>>WELCOME I'M WIN ARIAS WELCOME YOU ALL T) SESSION OF THE DEMYSTIFYING MEDICINE COURSE AT THE NIH OF THIS YEAR, 2023. SINCE ITS CREATION IN 1999, THE PURPOSE OF THIS COURSE IS TO BRIDGE EXCITING DEVELOPMENTS IN BIOLOGY AND ENGINEERING WITH MEDICINE. AND THIS IS A REAL CHALLENGE, BECAUSE THE RATES OF ACQUISITION OF NEW INFORMATION, TECHNOLOGY, LANGUAGE, IN BIOLOGY AND ENGINEERING CONTINUES AT AN ALMOST LOGARITHMIC RATE. AND ITS LINKAGE TO UNDERSTANDING MEDICINE AND DISEASE DOES NOT PROCEED AT THAT RATE, HENCE THE GAP GETS BIGGER AND BIGGER. THE COURSE THIS YEAR WILL BE VIRTUAL, WHICH PERMITS US TO ACCESS SPEAKERS FROM ALL AROUND THE WORLD, AND IT IS HELD ON TUESDAY AFTERNOONS FROM 4:00 TO 6:00 EASTERN STANDARD TIME FROM TODAY UNTIL THE MIDDLE OF MAY. PLEASE KNOW THAT ALL PREVIOUS SESSIONS FROM THE VERY BEGINNING, 1999, ARE ARCHIVED. AND THE LINK FOR THAT IS GIVEN ON THE SLIDE, AND YOU'RE ENCOURAGED TO ACCESS ANY AND ALL OF THAT MATERIAL. NOW THE REAL PURPOSE OF THIS COURSE SO TO BR IS TO BRIDGE WHE MIGHT CALL SILOS OF INFORMATION. THESE GREAT ADVANCES IN BIOLOGY, ENGINEERING AND SO FORTH, SOME OF THEM ACQUIRE ALMOST A LANGUAGE OF THEIR OWN, AND YOU CAN THINK OF THEM AS SILOS OF INFORMATION. NOT BEING COMMUNICATED MUCH BEYOND THE SCOPE OF THE INDIVIDUAL SPECIALIZATION. AND THE SAME IS TRUE IN MANY AREAS OF CLINICAL MEDICINE. SO THIS IS A COURSE THAT CONVERTS SILOS TO BRIDGES. IT'S A COURSE IN BRIDGE ENGINEERING, AND AS ILLUSTRATED IN THE PHOTOGRAPH OF THE WORLD FAMOUS BROOKLYN BRIDGE, WE ARE LIKE THE TWO INDIVIDUALS ON THE CATWALK, EXCHANGING INFORMATION, KNOWLEDGE, AND CHALLENGING EACH OTHER WITH UNANSWERED QUESTIONS. TODAY'S SPEAKER, AS YOU KNOW, IS ANTHONY FAUCI. TONY IS AN EXEMPLARY PHYSICIAN SCIENTIST. HE IS GLOBALLY RECOGNIZED, PUBLICLY TRUSTED, AN EXPERT IN INFECTIOUS DISEASE, AND IN PRESENTING FACTS UPON WHICH POLICIES ARE BASED. AND THIS OCCURRING IN VERY DIFFICULT TIMES. AS THE DIRECTOR OF THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES FROM 1984 TO JUST RECENTLY, NOW WHAT'S BEING REFERRED TO ALREADY AS THE FAUCI ERA, HE IS CHARGED OR THE INSTITUTE IS CHARGED WITH EXTENSIVE RESEARCH PORTFOLIO OF BASIC AND APPLIED RESEARCH TO PREVENT, DIAGNOSE AND TREAT ESTABLISHED INFECTIOUS DISEASES, HIV/AIDS, INFLUENZA, DIARRHEA, TUBERCULOSIS, MALARIA, AS WELL AS EMERGING DISEASES SUCH AS EBOLA, ZIKA, AND TODAY'S TOPIC, COVID-19. TONY HAS ADVISED SEVEN PRESIDENTS ON HIV/AIDS, COVID-19, AND OTHER HEALTH ISSUES. HE'S A PRINCIPAL ARCHITECT OF ONE OF THE MOST SUCCESSFUL VENTURES IN GLOBAL PUBLIC HEALTH, THE PEPFAR PROGRAM, WHICH IS THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF. MAINLY IN AFRICA. PEPFAR HAS BEEN CREDITED WITH SAVING MORE THAN 20 MILLION LIVES FROM HIV/AIDS. IN ADDITION TO THIS GLOBAL RESPONSIBILITY WITHIN THE FIELD AND WITHIN THE PLANET ITSELF, TONY HAS BEEN THE LONG-STANDING CHIEF OF THE LABORATORY OF IMMUNOREGULATION, WHICH GAVE MAJOR, MAJOR CONTRIBUTIONS TO UNDERSTANDING HOW THE HUMAN IMMUNE SYSTEM IS REGULATED, AND PARTICULARLY HOW HIV DESTROYS THE BODY'S DEFENSES, MAKING THEM MORE SUSCEPTIBLE TO INFECTIOUS DISEASES. IN THE LISTING OF OUTSTANDING SCIENTISTS, I NOTICED THAT TONY IS LISTED AS THE 44TH MOST CITED LIVING RESEARCHER ON THE PLANET. HE'S PUBLISHED OVER 1400 SCIENTIFIC CONTRIBUTIONS, TEXTBOOKS, AND SO FORTH. WHAT MANY OF YOU MAY NOT KNOW IS THAT HE IS AN OUTSTANDING PHYSICIAN AND A TEACHER, AND THROUGH ALL HIS YEARS HERE AT THE NIH, HE'S CONSISTENTLY MADE ALMOST DAILY ROUNDS ON PATIENTS AT THE HOSPITAL OF THE NIH. WHERE HE'S BEEN AN OUTSTANDING TEACHER AND MOTIVATING YOUNG PEOPLE AND INFORMING THEM ABOUT THE CHALLENGES IN INFECTIOUS DISEASE, A IN SPECIFIC AND IN MEDICINE IN GENERAL. NOW FOR ALL OF THESE ACTIVITIES, HIS ACTIVITIES HAVE RECEIVED CONSIDERABLE AWARDS. SOME OF THE REMARKABLE ARE THE PRESIDENTIAL MEDAL OF FREEDOM, WHICH IS THE HIGHEST HONOR THAT CAN BE GIVEN BY THE PRESIDENT. HE RECEIVED THE NATIONAL MEDAL OF SCIENCE, AND MANY, MANY, MANY OTHERS. OF INTEREST. HE HAS RECEIVED SOMETHING LIKE 58 HONORARY DEGREES. HE HAS PLAYED A MAJOR ROLE IN THE PROBLEMS CONFRONTING THE COVID-19 PANDEMIC. AND WE'RE MOST HONORED TO HAVE HIM SPEAK TODAY AND I WOULD NOTE THAT HE HAS BEEN GENEROUS ENOUGH TO GIVE IT HIS TIME TO GIVE THE OPENING LECTURE FOR THE PAST FIVE YEARS IN THE COURSE OF DEMYSTIFYING MEDICINE. SO TODAY, TONY WILL SPEAK TO US ABOUT PANDEMIC PREPAREDNESS AND RESPONSE: LESSONS FROM COVID-19. TONY, THANK YOU VERY MUCH. >>THANK YOU VERY MUCH, WIN. IT'S REALLY A GREAT PLEASURE TO AGAIN BE WITH YOU TO LAUNCH THIS EXTRAORDINARY SERIES THAT YOU'VE PUT TOGETHER FOR SO MANY YEARS. AS YOU ALLUDED TO IN YOUR INTRODUCTION, I'M GOING TO BE TALKING ABOUT COVID AND LESSONS THAT WE'VE LEARNED OVER THE LAST THREE YEARS IN THE CONTEXT OF PANDEMIC PREPAREDNESS AND RESPONSE. BUT BEFORE WE DO, I WANT TO JUST PUT INTO CONTEXT WHERE WE ARE RIGHT NOW IN COVID, AND THEN I'LL GET INTO THE SERIES AND MENU OF LESSONS THAT WE NEED TO PAY ATTENTION TO. AS WE ALL KNOW NOW, WE'VE BEEN THROUGH AN HISTORIC JOURNEY OVER THE LAST THREE YEARS. AND LITERALLY, THREE YEARS AGO YESTERDAY, ON JANUARY 9TH, 2020, CHINA IDENTIFIED A NEW STRAIN OF A CORONAVIRUS THAT WAS THE SOURCE OF A PNEUMONIA OUTBREAK AMONG INDIVIDUALS IN CENTRAL CHINA IN THE CITY OF WUHAN. AT THAT TIME, THERE WERE MANY UNKNOWNS ASSOCIATED WITH THE VIRUS, PARTICULARLY THE EFFICIENCY OR NOT WITH WHICH IT SPREAD FROM ONE PERSON TO ANOTHER. IF YOU THEN FAST FORWARD THREE YEARS FROM YESTERDAY, AND SEE WHERE WE ARE NOW, WITH THE GLOBAL COUNT, AN ASTOUNDING 664 MILLION REPORTED CASES, WHICH IS UNQUESTIONABLY AN UNDERCOUNT, AND REPORTED DEATHS APPROACHING 7 MILLION, WITHOUT A DOUBT, AT LEAST A TWO AND POSSIBLY THREE FOLD UNDERCOUNT. THE UNITED STATES UNFORTUNATELY FOR US HAS BEEN ONE OF THE IF NOT THE MOST HARD-HIT COUNTRY WITH OVER A MILLION REPORTED CASES AND OVER 1 MILLION REPORTED DEATHS. AND ON A POPULATION BASIS, WE HAVE DONE WORSE THAN VIRTUALLY EVERY OTHER COUNTRY IN THE WORLD. THIS HAS BEEN A MOST UNUSUAL EXPERIENCE, THAT WHEN THE FIRST WAVE HIT, WE WERE HOPING THAT THIS WOULD BE A ONE-OFF WHERE WE WOULD HAVE A WAVE OF CASES IN EARLY MARCH OF 2020, AND THEN IT WOULD TURN DOWN AS THE WINTER ENDED AND SUMMER APPROACHED. BUT AS YOU CAN SEE FROM THIS GRAPH OF CONFIRMED CASES IN THE UNITED STATES, UNFORTUNATELY THAT WAS NOT TO BE WHAT HAPPENED, AS WE AND THE REST OF THE WORLD WERE HIT WITH SEQUENTIAL VARIANTS, WHICH WAS TRIGGERED BY MUTATIONAL CHANGES IN THE SPIKE PROTEIN OF THE NOVEL CORONAVIRUS, GIVING US THE FAMOUS ALPHA, THEN DELTA IN SEPTEMBER OF 2021, AND THEN OMICRON IN THE EARLY WINTER OF 2021 AND 2022, AND NOW WE ARE NOW ON JANUARY OF 2023. I WANT TO POINT OUT, WHEN PEOPLE ASK WHERE WE ARE IN THE OUTBREAK, ALTHOUGH WE ARE STILL IN THE MIDDLE OF A PANDEMIC, THE FACT IS, WE ARE DOING MUCH, MUCH BETTER THAN WE WERE DOING AT THE PEAK OF OMICRON, WHICH STARTED IN NOVEMBER OF 2021, AND SPILLED OVER INTO THE FIRST MONTHS OF 2022, AND SINCE THEN, AS I'M GOING TO SHOW IN A MOMENT, WE'VE HAD MULTIPLE OF DERIVATIVE VARIANTS OUT OF OMICRON. SO THIS SLIDE IS SHOWING CASES, THIS SLIDE ARE HOSPITAL ADMISSIONS, WHICH AS YOU CAN SEE AGAIN THE BIG DIFFERENCE BETWEEN TODAY, ON THE RIGHT-HAND PART OF THE SLIDE, AND THE PEAK THAT WE SAW WITH OMICRON IN JANUARY OF 2022. THE BOTTOM LINE OF THIS ALL IS ALTHOUGH WE ARE STILL IN A PANDEMIC WITH A LOT OF CASES, THE RATIO OF CASES TO HOSPITALIZATIONS, WITH HOSPITALIZATIONS BEING LESS BUT NONETHELESS QUITE SIGNIFICANT, WITH STILL TODAY HAVING A CONSIDERABLE NUMBER, BUT THIS IS EXPRESSED RATHER DRAMATICALLY IN THIS SLIDE, WHICH IS DEATHS, AND AGAIN, IF YOU LOOK AT THE DEATHS ASSOCIATED WITH ALPHA, DELTA AND OMICRON, LOOK AT THE SEVEN-DAY ROLLING AVERAGES COMPARED TO THE DEATHS THAT WE'RE SEEING TODAY. SO ALTHOUGH AGAIN TO EMPHASIZE, WE ARE STILL IN THE MIDDLE OF A PANDEMIC, THE HOSPITALIZATIONS AND DEATHS ARE LOWER FORGIVEN NUMBER OF CASES THAN WE WERE SEEING WITH OMICRON, DELTA AND ALPHA. NOT TO BE COMPLACENT ABOUT THAT, BECAUSE AGAIN, WE ARE NOW IN THE WINTER FOLLOWING THE HOLIDAY SEASON, AND AS WE'RE SEEING IN EUROPE, WE'RE EXPECTING TO SEE AN UPTICK IN CASES, AND WITH THAT, LIKELY AN UPTICK, CERTAINLY NOT AS BAD AS WE SAW LAST YEAR, BUT AN UPTICK IN HOSPITALIZATIONS. SO WHY ARE WE SEEING A PERSISTENCE OF HIGH RATES OF CASES, HOSPITALIZATIONS, AND DEATHS? RIGHT NOW ENTERING OUR FOURTH YEAR OF THIS OUTBREAK? AND IT HAS TO DO WITH A NUMBER OF DIFFERENT FACTORS THAT ARE CONVERGING AND CONFLATING. FIRST, THE INCREASED TRANSMISSIBILITY OF NEW VARIANTS AS I'M GOING TO SHOW YOU IN A MOMENT, THE XBB.1.5 IS CONSIDERABLY MORE TRANSMISSIBLE AND INVASIVE OF IMMUNITY THAN THE PRIOR VARIANTS. IN ADDITION, WE KNOW QUITE PECULIAR TO THE IMMUNITY OF VIRUSES IS THE WANING IMMUNITY TO PRIOR INFECTION AND/OR VACCINATION. SOMETHING WE DON'T SEE WITH MEASLES OR POLIO OR OTHER INFECTIOUS DISEASES THAT WE HAVE DECADES AND DECADES OF EXPERIENCE WITH. IN ADDITION, THERE'S BEEN A RELAXATION OF MITIGATIONS, SUCH AS MASKING AND INDOOR CONGREGATING. IF WE GO NOW ON AN AIRPLANE COMPARED TO LAST YEAR, A RELATIVELY SMALL PERCENTAGE OF PEOPLE ARE WEARING MASKS I, AND THE SAME HOLD TRUE TO CONJUGATE SETTINGS INDOOR. THIS IS THE FAMILY TREE OF THE SARS-COV-2, GOING FROM LEFT TO RIGHT ON THE SLIDE WITH THE WA1 AS THE INSES TRAL STRAIN AND THE BRANCHES OF ALPHA, BETA, DELTA AND GAMMA OFF OF THE ANCESTRAL STRAIN, BUT ONE THING THAT HAPPENED OVER A YEAR AGO IS LOOK HOW OMICRON VEERED OFF DRAMATICALLY FROM THE INITIAL NIDUS OF THE ANCESTRAL STRAIN. AND OVER THE LAST YEAR, WE'VE HAD A PROGRESSION OF SUBVARIANTS OF BA1, BA3, BA2, BA4-5, RECENTLY THE BQ.1.1 AND NOW THE BEGINNING OF THE DOMINANCE OF THE XBB.1.5 ON THE FAR RIGHT-HAND SIDE OF THE SLIDE. AND AS SHOWN ON THIS NEXT SLIDE, WITH THE PROGRESSION OF THESE VARIANTS HAS BEEN A PROGRESSION IN THE ABILITY OF THESE VIRUSES TO TRANSMIT. WITH XBB.155 MORE TRAN MISCIBLE THAN B4 AND BA.5. AGAIN, THESE VIRUSES ARE NOT MORE SERIOUS IN THEIR PATHOGENESIS OR THE SEVERITY OF DISEASE, BUT CLEARLY THEY HAVE TRANSMISSION ADVANTAGE AS YOU CLIMB UP THIS LADDER OF EVOLUTION OF VARIANTS. THIS IS A COMPLICATED SLIDE BUT IT SHOWS YOU FROM LEFT TO RIGHT HOW ONE VARIANT FOR EXAMPLE ON THE FAR LEFT WHICH IS THE DOMINANT VARIANT OF BA.4-5 IN THE LIGHT PURPLE GETS TAKEN OVER AS YOU GO FROM LEFT TO RIGHT AS THE DARKER PURPLE NOW OF THE XBB.1.5, WHICH IS NOW 27 TO MORE PERCENT NATIONALLY AND AS MUCH AS 50 OR MORE PERCENT IN CERTAIN REGIONS OF THE COUNTRY, SUCH AS THE NORTHEAST. NOW WHERE ARE WE IN THE MEDICAL MANAGEMENT OF THIS PARTICULAR DISEASE? THERE ARE THREE APPROACHES TO IT. ONE IS THE CONTROL OF SYMPTOMS. MOST PEOPLE WHO ARE MODERATELY OR MILDLY SYMPTOMATIC CAN BE HANDLED WITH ANTI-INFLAMMATORY AND OTHER AGENTS AT HOME. FOR THOSE REQUIRING HOSPITALIZATION AND END ORGAN SUPPORT SUCH AS VENTILATION AND CONTROL OF FLUIDS AND BLOOD PRESSURE, THAT USUALLY REQUIRES HOSPITALIZATION OF COURSE. BUT THERE ARE THERAPEUTICS NOW THAT CAN ACTUALLY BE GIVEN AND HOPEFULLY CAN BE GIVEN AS HAS BEEN THE CASE OF LATE AS AN OUTPATIENT TO PREVENT PEOPLE FROM REQUIRING HOSPITALIZATION. AND THESE ARE SOME OF THE COVID-19 THERAPEUTICS. THAT EITHER TARGET THE VIRUS, THE MOST COMMONLY USED NOW IS PACPAXLOVID, WHICH IS A COMBINAN OF A PROTEASE INHIBITOR AND RITONAVIR BOOST. REMDESIVIR AND MOLNUPIRAVIR. AND THEN THERE ARE OTHER APPROACHES TO THERAPY THAT MODERATE AN ABERRANTLY ACTIVE IMMUNE RESPONSE. AND FOR THIS, WE HAVE DEXAMETHASONE, AS WELL AS CERTAIN MONOCLONAL ANTIBODIES LIKE TOCILIZUMAB AND OTHER IMMUNOMODULATORS, AS WELL AS ANTICOAGULANT THERAPY IN INDIVIDUALS WHO ARE GETTING MICRO THROMBI. NOW, THE NIH HAS PUT TOGETHER AN EXPERT PANEL OF A CONSIDERABLE NUMBER, ANYWHERE FROM 30 TO 40 EXPERTS IN THE FIELD WHO ARE PROVIDING LIVING DOCUMENT THAT'S OFTEN UPDATED IN REALTIME AS NEW CLINICAL DATA ACCRUE. YOU CAN HAVE ACCESS TO THIS BY GOING ONLINE TO COVID19TREATMENTGUIDELINES.NIH.G OV. AND IF YOU LOOK AT THE RECOMMENDATIONS CONTAINED IN THOSE GUIDELINES, FOR THE TREATMENT OF OUTPATIENTS WITH DISEASE NOT SERIOUS ENOUGH TO REQUIRE HOSPITALIZATION, AGAIN AS I MENTIONED, THE RITONAVIR BOOSTED NIRMATRELVIR, WHICH IS PAXLOVID, AS WELL AS REMDESIVIR, ARE THE TWO TOP CHOICES. ALTERNATIVES FOR THOSE IN WHICH THIS IS NOT FE FEASIBLE IS MOLNUPIRAVIR. -- ONLY IF A PERSON REQUIRES DAMPENING OF THEIR ABERRANT RESPONSE IN A HOSPITAL SETTING. WE MOVE QUICKLY ON TO VACCINES BECAUSE THIS IS SUCH AN IMPORTANT COMPONENT OF OUR RESPONSE. WE NOW HAVE FOUR COVID VACCINES AVAILABLE IN THE UNITED STATES. THE PFIZER, BIONTECH AND MODERNA MRNA, THE PROTEIN SUBUNIT AS WELL AS THE J & J, WHICH IS A VIRAL VECTOR VACCINE PRESENTATION OF THE IMMUNOGEN. AS YOU KNOW MOST RECENTLY, THE CDC HAS RECOMMENDED THE FIRST UPDATED BA4/BA5 BOOSTER, WHICH WAS DIRECTED AGAINST THE BA4/5 WHICH WAS PREVALENT AT THE TIME, BUT AS I SHOWED YOU ON A PRIOR FAMILY TREE SLIDE, THIS HAS NOW BEEN TAKEN OVER BY XBB.1.5. BUT XBB.1.5 IS A DERIVATIVE OF SUBGROUP OF OMICRON, SO ALTHOUGH ANTIBODIES AGAINST THIS ARE NOT AS NEUTRALIZING, THERE STILL IS ANTICIPATED TO BE A DEGREE OF PROTECTION LIKELY AT THE T-CELL AND B CELL MEMORY LEVEL. NOW, UPDATED BOOSTERS ARE STRONGLY RECOMMENDED FOR ANYONE AGE 5 YEARS OF AGE AND OLDER, IF IT'S BEEN AT LEAST A COUPLE OF MONTHS SINCE THE LAST DOSE, AND INDIVIDUALS 6 MONTHS TO 4 YEARS WHO COMPLETED THE MODERNA PRIMARY SERIES AND IT'S BEEN AT LEAST 2 MONTHS SINCE THE LAST DOSE. NOW, DO THESE VACCINES WORK? THE ANSWER IS UNEQUIVOCALLY YES. AND THE DATA ARE RATHER STRIKING. IF YOU COMPARE THE SITUATION OF HOSPITALIZATIONS IN UNVACCINATED INDIVIDUALS COMPARED -- AND THIS IS PER HUNDRED THOUSAND PEOPLE 18 YEARS OF AGE OR OLDER, COMPARED TO PEOPLE WHO ARE VACCINATED WITH NO BIVALENT BOOST, 196 DOWN TO 33, AS WELL AS THOSE WHO RECEIVED THEIR UPDATED BIVALENT BOOST GOES DOWN TO 12 PER HUNDRED THOUSAND PEOPLE OF THAT AGE GROUP. THE SAME HOLDS TRUE WHEN ONE LOOKS AT DEATHS. THAT IN THIS SITUATION -- I MEAN OF INCIDENCE, EXCUSE ME. IF YOU LOOK AT THIS PARTICULAR SLIDE, THERE'S A 18.6 TIMES LOWER RISK OF DYING FROM COVID IN PEOPLE WHO ARE VACCINATED WITH AN UPDATED BOOSTER VACCINE, AND A 3.1 LOWER RISK OF TESTING POSITIVE FOR PEOPLE IN THIS PARTICULAR AGE CATEGORY. SO WHETHER OR NOT A VACCINE WORKS OR DOESN'T WORK IS VERY, VERY CLEAR WHAT THIS MEANS. NOW, LET'S GO TO THE NEXT SLIDE. THERE YOU GO. SO, IF YOU LOOK AT THE EFFECTIVENESS IN REAL WORLD EFFICACY DATA THAT COMES FROM ISRAEL, A VERY RECENT STUDY POSTED JUST SEVEN DAYS AGO OF 622,000 PEOPLE IN A HEALTHCARE SYSTEM IN ISRAEL, THERE IS NO DOUBT THAT THE HOSPITALIZATIONS, IF YOU LOOK COMPARING PEOPLE WHO ARE BIVALENT RECIPIENTS VERSUS THOSE THAT WERE NOT, THE DIFFERENCES IN HOSPITALIZATIONS AND DEATH ARE VERY CLEAR. THIS IS AN IMPORTANT SLIDE BECAUSE PEOPLE WILL ASK, DO YOU REALLY NEED THE UPDATED BUY VADATED BIVALENTBOOST? THIS IS THE FIRST REAL WORLD DATA STUDY, ALBEIT FROM ISRAEL, WHICH HAS A VERY GOOD WAY OF TRACKING THIS, OF THE EFFICACY AND THE IMPORTANCE OF KEEPING UPDATED ON YOUR BOOSTERS. SO THAT'S THE FUNDAMENTAL BACKGROUND OF WHERE WE ARE. SO LET ME MOVE ON TO THE NEXT PHASE OF THE DISCUSSION. WHERE I'VE PICKED OUT SEVEN LESSONS FROM COVID-19. AND I'M GOING TO SPEND A BIT -- VERY SHORT PERIOD OF TIME PICKING OUT WHAT I FELT WOULD BE THE SALIENT FEATURES OF WHAT THE LESSON WOULD BE FROM EACH OF THESE COMPONENTS. NOW, I COULD SPEND AND HAVE ACTUALLY DONE THIS, MOST OF THE LECTURE ON EACH OF THESE POINTS, BUT BECAUSE WE DON'T HAVE THE TIME TO DO THAT, I'VE JUST SELECTIVELY PICKED OUT A COUPLE OF SALIENT FEATURES FOR EACH. SO LET'S START OFF WITH ONE OF THE MOST IMPORTANT LESSONS. THAT GLOBAL INFORMATION SHARING AND COLLABORATIONS ARE ESSENTIAL TO A SUCCESSFUL RESPONSE. AND WHAT I MEAN BY THAT ARE THINGS LIKE SURVEILLANCE DATA, INFECTED AND CONVALESCENT PATIENT SAMPLES, THE SHARING OF RESEARCH REAGENTS, VIRAL GENOMIC DATA, VIRAL ISOLATES, AND WHAT I SHOWED YOU LITERALLY A MOMENT AGO WAS THE REAL WORLD CLINICAL DATA THAT THE ISRAELIS MADE KNOWN TO THE REST OF THE WORLD IN REALTIME. IF WE CAN DO THAT, WITH THE KIND OF TRANSPARENCY THAT WE WISH HAD HAPPENED DURING THE EARLY MONTHS AND YEAR OF COVID-19, I BELIEVE WE WOULD HAVE BEEN A BIT BETTER OFF THAN WE WERE DURING THOSE EARLY YEAR OR TWO. ANOTHER IMPORTANT LESSON THAT WE LEARNED, THAT EXISTING CLINICAL TRIAL INFRASTRUCTURE CAN AND SHOULD BE UTILIZED, AND WE HAVE A VERY COGENT EXAMPLE OF THAT. WHAT NIH DID, PREDOMINANTLY NIAID BUT IT WAS AN ALL-NIH EFFORT, WE LAUNCHED A CLINICAL TRIAL NETWORK THAT HAD ALSO BEEN ESTABLISHED LITERALLY DECADES AGO FOR HIV, WE LEVERAGED THAT TO TEST COVID-19 VACCINE AND OTHER PREVENTION TOOLS. WE CALL THAT THE COVID-19 PREVENTION NETWORK, OR COVPN. WHICH WE ESTABLISHED BY MERGING FOUR EXISTING NIAID-FUNDED CLINICAL TRIALS NETWORKS AS ILLUSTRATED ON THIS NEXT SLIDE. THE HIV VACCINE TRIALS NETWORK, THE HPTN PREVENTION TRIALS NETWORK, OUR INFECTIOUS DISEASES CLINICAL RESEARCH CONSORTIUM, AND THE ORIGINAL AIDS CLINICAL TRIAL GROUP, OR ACTG. THESE WERE MERGED TO FORM THE COVID-19 PREVENTION NETWORK, WHICH IS RESPONSIBLE AND IS STILL RESPONSIBLE FOR THE ARRAY OF VACCINE TRIALS, MONOCLONAL ANTIBODIES, AND NOW THERAPEUTICS. THIS IS SHOWING THE EXTRAORDINARY SCOPE OF THE NIAID COVID-19 PREVENTION NETWORK. GOING FROM THE UNITED STATES, NORTH AMERICA, SOUTH AMERICA, AFRICA, AND NOW IN SOME CASES ASIA. THIS IS SOMETHING THAT WE WILL CONTINUE TO KEEP WARM AS IT WERE, IN ANTICIPATION OF FUTURE OUTBREAKS. THE NEXT, AND THIS IS IMPORTANT PARTICULARLY FROM THE NIH STANDPOINT, IS THAT PRIOR SCIENTIFIC ADVANCES THOROUGHLY ENABLE THE RAPID VACCINE DEVELOPMENT, WHICH WE WERE FORTUNATE ENOUGH TO EXPERIENCE DURING THE COVID ERA. I ARTICULATED THIS IN A COMMENTARY THAT I WROTE IN SCIENCE IN WHICH I SAID THAT THE SPEED AND EFFICIENCY WITH WHICH THESE HIGHLY EFFICACIOUS VACCINES WERE DEVELOPED AND THEIR POTENTIAL FOR SAVING MILLIONS OF LIVES ARE DUE TO AN EXTRAORDINARY MULTIDISCIPLINARY EFFORT THAT INVOLVES BASIC, PRE-CLINICAL AND CLINICAL SCIENCE THAT HAD BEEN UNDERWAY, AND THIS IS IMPORTANT, COMPLETELY OUT OF THE SPOTLIGHT, UNDER THE RADAR SCREEN, LITERALLY FOR DECADES BEFORE THE UNFOLDING OF THE COVID-19 PANDEMIC. AND IN FACT, SCIENCE MAGAZINE IN DECEMBER OF 2020 DEEMED THIS EFFORT THE SCIENTIFIC BREAKTHROUGH OF THE YEAR. AND WHAT IT REALLY AMOUNTED TO WAS THE DECADES OF RESEARCH THAT WAS FUNDED, FOR EXAMPLE, LIKE NOW WELL-KNOWN INVESTIGATORS DREW WEISSMAN AND KATIE KELLY WHO ACTUALLY WERE DOING MRNA VACCINATION WORK, NOT EVEN VACCINATION WORK, THEY WERE WORKING WITH MRNA GENERICALLY FOR VACCINES. COVID WASN'T EVEN ON ANYBODY'S MIND AT THE TIME. AND BARNEY GRAHAM AND HIS COLLEAGUES AT THE VACCINE RESEARCH CENTER WERE WORKING ON STRUCTURE-BASED VACCINE DESIGN AND MUTATIONAL STABILIZATION OF IMMUNOGENS, AND WHEN THAT WAS PUT TOGETHER WITH THE MRNA, WE HAD SOMETHING THAT WAS UNPRECEDENTED: A VACCINE THAT IN A PERIOD OF 11 MONTHS WENT FROM THE FIRST IDENTIFICATION OF THE VIRUS TO A HIGHLY SUCCESSFUL VACCINE BEING TESTED IN TENS OF THOUSANDS OF PEOPLE, AND GOING INTO THE ARMS OF PEOPLE 11 MONTHS LATER, IN DECEMBER OF 2020. AND THE RESULTS HAVE BEEN STRIKING. IF YOU LOOK AT THE WORK THAT WAS DONE DECADES AGO BY KATIE CAROLIK, DREW WEISSMAN, BARNEY GRAHAM, PETER -- AND THEIR COLLEAGUES, KI SIZZY CORBETT, TY DID NOT REALIZE AT THE TIME WHAT THEIR WORK WAS GOING TO RESULT IN. BUT IF YOU LOOK AT THE RECENT STUDY BY THE COMMONWEALTH FUND JUST IN THE PERIOD FROM DECEMBER THE 12TH, 2020 TO NOVEMBER 30TH OF THIS PAST YEAR, OVER 3 MILLION DEATHS WERE AVERTED, 18 MILLION HOSPITALIZATIONS, OVER 120 MILLION INFECTIONS, AND A COST SAVING OF APPROXIMATELY $1 TRILLION. BASED ON THE INVESTMENT THAT WAS MADE IN THE DEVELOPMENT OF THESE VACCINES THAT STARTED REALLY DECADES AGO. NOW, THAT'S NOT THE END OF THE STORY. BECAUSE AS WE ALL KNOW NOW, PAINFULLY, THE PAST 20 YEARS, THREE CORONAVIRUS HAVE CAUSED MAJOR DISEASE OUTBREAKS. SARS, MERS, AND COVID-19. AND SINCE SEPTEMBER OF 2020, FIVE SARS-COV VARIANTS REHAVE EMERGED AND AS I SHOWED YOU WITH A PROGRESSIVE ENHANCED DEGREE OF TRANSMISSIBILITY. SO OBVIOUSLY INNOVATIVE APPROACHES ARE NEEDED TO INDUCE BROAD AND DURABLE PROTECTION AGAINST CORONAVIRUS IN GENERAL REFERS TO AS NEXT GENERATION VACCINES. THE PURPOSE OF THESE, THEY MUST HAVE SOME KEY PROPERTIES. ONE, ENHANCED BREADTH SO THAT YOU DON'T LOSE PROTECTION AS YOU EVOLVE INTO THE NEXT VARIANT. REFER TO THAT AS VARIANT-PROOF. THE OTHER IS IMPROVED DURABILITY, ONE OF THE VERY FRUSTRATING ASPECTS OF WHAT WE'RE DEALING WITH NOW IS THE SHORT DEGREE OF DURABILITY OF PROTECTION WHICH IS MEASURED IN MONTHS TO A YEAR AS OPPOSED TO, FOR EXAMPLE, WHAT WE SEE WITH MEASLES AND SMALLPOX AND POLIO, IN WHICH EITHER VACCINE OR INFECTION-INDUCED IMMUNITY IS MEASURED MINIMALLY IN DECADES AND MAXIMALLY FOR A LIFETIME. AND IN ADDITION, SOMETHING THESE VACCINES, AS GOOD AS THEY ARE, IN PREVENTING SEVERE DISEASE, THEY DO NOT VERY EFFECTIVELY BLOCK INFECTION AND HENCE TRANSMISSION. SO THE NEXT GENERATION OF VACCINES HAVE TO BE PAN CORONAVIRUS OR AT LEAST PAN SARS COV-2 VIRUSES, SO LET'S TAKE A LOOK AT QUICKLY WHERE WE ARE WITH PAN-CORONAVIRUS VACCINES. IN JANUARY OF LAST YEAR, JUST A LITTLE BIT OVER A YEAR AGO, LESS THAN A YEAR AGO, WE WROTE A PROSPECTIVE OF THE URGENT NEED FOR UNIVERSAL CORONAVIRUS VACCINES. TWO KEY APPROACHES, WHICH YOU LOOK FOR A COMMON ELEMENT SUCH AS A COMMON NON-MUTABLE OR DOMINANT AREA OF, FOR EXAMPLE, THE SPIKE PROTEIN, AND MAKE A VACCINE THAT IS DIRECTED AGAINST THAT COMMON ELEMENT. THE OTHER IS TO MAKE A MOSAIC OF A BROAD ARRAY OF THE CORONAVIRUSES, PARTICULARLY AMONG THE BETA CORONAVIRUSES. EACH OF THESE APPROACHES HAVE HAD SOME DEGREE OF EARLY SUCCESS. AND THESE ARE SOME OF THE PAPERS -- I DON'T EXPECT YOU TO GO THROUGH EACH OF THESE, I JUST WANTED TO SHOW IT FOR EFFECT, THAT IN ANIMAL MODELS, WE'RE STARTING TO SEE A DEGREE OF SUCCESS IN THE ELICITATION OF BROADLY PROTECTIVE SABECO AND OTHER CORONAVIRUSES IMMUNITY BY A VARIETY OF APPROACHES. NANOPARTICLE, VECTOR-BORNE, ET CETERA. THE OTHER IMPORTANT GOAL, AND THIS IS SOMETHING THAT A LOT OF ATTENTION HAS BEEN PAID OF LATE, IS THE DEVELOPMENT OF MUCOSAL VACCINES. AGAIN, THERE ARE A NUMBER OF COMMENTARIES ON THIS, THIS IS ONE THAT'S PARTICULARLY GOOD IN SCIENCE IMMUNOLOGY LOOKING AT THE IMPORTANCE OF THE DEVELOPMENT OF NASAL AND OTHER MUCOSAL VACCINES. THE REASON IS THAT WHEN YOU GIVE AN INTRAMUSCULAR OR INTRADERMAL, YOU GET A VERY, VERY GOOD IMMUNE RESPONSE SYSTEMICALLY, AND THE PROTECTION MUCOSALLY IS DEPENDENT IN MANY RESPECTS ON A HIGH LEVEL OF ANTIBODY THAT WOULD SPILL OVER INTO THE MUCOSAL SURFACE OF THE NASOPHARYNX. AND WHEN THE ANTIBODY LEVELS NATURALLY DIMINISH, WHICH IS A NORMAL PART OF THE IMMUNE RESPONSE, THAT PROTECTION AGAINST INFECTION DIMINISHES, WHEREAS THE PROTECTION AGAINST SYSTEMIC DISEASE ONCE INFECTION OCCURS DOES PRETTY WELL. INTRANASAL VACCINES HAVE A DIFFERENT STRATEGY, TO TRIGGER THE RESPONSE AT THE UPPER AIRWAY THAT WOULD LAST BECAUSE THE IMMUNE RESPONSE WOULD BE RESIDENT IN THE UPPER AIRWAY. AS SHOWN ON THIS SLIDE HERE, AND THE REASON THIS IS REALLY A TRANSFORMATIONAL APPROACH, BECAUSE THERE'S MUCH FASTER IMMUNITY RECALL I OF THE VIRAL EXPOSURE WHEN THE ANTIBODIES AND THE MEMORY CELLS AND THE CD4 AND CD8-POSITIVE T-CELLS ARE RIGHT THERE IN SIGHT, AT THE AREA OF EXPOSURE. IN ADDITION, THIS TYPE OF AN APPROACH IS GEARED AT BLOCKING INFECTION AND TRANSMISSION, AND OBVIOUSLY THERE'S THE ADDED BENEFIT OF THERE BEING A NEEDLE-FREE DELIVERY. AND AGAIN, HERE ARE SOME EXAMPLES, PROMISING EXAMPLES OF WHAT'S APPEARING IN THE LITERATURE. AS YOU CAN SEE EACH OF THESE ARE IN ANIMAL MODELS AT THIS POINT. RHESUS MACAQUES OR HAMSTER MODELS. THERE HAVE BEEN SOME HUMAN STUDIES THAT HAVE COME FROM OTHER COUNTRIES SUCH AS CHINA AND INDIA. WE DON'T HAVE A GOOD HANDLE YET, ALTHOUGH THESE HAVE BEEN APPROVED, AS TO WHAT THE DATA ARE ON THE CLINICAL TRIALS THAT LED TO THE APPROVAL OF THESE VACCINES. BUT ASSUMING THAT IT WAS A REASONABLE APPROACH, THIS IS GOOD NEWS IN OUR QUEST TO DEVELOP NASALLY, MUCOSALLY ADMINISTERED VACCINES. MOVING ON TO THE NEXT LESSON. THAT PROTOTYPE AND PRIORITY PATHOGEN APPROACHES WILL ENABLE PANDEMIC PREPAREDNESS. THERE ARE TWO WAYS OF LOOKING AT THAT. THE PRIORITY PATHOGEN IS TO ANTICIPATE AND TO PICK OUT PATHOGENS, IN THIS CASE, ALL VIRUSES, THAT ARE AT PARTICULAR DANGER OF EVOLVING INTO A PANDEMIC. LIKE HEMORRHAGIC FEVER, OR NPA, OR MARBURG VIRUSES AND EBOLA. WE ALREADY HAVE COVID COVID-19 N THERE, IT'S ALREADY DONE IT. THE OTHER APPROACH IS WHAT WE CALL A PROTOTYPE PATHOGEN APPROACH. WHICH IS FAVORED BY US IN MANY RESPECTS FOR THE FOLLOWING REASON: BECAUSE AS BARNEY GRAHAM AND KIZZY CORBETT HAVE COMMENTED ON IN A REVIEW IN THE JCI A COUPLE OF YEARS AGO, THAT WHEN YOU LOOK AT A PROTOTYPE PATHOGEN APPROACH, WHAT YOU DO IS YOU PICK A PARTICULAR FAMILY OF PATHOGENS, AND YOU BUILD ON PRIOR EXPERIENCES WITH THAT PARTICULAR FAMILY. THE ONE WE HAVE THE OBVIOUS MOST EXPERIENCE WITH RECENTLY IS THE FAMILY OF CORONAVIRUSES, IN WHICH WE HAD EXPERIENCE FIRST WITH THE COMMON COLD CORONAVIRUS, THEN WITH SARS-COV-1, THEN WITH MERS, AND THEN ALONG CAME COVID-19. SO WHAT DO YOU LEARN ABOUT THIS? HOW DO YOU LEARN FROM EXPERIENCE? YOU LEARN A LOT ABOUT THE BASIC VIROLOGY. YOU CAN DEVELOP ASSAYS FOR PRE-CLINICAL AND CLINICAL SETTINGS. YOU DEVELOP ANIMAL MODELS THAT ARE UTILIZABLE ACROSS THE SPECTRUM OF THIS FAMILY. ANTIGENIC TARGETS ARE OFTEN SIMILAR. PLATFORMS FOR DIAGNOSIS, THERAPIES, AND VACCINES ARE OFTEN CROSS-CUTTING ACROSS THE FAMILY. POTENTIAL IMMUNE CORAL L CORRELE USEFUL, AS WELL AS MANUFACTURING FOR VACCINES, STRATEGIES APPLICABLE ACROSS THE FAMILY. THESE ARE EIGHT OF THE ALMOST 20 OF THE VIRAL FAMILIES THAT ACTUALLY ARE OF A CONSIDERABLE PRIORITY. THESE ARE THE MOST PRIORITY. IF YOU LOOK AROUND, YOU SEE, FOR EXAMPLE, THE PARAMYXO VIRUSES WITH NIPAH THAT WE'RE WORKING ON, THE BUNY VIRUSES WITH THE HEMORRHAGIC FEVERS, AND OF COURSE THE UPPER LEFT, THE CORONAVIRIDAE WITH THE VIRUSES I JUST MENTIONED. MOVING ON TO THE NEXT LESSON. THE CONTINUED SURVEILLANCE OF THE HUMAN ANIMAL INTERFACE IS ABSOLUTELY CRITICAL. AGAIN, MY COLLEAGUE DAVID MORANS AND I WROTE AN ARTICLE RECENTLY SAYING THE COVID PANDEMIC IS YET ANOTHER REMINDER ADDED TO THE GROWING ARCHIVE OF HISTORICAL REMINDERS THAT IN OUR HUMAN DOMINATED WORLD, IN WHICH OUR ACTIVITIES ENCROACH UPON THE ENVIRONMENT BY REPRESENTING AGGRESSIVE, DAMAGING AND UNBALANCED INTERACTIONS WITH NATURE, WE CAME TO THE CONCLUSION THAT WE WILL INCREASINGLY PROVOKE NEW DISEASE EMERGENCES. IN FACT, THAT LEADS TO THE ONE HEALTH APPROACH AS THE REALIZATION THAT THERE ARE EMERGING AND REEMERGING ZOONOTIC INFECTIONS THAT WILL BE A PERPETUAL CHALLENGE AND THAT HUMAN HEALTH IS INTIMATELY CONNECTED TO THE HEALTH OF ANIMALS BECAUSE OF OUR SHARED ENVIRONMENT AND OUR EVER INCREASING ENCROACHMENT UPON THE ENVIRONMENT OF THESE OFTEN ANIMALS IN THE WILD. AND IN FACT, RECENT STUDIES ON THE PAST SUMMER OF A VERY STRICT AND COMPREHENSIVE ANALYSIS OF THE COVID-19 OUTBREAK IN WUHAN LED A LARGE GROUP OF INDEPENDENT AND HIGHLY RECOGNIZED EVOLUTIONARY VIROLOGISTS TO COME TO THE CONCLUSION THAT ALTHOUGH WE WILL KEEP AN OPEN MIND AS TO THE ORIGIN, THAT IT IS MUCH MORE LIKELY THAT THIS WAS AN EMERGENCE NATURALLY FROM ANIMALS IN THE WUHAN MARKET TO HUMANS LEADING TO THE OUTBREAK. AND A NUMBER OF OTHER STUDIES SHOWED THAT THERE ARE BATS NOW THAT HAVE VIRUSES THAT ARE JUST A MUTATION OR A FEW MUTATIONS AWAY FROM WHAT WE WOULD CONSIDER TO BE THE VIRUS OF SARS-COV-2. SO WE STILL HAVEN'T NAILED DOWN THE ORIGIN. WE KEEP AN OPEN MIND THAT IT COULD POSSIBLY HAVE BEEN A LAB LEAK, BUT THE DATA ARE VERY STRONGLY POINTING TO THIS ANIMAL-HUMAN INTERFACE ISSUE. NEXT, THERE ARE LONG-STANDING SYSTEMIC HEALTH AND SOCIAL INEQUITIES THAT DRIVE PANDEMIC DISPARITIES. AND WE REALLY NEED TO PAY ATTENTION TO THESE BECAUSE THEY'VE BEEN AROUND FOR A WHILE, THEY ARE REAL, AND THEY ACTUALLY CAUSE A GREATER DEGREE OF SUFFERING AND DEATH THAN IS ACTUALLY NECESSARY. THESE ARE SOME OF THE ISSUES THAT LEAD TO INEQUITIES AND DISPARITIES. THE FIRST IS DISCRIMINATION THAT GOES BACK LITERALLY DECADES AND CENTURIES THAT WE'VE SEEN IN OUR COUNTRIES WITH THE DISENFRANCHISEMENT OF CERTAIN MINORITY GROUPS TO THE HEALTHCARE SYSTEM AND THE LACK OF HEALTHCARE ACCESS AND USE. ALSO, THERE ARE OTHER THINGS THAT WE REALLY DIDN'T FULLY ANTICIPATE UNTIL SA SARS-COV-2 CAME, AND THAT IS A PERSON'S OCCUPATION. BECAUSE FOR EXAMPLE, OUR MINORITY POPULATIONS, OUR BROWN AND BLACK POPULATIONS, AFRICAN AMERICAN, HISPANICS AND OTHERS, ARE DISPROPORTIONATELY IN ESSENTIAL WORK SETTINGS WHERE REMOTE WORK OR PHYSICAL DISTANCING IS EXTREMELY DIFFICULT IF NOT IMPOSSIBLE. SO AT A TIME WHEN PEOPLE WERE HUNKERING DOWN, THESE INDIVIDUALS WERE CONTINUALLY EXPOSED AND SO AT A HIGHER RATE OF INITIAL INFECTION. IN ADDITION, AS WE KNOW FROM THE UNDERLYING CO-MORBIDITIES THAT MANY OF THESE PEOPLE HAVE, THAT ONCE INFECTED, THEY HAD A HIGHER RATE OF HOSPITALIZATION AND DEATH. THAT HAS BEEN A BIT OVER THE LAST THREE YEARS NORMALIZED TO THE GENERAL GROUP, BUT THERE STILL IS THAT EXISTING DISPARITY. IN ADDITION, DISPARITIES OF EDUCATION, INCOME, AND WEALTH GAPS HAVE PLAYED AN IMPORTANT ROLE, AND ANOTHER ISSUE THAT WE NEED TO PAY ATTENTION TO IS HOUSING. SOME PEOPLE, GENERALLY BASED ON THEIR ECONOMIC STATUS, LIVE IN CROWDED CONDITIONS. AND IT IS QUITE DIFFICULT TO FOLLOW THE PREVENTION STRATEGIES THAT WE TALK ABOUT WHEN THEIR STATUS IN LIFE, INCLUDING THEIR HOUSING, MAKES IT VERY DIFFICULT TO IMPLEMENT THIS. AND THEN FINALLY, MISINFORMATION AND NOW, AS WE'RE SEEING, DISINFORMATION IS TRULY THE ENEMY OF PUBLIC HEALTH AND PANDEMIC CONTROL. THESE ARE JUST A FEW OF THE LITERALLY THOUSANDS OF EXAMPLES OF THE MISINFORMATION AND DISINFORMATION THAT HAS OCCURRED AROUND EVERYTHING FROM THE ORIGIN OF THE VIRUS TO THE VACCINES, TO THERAPIES, TO A VARIETY OF OTHER ISSUES. THE CLAIMING THAT VACCINATIONS CAUSING DEATHS OF ATHLETES, THE ANTI-VACCINE PROPAGANDA OF ROBERT F. KENNEDY, JR., THE PREPOSTEROUS IDEA, AND I SAY THIS WITH SOME DEGREE OF ROLLING MY EYES, THAT BILL GATES AND I PUT CHIPS IN VACCINES SO THAT WE COULD MONITOR PEOPLE. THAT SOUNDS LUDICROUS TO MANY, BUT IT IS ASTOUNDING, HOW MANY PEOPLE BELIEVE THAT. THAT WOULDN'T BE AN ISSUE, EXCEPT THAT THAT LEADS TO PEOPLE DECIDING NOT TO GET VACCINATED, WHICH INDIRECTLY CONTRIBUTES STRONGLY TO PEOPLE GETTING INFECTED, REQUIRING HOSPITALIZATIONS, AND IN SOME CASES, DYING. SO MISINFORMATION AND DISINFORMATION IS THE ENEMY OF PUBLIC HEALTH, BECAUSE IT CAN ACTUALLY LEAD TO AVOIDABLE DEATHS. OKAY. WHAT ABOUT THE FUTURE? WHERE ARE WE NOW, AND WHAT IS THE END GAME FOR -- THIS WAS 2022 I MADE THIS SLIDE IN THE END OF 2022. WHAT IS THE END GAME FOR 2022 AND BEYOND? WELL, IF YOU LOOK AT PANDEMICS, AND LOOK AT THE PANDEMIC PHASE WHICH WE WERE IN AND STILL ARE TO SOME RESPECTS OVER THE PAST FEW YEARS, WE'VE SEEN THE DECELERATION OF NEW CASES, BUT I FIND IT USEFUL WHEN PEOPLE ASK, WHAT IS GOING TO HAPPEN WITH COVID-19? IS THIS GOING TO BE WITH US FOREVER, AND IF SO, IN WHAT FORM? WELL, LET'S TAKE A LOOK AT THE HISTORY OF VIRUSES. WILL WE BE ABLE TO ERADICATE COVID? I AM ALMOST CERTAIN THAT THE ANSWER TO THAT IS GOING TO BE NO. WHY? WE ONLY ERADICATED ONE PATHOGEN FOR HUMANS IN PUBLIC HEALTH HISTORY. AND THAT IS SMALLPOX. AND THERE ARE A NUMBER OF REASONS WHY THAT ARE DIFFERENT FROM COVID. SMALLPOX IS A PHENOTYPICALLY STABLE VIRUS. THE SMALLPOX THAT WE HAD DECADES IF NOT CENTURIES AGO IS ESSENTIALLY THE SAME AS THE SMALLPOX THAT WAS ELIMINATED BACK IN 1980. WE HAD A WIDELY ACCEPTABLE GLOBAL VACCINATION CAMPAIGN, AND AS I MENTIONED EARLIER IN THE TALK, UNLIKE THE SITUATION WITH COVID, THE VACCINE OR INFECTION-INDUCED IMMUNITY IS HIGHLY DURABLE, USUALLY MEASURED IN DECADES OR A LIFETIME. THAT'S WHY WE WON'T BE ERADICATING COVID-19 OR SARS-COV-2. THAT'S ELIMINATION. NOW, LET'S TAKE A LOOK AT THE INFECTIONS THAT WE'VE ELIMINATED FROM THE UNITED STATES. BUT A NUMBER OF DEVELOPED NATIONS HAVE ALSO DONE THIS. POLIO WAS ELIMINATED IN 1979. MEASLES IN 2000. AGAIN, HOW WAS THIS POSSIBLE? LET'S TAKE A LOOK AT IT. BESIDES THE LACK OF AN ANIMAL RESERVOIR, WHICH IS TRUE OF ALSO SMALLPOX, POLIO AND MEASLES ARE PHENOTYPICALLY STABLE VIRUSES. YOU DON'T GET THAT SEQUENTIAL EVOLUTION OF VARIANTS THAT I SHOWED YOU ON PRIOR SLIDES THAT WERE SEEN AS A RESULT OF THE MUTATIONS IN SARS-COV-2. YOU DON'T SEE THAT IN POLIO OR MEASLES. NEXT, WE'VE HAD HISTORIC, WIDELY ACCEPTED NATIONAL VACCINATION CAMPAIGNS. FOR MEASLES AND POLIO, UNLIKE THE FACT THAT ONLY 68% OF OUR POPULATION IS VACCINATED WITH THE SARS-COV-2 VACCINE, AND ONLY ABOUT 14% OF PEOPLE WHO ARE ELIGIBLE HAVE RECEIVED THE UPDATED BA4/5 VACCINE. IMPORTANTLY, EITHER INFECTION-INDUCED OR VACCINATION-INDUCED IMMUNITY AGAINST POLIO AND MEASLES LAST FOR LITERALLY DECADES, IF NOT A LIFETIME. SO THEN WE GET TO SARS-COV-2. I'VE ALLUDED TO IT A FEW TIMES OVER THE PAST COUPLE OF MINUTES. AGAIN, SARS-COV-2 IS PHENOTYPICALLY AND GENOTYPICALLY DIVERSE. IF YOU LOOK AT THAT SLIDE I SHOWED YOU A LITTLE BIT AGO, THERE WERE MULTIPLE PEAKS IN THOSE OUTBREAKS OF ALPHA, BETA, DELTA, GAMMA, OMICRON AND THEN SUBLINEAGES OF OMICRON. YOU DON'T SEE THAT WITH MEASLES OR WITH POLIO. THE NEXT, WE CERTAINLY DON'T HAVE A WIDELY ACCEPTED VACCINE SITUATION, WHERE IF ANYTHING, THERE IS AN EMERGING AND GROWING ANTI-VAX FEELING IN THIS COUNTRY. AND THEN AGAIN, AS I'VE SHOWED YOU MANY TIMES, THE VACCINE AND INFECTION-INDUCED IMMUNITY WANES OVER A PERIOD OF MONTHS AS OPPOSED TO YEARS AND DECADES. AND SO WHAT ARE WE GOING TO BE LEFT WITH? WE'RE GOING TO BE LEFT WITH WHAT I THINK IS A GOOD ACCEPTABLE CONTROL OF THE SPREAD OF THE VIRUS. NOW, CONTROL MEANS DIFFERENT THINGS TO DIFFERENT PEOPLE. WHAT I'M TALKING ABOUT IS A LEVEL OF CONTROL OF TRANSMISSION AND ACQUISITION THAT RENDERS SARS-COV-2 AMONG A NUMBER OF VIRUSES THAT DOES NOT DISRUPT THE SOCIAL ORDER AND THE DEGREE OF HOSPITALIZATIONS AND DEATH AT A LOW ENOUGH LEVEL, AGAIN, NOT TO HAVE THE DISRUPTIVE NATURE THAT WE'VE SEEN. SOME REFER TO THAT AS A RETURN TO NORMALCY. SOME REFER TO THAT AS ACCEPTABLE ENDEMICITY. THIS WOULD BE SIMILAR TO SOME OF THE RESPIRATORY VIRUSES THAT WE HAVE HAD EXPERIENCE WITH CHRONICALLY OVER YEARS. SUCH AS THE COMMON COLD CORONAVIRUSES, INFLUENZA RSV, RHINOVIRUSES, ET CETERA. THIS IS NOT GOING TO HAPPEN SPONTANEOUSLY. IT'S GOING TO LIKELY REQUIRE INTERMITTENT BOOSTING OVER TIME, SUCH AS WHAT WE DO ON A YEARLY BASIS WITH INFLUENZA. OBVIOUSLY IF A BRAND NEW VARIANT THAT'S VERY DIFFERENT FROM ANYTHING ELSE COMES ALONG, WE WILL HAVE TO ADDRESS THAT IN REALTIME. BUT WE'RE TRYING TO GET INTO A CADENCE OF A REGULAR UPDATING OF A BOOST MATCHED, HOPEFULLY, TO WHAT THE PREVALENT CIRCULATING VARIANT IS IN SOCIETY AT THAT TIME. BUT THERE ARE ALSO OTHER THINGS THAT WE CAN PRACTICE. COMMON SENSE, RESPIRATORY HYGIENE, VOLUNTARY MASKING, ATTENTION TO VENTILATION, AS WELL AS KEEPING UP WL, AS I MENTIONED AT THE BEGINNING OF THE TALK, ON EFFECTIVE ANTIVIRALS AND MONOCLONAL ANTIBODIES. SO AGAIN JUST TO RECAPITULATE, THESE ARE THE LESSONS THAT WE CAN AND SHOULD HAVE LEARNED FROM COVID-19, WHICH WILL CONTINUE TO HELP US EVEN AS WE ARE STILL GOING THROUGH COVID-19, BUT HOPEFULLY OUR CORPORATE MEMORY WILL BE SUCH THAT WE WILL NOT FORGET THESE AS WE FACE IN THE FUTURE IN AN UNPREDICTABLE WAY THE INEVITABILITY OF FUTURE OUTBREAKS. AND I'LL END WITH THIS FINAL SLIDE THAT MY COLLEAGUES DAVID MORENS AND GREG AND I WROTE, NOW, 14-PLUS YEARS AGO IN THE LANCET INFECTIOUS DISEASES, THAT THE BIG LESSON OF ALL IS THAT WE'VE LEARNED THAT INFECTIOUS DISEASES ARE TRULY A PERPETUAL CHALLENGE. EMERGING INFECTIONS, BRAND NEW OR RE-EMERGING, THEY'VE BEEN WITH US SINCE BEFORE RECORDED HISTORY. HISTORY HAS RECORDED THEM AS WITH THE FAMOUS PANDEMIC OF 1918, OTHER INFLUENZA PANDEMICS, EBOLA, ZIKA AND NOW COVID, AND THE FUTURE WILL SURELY HAVE FOR US ADDITIONAL PANDEMICS. SO JUST AS EMERGING INFECTIOUS DISEASES ARE A PERPETUAL CHALLENGE, WE MUST MAKE PREPAREDNESS AND RESPONSE SOMETHING THAT IS PERPETUAL IN ITS NATURE, AND NOT TRANSIENT. I'LL STOP THERE. THANK YOU FOR YOUR ATTENTION. >>THANK YOU, THANK YOU VERY MUCH, TONY. WE HAVE A FEW QUESTIONS. IN FACT, THERE ARE SO MANY QUESTIONS, WE COULD KEEP YOU BUSY FOR ANOTHER FEW HOURS IF YOU HAD THE TIME. AT ANY RATE, JOHN SAYS, THERE SEEMS TO BE A LIMITED NUMBER OF OBSERVATIONAL STUDIES FOCUSING ON THE EFFECTS OF DIFFERENT VACCINE BOOSTER INTERVALS. DOES BOOSTING RESULT IN LONG-TERM BENEFITS OR SIMPLY A TRANSITORY BUMP IN PROTECTION? AND THE SECOND PART OF THAT IS, SHOULD NEWLY EMERGING STRAINS BE TREATED IN EFFECT AS A NEW VIRUS, BRINGING ABOUT THE ESSENTIALLY CREATION OF A NEW AND MORE SPECIFIC VACCINE? DO YOU WANT TO RESPOND TO THAT? >>YEAH, WELL, THE FIRST PART IS, IT DEPENDS ON IF YOU'RE TALKING ABOUT PROTECTION AGAINST INFECTION OR PROTECTION AGAINST SEVERE DISEASE THAT MIGHT LEAD TO HOSPITALIZATION. IF YOU LOOK AT PROTECTION AGAINST INFECTION, THAT'S CORRELATED WITH THE DEGREE OF ANTIBODY THAT SPIKES UP, AND THEN AS YOU WOULD EXPECT, BECAUSE THAT'S NORMAL IMMUNOLOGY, THAT THE ANTIBODY LEVELS WILL GO DOWN OVER A PERIOD OF TIME. IF THAT WERE NOT THE CASE, WE'D ALL BE HYPERGAMMA GLOBULINEMIC WITH RESPONSE TO EVERY PATHOGEN WE GET INFECTED WITH. SO THAT'S GOING TO BE TRANSIENT. BUT WHAT DOES LAST MUCH LONGER, AND IN A BROADER WAY WITH GREATER BREATH, ARE CD4 AND CD8 T-CELLS THAT TO SOME EXTENT -- AND TO SOME EXTENT MEMORY B CELLS. AND SO YES, THE RESPONSE AND THE PROTECTION AGAINST INFECTION IS IN MANY RESPECTS MORE TRANSIENT AND SENSITIVE TO DURABILITY THAN IS THE RESPONSE TO PROTECTION AGAINST SEVERE DISEASE. SO THAT'S THE ANSWER TO THE FIRST QUESTION. THE ANSWER TO THE SECOND QUESTION, I DON'T THINK IT'S NECESSARILY CORRECT TO SAY THAT A DIFFERENT STRAIN OF CORONAVIRUS IS AN ABSOLUTELY NEW VIRUS. BECAUSE THERE'S ALWAYS A DEGREE OF CROSS-PROTECTION, AND THAT'S ACTUALLY A GREAT QUESTION FOR ME TO MAKE ANOTHER POINT THAT I DIDN'T -- I MADE BUT I DIDN'T MAKE IT AS COMPLETE ENOUGH IN THE DISCUSSION, IS THAT AS WE ARE FACING AN XBB.1.5, ALTHOUGH ON THE PHYLOGENETIC TREE, IT'S DISTANT A BIT FROM BA.4/5, THERE IS CROSS PROTECTION AT THE T-CELL LEVEL, SO IT WOULD BE INACCURATE TO SAY IT'S A BRAND NEW VIRUS. BECAUSE IT ISN'T. IT'S ACTUALLY A SUBLINEAGE OF A COMBINATION OF A RECOMBINANT OF BA2. AND I KNOW WE DON'T HAVE THE SLIDE UP NOW, WIN, BUT IF WE WERE TO SHOW THE SLIDE, YOU WOULD SEE THAT THE BA2 IS TO THE LEFT AND WHEN YOU GO TO THE RIGHT, YOU SEE THE SUBLINEAGE OF AN XBB.1.5. SO IT IS PART OF THE SAME VIRUS. IT'S NOT AN ENTIRELY DIFFERENT VIRUS. >>SO BOB ASKED A QUESTION WHICH IS IN, I GUESS, EVERYONE'S MIND. GIVEN THE CURRENT GENERAL RELAXATION OF MASKING AND OTHER SAFETY PROCEDURES, AND WITH A LACK OF REAL INSIGHT INTO LONG COVID FORMATION, WHAT'S YOUR RECOMMENDATION AS TO WHETHER PEOPLE SHOULD GO ON A TWO-WEEK CRUISE TO THE CARIBBEAN OR EVEN FLY IN AN AIRPLANE, WHAT IS YOUR PERSONAL FEELING ON THAT? >>WELL, THAT IS REALLY THE QUESTION OF THE MONTH OR THE YEAR OR THE QUARTER OR WHAT HAVE YOU. BECAUSE EVERYONE IS SO FATIGUED WITH COVID, THEY DON'T WANT TO HEAR ABOUT MASKING -- UNFORTUNATELY MOST PEOPLE DON'T WANT TO HEAR ABOUT BOOSTERS, WHICH IS REALLY UNFORTUNATE, BUT PEOPLE REALLY WANT TO BE DONE WITH COVID. AND THAT DOESN'T GET US AWAY FROM THE FACT THAT COVID IS NOT DONE WITH US. AND PARTICULARLY WITH THE ISSUE OF LONG COVID, THAT IF YOU GET INFECTED EVEN WITH A MILD TO MODERATE DEGREE OF INFECTION, YOU CAN GET LONG COVID. SO PEOPLE WERE SAYING, WELL, YOU KNOW, WE'RE THREE YEARS NOW GOING INTO THE FOURTH YEAR. I'M NOT REALLY INTERESTED IN PROTECTING MYSELF AGAINST INFECTION. I'VE GOTTEN VACCINATED, AND SO I'M GOING TO DEPEND ON THAT. WELL, OBVIOUSLY THERE'S A DEGREE OF VALIDITY TO THAT APPROACH. BUT RIGHT NOW, GIVEN THE FACT THAT WE'RE SEEING AN UPTICK OF INFECTIONS, WIN, WHEN I GO INTO A CROWDED CONGREGATE INDOOR SETTING AND I DON'T KNOW THE STATUS OF WHETHER OR NOT PEOPLE HAVE BEEN TESTED, I WEAR A MASK. I JUST GOT OFF A PLANE TO A MEETING THAT I WAS AT LAST WEEK, AND I WORE AN N95 FOR THE ENTIRE TRIP ON THE PLANE. I WAS A RELATIVE MINORITY OF PEOPLE WEARING A MASK. BUT THERE IS STILL TRANSMISSION GOING ON OUT THERE, AND IT DEPENDS UPON HOW RISK-AVERSE YOU WANT TO BE. DO YOU HAVE A PERSON AT HOME WHO IS VULNERABLE, AN ELDERLY PERSON, A PERSON WITH AN UNDERLYING CONDITION? WOULD YOU WANT TO BRING AN INFECTION HOME EVEN THOUGH YOU MAY BE PROTECTED AGAINST SEVERE DISEASE? YOU'VE GOT TO TAKE THOSE THINGS INTO CONSIDERATION. BUT AGAIN, THE GENERAL FEELING IN THE COUNTRY IS PEOPLE WANT COVID BEHIND US AND BY BEING BEHIND US, THEY'RE NOT PARTICULARLY INTERESTED IN ANY OF THE INTERVENTIONS OR THE MITIGATIONS. >>WE HAVE ANOTHER INTERESTING QUESTION HERE. IS IT THE GENERALIZATION THAT MESSENGER RNA VACCINES WILL REQUIRE REGULAR BOOSTERS TO REMAIN EFFECTIVE AS COMPARED, LET'S SAY, TO THE -- WHAT USED TO BE LIVE-ATTENUATED VIRUSES OR INDIVIDUAL PROTEINS AS A VACCINE? >>THAT'S A GREAT QUESTION AND WE DON'T HAVE A DEFINITIVE ANSWER FOR THAT, FOR THE SIMPLE REASON THAT THIS IS ALL THE EXPERIENCE WE HAVE, SUBSTANTIAL EXPERIENCE, IS WITH ONE VIRUS, CORONAVIRUS, AND AN MRNA. SO WE KNOW THAT LANGE LONG BEFOE MRNA, CORONAVIRUS' IMMUNITY WAS VERY TRANSIENT. WE KNOW THAT FROM DECADES AND DECADES OF EXPERIENCE WITH THE COMMON COLD. WE GET REINFECTED WITH THE COMMON COLD EVERY YEAR OR TWO OR THREE. YOU WOULD NEVER SEE THAT WITH MEASLES. YOU WOULD NEVER SEE THAT WITH MUMPS. YOU WOULD NEVER SEE THAT WITH POLIO. SO IS IT THE NATURE OF CORONAVIRUSES, OR IS IT THE NATURE OF MRNA, OR IS IT BOTH? SO I'D HAVE TO TELL -- OR RESPOND TO THE PERSON WHO ANSWERED THE QUESTION, I DON'T KNOW THE ANSWER TO THAT. AND WE'RE GOING TO FIND OUT WHEN YOU GET MORE AND MORE UTILIZATION OF MRNA VACCINES WITH DIFFERENT PATHOGENS. >>I THINK IT WAS IN 2020, I REMEMBER I GUESS READING SOMETHING THAT YOU HAD WRITTEN ABOUT THE LIKELIHOOD THAT MESSENGER RNA TECHNOLOGY WAS GOING TO FEEDBACK INTO HIV VACCINE DEVELOPMENT. NOW GRANTED TODAY YOU'RE DISCUSSING COVID, BUT WE HAVE YOU HERE. WOULD YOU COMMENT ABOUT THAT STATUS? >>WELL, WE'RE ALREADY THERE. THERE ARE A NUMBER OF MRNA VACCINES FOR HIV THAT ARE ALREADY IN PHASE ONE TRIALS, AND THERE ARE A NUMBER THAT HAVE ACTUALLY BEEN IN NON-HUMAN PRIMATE STUDIES. PAL ALLUSO IN MY FORMER LAB HAS PUBLISHED A VERY NICE PAPER ON THE NON-HUMAN PRIMATE MODEL. AND OTHER GROUPS FROM LA HOYA LA HOYAHAVE A STUDY THAT'S EVENR ADVANCED THAN THAT. >>HOW DO YOU DEAL -- HOW DO YOU RECOMMEND THAT PEOPLE DEAL WITH VACCINE SKEPTICS? >>WELL, VACCINE SKEPTICISM IN AND OF ITSELF IS NOT A MORTAL SIN. IT'S SOMETHING THAT YOU CAN UNDERSTAND THAT PEOPLE ASK QUESTIONS ABOUT A NEW PRODUCT WITH REGARD TO ITS EFFICACY AND ITS SAFETY. SO RATHER THAN BE PUT ABACK BY SKEPTICISM, YOU TRY TO ENGAGE WITH A PERSON OR A GROUP WHO ARE SKEPTICAL BECAUSE THEY MAY HAVE SOME VERY VALID QUESTIONS THAT DESERVE FURTHER EXPLANATION AND ANSWERING. AND I BELIEVE THAT IF A PERSON IS NOT AN HARD CORE ANTI-VAX PERSON BUT DOES HAVE SOME CONCERN AND SKEPTICISM, IF YOU ENGAGE THAT PERSON AND TRY AND TALK ABOUT DATA AND EVIDENCE THAT WE KNOW IS REAL, THAT HAS BEEN COLLECTED IN AN APPROPRIATE MANNER, PERHAPS YOU CAN DIMINISH SOMEWHAT THAT SKEPTICISM. THERE'S A BIG DIFFERENCE BETWEEN TOTAL OUTRIGHT ANTI-VAX, REGARDLESS OF WHAT YOU SAY, AND THE LARGER NUMBER OF PEOPLE WHO HAVE A CERTAIN DEGREE OF WHAT MIGHT BE HEALTHY SKEPTICISM ABOUT VACCINES. AND ONCE YOU EXPLAIN THE FACTS TO THEM, HOPEFULLY YOU'LL WIN THEM OVER. >>WE HAD SEVERAL QUESTIONS THAT PEOPLE ARE ALWAYS ASKING AND THINKING ABOUT, AND THAT IS, CAN YOU SUMMARIZE HOW COUNTRIES THAT ARE NOT AS ECONOMICALLY PROSPEROUS AS WE ARE HAVE DONE SUCH A MUCH BETTER JOB IN HANDLING THE COVID PANDEMIC THAN WE HAVE? I REALIZE THAT'S A HUGE COMPLEX THING, BUT PERHAPS YOU WOULD COMMENT ABOUT IT. >>YEAH, IT'S A QUESTION THAT CAN BE ANSWERED BY VOLUMES, WIN, BECAUSE IT'S SO COMPLICATED, BUT ONE OF THE THINGS THAT I'VE HAD PAINFUL EXPERIENCE WITH OTHER THE LAST THREE YEARS IS THE FACT THAT WE'VE HAD A POLITTE SIZATA POLITICIZATIONOF THIS OU, THE LIKES OF WHICH I'VE NOT SEEN TO THIS EXTENT IN ANY OTHER COUNTRY. IF EVER THERE WAS A TIME WHEN YOU DIDN'T WANT TO HAVE A HISTORIC DEADLY OUTBREAK THAT'S KILLED A MILLION AMERICANS IS WHEN YOU'RE IN A SITUATION WHERE THE DEGREE OF DIVISIVENESS IN THE COUNTRY IS PROFOUND. IT'S THICK. PEOPLE ARE MAKING DECISIONS ABOUT WHETHER TO GET VACCINATED OR NOT BASED ON POLITICAL IDEOLOGY. THAT JUST DOESN'T SEEM TO MAKE MUCH SENSE THAT THAT'S THE CASE. IN ADDITION, AS RICH AS WE ARE, OUR HEALTHCARE SYSTEM IS NOT REALLY AT A HIGH LEVEL COMPARED TO MANY OTHER COUNTRIES, WHERE YOU HAVE A UNIFORMITY OF ACCESS TO HEALTHCARE. WE STILL HAVE -- AND I GAVE ONE OR TWO OF MY SLIDES THAT I SHOWED DURING A PRESENTATION ACTUALLY, ADDRESSED THAT, THAT THERE'S A TREMENDOUS DEGREE OF DISPARITY, OF ACCESS TO EVERYTHING FROM HEALTHCARE IN GENERAL, TO VACCINATION, TO THERAPY, ET CETERA. SO IT'S UNFORTUNATE THAT AS RICH AS WE ARE, THAT WE HAVE NOT DONE NEARLY AS WELL AS WE SHOULD HAVE DONE WITH REGARD TO THE RESPONSE TO THIS OUTBREAK. >>THERE HAS BEEN INQUIRY TOO ON THE VIEWS OF THE EFFECT OF GLOBAL WARMING ON THE PANDEMIC AND OTHERS. I REALIZE THAT FITS INTO THAT LARGE CATEGORY OF WHAT WE ARE DOING IN OUR INTERACTION WITH NATURE. BUT ARE THERE ANY SPECIFIC ASPECTS OF GLOBAL WARMING THAT HAVE BECOME APPARENT REGARDING COVID? >>YOU KNOW, NOT REALLY, WIN. I MEAN, I GUESS YOU COULD SORT OF STRETCH A BIT TO SAY THAT THERE IS BUT THERE'S NOT REALLY ANYTHING THAT I THINK HAS A SUBSTANTIAL IMPACT. GLOBAL WARMING, PARTICULARLY WHEN YOU'RE DEALING ABOUT THE RANGE OF VECTORS LIKE MOSQUITOES, THAT CLEARLY CAN HAVE AN IMPACT ON THE EMERGENCE OF NEW INFECTIOUS DISEASE IN LOCATIONS IN WHICH IT WAS NOT READILY APPARENT THAT THEY OCCURRED THEN. THERE ARE A NUMBER OF OTHER EXAMPLES BUT THAT'S PROBABLY THE BEST ONE. >>DO YOU THINK THERE'S A NEED TO DEVELOP A BETTER MASK? >>UH, YEAH, I MEAN, YOU ALWAYS WANT TO DEVELOP BETTER PROTECTIVE EQUIPMENT. BEFORE WE GO THERE, I WOULD RECOMMEND THAT PEOPLE WEAR AN N95 OR A KN95 BECAUSE THEY CLEARLY -- THERE'S VERY GOOD DATA SHOWING WHY THEY ARE SUPERIOR, FOR EXAMPLE, TO CLOTH MASKS. >>THERE'S ALSO AN INQUIRY, ARE ANY OF THE RESPIRATORY VIRUSES -- ONCOGENES? >>NOT TO MY KNOWLEDGE. IT COULD BE, BUT I HAVEN'T HEARD THAT. >>I'M JUST CURIOUS, THERE WAS A VERY EXCITING STUDY BY NEHALL ALTON BONET HERE AT NIH ON THE ROLE OF THE SALIVARY GLAND AS A SITE OF REPLICATION OF MANY RNA VIRUSES, INCLUDING COVID. I WONDER IF THAT'S THE CASE, DOES THAT INFLUENCE SOME THINKING ABOUT THE SPREAD OF THE DISEASE AND ALSO PERHAPS APPROACHES TO VACCINATION? >>WELL, IF IT'S TRUE, WHICH I HAVEN'T READ THAT PAPER TO ANY DEGREE, BUT IF IT'S TRUE, IT CERTAINLY WOULD ARGUE FOR THE EFFECTIVENESS OF THIS VIRUS IN SPREADING FROM PERSON TO PERSON, IF YOU'RE HAVING IT REPLICATING IN SALIVARY GLANDS IN THE ORAL MUCOSA, THEN YOU'RE REALLY PUTTING OUT A LOT OF VIRUS FROM THAT UPPER AIRWAY, WHICH WOULD CERTAINLY HAVE AN IMPACT ON TRANSMISSION. SECONDLY, IT ARGUES MORE IN FAVOR OF ONE OF MY LAST FEW SLIDES WHEN I WAS TALKING ABOUT MUCOSALLY-ADMINISTERED VACCINES. >>IN TERMS OF THE MUCOSAL -- >>RIGHT. >>ANOTHER QUESTION THAT POPS UP IS, HEPATITIS C IS, TO MY KNOWLEDGE, THE ONLY VIRUS THAT IS KNOWN TO BE CURED BY A PHARMACEUTICAL. >>RIGHT. >>QUITE AN AMAZING -- REALLY AN AMAZING DISCOVERY. MUCH OF THE EMPHASIS IN COVID WAS FOR THE DEVELOPMENT OF A VACCINE, AND OF COURSE THE PROGRESS REGARDING ANTIVIRAL AGENTS. BUT IS THERE INTENSIVE EFFORTS TO TRY AND DEVELOP A PHARMACEUTICAL APPROACH TO TREAT THE VIRUS IN THE HOPES THAT SOMETHING CAN BE DEVELOPED THAT WILL MAKE IT BEHAVE LIKE HEPATITIS C, WHEN IT'S TREATED? >>WELL, I THINK WE'RE MIXING APPLES AND ORANGES A LITTLE BIT, WIN. LET ME EXPLAIN. HEPATITIS C IS A CHRONIC VIRAL INFECTION. SO PAXLOVID IS VERY GOOD AGAINST COVID. BUT PAXLOVID REALLY HELPS YOU TO CLEAR COVID SOONER THAN YOU WOULD OTHERWISE CLEAR IT. BECAUSE MOST OF THE BODY'S IMMUNE SYSTEM IS GOING TO CLEAR COVID -- SARS-COV-2 ANYWAY. WHEREAS HEPATITIS C IN ITS CHRONIC FORM, YOU JUST DON'T CLEAR IT. AND THAT LEADS TO DAMAGE TO THE LIVER, LEADING TO CHRONIC LIVER DISEASE AND LIVER CANCER. BUT IN ANSWER TO YOUR QUESTION, SPECIFICALLY, THERE IS A CONSIDERABLE EFFORT FOR THE DEVELOPMENT OF BETTER ANTIVIRALS FOR COVID. AND THAT'S THE ANTIVIRAL PROGRAM FOR PANDEMICS, OR APP, WHICH WE PUT TOGETHER AS PART OF OUR PANDEMIC PREPAREDNESS AND RESPONSE APPROACH, WHICH I MIGHT PUT IN A LITTLE PLUG HERE. I'M NO LONGER ARGUING THE BUDGET FOR THE NIH BECAUSE I'M NOT OFFICIALLY IN THE NIH ANYMORE, BUT WE REALLY DO NEED MONEY FOR THAT. AND THE CONGRESS, AS YOU KNOW, IN THE NU NEW BUDGET APPROACH DS NOT INCLUDE THE MONEY FOR COVID IN THAT. AND THAT IS A GREAT DISAPPOINTMENT TO THOSE OF US WHO HAVE BEEN PUSHING FOR CONTINUED RESOURCES FOR PANDEMIC PREPAREDNESS AND RESPONSE. >>WHAT'S YOUR FAVORITE YOGIISM? >>MY FAVORITE YOGIISM IS IT AIN'T OVER TILL IT'S OVER, AND THAT IS CERTAINLY APPLICABLE TO COVID RIGHT NOW. >>THERE'S ANOTHER QUESTION HERE ASKING ABOUT INTERNATIONAL RESTRICTIONS ON GAIN OF FUNCTION STUDIES USING INFECTIOUS VIRUSES. IS THERE INTERNATIONAL RESTRICTION ON THIS? WHAT IS THE STATUS? >>NO. WELL, YOU'VE GOT TO BE CAREFUL WHEN YOU USE THE WORD GAIN OF FUNCTION, BECAUSE YOU KNOW, GAIN OF FUNCTION MEANS A LOT OF DIFFERENT THINGS TO A LOT OF DIFFERENT PEOPLE. IF YOU MEAN DOING RESEARCH THAT ENHANCES THE PATHOGENESIS OR THE TRANSMISSIBILITY OF A DANGEROUS PATHOGEN, THERE IS NO INTERNATIONAL RESTRICTION. THE FEDERAL GOVERNMENT CAN PUT A RESTRICTION ON RESEARCH THAT WE FUND, BUT THERE'S NO INTERNATIONAL GLOBAL AGREEMENT ON THAT, AND SOME COUNTRIES CAN DO WHATEVER THEY WANT TO DO. WHICH IS UNFORTUNATE. >>SO I'M JUST LOOKING HERE, WE HAVE THREE SORT OF PERSONAL QUESTIONS. WHICH I'M GOING TO LUMP TOGETHER. HOW DO YOU DO THE MANY THINGS THAT YOU DO? DO YOU EVER SLEEP? DO YOU EVER TAKE A VACATION? DO YOU KEEP A DIARY? ARE YOU GOING TO BE ABLE TO REMEMBER ALL THESE THINGS SO YOU CAN EDUCATE US AND OUR CHILDREN AND GRANDCHILDREN AND SO FORTH, BECAUSE THIS PERIOD IN HISTORY IS NOT SOMETHING THAT IS GOING TO BE RELEGATED TO A FOOTNOTE. I HOPE. AND I GUESS THE LAST PART OF THE PERSONAL QUESTION, IF YOU WANT TO SHARE WITH US, IS WHAT COMES NEXT? >>ALL RIGHT. SO THERE ARE FIVE QUESTIONS THERE. ALL RIGHT. DO MANY THINGS. WELL YOU'VE GOT TO BE WELL ORGANIZED AND COMPARTMENTALIZED AND DESIGNATE A CERTAIN AMOUNT OF TIME FOR SOMETHING AND ORGANIZE IT IN A WAY AND GET IT DONE. AND I DID THAT FOR DECADES IN MY 38 YEARS AS DIRECTOR OF NIAID, WHERE I DID CLINICAL MEDICINE, I DID BASIC RESEARCH, I DID CLINICAL RESEARCH, I DID POLICY, AND I RAN THE INSTITUTE, AND YOU'VE GOT TO BE VERY WELL ORGANIZED AND REALIZE THAT YOU'VE GOT TO SACRIFICE BECAUSE YOU'RE NOT GOING TO DO THAT IN AN #-HO 8-HOUR DAY AND A 5-DAY WEEK, SO EACH PERSON'S GOT TO MAKE THEIR OWN INDIVIDUAL DECISION, ARE THEY WILLING TO MAKE THE SACRIFICES THAT ARE REQUIRED TO DO A LOT OF DIFFERENT THINGS, ESSENTIALLY SIMULTANEOUSLY. IT'S NOT FOR EVERYBODY, BUT FOR THOSE WHO DO IT, YOU NEED TO ORGANIZE YOURSELF WELL AND COMPARTMENTALIZE. THE NEXT QUESTIONS ARE EASY. I HAVEN'T TAKEN A VACATION IN SO LONG, WIN, I DON'T EVEN REMEMBER. SO WE WON'T EVEN TALK ABOUT THAT. I DON'T SLEEP A LOT. I'M TRYING NOW. IT'S AN INTERESTING STORY ABOUT SLEEP, BECAUSE I GENERALLY GET ABOUT 6 HOURS, 6 1/2 HOURS OF SLEEP. DURING THE EARLY YEAR OF THE PANDEMIC IN 2020, I WAS GETTING LIKE 3 AND 4 HOURS OF SLEEP. WHICH IF IT WASN'T FOR MY WIFE CHRISTINE, WHO FORCED ME TO JUST LITERALLY SAY YOU'RE NOT IN A MARATHON -- YOU'RE NOT IN A SPRINT, YOU'RE IN A MARATHON, YOU'D BETTER GET SOME SLEEP, THAT CHANGED ME. SO RIGHT NOW, I TRY TO GET ENOUGH SLEEP SO THAT I CAN FUNCTION WELL. DIARY, YES. I'VE BEEN KEEPING NOTES FOR A LONG PERIOD OF TIME. WHICH HOPEFULLY I WILL AT SOME POINT, WHEN I GET MYSELF RE-ESTABLISHED OUTSIDE OF THE NIH, WILL WRITE A MEMOIR. AND THAT -- THE FIFTH QUESTION, WHAT'S NEXT. I'M GOING TO CONTINUE TO BE INVOLVED IN PUBLIC HEALTH AND MEDICINE AND SCIENCE. IT'S GOING TO BE IN A DIFFERENT VENUE. OBVIOUSLY IT'S NOT GOING TO BE IN THE FEDERAL GOVERNMENT SINCE I STEPPED DOWN, BUT I'M GOING TO BE TRYING TO UTILIZE MY MULTIPLE YEARS, 54 YEARS AT THE NIH AND 38 YEARS AS DIRECTOR OF THE NIAID TO SERVE AS AN EXAMPLE FOR YOUNGER PEOPLE WHO WANT TO GET INVOLVED IN SCIENCE AND IN MEDICINE AND PUBLIC HEALTH, AND HOPEFULLY SOME OF THEM WILL GET INVOLVED IN PUBLIC SERVICE. SO I'M GOING TO BE LECTURING LIKE I'M DOING NOW, TODAY, I'M GOING TO BE WRITING, AND I'LL CONTINUE TO WRITE, AND THEN HOPEFULLY, I WILL GET INVOLVED IN A PROJECT THAT WILL BE ONE THAT CONTINUES TO CONTRIBUTE TO THE PUBLIC SERVICE AND PUBLIC HEALTH. BUT I DON'T KNOW WHAT THAT VENUE IS GOING TO BE YET. >>WELL, LISTEN, TONY, ON BEHALF OF THE MANY, MANY, MANY PEOPLE WHO LISTENED TO YOU THIS AFTERNOON, WE ALL CAN'T THANK YOU ENOUGH FOR ALL OF THE GREAT THINGS THAT YOU'VE DONE, AND LOOK FORWARD TO GREAT THINGS IN THE FUTURE . INCLUDING PERHAPS SPEAKING NEXT YEAR IN THE OPENING -- >>WIN, I'M GOING TO STAY IN WASHINGTON, THAT'S ONE THING THAT'S FOR SURE. THANK YOU. SEE YOU LATER. >>THANK YOU VERY MUCH. >>TAKE CARE. THANK YOU VERY MUCH.