine Featured Expert:
Gregory A. Poland, M.D., emeritus consultant, Division of General Internal Medicine; Mary Lowell Leary Emeritus Professor of Medicine; director, Mayo Vaccine Research Group Featured Expert:
Abinash Virk, M.D., consultant, Division of Infectious Diseases; professor of medicine Featured Expert: Claudia R. Libertin, M.D., consultant, Division of Infectious Diseases; professor of medicine
Featured Expert: Joseph D. Yao, M.D., chair, Division of Clinical Microbiology, associate professor of laboratory medicine and pathology and medicine, assistant professor of microbiology
Click here to claim credit and view faculty disclosures. Select Register to begin the credit claim process.
The views and perspectives shared in these resources are presented based on information available at the time of recording.
welcome on behalf of the Mayo Clinic School of continuous Professional development. I'd like to welcome you to the Mayo clinic Covid 19 live webinar series. I'm Whitney Pruitt your host for today's webinar updates on Covid 19 variants, disease prevention and management. This webinar is accredited for one am a pr a category one credit. A record of attendance will be provided for all other health care professionals. Here are the disclosures for today's activity before we get started, we'll cover a few points. The first is how to claim credit. If you'd like to claim credit after the webinar, please visit ce dot mayo dot e d u slash Covid 0909. You'll need to log into the site and if this is your first time visiting, you will need to create an account profile After you've done this and logged in, you'll see an access code box, you'll want to type in today's code which is COVID 0909. This will value to access the course to complete a short evaluation and then you'll have the ability to download or save your ce certificate. This Lincoln code will be dropped into the chat box throughout today's webinar. The second item is hell will facilitate questions. You'll see at the bottom of your screen the chat and Q and a function. If you have any questions during this webinar for today's presenters. It's important that you dropped them into the Q and a channel rather than the chat box. This will help to ensure that the panel can see your questions there is also a helpful up vote button so be sure to up vote the questions that you would like to see answered if you're experiencing any technical issues during this. Please use the chat feature to share some of our support team. Tennis is and here are today's learning objectives which will be covered throughout the webinar. It's my pleasure to introduce our moderator for today. Doctors emblem to my skin. Dr timothy is a professor of medicine at Mayo Clinic in Rochester Minnesota where he directs the Mayo clinic HIV program, the Mayo Clinic Global HIV education initiative and the Mayo Clinic Center for tuberculosis. With that I'd like to turn things over to my skin. Thank you with me. Hello everyone and welcome to another edition of our ongoing program featuring updates and insights into pressing issues related to the COVID-19 pandemic. As in previous sessions we have a panel of expert faculty from the Mayo clinic who will provide brief introductory remarks and then respond to questions from you the audience. Our expert faculty are dr Gregory Poland mary Lowell, leary emeritus professor of medicine, director of the Mayor vaccine research group. Distinguished investigator of the Mayo clinic and editor and chief of the journal vaccine. Next dr Avinash Berg consultant in the division of infectious diseases, professor of medicine, Culture of the COVID-19 vaccine allocation and distribution group and chair of the enterprise antimicrobial stewardship that a claudia libertine consultant in the division of infectious diseases Professor of medicine and director of infectious diseases, clinical research at Mayo clinic florida. Finally dr joseph ya'll consultant in the division of clinical microbiology. Associate professor of laboratory medicine and pathology and Associate professor of medicine. We will begin with Dr. Avinash Berg providing us an update on the status of the Global COVID-19 and its variants. Avinash. Thank you. Doctor Stein Meghan. Uh I'm honored to be here. I'm going to talk about the variants of SARS COv two just to make sure that everyone is on the same page. In regards to understanding SARS-COV-2 variants. This is the schematic of stars Kobe two on the left. You can see that it has a cell membrane, it has an envelope, it has various proteins on the outer surface. The most important of these being the spike protein or the S protein Within the center of the cell. There is the are any of the Sars-Cov-2 virus which has jeans for numerous uh functions of the protein. It's off the virus itself including the gene for spike protein and the receptor binding domain on the right. You see the a schematic of the spike protein which essentially shows various segments of the spike protein of which the most important is the uh receptor binding domain which helps the attachment to the rescue resells and entry into the rescue resells and cause its pathogenesis. So when we look at these variants, what is borders, what do these variants mean? So in the normal course of our any viruses or even other viruses but more particularly for RNA viruses, They do have some mutation all changes. Some of these mutation all changes As they are replicating our of not clinical significance and are essentially um go unnoticed in terms of change in the pathogenesis early. However, some of these mutations do actually increase transmissibility or have an impact in regards to uh response to treatments or vaccine uh serology uh and effectiveness. Uh some of these are significant such that they become what we call variants of concern. And most of these mutations, particularly in relation to Sars-Cov-2 are in the spike protein and the uh receptor binding domain such that it impacts the transmissibility and response to uh convalescent sarah or vaccine syrah that is produced after vaccination. So just a schematic. Another of showing you these mutations. This is SARS-COV-2. The original Wuhan strain. The wild strain did not have any of these mutations. However, subsequently there were numerous mutations that emerged, first of which was the D 614 G mutation which uh give the virus more transmissibility and this as you can see and this does not include all the variants that we have currently but this has been uh seen in most of the subsequent variants. However, there are other mutations like the N five or one why that are only seen in some uh some of the variants but not in all. For example the N five or one why does not occur in the delta variant. Another mutation e. For it for K which is significant in terms of its transmissibility and lack of response to vaccines. Has been seen in certain uh variants, particularly the Byetta variant or the South african variant and also in some of the alpha variants. Uh And delta variants have other uh mutations that don't necessarily overlap all of these that we show here As the pandemic has continued. The number of mutations that have been accrued by Sars-Cov-2 have continued to increase. So on the Y-axis. You see the number of mutations that are seen from the original 19 a strain and as we go towards the current time, you can see that the number of mutations have continued to increase. The dark blue here is the beta or uh better uh strain actually um the alpha very in right here and the green here is the delta which is the current predominant strain globally. So based on how how much the virus transmission transmission and disease severity changes. Uh W. H. O. And various uh national authorities have labeled them as variants of interest or variants of concern. Currently the variance of concern are alpha, beta, gamma and delta. And as I mentioned, Delta is the predominant global strain at present and was originally identified back in India in uh late 2020. Uh many studies have shown a decrease effectiveness to the convalescent sarah as well as vaccine terra and this will be discussed further uh in a short while the in the U. S. There is also another definition variants of high consequence. This is basically variants of concern that now have become significantly reduced in terms of their uh treatment efficacy or vaccine preventive efficacy and also an impact on health care infrastructure in the sense that the hospitals are overflowing and patients are more and more getting transmission transmission of SARS cov two such that the whole infrastructure is beginning to really have a difficult uh oh control of the pandemic. These are called variants of high consequence. Currently there is no variant of high consequence in the United States. If if it is ever identified these have to be reported to the World Health Organization under the International Health Regulations. So that global response can be instituted currently in the United States. Uh as you can see that the pandemic has is going back into its third wave and based uh from the native here in on june 14th 2021 we are currently at 157 160,000 cases a day. At the native we were at around 8000 cases a day. And the predominant strain, as you can see here is the delta variant um at the top for being the alpha beta and the gamma variants. And you can see that those of all essentially decreased in the amount within the infections in the United States and similarly globally as well. But that um my conclusions are that the pandemic is ongoing. New variants are expected to emerge. The current global uh strain is the delta um and we expect more variants of interest and concern to emerge and we have to continue uh vigilance at a national and global level uh to control the pandemic and with that over to DR yao thank you thank you for the continue education committee for the opportunity to present my portion of CMI. Today I'm going to talk about um testing for the variants of SARS Kobe too. Currently in the United States and most parts of the world. There are two general methods for detecting and determining variants. Um a rapid method rapid meaning less than 24 hours of turnaround time is detection using amplification method on despite protein encoding decoding mutations and look at the profile to determine whether they belong to those of V. O. C. Or V. O. I strains. A more complete but labor intensive and perhaps more expensive method is to sequence the genome of the virus in the positive clinical samples Now. The genome as you saw from some of the slides in Dr. Burke's presentation previously. It's about 30,000 basis long and these sequencing methods will amplify and sequence um either almost 98% or near total of the entire sequence and compare the sequence sort of like fingerprint to that of the original Wuhan strain of SARS COV two to look for mutations and changes. Um I also want to stress that all the emergency use authorization essays in the United States for molecular detection of Sars-Cov-2 currently can detect variants but they cannot determine whether it's a wild type or a variant strain. Similarly with the neurologic antigen tests, they can also detect the variants but cannot distinguish among the different variants. Just a general uh schematic diagram uh illustration of how these two methods work on the left hand side is what I call the signature mutation profiling. And you can see among the different variants, they have signature mutations in the uh spike protein encoding region uh indicated in red. So the alpha variant has the 69 70 double deletion in the spike protein region as well as the N 51 Y that is also common to the beta variant and the gamma variant. Um The California strain, which is the epsilon variants have these unique L 45 are mutations. Um And so a combination of profile of these mutations can uh suggest that what we're dealing with in the positive samples are such strains. Now, the more definitive way to determine strain is to use genomic sequencing on the right hand side. You see that the first right hand side is the genome and the genome can be amplified in various segments. So these are the multiple M. Pecans and using software were able to line up and clean up the overlapping region of the genome to arrive at a consensus genome sequence at the very end at the bottom. And then using sophisticated software were able to compare this consensus sequence from the patient's train to that of the wild type or reference strain and then determine um using public databases to determine what lineage or clade the strain came from. And I'm just going to take off that laser pointer and then just click it. There you go. Thank you. Uh Now there are advantages and disadvantages of these two methods. As I briefly mentioned, the rapid method has low complexity. It has high throughput but and also relatively expensive However, because of the limited mutations being detected we cannot determine the exact lineage er clade and also when we have new mutations or new variants uh emerging the essay has to undergo redesign of the amplification methods and probes along with the software. So this requires constant update to the essay. The genomic sequence method will provide genomic lineage and played. I won't need any major update to the S. A. Design but may require some software upgrade uh to determine what new variants or mutations are being detected. Now the con against the genomic sequence exactly the opposite Or come to those of the rapid tests. Uh it will take because it's a highly complex test. It does take 2-3 days to get a result. It has limited throughput Unless one has multiple instruments and sufficient laboratory personnel. Um And also it is quite expensive because of the labor intensity required for such tests Currently at our institution. We divide the test indications to two groups. One is for surveillance or infection control purposes, such as if the institution is interested to know what is the current circulating variant in the infected population. Either inpatient or outpatient. If a patient is persistently positive from clinical testing Uh such as more than 30 days apart. Is it a reinfection or is it a persistent infection such as what we see in some of the severely immuno compromised individuals? The second group um is less well defined uh will be those needed for direct patient care needs. Um In this case uh If one is interested uh in finding out whether this is a vaccine breakthrough or vaccine escape mutants. Um and especially if one vaccine is found to be less effective than the other. Again, certain variants, this may be important to know um those who perhaps have no response or low response to convalescent plasma treatment or two monoclonal, anybody therapy, I want to spend one or two slides on neutralizing antibodies. Since from our last cmi sessions there are quite a lot of interest in when and how can we ask for neutralizing antibodies to determine protective immunity in the vaccinated or previously infected individuals. Uh from what we know the antibodies produce either from previous infection with SARS COV two or vaccination can either be binding antibodies or neutralizing antibodies. The binding anybody's actually do not have significant protection against a future infection. Whereas the neutralizing antibodies will bind to the receptor binding domain, the R. B. D. Domain in one of dR Burke's initial slides of the virus. It will actually prevent the virus from attaching to human cells and cause infection. So it has a function of protection for the vaccinated individuals. Um So these are very important to determine um immunity. Now the problem is that uh currently the commercial essays for determining I. G. Or I. G. M. For serology do not distinguish binding anybody's from neutralizing antibodies. So very specialized tests, mainly in research laboratories are needed to determine the presence or absence of neutralizing antibodies. And the classical way of determining presence of neutralizing antibody is to use plaque reduction neutralization tests. I won't go over the details of this test but you can imagine that this is a very very manual, labor intensive way to determine the presence of such antibodies and it's really impractical to be performed in routine clinical laboratories. Um And it does require the use of live viruses which is a biosafety level three facility and not too many clinical labs have such a level of biosafety facility. Um Another way is to actually use um novel methods using Sudha type viruses such as a particular store mastitis virus or lenti virus vector that can express despite protein expressed from stars Kobe too, these can be now performed in BSL to safety laboratories which is what most clinical virology lab in the country. Hast facilities for it can be done in a micro title well played format. But the major problem we see is that there is no standardized method to perform such tests and as a result the results generated from these different tests are not standardized and very variable. The most important lack of knowledge we have currently is that we don't know what is the level minimum threshold of neutralizing antibodies present in the infected or previously vaccinated individual that would correlate with protective immunity. So the bottom line is that we don't recommend asking requesting or performing neutralizing anybody's to determine um protective immunity until further data is available on this uh neutralizing anybody threshold. Oh and here and pass on to dr Poland yeah. After pulling your immediate, sorry. Here we go. Are you able to I'm hearing I'm hearing you. And if you just click your mouse here you'll be able to advance. There you go. All right well I'm going to talk just briefly about a few points that Dr Tamez Gin asked me to address. Oops did I go to the first one? Whoops can we go back thank you. Um thank you. So so just a few points to make if you look at neutralization of SARS cov two isolates. I wanted to point out a couple of things. One is that as we go to certain variants and here you see in green, the original Wuhan ancestral strain versus an orange the P wants so called P one variant. You do indeed see a reduction in neutralization of those isolates. If you look at vaccines that are currently authorized in the U. S. Or in the EU you see that we have of course to M. RNA vaccines one adenovirus vector vaccine whereas in the Eu they have to adenovirus vectored vaccines. What's important is that against essentially all of the variance of concern with perhaps the one exception being the alpha variant, there's been noticed reduced neutralization activity from vaccine induced immunity. Now part of the reason that you're hearing about breakthrough infection I thought was summarized well by this graph by a friend and colleague of mine Natalie Dean at University of florida. If you look at the top part of the graph, this is a vaccine that prevents disease but not infection. So this models what our current vaccines do And you see two columns before and after and what you notice is that the orange part of the column, the asymptomatic goes from, you know about 30% or 25%, something like that to being more like 70 or 80%. So indeed the three vaccines that we have available in the U. S. Are more disease blocking than they are infection blocking a vaccine that would prevent disease and infection is visualized below where you would eliminate most if not all of the severe, moderate and much of the mild disease, leaving only the asymptomatic. So as you hear about breakthrough cases and there is a spectrum in them um breakthrough cases are expected. It would be impossible given the vaccines we have that breakthrough cases would not occur. The difference is that these breakthrough cases are predominantly asymptomatic, mild and in some cases moderate now this is a graph of a theoretical construct for how we think about this in vaccine ology. And if you look at number one. So what happened is that if you've got an M. RNA vaccine as I did we got two doses and that's an attempt to initially build immunity very quickly. Uh huh antibodies. Wayne with time that's expected. But could they wayne to a level that now makes one susceptible again. And that's what you see is number two. What would be called a late booster. The other possibility is that a viral variant arises sufficiently different from the ancestral strain that we initially immunized against such that you have to refocus immunity to what would be called a variant focused booster or dose. And the the tension right now in the field Is between .2 and .3 who should be re immunized. When should they be re immunized and what should they be re immunized with. I was also asked to talk about licensure. So full license licensure was granted to Pfizer on 23 August for for persons over the age of 16 they incur a post licensure commitment for a whole variety of studies that will go out to 2025. These are all safety studies primarily around the issue of mile card itis. The other vaccines will follow as they get all of their data in and to the FDA in terms of routine boosters which I've mentioned. There's a whole lot of data that needs to be considered including are we seeing increased susceptibility as a result of time as a result of new variants the combination of the two. Is there an issue with the effectiveness of boosters and what would be the safety timing dozing and for whom as I mentioned do we use a late booster or a variant focused booster? There are issues at least theoretical in the field of vaccine ology to think about in terms of what's been called trained immunity and antibody dependent enhancement of disease. By developing sub neutralizing antibodies to a variant virus different enough from the original virus and other issues to the FDA will actually need to consider a variety of these issues. 17 September Finally a third dose or late additional dose has been authorized by the FADA and approved by the chip. For persons who are moderately to severely immunocompromised comprising roughly about 3% of the US adult population. You see some of the indications there for what immuno compromised means. Well what about Children? We expect that there will be an E. U. A. For the Pfizer vaccine for 5 to 11 year olds by the end of september. That's of course a loose date but that's what the internal chatter is suggesting. The dozing in Children will be 10 micrograms. So a third the adult dose um Pfizer is conducting their studies and kids six months to four years of age and they're using 1/10 the adult dose or three micrograms. We don't have those study results pending because they started later. Madonna will follow after Pfizer and J and J after Moderna. And with that I think I hear to my four or 5 minute timeframe on to dr liberty. Thank you. It's an honor to be here in terms of where and what is happening globally with delta variant global cases of covid 19 are reported here in the last 14 days and we could see that they're taking off in the United States, the U. K. Botswana, the Middle East. In some portions of south America. The hospitalizations have escalated in United States to the extent that the number of people infected have reached 40 million and deaths unfortunately have reached 645,000 transmission is very high and what I'm going to be targeting to discuss with you is the which is why delta is so contagious and transmissible. This is taken from a nature article. It's a computer simulation of despite protein and the delta variant is highly transmissible. It has gal icons. The cover actually despite protein and the flexibility of despite protein is kind of like an elbow, shoulder and wrist where it can move around so that the receptor binding domain can find the ace two receptor which increases its contagiousness. And then another feature of it. It uses the host protein fear on to cut amino acids to allow the spike protein to move forward and in fact the next cell very efficiently. So what is different about the delta variant? The key answer here's transmissibility. It's estimated to be at least 60% more than the original or the alpha variant strain. Each individual can in fact 8-9 people. Unlike the original state strain where an infected person would potentially transmit to two people, the delta variant may cause more severe illness. And this was suggested from Canada from Scotland and that we should anticipate seeing patients infected with DELTA two more likely be hospitalized. And I think we're experiencing that all three United States. But the question I was asked to answer is who is being hospitalized and the answer really is who is unvaccinated. We have about 332 million people in the United States and we see in the upper right hand corner here that only about 53% of the total population has been vaccinated, not because of availability but For other reasons those that are over the age of 65. We see that they're carrying their share of being vaccinated at 80 and now 92 Percent have taken at least one dose. The gap exists here in those that are aged 12 through 65 where we only have about 62% of our population being vaccinated. So who is becoming hospitalized? It's the unvaccinated those that are less than 65 years of age. And unfortunately as a consequence of the vaccine not being available to those under the age of 12, 1 out of four Children um Were reported as infected in United States as of 9-21, 1 out of four of our kids that don't have the availability in order to take. The vaccine is actually crushing of those. And doctor on Poland nicely already alluded to the issues of breakthrough infections. They do exist. We are not surprised that they exist. But what is important is they are not people that have breakthrough infections comprised point oh 4% of the people that have severe enough disease to present to the hospital. And most importantly only 40.1% have died from the disease from a breakthrough infection. So the unvaccinated are the ones most likely to be hospitalized in just this past weekend. Mmwr we saw data Coming from L. A. county showing that from May 1 to the end of July that there was a 29 29 times greater than the unvaccinated people being hospitalized. So what are we seeing? We're seeing younger people less comorbidities and rapid decompensation, oxygen wise when they hit the hospital there earlier onset of symptoms may be that of the simple cold symptoms, ear aches, nausea, vomiting and diarrhea to the extent that they get dehydrated and present to the E. D. With sync api cough, chills, fevers and my ulcers and there's less predominance of loss of taste or smell. The higher risk of hospitalization and severity disease we've talked about in terms of therapeutic management options. Um There's not much more to stay here other than we have what we previously had. Um for the original strains we have remdesivir which shortens the time to recovery. We use decks and methadone to reduce the mortality and we require here that you must be have four leaders of oxygen before you would get the decks of methadone six mg Daily for 10 days. We've implemented the Codex Protocol where a study has revealed that alive and ventilator free days um using dexamethasone 20 mg daily for five days decreased to 10 mg daily for five days improved. Covid a RGs. So this required Burling criteria of a RGs to be met. Tuscaloosa map improves survival. And we're using it exclusively on when it is available to those who exhibit rapid respiratory decompensation. The example would be somebody comes in then escalates the needs for leaders and then rapidly goes to high flow or bypass. Unfortunately, there's we're utilizing tuscaloosa bob about 400% above pre covid levels. We've added parasitic nip with somewhat softer data as a jak inhibitor to be of benefit. The studies actually were done prior to decks and methadone being available but we do use it in combination with six mg of dexamethasone. Own the significant change that has occurred is with a dual monoclonal Regeneron. We're now in hospitalized patients who are infected that are emitted for another ideology. We may give them a monoclonal antibody that is the biggest change that has occurred in the past month. And with that I'm going to close and transfer this back to see me. Thank you everyone for really read presentations and giving us the background to respond to the audience questions and there's many of them. Uh I will start with a question about the move variant and what it is and where we are with it and maybe a bit as you can start with that maybe. Yes. So the mu variant uh is not uh absolutely knew it was first identified in Colombia in January 2021. Uh currently globally there's only about less than 1% presence of the new variant. However, it seems to be increasing both in Colombia as well as in Ecuador uh and currently it has been identified in almost all of the States in the United States but again the percent compared to the number of other cases such as the delta cases mu is very very small. Uh There are some preliminary data to show that maybe there's decreased response to vaccine and maybe monoclonal antibodies with um you variant. Um And so that's one of the concerns. But this is preliminary information. And the second thing that's important to know is that overall the incidence of muse seems to be decreasing overall. Thank you. Does anyone else want to add to this? If not, I will proceed to the next question. And the next question has to do with vaccines. So there was a recent approval, the first approval for a covid vaccine. And there are a couple of questions associated with that approval. Uh First is what is the difference between the emergency use authorization and the standard B. L. A. F. D. A. Approval that we know from before. What's the difference between those two And what's the implication? Yeah, I'm happy to take that questions in uh with an E. U. A. There are basically four criteria that have to be met before FDA would grant that. The first is that the secretary of Health and human services would have to declare a public health emergency. The second is that of the known scientific data. Uh There's reason to believe there's benefit. The third is that that benefit outweighs any known risks. And the fourth is that there's really no other available countermeasure. So with those four criteria, um all three of these vaccines received their EU A. With A. B. L. A. What happens now is that you have adequate safety and efficacy data that the FDA can review and its considerable where you have safety data that reaches out initially it was two months. They moved it to six months. Um And you're looking at millions of pieces of data I previously said on that FDA committee and I will tell you that if you visualize the largest freight elevator that you can imagine. If you printed out all the clinical trial data, they would not fit on that elevator. And each piece of that of those pieces of paper have to be reviewed by hand by human eyes um in order for an approval to occur. And that has happened of course with the Pfizer vaccine. Thank you. A related question. Is should new preparations of vaccines addressing the variants that are of concern now be prepared as opposed to boosters of the older versions of the vaccines. It's a great question that is happening um Both at Pfizer and Moderna I imagine. But don't know for sure that that's happening at J and J. That the big issue is how will what will be the regulatory pathway at the FDA for this. The proposal has been to treat it much like influenza where we have strain changes nearly every year. Um and they're basically a few safety and ferret studies that are done as opposed to requiring new large scale clinical trials each time which I think we would all agree is not really feasible. Very good. Have been actually you want to add to this? Uh No except that you know there is a lot large number of data now you know in the U. S. And globally for both all three of these vaccines and some preliminary information with um you know Madonna uh the the prior kind of formulation and the beat A formulation showed that they were fairly similar in terms of the immune responses in the small number of patients that have been studied for that. So again do we need to have these variant mediated vaccines or will the original booster actually take care of it? We don't know that's that's being studied. Thank you. And uh I think a very interesting question just came up and and that was for those who are vaccinated and present with breakthrough infections. Do they experience the long hauler syndrome? Do they experience it to the same extent? To a lesser extent. Do we have any information on this? There's actually have been some studies. And the bottom line of those is that the risk of long haul uh covid is reduced by at least 50%. Again, another advantage of being vaccinated and the severity tends to not be uh let me say it a different way tends to be less severe than in the unvaccinated. Yeah. Yeah. So in fact Greg uh just nine days ago september 1st the Lancet infectious diseases are the big paper from the U. K. Where vaccines not only prevent serious infection and hospitalization but also uh prevent uh you know the magnitude of the number of long hauler syndrome. So it's so good. So uh there is a question about uh uh a a person who developed anaphylaxis to polyethylene glycol which is a vehicle used in the in the RNA vaccines I think. And so the question is if someone had enough access to peg polyethylene glycol what are the options for vaccination? Um Andy yeah. Yeah I'll take a stab at it too. I agree with Claudia that J. And J assuming there's no contra indication there. However having said that I would say that it's worth visiting with an allergist. Knowledgeable in this interestingly enough there was a study done and I just can't place it in my mind now. What journal it was in in people that it had allergic reactions. Not anaphylaxis but quote allergic reactions and the vast majority of them were able to get a second dose safely. So something like that is serious enough that I would visit with an allergist get tested and determine what the best course is. But you know the simple straightforward answer is exactly as Claudia said. We use a different preparation. Yeah. Am I correct in perhaps remembering that Peg is used only in the M. R. And a platform, correct The three of the three covid vaccines and here in florida. We do have anybody with that history be seen by the allergist before going next to the J and J. Especially when there was an issue of what vaccines were available. So there's another interesting question. Uh and I wonder if we have the answer for this. So there are mutations, there are variants and there are strains so you know, SARS cov one? SARS MERS SARS cov two and then uh SARS COv three perhaps. So what distinguishes, you know, how much medication does that have to happen for this to be designated a new strain as opposed to a variant Kind of goes back to the follow genetic tree for these viruses. So for between MERS and SARS and Sars-Cov-2 there has to be a fairly significant differences in the genome. Uh you know, more than 2% of the genome has to be different for it to be called the new strain. Whereas with the um variants there are um mutation all changes uh that don't make it a completely different virus. And and uh the mutations maybe one or two or could be many um you know and just has some changes in there pathogenic city. I don't have. Uh Door anybody else wants. Yeah but I would agree. Sometimes there's an additional criteria used in regards to any Fiona typical differences induced by by that. Strange but joe anything to add in terms of quantification of those differences. Yeah. Uh I'm not sure what the current international Committee on Taxonomy of viruses used for vaccinating the strange differences. But uh DR burke is correct that generally we use 2% or more differences in the nucleotide basis uh will constitute a new strain um And then to go into a different virus requires a lot more differences. Um but you know, different database also use different criteria. So it's not standardized at this time but in general 2% is what we use for strain designations. Very good. Another question was that vaccination status is used for entry into various places and whether ah experiencing the infection itself. Whether that might qualify for that purpose hospital and how might that work? Mhm. Yeah. This is a tough question. We we might even have a little bit of differences here. I'll give you my view on it. Part of the problem is that we're wanting to do something um societally to encourage people to get vaccinated and to protect other people at the same time as time moves along and we develop more variants, they'll be wobble around whether somebody actually is protected. I point you to an article that came out two days ago in an emerging infectious diseases showing a shockingly high rate of non zero conversion in people who had documented infection by pcR swab. That was really interesting that the magnitude of that. The other thing is that we consider that people quote get vaccinated and they're protected when the reality of it is that and this is based on CDC data that just came out yesterday. The reality of it is that For people particularly over the age of 65 or who have a variety of comorbidities and or immuno suppression or auto immune disease that's being treated. There's a fair number of them that do not develop a robust immune response as clinicians. We we see that kind of the archetype for it was the solid organ transplant patients. But it's it's true for a broader array as it is with every vaccine that I've ever studied. And so we've been a little bit naive of saying oh you're vaccinated. You're protected. Well you know if you're like the five of us on the screen here yeah you are protected almost certainly but we don't represent the broader population. Thank you Greg. I have a question how long after the natural infection was that serology done in that emerging infections paper? Good question. Avinash. I don't know off the top of my head, I'll send it to you right after this and I think another part of this that's the problem is we do not have we do not know what the neutralizing antibody protective level is and that is very key for us um whether you're vaccinated or not we don't know what level one needs to achieve to be protected from disease. Yeah I think by the way we will very shortly get that because the challenge trials in the U. K. Have started now and based on the safety of those NIH has signaled their willingness to fund challenge trials here in the U. S. Which will be beneficial for that correlated protection and also for understanding very quickly whether next generation covid vaccines will be effective. Thank you. So along the same lines not directly related to this but there was some confusion between binding antibodies and neutralizing antibodies. And and can you clarify that for us? Uh Job. Yes. Um So the binding form natural infection as well as from vaccine we will have both types of antibodies generated. Um But we don't currently recommend Testing for either one. Um The laboratory tests that we currently offer for I. G. M. And I. G. Can measure both but it cannot distinguish Between the two types of two groups of antibodies. Um But what we actually need for protective immunity is actually the neutralizing antibodies and the threshold of minimum levels that will confer protective immunity is unknown at this time. Is it fair to say that the neutralizing antibodies are not solely the only protective immunity that there are other things like T cells and things that we can't readily measure correct. A few people nodding their heads. I think dr Poland is the expert to answer that question most definitely. But we'll alter for at least a correct yeah. No there's no there's no question that a major if not more important arm over the long term is cellular immunity. Our lab just submitted a paper looking at uh manoa healthcare workers measuring antibody level and measuring their B cell memory pool and it's very clear that antibodies begin to wane over time just a few months but that B cell memory pool continues to increase. And B cells and t cells are critical to how we respond to infections. So unfortunately I think as joe mentioned uh we don't we don't have a way clinically and easily to do those measurements. We do them in my lab but they're tedious. Thank you. So that this is a this is a great question. So this is our I think our fourth, even though it seems like one huge pandemics, uh the fourth surge. So are the surge is a reflection of some inherent virus property or are they reflections of deficiencies in public mitigation efforts or both or both? And and probably still that we have so many uh you know non immune individuals. People who are essentially at risk of getting infected with the combined substantially increased transmissibility. It's a matter of uh you know, it's going to continue to increase. But what has happened with the delta is that at the same time we've also stopped having mask mandates and you know people have gotten a little bit more complacent in terms of you know, social distancing and other preventive mechanisms. I think it's a combination of factors that's getting us into this and again, what is going to happen with the schools opening colleges opening? I think that's yet to be seen. I think those are the distorting effects of human behavior are really key here as well as other things. So um seasonality has become apparent. Large venues where people crowd together, school's football games, et cetera are of grave concern as we as we enter into the fall. Similarly with temperature, vapor pressure, humidity and amount of UV light. Those have been demonstrated to be important. So it's you know, they're not all equally important, but it's a pretty complex equation to understand why we start to see a particular variant takeoff or why we begin to see a surge in one area and not another area. Yes. Um following up on an issue that you just raised Greg, we will be entering at least in the Northern hemisphere, the influenza season shortly. And so how do you see that playing out, what is being done in preparation for that? Um, I'm laughing in that. I have studied influenza for almost 40 years and my my mentor once told me early on, he said when you've seen one influenza outbreak, you've seen one outbreak in in other words, it's really hard to, to prognosticate. I am concerned about a few things. So normally younger kids would have gotten two doses, we know that kids are behind on vaccines. So we're going to have a cohort of kids who don't have influenza immunity, who are going to be crowded into into schools where masks are banned unbelievably. Um, so that's going to be an issue. Uh there were a total of 2400 known infections in the us with influenza last year. We normally see that a day um, when, when there's a, you know, normal influenza season. So a lot of us are going to experience waning immunity. And if we see a variant or a drifted strain of influenza, that's particularly infectious and and bad. We could truly have what was called last year, a twin endemic and didn't occur because we were wearing masks. Um, and and I'm very worried about what that means on health care workers and the surge demand that has already surpassed in some states the ability to manage it. Mhm. I must say that I share your worry. And as you're going to say something, I was just going to say that given the, you know, hesitancy with covid 19 vaccine, I'm also concerned that this year there may be additional hesitancy to take the influenza vaccine because we had so few influenza cases the previous year which may further potential at the problem of influenza and the twin pandemic. You know, the other factor with that Novavax has already started, but manufacturers are latching onto the idea of making a combined Covid influenza vaccine. Would that covid component caused people to be reluctant to get influence simultaneous influenza vaccination. So talking about combined vaccinations, joe how about combined laboratory testing for respiratory viruses of interest? Yes, good question. So at our website, both internal and external. We are advising providers um to think carefully, especially when they are doing the influenza season. Since the symptoms are clinically very hard to distinguish between influenza and sometimes respiratory its in situ a virus infection and COVID-19 so in adults and otherwise healthy Children, we recommend testing simultaneously during the flu season for SARS Kobe to and flu A flu B. And we currently do have cases of flu A flu be reported in the United States even as early as july this year. So there are tests, one click offers three tests Sars-cov-2 flu a flu be now in certain pediatric patients and immuno compromised adult patients. We do recommend also looking for RSV so again, single click get four results I'm afraid our time is up. This concludes today's webinar. I thank our expert faculty for their great presentations and insights and that. I thank you the audience for joining us today and for sharing your Topics of concern and interest as regards COVID-19. Thank you. Thank you. Thank you