Interestingly enough, Dr. Murray Goldstein, who is now on our board as a kind of ex-officio member, we have a commemorative lecture in his honor. This is given each year in honor of Rear Admiral Murray Goldstein, a founding member of the College and the Division of Public Health and General Preventive Medicine. Dr. Goldstein was designated a fellow in 1985 and served as president of the College in 1990. Rear Admiral Murray Goldstein is an osteopathic physician with a postdoctoral clinical training in internal medicine and neurology and research training in epidemiology and clinical research. Dr. Goldstein was the first DO to reach flag rank, serving as the Assistant Surgeon General of the U.S. Public Health Service at the National Institutes of Health for 40 years. He served for 11 years as the director for the National Institute of Neurological Diseases and Stroke, the federal government's focal point for brain research. In 1975, while at the National Institute of Neurological Disorders, he organized the first NIH research symposium on the research status of spinal manipulative therapy. Following this in-depth analysis of what was known at that time about spinal manipulative therapy and the principles on which it was founded, recommendations were made about additional areas of research to targeted additional attention and priorities were established for research training in chiropractic and osteopathic professional schools. Thus, the stage was set for further study of the broad area of manual therapy as an interdisciplinary and interprofessional collaborative research. Dr. Goldstein served as the medical director for the United Cerebral Palsy Research and Educational Foundation in Washington, D.C. He has a world-renowned authority on neurological disease. Recently, he retired from the American Osteopathic Board of Preventive Medicine, on which he served for many years. Dr. Goldstein also serves on the National Center for Complementary and Alternative Medical Education and Training Review and the Advisory Board of the National Headache Foundation. This is a named lecture given at the spring convention of the AOCOPM by someone who exemplifies service in the field of public health and preventive medicine. This year, we are giving this award to Dr. Joseph Gustaldo, who is in infectious disease in Ohio Health, which is nine hospitals in the state of Ohio and over 30,000 employees. He has been the spokesperson, speaking of media, for Ohio Health, has led us in infectious disease. During the height of the COVID pandemic, he would give, I think, daily fast facts by Dr. Gustaldo on COVID. He attended Wright State University for medical school, did his residency at the Ohio State University Hospital in internal medicine, and then a fellowship at the Ohio State University Hospital in infectious diseases. He has been wonderful within our group. He has included myself, the senior medical director in occupational medicine, and the medical director for the associate health in various emails that would connect us up to grand rounds at the University of San Francisco or John Hopkins when he found an especially good update on COVID. We will be giving the plaque, or we will be giving the... Okay, we are giving his commemorative lecture plaque to Dr. Gustaldo this year. His topic is on... Are we bringing that up? His topic is on COVID-19. He made sure he did not record it until day before yesterday because one of the things he has been excellent about is trying to be very current on what is happening. For a while, I don't know if he still is, he made sure he was in touch with various infectious disease colleagues across the nation in which they would commiserate on what to do and what do we know and how are we going to handle going forward. Hello, my name is Dr. Joe Gustaldo. I'm an infectious disease specialist. I am the system medical director of infectious diseases for Ohio Health, and I also serve as the medical director of patient quality and safety at Riverside Methodist Hospital. I've been a practicing infectious disease doctor for over 20 years, and in my professional responsibilities, I have been really heavy doing essentially much COVID-19 work for over two years now. It is my privilege to address the American Osteopathic College of Occupational and Preventative Medicine with my perspectives on COVID-19. We have all been living with COVID-19 now for over two years. In fact, we are now in three years. This is a nice cartoon that I think is really a representation of myself, other health care workers, and for that matter, the general public. We have really been through a lot collectively together through COVID-19. We have learned a lot. We know much more today than we knew when this virus first came on the scene in December of 2019. Moving forward, we still have much to learn. However, in the mindset of where COVID-19 is today, the situation is very different. SARS-Coronavirus-2, the virus that causes COVID-19, is not going away. This slide really represents seven high-level points that I really want to spend some time talking to and really give guidance to you so we can talk individually to our patients in our communities. First of all, we really need to have a process in place for people to have access to tests and to get test results back in real time. This is no longer the spring of 2020 when we had supply chain issues with PCR tests. As a country, we now have easily available PCR tests and home antigen tests. We need to be on point talking to health care workers and to patients about outpatient medications for at-risk people with COVID-19. Specifically, in addition to monoclonal antibodies, I'm also referring to two FDA-authorized five-day courses of antiviral pills. We need to be on point talking about wearing masks. Masks are an important mitigation tool that we have in the box. Specifically, we should really focus on a well-fitted one-way mask. In those contexts, I'm referring to KN95 masks and N95 masks. These masks are the ones that perform the best in protecting the wear from getting infection with SARS-Coronavirus-2. We really need to be on point in staying in line with communications that come out from public health and following those recommendations. In our country, we are blessed not only to have the CDC, but we also have professionals at state and local health care departments, and their job is to protect us. I will admit that the message coming from public health sometimes is confusing to follow, and the message does change. However, it's important that we stay abreast of the changes and the recommendations. We now have wonderful vaccines. When it comes to what matters the most, are the vaccines keeping people out of the hospital and preventing people from dying? Yes, they are performing well. We want to be on point in giving people guidance on being up-to-date on their vaccines. We need to maximize air quality and ventilation. This is a respiratory virus. When we have proper ventilation and circulation of air, that dilutes the virus and essentially makes it a lower risk situation. And finally, I really want to emphasize about us caring for each other. I care for my colleagues. I care for my community. I care for my family, but most importantly, I care for my patients. SARS-Coronavirus-2 has killed over 1 million Americans, and that trajectory is going to continue. As an infectious disease doctor, I would be remiss if I did not comment on healthcare disparities, especially in the context of COVID-19. This is a graph from the Centers for Disease Control showing the risk of COVID-19 hospitalizations by race, ethnicity, compared to white non-Hispanic persons. If somebody is a member of the American Indian or Alaskan Native community, they are 3.2 times more likely to be hospitalized compared to COVID-19. That's 2.5 times in the Black or African American community and 2.4 times in the Hispanic and Latino community. I'm hopeful that as we come through COVID-19, as a society, we will have better tools in place to remove healthcare equities that have been there for so many other diseases and conditions. The federal government has created a one-stop shopping website, COVID.gov. This has been up and running now for no more than four to six weeks. This is a website people can go to to get an idea of how much COVID is in their community. There is guidance there on masks. There's guidance there on how to find the pills as an outpatient. There's information on there about vaccines and boosters, and most importantly, how to get tests. As I previously stated, in our country, we have now amassed over 1 million deaths from COVID-19. Recently, the World Health Organization has estimated that there have been approximately 15 million excess deaths associated with a COVID-19 pandemic in 2020 and 2021 alone. 15 million deaths. That population size is enough really to bring tears to anybody's eyes. Let's start off with some national data. This is information from the New York Times, and I have consistently used the New York Times for information regarding COVID. On the red line is a seven-day moving average of the PCR test results. When labs do PCR tests, legally, they are required to report to their state health department the amount of PCR test results. We're all very familiar with this type of line, and this represents how much COVID is out there in the community. During the Omicron surge in our country, per day, we were close to 800,000 positive PCR tests, 800,000 cases of COVID-19. Moving forward, that red line of PCR tests is going to become less reliable because up to 40 to 50 percent of all tests now being done are home antigen tests. Nationally, in our country, our cases are up. On a seven-day moving average, cases are up 50 percent to approximately 70,000 cases a day. Hospitalizations, a lagging indicator, along with ICU admissions, another lagging indicator, are starting to go up. However, in the context of the Omicron surge that we had this past winter, cases are not that high. These are hot spots, and this is really representation of what's going on in our country now. We are now in a reprieve nationally. However, there are hot spots of COVID-19. As you can clearly see in New York and New England and some places in the upper Midwest, there are more hot spots of COVID-19. This is a heat map, and the darker the color are are more cases, average cases, per 100,000 in the past week. Dr. Ashish Jaha is the COVID-19 response coordinator at the White House. He is somebody that I follow closely in the media and also on social media. Dr. Hasash Jahan did recently place some slides in Twitter that I'd like to share with this group. Dr. Jaha shared this slide on May 8th from Twitter. These are looking at specific cases of COVID-19 in the community. These are cases per 100,000 population, and you could see there the lowest of the valley is really in mid-March. New York, for example, had 11 average cases per 100,000 population. You could see a gradual rise to where we are now with Rhode Island, Massachusetts, New York, and Connecticut. These are the hot spots of where COVID-19 is now occurring in our country. However, a buzzword for 2022, I think and I hope, is decoupling. Even though cases are going up in those same states, these are the deaths per 100,000 population. So, in the context of community cases going up, we are not seeing the same increase in deaths when you look at Massachusetts, New York, Connecticut, and Rhode Island. Another website that I go to for statistics is Our World in Data. These are weekly new hospital admissions for COVID-19 per 1 million in the United States. Look how high we were during last winter, the Delta wave, and the Omicron peak. You can see where we are now in the United States. Hospitalizations are going up, but not to the same extent from where we were during the Omicron wave. Let's next talk about some CDC maps and CDC statistics. Recently, the CDC created a map for the public called COVID-19 Community Level. The COVID-19 Community Level is a new tool to help communities decide what prevention measures to be taken based on the latest data. Every community in the United States is classified as low, medium, and high. Green or low means there's really limited impact on health care systems with low levels of severe illness. Medium is some impact on health care systems with more people with severe illness, and high is high potential for health care systems strain with high level of severe illness. The guidance on community level for people best to protect themselves is more uniform with some aspects. First of all, regardless of community level, some people may choose to mask at any time. And of course, with any community level, people with symptoms, a positive test, or exposure to someone should wear a mask and get tested appropriately. If we do have high community level, the CDC recommendation is to wear a mask indoor settings regardless of vaccination status, including schools. In the medium level, the guidance is if somebody has potential increased risk to really talk to their health care provider about wearing a mask. And then for low, the recommendation to wear a mask is not as robust. The CDC community levels are based on the number of new cases in the county in the past seven days divided by the population in the county multiplied by 100,000, new COVID-19 admissions per 100,000 population, and the percent of staff of inpatient beds in use by COVID-19 patients. In other words, the community levels are really a reflection of how much COVID activity is going on at the hospital level. Are the hospitals under stress? This is the current CDC community level map from May 9th, 2022. And from looking at this, you could see that 87.69% of the United States is officially in the low or green community level. Of note, you will see some red in New York and New England. Based on the guidance from the CDC, in those red counties, regardless of somebody's vaccination status, the recommendation is to wear a mask indoors, including schools. A different map that the CDC has, and this does cause some confusion for the public and those not understanding what this represents, the CDC also still has levels of community transmission. This is the amount of COVID that we see based on PCR test results. You see a lot of red on this map. And of course, this is concerning. Based on this map, approximately 34% or a third of the country is considered to have high levels of community transmission. One of the things that's been really challenging for me personally and for public health talking about COVID-19 is any topic related to COVID-19, there are no absolutes. And when you talk about all of these things, the discussion is full of caveats. When we talk about personal protective equipment and wearing masks, it's full of caveats. What type of mask are you wearing? Is it a high quality mask? Is it well-fitted? Is the mask covering your nose, your mouth, and your chin? Is the mask guidance for public or health care? Those are different. There's a lot of caveats when it comes to testing. We are all familiar with COVID-19. We are all familiar with PCR tests. Somebody can be PCR detectable without being transmissible. Antigen testing also has a learning curve associated with it. When it comes to treatments, there are treatments that inhibit viral replication like Molnupiravir and other agents that I'm going to talk about. And there are also anti-inflammatory agents. Using all of these medications are full of caveats. In addition, talking about vaccines is full of caveats. When we talk about vaccines and immunity, it's not black and white. There's different layers of protection from your immune system. There's different vaccines, there's different schedules, and those are becoming more complicated for people to follow. Moving forward, messaging on this is going to be more full of caveats, and it will likely be more confusing for people. However, we have to have faith in following the science as it comes out. One of the things I think there's opportunity is talking to the public. You know, recently in the court system, there was a judge who threw out the federal mask mandate. However, the headline should have been, in my opinion that the CDC continues to recommend that people wear masks in indoor public transportation settings at this time. Unfortunately, the headline of the news is that you don't have to wear a mask anymore when you're traveling on a plane. That is a legal decision and that is indeed the case. However, it is still the public health guidance for all of us to wear masks indoors in public places during transportation. Another area I think there's huge opportunity is really paying attention to the air quality. This is a respiratory virus. This is predominantly spread through droplets. Smaller droplets can stay suspended in the air. We call that aerosolization. And hence that's why it's very important to have ventilation and filtration of the air. Ventilation dilutes the air and can remove suspended particles and filtration obviously removes particles and pathogens from the air. On May 29, 2022, the White House Science Office had a virtual event called Let's Clear the Air on COVID-19. The most common way for COVID-19 to be transmitted from one person to another is through tiny airborne particles of the virus hanging in indoor air for minutes or hours after an infected person has been there. We can and should talk more about making indoor environments safer by filtering or cleaning the air. Moving forward, people need to have a plan. If you are symptomatic, how do you get tested? How do you get tested? How do your community, how do your patients get tested? If a person has an at-risk condition with COVID, how do those people get access to providers for outpatient medications? How do providers order these medications and how do people receive these medications? At-risk conditions intentionally are left to be vague. This is an incomplete list of the CDC's website recommendations for people who are at risk for COVID-19 and these would be people who regardless of their vaccination status would qualify for outpatient treatments. Let's reflect on some of those. Anybody with disabilities, anybody who's physically inactive, somebody who's pregnant, somebody who's immunocompromised, anybody with kidney, liver, or lung disease, diabetes, physical inactivity, overweight, or obesity. That applies to many people in my community and my family. Let's reflect a little bit on the outpatient COVID-19 treatments and again, these are for anybody with an at-risk condition with confirmed COVID-19 regardless of their vaccination status. These medications are not a substitution for the vaccine. More and more people are knowing about these medications too. Recently in my mail at home, I had a little card sent to me that was mailed out by Pfizer bringing attention to people about these medications. Part of the challenge is getting the word about these medications out there not only to patients but also to providers. Speaking here at Ohio Health and where I'm at in Columbus, Ohio, we have the medications on the shelf. There are more retail pharmacies that do have them and it's all about getting the message out there to the public and to providers about accessing these medications. These medications we really want to use earlier on in the disease process. I got this diagram from Dr. Singh et al. It's an NIH publication. It's a preprint and this circle really represents the disease process of COVID-19. Earlier on in the disease process, it's all about the replication of the virus. This is really where the antiviral medications Remdesivir, Molnupiravir, and Paxlavid have a role. In addition, this is the same window period where we would consider using neutralizing monoclonal antibodies. In the severe or critical arena, that's when people get admitted to the hospital, they have an oxygen requirement, and really the benefit of these antiviral medications, specifically the pills, is really not there. Let's talk about the risk reduction. Paxlavid is the trade name of a Pfizer product. It consists of two different protease inhibitors. One protease inhibitor, Ritonavir, is a repurposed HIV protease inhibitor. The second protease inhibitor, Nermatulavir, is a novel protease inhibitor. In the clinical trial, Paxlavid, if taken within five days of symptom onset, the people who took the pill compared to the placebo had an 85% risk reduction in being hospitalized or dying. Option number two, I put in small letters, and that is IV remdesivir. Its risk reduction is about 85%. It's a three-day course based on the Pine Tree trial. In Ohio, at my healthcare system at Ohio Health, and in many places nationally, IV remdesivir really has too much of an operational lift, and many places are not using it. Option number three are the monoclonal antibodies, and I put the word 70% to 80% risk reduction in parentheses because we really don't have real-world data on our only currently used monoclonal antibody called Botovilumab. If you remember earlier on in the pandemic, we have been through many monoclonal antibodies from Lily and Regeneron due to variants and the lack of activity of those previous products with our current variants, those have been withdrawn by the FDA for emergency use authorization. When it comes to Bevtilovumab, the only data we have are test tube neutralization studies, but nonetheless, it is a tool in the box. And then finally, choice number four is really the option of last resort, is molnupiravir. Its risk reduction is 30%, and like Paxilavid, has to be taken within five days of symptom onset. The NIH is very clear in stating that molnupiravir should only be used as a last resort. Busy slide, but I really want to go through information on the Pfizer product, Paxilavid. First of all, in the clinical trial for both Paxilavid and molnupiravir, all of the participants, all of the volunteers were unvaccinated. We do not have real-world data on how these products perform in vaccinated individuals. Nonetheless, in the clinical trial of approximately 2,100 people for Paxilavid, Paxilavid had a risk reduction of 89% if taken within three days of symptom onset, and 85% within five days of symptom onset. The number needed to treat was 18. Deaths in the placebo with Paxilavid were 12 versus zero who received Paxilavid. The Paxilavid clinical trial has been fully published in the February 16th edition of the New England Journal of Medicine. The clinical concern and the clinical challenge for Paxilavid really is its Achilles heel. Since it contains ritonavir, there are many drug interactions with Paxilavid. Ritonavir is a potent inhibitor of cytochrome P450, hence there are many drug interactions that include statins, blood thinners, cardiovascular medications. Many of the drug interactions are quite manageable. Many of them are also absolute contraindications. I would strongly advise everybody to download the University of Liverpool's free smartphone app and also to look up the University of Liverpool COVID-19 drug interaction site online to easily identify and manage drug interactions with Paxilavid. The mechanism of action of Paxilavid is it is a protease inhibitor. I have been prescribing for over 20 years protease inhibitors to my patients living with HIV and it's something we're very familiar with. We also use protease inhibitors in the management of hepatitis C infection. Ritonavir and Nirmachavir does have a cost of about five days of $530. However, at this time, these medications are free to individuals because the federal government has purchased them. These medications are not authorized to be started in the hospital. The pills need to be swallowed whole. They can be taken with or without food. The pill burden for one dose, molnupiravir is four pills twice a day for five days. Paxilavid, as I said previously, is a cocktail of two different pills. It's a total of three pills twice a day for five days. Paxilavid comes in a blister pack. Paxilavid is authorized for those 12 and older. There also is warnings and contraindications not to give it to people with an EGFR less than 30 or people who have advanced liver disease. With Nirmachavir, there is also a dose adjustment needed with an EGFR greater than 30 and less than 60. With an EGFR greater than 60, the Paxilavid dose is the normal dose of three pills BID. Molnupiravir, as I said previously, should be the drug of last resort. No drug interactions. No considerations for dose adjustment with renal insufficiency or liver disease. Molnupiravir in animal models potentially is mutagenic. For that reason, molnupiravir is not recommended during pregnancy or breastfeeding. It's authorized only for those 18 or older. Paxilavid, as I said previously, Paxilavid is really where I see there's a lot of excitement it does perform well in the real world. I've prescribed it to many people. Paxilavid is not indicated for post-exposure prophylaxis. Pfizer did have, through a press release, a trial for post-exposure prophylaxis called the EPIC trial and there was no statistically significant difference using Paxilavid versus placebo for post-exposure prophylaxis. Also new with Paxilavid is what's being described really as a viral rebound. We really need more data on this. There is a preprint of an individual case in a veteran where they were treated with a five-day course of Paxilavid. They got better seven to 10 days after the Paxilavid course ended. Patient symptoms returned and they were found to have a brisk rise in their viral load. The FDA at this time is getting more information and currently the FDA does not recommend or allow for longer or repeat courses. Of note, this same phenomenon was also described in the Paxilavid clinical trial in those who received the drug and also in those who received the placebo. In addition with Paxilavid, we don't have answers on its symptoms. Does Paxilavid improve symptoms? Do people get better quicker? We don't know yet. I would be remiss if I did not remember to mention Evusheld. Evusheld is a trade name of two different long-acting monoclonal antibodies. They're given as intramuscular injections. This is another tool in the box specifically for those who are moderately or severely immunocompromised. So COVID-19 for the remaining of 2022. Nationally, we were in a reprieve and some places are still in a reprieve. We now have areas with high levels of transmission. Is decoupling between community cases and hospitalizations going to occur? We're seeing that a little bit. Will it last? I feel confident in saying that this fall and winter of 2022, more COVID is expected. In fact, Dr. Jaha was on the media recently, yesterday, really saying that this fall and winter, there could be a pretty sizable wave of COVID-19. On May 6th, the White House projected and actually made the announcement that they projected maybe 100 million COVID infections occurring this fall and winter. Again, the thing to keep in context is, does that mean necessarily we are going to have a hospital surge like we had this past winter with Omicron? To be determined. We have vaccines, we have better messaging on masks, and more importantly, we have pills. How long will this current COVID-19 reprieve last and why is it going up? You know, we can't say how long the reprieve will last, it is going up, but the reason it's going up is multifactorial. Yes, we do have more transmissible variants that are out there, but we also too have de-escalation of masks with everybody, including myself, having COVID and pandemic fatigue. Also too, there's some waning of immunity and immunity from previous infections and immunity from vaccines. More variants are expected. This virus is not going away. What really acts as fodder for variants, immunocompromised people, it takes them more to clear the virus. More reservoirs, they could potentially act as conduits for variants, and then most importantly too, the lack of global containment, meaning that we still have work to do as a global community to get vaccines into underserved areas. With any new variant or any new sub-variant, there are things that we need to know really as quickly as possible, and when you hear about a new variant or a new sub-variant, it's not a cause for alarm. After Delta, we also had the Mu and Lambda variant. We identified them. They never came to fruition. When there is a new variant, there are many things I want to know right away as an infectious disease doctor. Number one, is the variant more transmissible? Is the variant associated with a higher severity of illness? Does the variant have evasion from immunity, specifically vaccines, previous infection, and does it evade immunity from monoclonal antibodies? What about how the new variants work with our new therapeutics? Will we have antiviral resistance someday? What about with tests? Will the new variants still be detected in our PCRs and our antigen tests? Right now, with our current lay of the land with variants and sub-variants, our vaccines are still working, especially with a booster, our treatments are working, and our tests still pick up all identified variants and sub-variants at this time. The big thing you're hearing about now is BA.2 and BA.2121. It has displaced BA.1. It is more transmissible. So far, it's not associated with a higher severity of illness. As I said previously, the vaccines still work, especially in the context of the booster. The oral medications are still effective against it, and our tests will still detect what we are dealing with in our country. One of the tools I look at every week is the CDC variant report called the Nowcast. I followed this for many, many months, and I've always been very interested to see different variants come and go. And as you can see there in the orange box, the thing that is taking off is BA.2121, with a little bit of fading away of BA.2. And for all practical purposes, the original Omicron variant that we had this past winter is fading away. One of the things that I've learned is the variant that we see mostly is the variant that's most transmissible. Let's talk about immunity. Talking about immunity is not black and white, and it's full of caveats. There's immunity from infection, which is antibody-mediated, and there's immunity from severe disease, from long-lasting memory cells. Immunity after infection does occur, but it's full of caveats. It's variable depending upon somebody's age, severity of illness, and specifically what variant they got infection with. It's challenging, and for that matter, very cavalier to have a blanket statement regarding immunity after infection and apply it to everybody. In other words, getting immunity after infection is not as known than the type of immunity we get from a vaccine. Laboratory antibody levels are not standardized, and they're still not meant to be used as a marker of immunity or for anybody to make a decision about getting a vaccine. The best type of immunity is actually hybrid immunity. That's immunity that people get from being vaccinated and then having a post-vaccination infection. As I previously stated, talking about immunity is very nuanced. There's immunity from infection, which is antibody-related, and that is never long-lasting for a respiratory virus, and then there's immunity from severe disease, which can be long-lasting in many people. This is a great diagram that I got from BioRender, and what you're really seeing here is a cartoon diagram of what happens after somebody gets vaccinated. After somebody gets vaccinated, they have a wonderful, nice rise in their antibody levels, and they also have robust response in their long-lasting T and B memory cells. Over time, antibody levels come down, and when antibody levels come down, that puts a person at risk for a post-vaccination infection. When antibody levels do come down, people can get a post-vaccination infection. However, most people still have their long-lasting B and T memory cells. If you do get an infection, those memory cells will ramp up, your antibody levels will come up again, and you still have a wonderful layer of protection against severe disease. In other words, if you are fully vaccinated, if you get a booster, and you do get a post-vaccination infection, if you're home with a cold, mild cold, or mild flu symptoms, that's the vaccine working. The COVID vaccines were never studied or intended to induce sterilizing immunity. Sterilizing immunity for most people is how the measles vaccine performs. What that really means is you cannot get infection, nor can you transmit it to others. If somebody is vaccinated, they are less likely to get infection compared to unvaccinated. And if not infected, somebody who is vaccinated cannot transmit the virus. In addition, vaccinated people clear the virus quicker, and they're not considered as transmissible. This is a little reflection on the Pfizer mRNA vaccine trial. Please keep in mind this was done pre-Delta, and only went on for three months. In the clinical trial, they had roughly 43,000 people. Half the people got the vaccine, half the people got the placebo. After they were vaccinated, they said, you know what, go live your life, and if you develop any symptoms, let us know so we can test you. The measured endpoint was symptomatic infection, asymptomatic infection was not measured. So what they had was 170 symptomatic COVID-19 patients, 162 were in the placebo group, eight were in the vaccine group. So there were still eight people who still had symptomatic infection. There were nine severe cases of COVID-19, and they were all in the placebo group, hence the word 95% efficacy. Efficacy refers to a clinical trial. In the real world, how vaccine performs is vaccine effectiveness. There are many things that can impact vaccine effectiveness. How well does a vaccine work is really dependent upon many things and a host. Older people don't perform, do not respond as well to vaccines compared to younger people, people who are immunocompromised. You'll see people who are previously infected, if they get the COVID-19 shot, they have a better response. Demographic factors, when there is less infection in the community, vaccine effectiveness for everybody goes up. In addition, there are vaccine factors, the mRNA vaccines do perform better than the adenovirus vector vaccine, such as the J&J vaccine. So in other words, there are many things that really impact how a vaccine performs in the real world, i.e. vaccine effectiveness. This is some real-world data looking at vaccine effectiveness. This is from the CDC. This is the weekly adjusted rates of COVID-19 associated hospitalization amongst adults age greater than 18 by vaccination status. And this is from the COVID-19 associated hospitalization surveillance network in 13 states from September of 2021 through January, 2022. We have information here from the Delta time and also during Omicron. The point is this, note the hospitalizations per 100,000 population. Look at the difference between unvaccinated, those who received the series were fully vaccinated and those who received a booster. This is the CDC information rates of COVID-19 deaths by vaccination status. And again, the same difference is there. Rate per 100,000 population. Unvaccinated, late January of 2022, 15.28. Fully vaccinated, no booster, 2.23. Fully vaccinated with a booster, 0.73 deaths per 100,000 population. When you break down this information by age, there really is the importance of staying up to date with your vaccine, especially with your age. So to date in our country, we have given close to 600 million vaccine doses. 250 million people are fully vaccinated and roughly 100 million Americans have received one booster. COVID-19 vaccines slow the spread of COVID-19. COVID-19 vaccines greatly reduce your risk of severe illness, hospitalization, and death. The vaccine, including boosters, are effective currently against all of the variants, including Omicron. All of the COVID-19 vaccines that are currently approved or authorized in the United States are proven to be safe. In fact, the Pfizer and Moderna vaccine for the first two shots are fully FDA approved. So for some messaging, some information, you guys. The mRNA vaccines are preferred over the adenovirus vaccine. In fact, the J&J vaccine should only really be used if somebody has a severe allergic reaction to an mRNA vaccine or people have some other strong concern about the mRNA vaccines. Waiting 90 days after receiving a monoclonal antibody, that guidance has been rescinded. And as I said previously, the Moderna and Pfizer vaccines are fully FDA approved for the primary series. Hopefully sometime soon, we will have the Novavax vaccine be reviewed. The Novavax vaccine and the Sanofi vaccine are more traditional vaccines. They are the spike protein with an immune adjuvant, very similar to the shingles vaccine. And then I know many people are anxiously awaiting vaccine availability for children below the age of five. And I'm hopeful we will get there sometime this summer. Children should be vaccinated during Omicron. This is a graph showing the COVID hospitalization rates among children age four and younger, being five times as high during the Omicron versus the Delta surge. Children are lower risk, but they are not zero risk. We need to be on point with the guidance on being up to date with our vaccines. The CDC recommendation right now is for everybody to get up to date with their vaccines. At this point in time, being up to date means that a person has received all of the recommended doses in their primary series and a single booster when eligible. Receiving a second booster right now is not necessary to be considered up to date. This is the CDC slide and the guidance on receiving the COVID vaccination series for non-immunocompromised people. And you could see there, the big recommendation is that dose four for those 50 and older is really an optional booster with mRNA vaccines. This is the CDC vaccination schedule for those who are immunocompromised. And those are the only people at this point in time who are eligible to receive a fifth dose of a vaccine. So my guidance, I tell my patients a second booster. Clearly, if somebody's immunocompromised, those people need to get every available vaccine. In addition, also receive Evigeld. I think if people are older, specifically by the age of 65, they should receive the second booster. Where it gets a little bit gray is in the 50 to 60 range. I think if somebody has at-risk conditions, especially if they're multiple, they should receive a second booster. There is no harm in getting a second booster. The benefit long-term, we don't know yet. If somebody's in the 50 range and healthy, it's really less pressing for them to get a booster, especially if they've had COVID during the Omicron surge. This fall, I do anticipate a more robust booster recommendation for a broader group of the population. Let's make some comments on long COVID. I could do a whole nother hour talk on this. Long COVID officially doesn't have a name called PASC, post-acute sequela of COVID-19. The NIH website is up and running, recovercovid.org. That's a treasure trove of information. I go there many times a week to really see what's happening in the research world when it comes to a long COVID. Roughly 15 to 30% of non-hospitalized patients will have long COVID, and roughly 80% of those hospitalized will have long COVID. One of the issues with long COVID is there's not a standard definition of what long COVID is. The World Health Organization gives guidance on it. The CDC gives guidance on it, but there's really no firm definition of long COVID. It basically refers to people who have had COVID where they have persistent symptoms that may wax and wane over a period of time. The most common symptom is fatigue, mental dullness, headache, shortness of breath, generalized pain, anxiety, depression, some heart palpitations, taste and smell disturbances. The pathophysiology is very much unknown. Chronic inflammation, reactivation of late nepstein bar virus infection, autoimmune-related, residual antigenic stimulation. And again, one of the reasons why I think it's frustrating for patients and even for clinicians taking care of these patients is the pathophysiology is not known, and we really don't know yet how to best support these patients. The recommendation really is a multi-specialty approach and it being a supportive approach. There's a lot of talk really on autonomic dystonia or dysfunction or dysautonomia with these individuals. What we really know is that recent literature has really shown that vaccines decrease the rate of long COVID. And with that, I will end my conversation. Again, thank you for allowing me this privilege to talk to you about COVID-19. Thank you. Thank you so much, Dr. Costaldo. We appreciate it. I know you're on board in the chat window. If you will and could unmute yourself, we could certainly entertain questions or if you have any final remarks that you may have want to make since your production. Yeah, so first of all, again, I just want to reiterate, I'm so honored to speak to this group. And most importantly, I want to thank the American Osteopathic College of Occupational Preventative Medicine on the Murray Goldstein Commemorative Lecture Award that I received. I don't know if you can see it in the camera, but I am truly honored and humbled by this recognition. And I will remember this presentation and treasure this recognition and plaque the rest of my life. I will be happy to share my slides. Of course, if anybody wants to email me, I will email them out. One thing that is new that I want to really emphasize is the opportunity to really get boosters into those who have not yet had them. Since I did this presentation, I actually heard a AMA video webcast where Dr. Peter Marks was presenting data on vaccine effectiveness during the time of Omicron and really showing that the effectiveness against hospitalizations and dying is very, very important to get boosters in people. The vaccine effectiveness is not as robust with Omicron with not being up to date with your vaccines, meaning one booster. And in the United States, for those 65 and above, a third of the people, 33% of people in that age group, according to CDC, is not up to date on their vaccines and even more so younger. So I think it's very important to get people up to date on their vaccines. We're really getting away from the vernacular of using a fully vaccinated, but we really want people to be up to date on their vaccines. And as I talked about before, I'm first to admit confusion on the messaging of boosters is important and the public and our patients are looking to us for guidance on that. Yeah, thank you so much. Dr. Goldstein is a special advisor to our board. He's in his late 90s now, but he's still sharp as a tack and I'm sure he would love to visit with you. What I'll do, I'll send you a link to the little script that Dr. Wriston read that might be nice to keep in your files, a little bit about Dr. Goldstein and the award. So I heard during your presentation, I just wanted to confirm this. I wanna make sure I heard it right, that you could do a whole hour for us on long COVID. Oh yeah, I mean, actually, I could talk on this stuff in my sleep, as you could tell. And I was, I don't know if you picked it up, but towards the end, I was really picking up the pace on my conversation because I wanted to get through all the topics, but there's so much here that's changing a lot. And I really think it's important for us as healthcare providers to be on point on really how to talk to patients on so many topics because again, the information changes and people do need help. And long COVID, we don't know a lot about it, but that is going to be something we're gonna have to deal with for years down the road. Absolutely. So Boston in late October, I'll send you the details and hopefully you could work that into your schedule and I'll get you some really good crab cakes if you're- All right, thank you. Any questions for Dr. Stubbs? Okay, if y'all don't mind, just come to the podium, that way we're not having to repeat the questions. So we're gonna have a lineup of questions for you. Thank you. Thanks for an excellent talk. I have a quick question just about the vaccines. I think last time I looked in this was a couple months ago because I know with the mRNA vaccines, when they were being developed, the idea was to, if there were variants, they could be tweaked to better match the spike protein epitopes. And I know with now what we know about Omicron is that it mostly, the match is still pretty good, but is there any, I haven't seen anything real recently, any thought about production of altered or mRNA vaccines, either one of our Pfizer or Moderna vaccines adjusted to meet any future variants? Yeah, thank you for that question. So the most recent buzz, you'll hear this word a lot in the news coming out of the FDA in Washington, DC, are next generation vaccines. And my crystal ball prediction is that what we're gonna have this fall is probably a bivalent mRNA vaccine that still includes the broad-based ancestral strain and also too likely with an Omicron-specific variant. Since we've had Omicron, what we've had so far are sub-lineages or sub-variants within Omicron, whether it be BA.2 or BA.2121, which is what we're dealing with now. And I don't know if I said this in a talk or not, but what's king of the mountain and what really takes off is the variant that's most transmissible. I'm very humble in saying that because, nobody can say with certainty what things are gonna be like this fall or winter, because conceptually there could be a very sinister variant that is pi. The next letter in the Greek alphabet is pi, and there will be a pi variant someday. But again, when you hear about a new variant does not mean that it's a time for an emergency or a time to be nervous. You know, since Delta, there was also the Lambda and the Mu variant, and those never really took off or came to fruition for concern. We had some discussion earlier about vaccine hesitancy, and there's a lot of discussion, at least in the lay press. Some association or question of association with hepatitis, that seems to be more linked to adenovirus with juveniles I'm talking. But have you seen anything with hepatitis? I think there's some evidence of liver function bumps with the vaccine, but there's also similar with the virus if you get infected. And early on, we saw a lot, it's relative, myocarditis with the vaccine, but I saw a number coming out of California Health Department, 16 times more likely to get myocarditis with the infection than with the vaccine. So what have you seen or have you seen anything in relating hepatitis or myocarditis with vaccine versus infection? Yeah, that's a great question. There's a lot there. So let me dive into the first thing you commented on. And worldwide, I think there's been a close, according to the World Health Organization, has been close to, I wanna say, anywhere from 170 to 200 cases of an acute hepatitis, mostly in children and adolescents. And they've been mostly identified in the United Kingdom so far. We don't know the exact cause yet. There has been positive testing in many people with adenovirus 41. Adenovirus 41 and all adenoviruses are very common in people. They cause mostly upper respiratory tract infections and conjunctivitis in immunocompetent people. And they can cause serious issues with immunocompromised people. So we really don't know about it. Association is not always causation. Is adenovirus cause it or is it an incidental finding in those who have positive tests? Something that is thought about a little bit, at least conceptually, is because children have not had the same exposure to a lot of respiratory viruses, maybe this is more of a manifestation for people who have a primary exposure to adenovirus 41. Is there something going on in the immune system with those previously having COVID or a combination of COVID and adenovirus? We just don't know yet. So again, stay tuned for that. You're right. So myocarditis. Myocarditis with vaccines was actually described with a smallpox vaccine first. So that's not necessarily new. And you're exactly right. When you look at the risk of myocarditis compared to infection with SARS-CoV-2 versus the vaccine, it is much higher with infection over the vaccine. Myocarditis from the vaccine, we know a lot about it. We know about the epidemiology of it. We know that it is with mRNA vaccines. We know it's men more than women. We know it's seen more so with the second dose of an mRNA vaccine compared to the first dose. We also know too that age-wise, it's usually adolescents to young adults. It's very uncommon in people above the age of 30. It's also too very uncommon in children five to 11. So again, it's adolescents to young adults. Based on really good data out of Canada, another mitigation recommendation is to space the second dose beyond the initial three or four week initial recommendation for Pfizer and Moderna. And that's another mitigation recommendation. And again, as a clinician, I would tell people too, if I have a 15-year-old man who's getting a second dose and he got Pfizer, I'd say come back at probably six to eight weeks instead of eight weeks. So again, the people who have had myocarditis from the vaccine, they have been described as quote mild. They have had resolution of their symptoms over a period of time and have gotten better with supportive care. But again, when you look at the totality of things like measuring the risk versus benefit of getting the vaccine, I think if you look at everything altogether, it's much more beneficial to get the vaccine over any potential risk. And that's life in general. You drive your car, you follow the speed limit, you put your seatbelt on, you have airbags, you have sensors, you don't text and drive. You have all these things that happen when you drive your car to protect yourself and you could still have a fatal car accident. So again, when you talk to the public, you get the gist. It's full of nuances. It's a detailed conversation. There's a lot of alternative narrative that's out there, but it's still more beneficial to get the vaccine over taking your chances of getting COVID and have to deal with long COVID too. Thank you so much. I have a question for you now. I had heard from a colleague, and this is probably that nuance you're talking about or on the dark web, which I've never visited, but it may be out there, that they are now, she was saying something about that the particles that are in the vaccine that they thought was going to stay in the Delta is actually being found, parts of the vaccine in other muscles of the body, like the heart or whatever. Have you heard any of that surfacing as part of that alternative conversation? I hadn't heard it. I don't watch news that much, but anyway. I thought I would ask it since that was a current conversation. Thank you. Thank you. And it brings me a smile to see you ask me a question. Thank you for that question. Look, when it comes to vaccines, I have heard everything. And after I answer your question, I'll tell you a little bit of what I've heard with Paxil a bit. So when you get vaccinated, what's happening is, as you guys know, you're delivering mRNA through a lipid nanoparticle. You're teaching yourselves to make the spike protein. The vast majority of what you're getting injected with stays within your muscle cells. You know, there's all of these stories and animal models out there looking at things like saying the spike protein is a cytotoxic and it gets all over the place. Theoretically, there may be some spike protein that gets in the bloodstream. But when you look at the vaccine-associated myocarditis, that's real. That's not from spike protein. That's an inflammatory response. One story I'll share with you really quick. You know, another thing that's out there with the vaccines is that the vaccines cause, the mRNA vaccines cause AIDS. In fact, there is an unnamed Senator from Wisconsin who was on record saying that there may be validity to the vaccines causing AIDS. So that narrative is out there. And that really ties in with Paxlivid. I'll share you a story really quick. In my pharmacy here at the hospital where I'm at, a patient did receive a prescription for Paxlivid. And in the era of doing their own research, the patient went online and looked at the ingredients in Paxlivid and found out that one of the components of Paxlivid was ritonavir, which is a repurposed HIV medicine that I've prescribed for my entire career, even during training. So that created a lot of anxiety for that person because that person thought the mRNA vaccines caused AIDS. And then they looked up saying, oh my gosh, ritonavir treats HIV. Aha, there's a connection there. So that person chose not to take the ritonavir and only took the other component of ritonavir. So, you know, for those people who follow an alternative narrative, I love those people. I respect those people. I want to sit down and listen to those people. And I really want to help guide them with appropriate information. Well, thank you again, very, very much. There is a couple of questions in the chat, but I'll hopefully leave you to answer directly regarding your contact info, et cetera. But we hope to see you again real soon, perhaps as soon as October. Ray, thank you for having me again.

Dr. Murray Goldstein

Dr. Joseph Gustaldo

COVID-19

public health

neurology

vaccination

pandemic management

healthcare communication

long COVID

virus variants