GOOD
AFTERNOON EVERYONE. MY NAME IS
DR. ALTAN-BONNET, AND
INVESTIGATOR IN HIV, AND
COCHAIR OF THE CVOID-19
SCIENTIFIC INTEREST GROUP. IT
IS A PLEASURE TO HAVE JEANNE
MARRAZZO.
DR. MARRAZZO WAS RECENTLY
APPOINTED AS THE DIRECTOR OF
NIAID, PREVIOUSLY THE DIRECTOR
OF THE UNIVERSITY OF ALABAMA
SCHOOL OF INFECTIOUS DISEASES
AND SHE EARNED HER BACHELORS
DEGREE ANALOGY FROM HARVARD
UNIVERSITY, HER MD FROM THOMAS
JEFFERSON UNIVERSITY AND A
MASTERS IN PUBLIC HEALTH AND
EPIDEMIOLOGY FROM UNIVERSITY IN
WASHINGTON AND COMPLETED
RESIDENCY AND CHIEF RESIDENCY
IN INTERNAL MEDICINE AT YALE
NEW HAVEN HOSPITAL AND DR.
MARRAZZO IS MADE FOR
GROUNDBREAKING CONTRIBUTORS TO
THE FIELD OF SEX WITH AS MANY
DISEASES AND RESEARCHERS PLAYED
A CRITICAL ROLE IN THE FEMALE
MICROBIOME, AND HIV FEMALE
TRANSMISSION AND APPLICATION
AND IS THE AUTHOR OF OVER 250
PUBLICATIONS AND HAS RECEIVED
NUMEROUS AWARDS AND HONORS
INCLUDING RECENTLY THE AMERICAN
SEXUAL TRANSMITTED DISEASES
ASSOCIATION'S THE THING WAS
CAREER AWARD AND MEMBER OF THE
COLLEGE OF AMERICAN PHYSICIANS
AND-- CHAIR OF THE AMERICAN
BOARD OF INTERNAL MEDICINE
COUNCIL. AND THE BOARD OF
INTERNAL MEDICINE COUNCIL
INFECTIOUS DISEASES BOARD.
THANK YOU FOR BEING HERE TODAY
AND WE LOOK FORWARD TO YOUR
TALK ON THE LATEST NIH
INITIATIVE REGARDING LONG COVID
DIAGNOSIS AND INTERVENTIONS.
>> DR. MARRAZZO:CAN YOU ALL SEE
THAT?
>> YES WE CAN SEE IT.
>> DR. MARRAZZO: ALL RIGHT GOOD
LET ME MINIMIZE THE OTHER
PICTURES HERE. FIRST OF ALL IT
IS A FANTASTIC OPPORTUNITY TO
SPEAK WITH YOU ALL TODAY AND
I'M DELIGHTED TO BE HERE, AND
ACTUALLY JUST CELEBRATING MY
ONE YEAR ANNIVERSARY AS OF A
COUPLE OF DAYS AGO. WHICH IS A
LITTLE HARD FOR ME TO BELIEVE.
BUT IT'S BEEN A GREAT YEAR,
LOOKING FORWARD TO THE ONE
AHEAD.
SO IT'S ALSO FUN TO TALK TO
THIS GROUP RIGHT NOW ABOUT WHAT
IS HAPPENING WITH A NEW
INITIATIVE, BUILDING ON THE
EXISTING RECOVER FRAMEWORK.
AND GOING OVER WHAT IS FOR YOU
FAMILIAR TERRAIN IN TERMS OF
WHERE WE ARE AT WITH LONG
COVID, NOT JUST TRYING TO
UNDERSTAND THE EPIDEMIOLOGY BUT
THE PATHOBIOLOGY, AND WHAT WE
ARE THINKING ABOUT IN TERMS OF
TREATMENT BUT MAYBE PROVIDE A
LITTLE PERSPECTIVE BASED ON
WHAT I HEARD, AND WHAT WAS
PRESENTED DURING THE INAUGURAL
WORKSHOP THAT JUST ENDED AS
SOME OF YOU KNOW YESTERDAY. 2
1/2 DAY WORKSHOP TO BRING
TOGETHER AS MANY PEOPLE AS WE
COULD, INCLUDING PATIENTS,
ADVOCATES, COMMUNITY MEMBERS,
RESEARCHERS, RECOVERY TEAMS,
HLIBI, NIAID AND CATS, THINKING
ABOUT THE FUTURE OF HOW WE
SHOULD DO CLINICAL TRIALS IN
LONG COVID AS I KNOW YOU KNOW
IT IS AN INCREDIBLY COMPLICATED
AREA.
AND IT IS AN AREA OF REALLY
URGENT NEED. SO I APOLOGIZE IF
SOME OF THE EARLY SLIDES ARE
LITTLE OBVIOUS TO ANY OF YOU
WHO KNOW A LOT ABOUT LONG COVID
I DO NOT CONSIDER MYSELF A LONG
COVID EXPERT AND I HAVE TREATED
LONG COVID, AND NOT CURRENTLY
DOING RESEARCH IN LONG COVID
BUT I WANTED TO PUT IN
PERSPECTIVE WHAT I THINK ARE
SOME OF THE STATE OF YOUR
THOUGHTS ABOUT WHERE WE ARE AND
MOST IMPORTANTLY FOR THIS ONE,
FOR THIS TALK THINKING ABOUT
HOW THAT GETS US TO THINKING
CREATIVELY AND URGENTLY ABOUT
CLINICAL TRIALS.
SO LET'S GO AHEAD AND GO
FORWARD.
THERE WE GO. ASSUMING YOU CAN
SEE ALL OF THAT.
SO, SOMEBODY AT THE MEETING
SAID, THEY HAD A DOLLAR FOR
EVERY TIME THEY HAD SEEN THIS
SLIDE THEY WOULD BE A RICH
PERSON BUT IT DOES MAKE SOME
REALLY NICE POINTS. AND
UNFORTUNATELY, JUST TODAY, AN
ARTICLE CAME OUT I BELIEVE FROM
-- TALKING ABOUT THE
PATHOPHYSIOLOGY, THAT HAS SOME
FANTASTIC GRAPHICS AND IF I HAD
TIME, I WOULD'VE UPDATED THE
SLIDE.
BOTH IN THE EXPERIENCE OF LONG
COVID, STUDYING AND TREATING
LONG COVID, IS A WIDE ARRAY OF
CLINICAL SYNDROMES AND SYMPTOMS
THAT WE SEE. ONE OF THE
IMPLICATIONS HERE IS THAT WE
REALLY, REALLY NEED A
MULTIDISCIPLINARY APPROACH.
RIGHT?
WE STARTED OFF AND I THINK
EARLY IN THE PANDEMIC, THE
EARLIEST INDICATIONS... AT
LEAST FROM MY PERSPECTIVE IT
WAS ON MANY, MANY PATIENTS WITH
COVID WHEN I WAS IN BIRMINGHAM.
MOST OF THE INDICATIONS WERE
CARDIOPULMONARY, PEOPLE HAD
PERSISTENT PROBLEM WITH
EXERCISE- INDUCED -- CARDIAC
PUBLICATIONS AND HAVING
PROSTHETIC DYSREGULATION OF THE
BLOOD PRESSURE AND HEART RATE.
SO WE HAVE REALLY EXPANDED THE
DEFINITION OF WHAT ENCOMPASSES
THE SYNDROME IN THE WORLD OF
LONG COVID CONSIDERABLY SINCE
THEN.
THIS SLIDE MAKES THE POINT THAT
THE LUNGS, HEART, PANCREAS, THE
IMMUNE SYSTEM, GASTROINTESTINAL
SYSTEM, SPLEEN, LIVER AND
NEUROLOGICAL SYSTEMS ARE THE
MAJOR ELEMENTS IN TERMS THE
AREAS AFFECTED.
IN PINK YOU HAVE NOT ONLY THE
SYMPTOMS PEOPLE REPORT; IN BLUE
YOU HAVE THE APOLOGY THAT AS OF
2023 HAD BEEN DOCUMENTED, USING
REALLY INCREASINGLY
SOPHISTICATED APPROACHES TO
CHARACTERIZING TISSUES.
FOR EXAMPLE, WE KNOW THAT THE
PANCREAS CAN BE NONNORMAL IN
LONG COVID; AND THAT IS ONE OF
THE REASONS THAT PEOPLE HAVE AN
ELEVATED RISK OF DIABETES.
WE KNOW THAT THERE ARE
EXTENSIVE DISORDERS IN THE
BLOOD VESSELS INCLUDING MICRO
CLOTS, INCLUDING ENDOTHELIAL
DYSFUNCTION AND MICRO
CUAGOLOPATHY AND DEVAIN
THROMBOSIS.
EARLY ON FOR THE FIRST COUPLE
OF YEARS PEOPLE COMPLAINING OF
GUT DISTURBANCES, ABDOMINAL
PAIN AND NAUSEA, PARTICULAR
SOMETIMES DIARRHEA, BUT THE
DISORDERS WERE DISMISSED
BECAUSE PEOPLE WERE, WELL, WHY
WOULD THE GUT BE AFFECTED?
WE NOW KNOW THAT WE CAN FIND
THE VIRUS IN THE GUT. CARDIAC
IMPAIRMENT WE KNEW ABOUT EARLY
ON BECAUSE WE ALL-- MANY OF US
ARE PEOPLE PRESENTING WITH
MYOCARDITIS, OUTSIDE OF THE ONE
ASSOCIATED WITH RMNA REGULATION
WHICH WAS REAL AND THE BRAIN
FOG OR COGNITIVE IMPAIRMENT,
ONE OF THE COGNITIVE SYMPTOMS.
BUT A LOT OF OTHER THINGS
INCLUDING DISORDERS OF SLEEP,
AND FATIGUE, AND CARDINAL
SYMPTOMS AS WELL; WHEN YOU LOOK
IN THE BRAIN YOU DO FIND NEURON
FORMATION. YOU CAN SEE REDUCED
BLOOD FLOW, POSSIBLY RELATED TO
SOME OF THE THROMBO PATHOLOGY I
TALKED ABOUT THE BELOW. AND--
PROPENSITY FOR CLOTS AND -- SO
THERE'S A TON GOING ON HERE
BOTH PATHOLOGICALLY AND
SYNDROMICALLY TAKING A STEP
BACK ABOUT HOW TO DESIGN
TRIALS, YOU CAN APPRECIATE THE
COMPLEXITY ABOUT TRYING TO
DEVELOP THE PRIMARY ENDPOINT,
OR SEND SECONDARY ENDPOINTS FOR
ANY CLINICAL TRIALS.
WHY IS THIS HAPPENING? WE STILL
DO NOT KNOW. THE NEXT SLIDE
I'M GOING TO SHOW YOU IS GOING
TO TALK A LITTLE BIT MORE ABOUT
THE EPIDEMIOLOGY ELEGY AND HOW
PREVALENT THIS IS -- AL-ALY HAS
BEEN A REAL CHAMPION FOR
PATIENT SUFFERING FROM THE
DISORDER.
THIS IS A NICE DIAGRAM THAT
GIVES YOU A SENSE OF THE ART
WOULD SAY COUNTERVAILING, NOT
REALLY CONTRADICTORY MECHANISM.
IT MAY TURN OUT THAT THERE ARE
MORE THAN ONE-- THERE IS MORE
THAN ONE MECHANISM AT PLAY
HERE.
PERSISTENT VIRUS HAS BEEN A
MAJOR CONCERN, BUT WE STILL DO
NOT KNOW IF IT IS A VIRAL
ANTIGEN. IS IT A SPIKE PROTEIN?
IS A VIRAL RNA? IS THERE ACTIVE
REPLICATION OF THIS VIRUS? WE
DO NOT KNOW.
WE DO KNOW THAT THE
PERTURBATIONS THAT WHATEVER IS
GOING ON WITH THIS HYPOTHESIS
OF THE PERSISTENT VIRUSES
PROPOSED, LEADS TO SOME OF THE
THINGS THAT ARE SHOWN IN YELLOW
THERE. AND BESIDE LYMPHOCITE
ACTIVATION. EXHAUSTION,
ANTIBODY SECRETION... AND ON
THE OTHER SIDE SEVERAL LABS
HAVE PROPOSED A COMPONENT OF
AUTOIMMUNITY THAT HAS
ESSENTIALLY ENGENDERED
PERSISTENT ORDER REACTION IN T
CELLS. SOME OF THAT HAS BEEN
LINKED TO THIS CONDITION,
REACTIVATING PARTICULARLY
HERPES VIRUSES LIKE ST VIRUS,
WHICH CONTRIBUTE TO ACTIVATION
OF T CELLS, PARTICULARLY HERPES
SIMPLEX VIRUS. BUT EDD HAS BEEN
THE MOST CLOSELY IMPLICATED.
THE BOTTOM LINE THAT ALL OF
THESE THINGS END UP LEADING TO
SYSTEMIC INFLAMMATION, TISSUE
DAMAGE AND TISSUE DYSFUNCTION
THROUGH THE PROCESSES LINK OR
NOTED IN THOSE PINK BOXES. I
MENTIONED THRHOMBOID
INFORMATION AND, PITUITARY
INFLAMMATION, MICRO GLIAL
INFLAMMATION INTERESTING TALK
IF YOU DO NOT GET A CHANCE TO
COME TO THE WORKSHOP. IT WAS
RECORDED AND WILL BE RELEASING
BOTH A BLOG AND MANUSCRIPT
SCIENTIFIC REPORT REALLY
FASCINATING DATA ON MICROGLIA
ACTIVATION THAT I HAD NOT QUITE
APPRECIATED.
MITOCHONDRIAL DYSFUNCTION-- YOU
COULD EXPLAIN THE MICRO VIRUS
DYSFUNCTION AND TRANSLOCATION.
THIS IS A COMPLEX
MULTISYSTEMIC, POSSIBLY
MULTIFACTORIAL CONDITION THAT
WE ARE REALLY IN NEED OF
LEARNING A LOT MORE ABOUT.
IT IS REALLY PREVALENT. AND I
WILL SAY THAT I THINK THE
NUMBERS THAT I AM GOING TO SHOW
HERE ARE PROBABLY A GROSS
UNDERESTIMATE PREVIOUS UNDER
PREVIOUS NATURE MEDICINE
REVIEW. HE THINKS AND WROTE THE
CUMULATIVE INCIDENCE MAY BE
ABOUT 400 MILLION CASES, WITH
THE NATIONAL ECONOMIC IMPACT OF
ABOUT A TRILLION, 1% OF THE
GLOBAL A COMMONALITY LISTENING
TO SOME OF PEOPLE LIVING WITH
LONG COVID AT THE MEETING OVER
THE LAST DAYS, I THINK THAT IS
PROBABLY AN UNDERESTIMATE. WHEN
YOU THINK ABOUT LOST LIFE
YEARS, PARTICULAR TIME FOR
CAREGIVERS, EFFECT ON FAMILIES
WHEN PARENTS AND CHILDREN ARE
AFFECTED. IT HAS BEEN QUITE
PROFOUND. I THINK IT IS WORTH
KEEPING THOSE IN MIND.
BUT LET'S LOOK AT THE MORE
FORMAL DATA HERE. A PAPER
PUBLISHED IN JANA IN OCTOBER
2022.
REMEMBER THIS IS PRETTY EARLY
IN THE PANDEMIC WHEN YOU THINK
ABOUT THIS. THIS IS PROBABLY
MOST REFERS TO PEOPLE WHO WERE
AFFECTED IN THE FIRST WAVE AND
PERHAPS IN THE DELTA WAVE BUT
NOT VERY FAR. NOT WHERE WE ARE
AT TODAY.
THIS DOES NOT REFLECT A LOT OF
REINFECTIONS; DOES NOT REFLECT
INFECTIONS WITH SUBSEQUENT
VARIANTS. AND THAT IS ONE OF
THE HUGE CHALLENGES WE ARE
GOING TO TALK ABOUT IN STAGING
TRIALS FOR LONG COVID.
SO WHEN YOU LOOK AT THE
PROPORTION WITH LONG COVID, OF
PEOPLE ACROSS THE GLOBE, THIS
IS THE GLOBAL BURDEN OF DISEASE
FOR THE LONG COVID COLLABORATOR
TEAM.
THE PROBLEMS OF COURSE DEPENDS
ON HOW YOU DEFINE IT. WE ARE
GOING TO TALK ABOUT THE
DEFINITION, BECAUSE THE
DEFINITION IS NOT
STRAIGHTFORWARD EITHER.
NOTHING THAT THEY USED I WOULD
SAY MOST LIBERALLY WAS
SOMETHING CALLED THE SYMPTOM
CLUSTER. AND WILL SHOW YOU WHAT
THAT MEANS IN THE SLIDE AFTER
THE NEXT ONE.
BASICALLY IT MEANS A GROUP OF
CLUSTERS OF SYMPTOMS, OR A
CLUSTER OF SYMPTOMS LIKE I
SHOWED YOU BEFORE, G.I.
SYMPTOMS, NEUROLOGICAL
SYMPTOMS, ETC.
PROBABLY THAT WAS THE MOST
COMMON MANIFESTATION BUT WHEN
YOU LOOK INDIVIDUALLY SYMPTOMS
ARE NOTED THERE, YOU SEE PRETTY
HIGH PREVALENCES.
THE OTHER THING YOU SEE IN THE
SLIDE IS THAT IT TENDS TO HAVE
A PREDILECTION FOR WOMEN. WE
KNOW THAT MANY AUTOIMMUNE-- IN
PARTICULAR PHENOMENA THAT DO
AFFECT WOMEN MORE, BUT NOT
SUBSTANTIAL PERCENTAGES OF MEN,
6%.
AND CRITICALLY WE HEARD IN THIS
MEETING ABOUT YOUNG PEOPLE WHO
HAVE LONG COVID PARTICULARLY
KIDS AND TEENAGERS. SOMETHING
THAT HAS BEEN VERY, VERY
UNDERAPPRECIATED.
ON AVERAGE WHEN YOU LOOK AT THE
DATA, WHEN YOU LOOK AT THESE
DATA, AND AT THE CDC'S PULSE
SURVEY PUBLISHED IN APRIL, IT
IS NOT TOTALLY INACCURATE TO
SAY THAT ABOUT 6-7% OF ADULTS
IN THE US ARE CURRENTLY
EXPERIENCE IN LONG COVID.
WE DO NOT KNOW WHAT THE DATA
OFFER PEOPLE YOUNGER THAN 20.
BUT IT IS HARD TO BELIEVE THAT
IT IS MUCH LOWER THAN THAT
BASED ON BOTH WHAT WE ARE
HEARING AND SOME MORE LIMITED
DATA THAT HAVE COME OUT.
SO, WHERE ARE WE NOW? CAN WE
PROJECT WHAT IS GOING TO HAPPEN?
WE'VE OVERHEARING ABOUT THE
SUMMER WAVE; I PERSONALLY KNOW
ABOUT FOUR PEOPLE WHO ARE DONE
WITH COVID THIS WEEK IS PRETTY
MUCH EVERYWHERE YOU LOOK. THE
DATA SUGGEST WHICH AFTER THE
SUMMER WAVE WHICH CONTINUES TO
BE THE OFFSPRING OF THE OMICRON
FAMILY WE PROBABLY HAVE SEEN A
DOWNTURN. BUT WE DON'T KNOW
WHAT IS GOING HAPPEN. THIS IS A
VERY, VERY IN SOME WAYS
PREDICTABLE AS YOU CAN SEE FROM
THE PEAKS AND VALLEYS, BUT IN
SOME WAYS A VERY UNPREDICTABLE
VIRUS. WE HAVE BEEN FORTUNATE
ENOUGH TO SEE A VARIANCE, NOT
COVERED BY THE CURRENT BOOSTER
RECOMMENDATION. AND CERTAINLY
NOT RESISTANT TO PAX-LOVID AS
FAR AS WE KNOW. BUT IT IS STILL
SOMETHING THAT WE HAVE TO WORRY
ABOUT.
AND WHEN I TALKED WITH PEOPLE
ABOUT THE RISK OF GETTING COVID
IT IS NOT JUST THAT WE HAVE
DONE MUCH BETTER AT PREVENTING
SEVERE ILLNESS, LIKE
HOSPITALIZATIONS AND EVEN DEATH
WITH VACCINATION. WE STILL
HAVEN'T PREVENTED LONG COVID
AND I WILL TALK ABOUT WHAT THE
DATA ARE FOR COVID VACCINE
PREVENTING LONG COVID. AND I
THINK THEY DO BUT THERE IS
STILL A SIGNIFICANT RISK THAT
YOU ARE GOING TO GET INFECTED
AND YOU MIGHT HAVE SET YOURSELF
UP FOR SOME CORRELATED LONG
COVID.
I DID NOT HAVE TIME TO MAKE A
SLIDE ON THIS, BUT ONE OF THE
PAPERS THAT CAME OUT THIS WEEK
AND THAT IS CHALLENGE, THE
FIELD IS MOVING REALLY FAST
NOW. WAS A PAPER IN NATURE I
BELIEVE THAT LOOKED AT
NEUROLOGICAL MANIFESTATIONS IN
PEOPLE WHO WERE HOSPITALIZED
WITH LONG COVID WILL AFTER THEY
WERE DISCHARGED.
BASICALLY IT SHOWED THAT THE
COGNITIVE DECLINE ASSOCIATED
WITH SEVERE COVID INFECTION
HOSPITALIZATION, WAS ASSOCIATED
WITH SEVERAL YEARS WORTH OF
NEUROLOGICAL AGING WAY BEYOND
WHAT THE TIMEFRAME WOULD BE IF
YOU HAVE NOT GOTTEN COVID.
SO I THINK AGAIN THE DATA A
REALLY STRONG THAT UNLESS YOU
CAN PREVENT THE VIRUS PROBABLY
FROM TRAVERSING THE OLFACTORY
NERVE, AND GETTING INTO YOUR
BRAIN ALMOST CERTAINLY, MAYBE
THROUGH OTHER MECHANISMS TOO,
YOU WILL NOT BE SUCCESSFUL IN
PREVENTING ENTRY INTO THE
CENTRAL NERVOUS SYSTEM. IT IS
VERY NERVE-RACKING.
LET'S TALK ABOUT THE
DEFINITION. YOU MAY HAVE HEARD
THAT THE NATIONAL ACADEMY OF
SCIENCES ENGINEERING IN
MEDICINE CAME UP WITH THE
DEFINITION JUST A COUPLE MONTHS
AGO. THAT IS NOT WHAT THIS IS
ABOUT. THE NASM DELUSION IS
INCREDIBLY INCLUSIVE DEFINITION
THAT DEFINES LONG COVID AS A
CASE WHERE A PERSON HAS HAD
SYMPTOMS COMPATIBLE WITH LONG
COVID, TACKING ON ALL THE
THINGS WE ARE TALKING ABOUT, AT
LEAST THREE MONTHS AFTER HAVING
LONG COVID AND PERSISTING OVER
TIME. IS VERY, VERY GENERAL. I
PROBABLY HAVE NOT GOTTEN THE
EXACT DETAIL OF THAT DEFINITION
RIGHT, BUT PARTLY IT IS
INCREDIBLY BROAD AND INCLUSIVE
INTERVIEW LISTEN TO THE FOLKS
AND READ THE REPORT THEY ARE
SAYING IS THEY WANTED SOMETHING
TO EMPOWER PATIENTS AND
CLINICIANS TO RECOGNIZE THE
BROAD NATURE OF LONG COVID.
BECAUSE A LOT OF PEOPLE MAY NOT
REALIZE THAT THE FATIGUE THEY
ARE SEEING, THE PALPITATIONS
THEY ARE FEELING, THE EXERTION
THEY'RE HAVING IS POTENTIALLY
RELATED TO A PREVIOUS EPISODE
OF COVID.
AND AGAIN THE NASM DEFINITION
IS NOT SOMETHING WE PROBABLY
WILL USE ON CLINICAL TRIALS. WE
NEED TO TALK ABOUT THAT. BUT
FOR CLINICAL TRIALS WHEN YOU
ARE TALKING ABOUT LOOKING AT
FUNCTIONAL IMPROVEMENT IN
PARTICULAR OR ENROLLMENT
CRITERIA YOU NEED TO THINK
ABOUT HOW YOU ARE GOING TO BE A
LITTLE MORE PRECISE. NOT TO BE
EXCLUSIONARY, BECAUSE WE HEARD
LOUD AND CLEAR THAT FOR THE
CLINICAL TRIALS WE WANT TO BE
OPEN TO AS MANY PEOPLE AS WE
POSSIBLY CAN.
BUT I WILL SHOW THIS. THIS IS
FROM RECOVER, AN NHLBI PROJECT
ALONG WITH NIAID. THIS WAS
WHEN THE FIRST PAPERS IT CAN
MOUNT FROM RECOVER, LOOKING
CAREFULLY AT SYMPTOMS AND THEN
PROVIDING THEM OR CALCULATING
WHAT IS CALLED THE "PAST
SCORE," THE POSTACUTE
SARS-COV-2 DESIGNATION.
WHAT THE GROUP DID WAS THROUGH
EXTENSIVE ANALYSIS OF MANY,
MANY PEOPLE ALMOST 10,000
PARTICIPANTS OVER SIX MONTHS OF
FOLLOW-UP; NOT LONG, LONG COVID
BUT SIX MONTHS OF FOLLOW-UP.
LOOKING AT THE SYMPTOMS THAT
PREDICTED THE HIGHEST
LIKELIHOOD OF THIS SOMEWHAT
OBJECTIVELY DEFINED PASC.
AND WHAT THEY CONCLUDED WAS
THAT HIS SCORE OF 12 WAS
OPTIMAL FOR DEFINING THAT AND
YOU CAN SEE THAT ONE OF THE
MOST SPECIFIC SYMPTOMS WHICH
WE'VE KNOWN SINCE THE EARLY
DAYS OF THE PANDEMIC-- I
REMEMBER WALKING ON THE
HOSPITAL WARDS WITH OUR MASKS,
AND SEEING COFFEE BEANS THERE,
HE WAS SUPPOSED TO USE THE
COFFEE BEANS AS A SURROGATE
MEASURE OF WHETHER OR NOT YOU
COULD SMELL. THAT WAS PROBABLY
ONE OF THE FIRST THINGS THAT
PEOPLE KNEW WAS HAPPENING.
SO SMELL, TASTE, ASMEA, POST--
MALAISE, ONE OF THE TOPIC YOU
WANT TO TALK ABOUT, EXECUTIVE
AREA AND THE POST SENSORY PART.
COGNITIVE BRAIN FOG. CHEST
PALPITATIONS. LOW SEXUAL
DESIRE. ABNORMAL MOVEMENTS AND
HAIR LOSS WAS LOOKED UP.
SO THOSE ARE THE COMPOSITE
SCORES. YOU CAN SEE THAT IF YOU
HAD SIGNIFICANT MALAISE, AND
SMELL OR TASTE DISORDERS YOU
ALREADY HAVE A COMPLEX GOING TO
GET YOU ABOVE THE MEAN.
HOW USEFUL IS THIS IN ENROLLING
PEOPLE IN CLINICAL TRIALS? IT
WILL BE INTERESTING TO SEE. WE
NEED TO DISCUSS THAT.
I MENTIONED THE ISSUE AS TO
WHETHER VACCINATION REDUCES THE
RISK OF LONG COVID. AND I
WOULD SAY THAT YOU CAN FIND
SORT OF VARIOUS ANALYSES TO
SUPPORT EITHER TAKE ON THIS.
BUT I LIKE THIS PAPER BY
BRANNOCK ET AL BECAUSE IT
REALLY WAS ABLE TO LOOK AT A
HUGE NUMBER OF PEOPLE, MODELING
A COHORT HERE.
YOU CAN SEE THE NUMBERS DOWN
THERE ARE QUITE SMALL. LOOKING
AT POTENTIAL 109,000 VACCINATED
VERSUS 78,000 VACCINATED
FOLLOWING THEM FOR ABOUT A YEAR
FOR THE LIKELIHOOD OF PASC OR
LONG COVID.
THIS IS MODELED ON THE DATA
FROM ELECTRONIC HEALTH RECORDS.
AND WE ALL RECOGNIZE ANYBODY
WHO HAS EVER WRITTEN A NOTE ON
THE PATIENT, IF YOU DO NOT SEE
PATIENTS, AND YOU HAVE TO
ANALYZE THE RECORDS YOU KNOW
WHAT LIMITATIONS ARE. THERE
OFTEN BUILT FROM BILLING. LOTS
OF COPY PASTE GOING ON; LOTS OF
NOISE, LOTS OF GARBAGE.
BUT FROM SOME KEY DIAGNOSIS AND
SOME SPECIFIC THEY CAN BE
INCREDIBLY USEFUL. WHEN YOU
HAVE A BINARY VARIABLE OF
VACCINATION VERSUS NOT, YOU CAN
MODEL THINGS TO HELP WITH
SUPPOSITION PREDICTING THE
OUTCOMES. END WHAT THIS GROUP
SHOWED IS THAT YOU DID REDUCE
THE PROBABILITY OF LONG COVID
SIGNIFICANTLY WHICH IS OWNED
SHOWN THERE AND I THINK MOST
OTHER ANALYSES HAVE SUPPORTED
THIS.
AGAIN IT DEPENDS ON WHEN YOU
GOT VACCINATED, WHICH VACCINE
YOU GOT, HOW MANY BOOSTERS YOU
GOT, WHEN YOU WERE SUSCEPTIBLE
TO WHICH VARIANT, AND WHAT YOUR
PREDILECTION FOR LONG COVID WAS
IN THE FIRST PLACE.
AGAIN THERE IS ALMOST NO SIMPLE
ANSWER TO ANY OF THESE
QUESTIONS. AND I REALLY WANT
TO KEEP COMING BACK TO THAT; IS
ONE OF THE THINGS THAT FUELS
MISINFORMATION. YOU CAN FIND
EVIDENCE TO SUPPORT VERY MUCH
ANY OF VIEW HERE. AND THERE ARE
REASONS WHY THE EVIDENCE IS NOT
WATERTIGHT.
WE TALKED ABOUT PATHOGENESIS.
I'M GOING TO SHOW YOU A FEW
STUDIES THAT I THINK ADDRESS
EACH OF THESE MAJOR CATEGORIES.
SO VIRAL REACTIVATION,
PERSISTENT VIRAL INFECTION--
MEANING YOU'VE GOT COMPONENTS
OF ANTIGENIC, IMMUNOGENIC VIRUS
THERE -- OR IMMUNE
DYSREGULATION PERHAPS WITH SOME
SUB- MECHANISMS OR MACROPHAGE
ACTIVATION, THE BIG BUCKETS.
LET'S TAKE A LOOK AT EACH OF
THESE.
THERE ARE A LOT OF PAPERS;
THERE IS NO WAY WE CAN
GOVERNMENT 45 MINUTES. I DO
WANT TO LEAVE TIME FOR
QUESTIONS BECAUSE THERE ARE SO
MANY QUESTIONS.
ONE OF THE FIRST PAPERS THAT
CAME OUT THAT WAS PRETTY
INDISPUTABLE AND GOT PEOPLE'S
ATTENTION EARLY-- EVEN WHEN
PEOPLE WERE DISPUTING WHETHER
THERE WAS SUCH A THING AS LONG
COVID. RIGHT?
ONE OF THE GREAT THINGS ABOUT
THIS MEETING WAS THAT WE HAD
SEVERAL PROVIDERS WHO TALKED
ABOUT HAVING TO CONFRONT
SKEPTICISM ABOUT LONG COVID AND
CHRONIC FATIGUE SYNDROME, AND
MYONIC ENCEPHALITIS. IT WAS
INFORMED BY THEIR BELIEF THAT
THESE WERE PSYCHOSOMATIC
CONDITIONS; TALKING TO PEOPLE
WITH LONG COVID IN PARTICULAR
AND HAVING THE WINDOW INTO
THESE INFECTION ASSOCIATED
CHRONIC CONDITIONS REALLY
CHANGED HER MIND ABOUT WHAT
PEOPLE WERE DEALING WITH.
AND I THINK THIS PAPER-- YOU
DON'T HAVE TO GO GET BRAIN
BIOPSIES TO PROVE THAT THE
COMMUNICATION WAS RIGHT WAS
IMPORTANT INVALIDATING WHAT
SOME OF THESE HYPOTHESES ARE.
THESE WERE AUTOPSIES ON 44
COVID PATIENTS FROM ACUTE
INFECTIONS, SEVEN MONTHS FROM
THE ONSET. YOU CAN FIND THE
VIRUS WIDELY DISTRIBUTED EVEN
IN PATIENTS WITHOUT
ASYMPTOMATIC OR MILD
INFECTIONS.
THEY HAD COVID, THEY APPEARED
TO GET BETTER. AND WENT ON TO
DIE OF SOMETHING ELSE.
THIS GROUP WAS ABLE TO SHOW
THAT REPLICATION WAS PRESENT;
PARTICULARLY IN PULMONARY AND
EXTRA PULMONARY TISSUES IN
EARLY INFECTION. NOT
SURPRISING.
BUT THEN THEY WENT ON TO LOOK
FOR RNA IN MULTIPLE SITES
INCLUDING THE BRAIN, AND THEY
WERE ABLE TO FIND UP TO 230
DAYS AFTER SYMPTOMS, BECAUSE
THE PEOPLE'S ATTENTION BECAUSE
IF YOU STILL HAVE THE VIRUS
PRESENT IN THE BRAIN, THE
ANTIGEN IS STILL THERE.
INTERESTINGLY THERE WAS A
POSSIBILITY OF INFLAMMATION OR
VIRAL CYTOPATHOLOGY OUTSIDE THE
LONG.
THE QUESTIONS THAT IS REALLY
RAISED AND THE CONCLUSIONS ARE
PRETTY WELL EXCEPT NOW, BUT
STILL VERY VALID. CLEARLY THE
VIRUS IS ABLE TO INFECT MANY
CELL TYPES; CORRELATES WITH
DIVERSE PATHOLOGIES GOING BACK
TO THAT EARLY SLIDE I SHOWED
YOU. BUT WE STILL DON'T KNOW
WHETHER THE PERSISTENCE OF
VIRUS PROTEINS OR VIRAL RNA IS
CORRELATED WITH LONG COVID. OR
THE CLINICAL COURSE OF DISEASE.
THIS IS A HUGE QUESTION RIGHT
NOW UNDER INTENSE INVESTIGATION
WITH NIH RECOVER AND ALSO IN
CLINICAL TRIALS WHICH I HOPE TO
TALK ABOUT IF WE HAVE TIME AT
THE END.
SO, A COUPLE OF PATHWAYS OF
INTERROGATION THAT HAVE
ADDRESSED THIS ONE. AND THIS I
THINK IS ONE OF THE MORE
PROVOCATIVE RECENT PAPERS.
AGAIN FROM MIKE PELUSO AND HIS
GROUP AT STANFORD, LANCET
INFECT DIS. THE LANCET GROUP
WAS AHEAD OF THE CURVE GETTING
THE SAMPLES EARLY ON, AND
ASKING CRITICAL QUESTIONS AND
THEY HAD 171 ADULTS AT SEVERAL
TIME POINTS IN 14 MONTHS
FOLLOWING RNA CONFIRMED
SARS-COV-2 INFECTION SO THEY
CLEARLY HAD VIRALLY CONFIRMED
INFECTION, ANOTHER CHALLENGE
WITH DOING LONG COVID STUDIES
BECAUSE SOMEBODY MAY COME IN
AND CLEARLY HAVE LONG COVID,
ARE YOU ABLE GOING TO DETECT
SIGNS OF THE VIRUS EASILY IN
THE PLASMA OR ANYWHERE ELSE?
MAYBE NOT. WE WILL COME BACK TO
THAT IF WE HAVE TIME.
MAY THEN COMPARE THIS PEOPLE TO
250 ADULTS WAS PLASMA WAS
COLLECTED BEFORE THE PANDEMIC.
THE BEAUTY OF HAVING BIO
DEPOSITORIES. YOU CAN ASK THE
QUESTIONS ABOUT WHAT WAS GOING
ON BEFORE 2020. THESE PEOPLE
HAD PURPORTEDLY NEVER BEEN
EXPOSED TO SARS-COV-2.
THEY USED A SINGLE MOLECULE
ARRAY DETECTION PLATFORM CALLED
QUANTERIX (PHONETIC) TO
EVALUATE WHAT THE PREVALENCE OF
ANTIGENEMA WAS IN PLASMA. WHAT
YOU CAN SEE HERE IS THE
PRE-PANDEMIC IT WAS A NEGLIGENT
SIGNAL WITHIN THE RANGE OF
ERROR FALSE POSITIVITY AND 3 TO
6 MONTHS YOU HAVE 5.4% AND
10-14 MONTHS ABOUT 7%.
THE CONCEPT AS YOU PROBABLY
HAVE PERSISTENT ANTENIMA IS
FOLKS. WHAT WAS HE DOING?
THEY WERE ABLE TO SHOW THE
PRESENCE OF THE VIRUS IN THE
GUT THEY GOT A HUGE AMOUNT OF
ATTENTION. NOBODY HAD LOOKED AT
THE GUT BEFORE. IT HAD NOT BEEN
SHOWN SO PERSUASIVELY IN SUCH A
WELL-CHARACTERIZED COHORT OF
HUMANS TO REALLY INDICATE THAT
THERE WAS SOMETHING GOING ON
HERE.
SO STILL NEEDED THOUGH, IS WHAT
ARE THE CLINICAL CORRELANTS OF
SARS-COV-2 AND PERSISTENCE, AND
IS THERE EVIDENCE OF PERSISTENT
VIRAL REPLICATION?
WHAT ABOUT THE IMMUNE PROFILE
INVOKES? HOW DO WE KNOW THAT
IMMUNE DYSREGULATION MIGHT PLAY
A ROLE?
ANALYZE PAPER FROM NATURE
FAMILIAR BEFORE LOOKED AT
PEOPLE WITH LONG COVID AND
THOSE WITHOUT AND THIS IS FROM
AKIKO OSAKI'S GROUP (PHONETIC),
THEY LOOK AT SEVERAL MARKERS OF
INFLAMMATION OR POTENTIAL
PATHWAYS FOR PERSISTENT IMMUNE
SIGNALING IN PEOPLE WITH LONG
COVID, AND THOSE WITHOUT.
AGAIN WELL-CHARACTERIZED
GROUPS. AND SOME OF THE THINGS
THAT YOU CAN SEE THAT WERE
HIGHER IN LONG COVID WERE
SEVERAL THINGS THAT SUGGEST AN
EXAGGERATED SPECIFIC. HUMORAL
RESPONSE, CIRCULATING MYELOID
RESPONSES; LIMITED SELECTED
ANTIBODIES AND EVIDENCE OF
HERPESVIRUS NAMELY EBV
ACTIVATION AS WE MENTIONED
BEFORE. AND LOW CORTISOL,
INTERESTING INFORMATION IN SOME
OF THE MEETING TALK ABOUT
VARIATIONS IN DAYTIME CYCLE
COVID SYMPTOMS THAT ARE BEYOND
WHAT WE KNOW ARE THE CYCLES OF
CORTISOL, IN EARLY-MORNING
AWAKENING, AND CORTISOL LEVELS
BEING HIGH IN THE MORNING.
I THINK THIS IS QUITE
INTERESTING. THIS DOES SUGGEST
THAT THERE IS SOME IMMUNE
REGULATION; AND I THINK THIS IS
BEING ACTIVELY PURSUED AS A
POSSIBLE ONE.
AND THE OTHER SIDE OF IMMUNE
DYSREGULATION IS AUTOIMMUNITY.
AND I THINK THAT THERE ARE
SOMEWHAT FEWER INVESTIGATIONS
THAT HAVE GONE DOWN THIS ROAD.
BUT I DON'T THING IT HAS BEEN
RULED OUT YET. JUST A COUPLE OF
PAPERS YET, AGAIN IN THE
INTEREST OF TIME THAT SUGGESTED
THAT THERE MAY BE MOLECULAR
MIMICRY BETWEEN CROSS REACTION
ANTIBODIES AND HOST PROTEINS
PARTICULARLY THE SARS-COV-2
PROTEIN.
PROBABLY ONE OF THE BEST
EXAMPLES OF THIS IS MISC IN
CHILDREN AND WE THINK THIS MAY
PLAY A ROLE THERE. IS UNCLEAR
WHETHER THAT IS RELATED TO THE
LIKELIHOOD OF LONG COVID AND
AGAIN I AM NOT A PEDIATRIC
IMMUNOLOGIST, BUT I THINK THAT
IS A VERY FERTILE GROUND AREA
TO LOOK AT, SINCE THE WAY THAT
THOSE KIDS PRESENTED WITH MISC
IS VERY DIFFERENTLY WHAT WE ARE
TALKING ABOUT HERE.
AND THEN, AUTO ANTIGEN PROFILE
LOOKING AT AT LONG COVID
PATIENT THAT WAS A LITTLE LESS
CLEAR-- AND SORRY FOR NOT
PRODUCING THE DETAILS-- BUT IT
HAS BEEN USED A LITTLE BIT TO
SAY WELL I DON'T THINK THIS IS
ACTUALLY PLAYING A ROLE.
SO AGAIN GOING BACK TO THOSE
THREE BIG MECHANISMS, HUGE
AMOUNT OF CONFUSION. SOME
COALESCENCE AROUND CERTAIN
PRINCIPLES. BUT TONS OF WORK TO
DO. AND WHY IS THIS SO
IMPORTANT TO RECOVERED TLC?
RECOVERED TLC IS RECOVERED LONG
COVID; IT WILL BUILD
UNRECOVERED SUCCESSES AND
LESSONS LEARNED AND WHAT WE
WANT TO DO IS TEST MORE
POTENTIAL TREATMENTS FOR LONG
COVID SYMPTOMS ARE THE CHANCES
GOING TO BE HOW DO WE DECIDE
WHAT TO TARGET WHEN THE
PATHOBIOLOGY IS POTENTIALLY
MULTIFACTORIAL? POTENTIALLY
DISTINCTIVE DEPENDING ON THE
SYMPTOM COMPLEX; AND NOT ALWAYS
PERHAPS DRUG-TARGETABLE, OR
DRUGGABLE PEOPLE SAY. LET'S
TALK A LITTLE BIT ABOUT THAT. I
WOULD LIKE TO SPEND AT LEAST 20
MINUTES OR SO HEARING YOUR
THOUGHTS. I SUSPECT THIS GROUP
HAS THOUGHT ABOUT THIS QUITE A
LOT.
SO THIS IS A QUICK DESCRIPTION
OF RECOVER-TLC, AND WE WANT TO
DEVELOP EFFECTIVE AND EFFICIENT
THERAPIES FOR LONG COVID. WE
WOULD REALLY LIKE TO LEAN
PHARMACOLOGIC SIDE, AND I WILL
COME BACK TO WHY THAT IS
CHALLENGING. WE WANT TO
DEFINITELY NOT REINVENT THE
WHEEL, BUILD ON THE FINDINGS
FROM THE RECOVERED COHORTS.
THERE PEOPLE WHO HAVE PROPOSED
PATHOBIOLOGY STUDIES USING THE
EXTENSIVE BIO RECOVER BIO
REPOSITORY WHICH HAS OVER
MILLION SAMPLES. SO THERE IS A
CLINICAL TRIAL IN THE RECOVER
FRAMEWORK, NOT TLC.
ONE OF THEM IS, REALLY KNOW,
RECOVER VITAL, A STUDY LOOKING
AT VARYING DURATIONS OF ORAL
PAXLOVID IN PEOPLE WITH COVID
TO PREVENT LONG COVID. AND, IT
IS A PLACEBO-CONTROLLED STUDY.
AND EMBEDDED IN THE TRIAL ARE
LOTS OF REALLY IMPORTANT
SURROGATE END POINTS THAT WILL
HELP US FIGURE OUT WHAT IS
HAPPENING TO PEOPLE WHEN YOU
GIVE THEM ANTIVIRAL FOR VARYING
DEGREES OF TIME. THERE ARE
PEOPLE IN THE TRIAL WHO DO NOT
HAVE THE TECHNICAL ANTIGEN
SARS-COV-2 IN THE BASELINE AND
SO WE ALSO HAVE A WAY TO LOOK
AT WHETHER PAXLOVID DID
ANYTHING IN PEOPLE, EVEN IF
THEY DIDN'T HAVE VIRUS PRESENT
IN THE PLASMA AT BASELINE.
SO IN STUDY THREE SYMPTOM
COMPLEX THIS IS, NEUROLOGICAL
DISEASE, CARDIOVASCULAR
DISEASE, AND I BELIEVE
FATIGUE-- I COULD BE WRONG. BUT
CLEARLY DEFINED SYNDROMIC
GROUPS. CLEARLY DEFINED
ENDPOINTS RELATED TO MOSTLY
IMPROVEMENT, FUNCTIONAL
IMPROVEMENT. AND PROGRESSION.
AND THEN THE ABILITY TO LOOK AT
ANTIGEN THROUGHOUT.
NOW YOU COULD ASK WHETHER
PAXLOVID IS THE RIGHT DRUG.
RIGHT? NOT AN EASY DRUG TO
TAKE. IF YOU HAVE TAKEN IT, IS
NOT JUST THE TASTE. BUT IT ALSO
HAS A LOT OF DRUG INTERACTIONS.
WE KNOW THAT FROM HIV TREATMENT
AND WHETHER THIS WILL BE A
SCALABLE INTERVENTION, I DON'T
KNOW. BUT I THINK IT HAS TO BE
STUDY AND WE WILL GET A SIGNAL,
WHETHER IT IS THE SIGNAL WE
WANT TO SEE OR NOT WE DON'T
KNOW.
THE OTHER THING ABOUT
RECOVER-TLC WE WANT TO DO THIS
FAST AND ACCURATE, BILLING IT
ON A MODEL THAT WAS USED IN THE
PANDEMIC. YOU MAY REMEMBER ACT
AND ACTIVE, TWO VERSUS 10 NOT
VERY QUICKLY TREATMENT TRIALS
FOR COVID AND DONE UNDER -- AND
THEN WITH ACTIVE A LOT MORE
INTERVENTIONS WERE INVOLVED, IN
THIS REPLY FROM TRIALS. SO YOU
COULD CONTINUE TO USE, AGAIN,
TOO COMPLICATED TO GO INTO
THEM, MORE ACCURATE,
SOPHISTICATED EPIDEMIOLOGICAL
DISCUSSION ABOUT PLATFORM
TRIALS.
THE IDEA IS YOU KEEP ON A
STUDY. YOU CAN ADD, SUBTRACT,
COMPARE, COMPARATIVE ARMS; YOU
ARE MAXIMIZING PARTICIPATION OF
PARTICIPANTS OVER TIME. YOU'RE
NOT STARTING OVER IF YOU DO NOT
HAVE TO. YOU CAN ALSO DISCARD
INTERVENTIONS, AND YOU FIGURE
OUT EARLY ON, GOING NOWHERE.
THAT IS IMPORTANT BECAUSE YOU
DON'T WANT TO HAVE TO BE DOING
STUDIES IN SERIES. RIGHT? WE
WANT TO BE DOING THESE THINGS
IN PARALLEL, SIMILARLY FOR
INCLUDING PEDIATRICS AND
STUDIES FOR WOMEN WHO WANT TO
GET PREGNANT. WE WANT TO TRY
TO DO THESE THINGS IN PARALLEL.
I DO NOT WANT US TO WAIT TO
STUDY SOMETHING IN WRITING
WOMEN UNTIL WE TAKE TWO YEARS
FOR EXAMPLE. TAKE TWO YEARS TO
SEE IF SOMETHING WORKS NOW WE
ARE GOING TO STUDY IN
ADOLESCENCE THAT IS A MISTAKE.
WE WANT TO MOVE QUICKLY.
WE WANT TO BE TRANSPARENT. WE
WANT TO HAVE PEOPLE INVOLVED IN
THE DECISION-MAKING HERE; MAKE
SURE PEOPLE KNOW WHY WE ARE
STUDYING CERTAIN THINGS. WHY
AREN'T WE STUDYING SOMETHING
ELSE THAT SOME PEOPLE HAVE
FOUND USEFUL?
SO TRYING TO PROVIDE ACCESS AND
SHARE DATA WITH THE PUBLIC AND
THE SCIENTIFIC COMMUNITIES IS
GOING TO BE A BEDROCK
PRINCIPLE.
PATIENT CENTERED CARE WITH
PARTNERS -- WE WILL HAVE
PATIENTS IN ALL OF OUR
COMMITTEES, WE FEEL THAT IS
IMPORTANT AND NOT JUST SITTING
ON THE COMMITTEE. WE REALLY
WANT THEIR PARTICIPATION. WE
ARE MODELING THIS THE WAY WE
HAVE WORKED WITH OUR HIV-AIDS
NETWORK OVER 30 YEARS NOW.
WHERE WE CREATED ESSENTIALLY A
COMMUNITY OF ADVOCATES. AND
PARTNERS, WHO ALMOST CARRY THE
WEIGHT IN TERMS OF EXPLAINING
THE STUDIES TO POTENTIAL
PARTICIPANTS AND PARTICIPANTS
IMPACTED. AND CAN BE PEER OR
EDUCATORS IN THE PRESENCE
POSSIBLE. PEOPLE WHO THERE ARE
NONWHITE IN PARTICULAR ARE MORE
LIKELY TO GET LONG COVID.
THERE'S A BIG DISPARITY HERE IN
TERMS OF WHO IS GETTING SICK.
WHO IS BEARING THE BRUNT, NOT
JUST THE PHYSICAL STRAIN, BUT
THE SOCIOECONOMIC STRAIN? WHO
CAN GET ACCESS TO SOPHISTICATED
CARE? WHO CAN GET ACCESS TO
PARTICIPATING IN RECOVER? LOTS
OF STORIES OF PEOPLE DRIVING
FOUR HOURS TO THE RECOVERY
APPOINTMENT. AND HAVING TO GO
THROUGH THE BATTERY OF TESTS,
THE QUESTIONNAIRES-- NOT ALWAYS
GOOD.
I MENTIONED PLATFORM PROTOCOLS.
AND THEN I MENTIONED THE
ABILITY TO ADAPT QUICKLY. SO
SOMETHING LOOKS LIKE IT IS NOT
WORKING, AND WE CAN
SADISTICALLY BE COMFORTABLE
WITH THAT. BE COMFORTABLE
PHYSIOLOGICALLY. WE THROW IT
OUT. WE DO NOT WANT TO WASTE
TIME. WE WANT TO HAVE AN ACTIVE
PORTFOLIO.
WHY ARE WE DOING THIS? BECAUSE
THIS HAS BEEN OUR BUSINESS FOR
A LONG TIME. RIGHT? WE HAVE
DONE VERY LARGE-SCALE, COMPLEX
TRIALS PARTICULARLY WHEN YOU
THINK ABOUT THE EARLY DAYS OF
THE HIV PANDEMIC. THE ONLY
THING WE GOT, VERY EARLY ON WAS
AZT. THERE WAS A SINGLE FROM
AZT THAT HELPED. IMMEDIATELY
THAT OPEN THE DOOR TO DRUG
DISCOVERY AND MORE IMPORTANTLY
TO INDUSTRY BUY-IN, PHARMA
BUY-IN, BECAUSE IT WAS A
GLIMMER OF HOPE THE DRUGS COULD
BE DEVELOPED THAT WOULD HAVE
THE POTENTIAL TO PATHWAYS IN
THE MARKET AND THAT IS JUST THE
REALITY.
I AM REALLY HOPEFUL THIS WILL
HAPPEN HERE. WE HAVE DONE A
LOT OF STUDIES TO GET PRODUCTS
REGULATORY APPROVAL. WE HAVE
HAD CONTACTED PARTICIPATION
FROM THE FDA YESTERDAY. JOHN
FARLEY AND MICHAEL KELLIHIERI
(PHONETIC) FROM THE FDA AND
THEIR EUROPEAN ASSOCIATE,
TALKING WITH THEM WAS CRITICAL.
WE HEARD FROM PATIENTS HOW
CHALLENGING IT WAS GOING TO BE
TO AGREE ON ENDPOINTS THAT THEY
FELT WERE FULFILLING CRITERIA
FOR APPROVAL. BUT THAT WERE
SPECIFIC ENOUGH AND ALSO
MEASURABLE ENOUGH TO HOLD UP
UNDER REVELATORY SCRUTINY. THAT
INTERACTION IS GOING TO BE
CRITICAL. THEY NEED TO BE ON
BOARD FROM DAY ZERO. AND SO IT
WAS INTERESTING TO HAVE THEM
THERE.
WE HAVE FISCAL SUPPORT. WE HAVE
PRIVATE SUPPORT AND
REPOSITORIES. EXCELLENT DSMB
GIVE ABILITIES AN EXCELLENT
BROAD CONTRACT SUPPORT AND I
MENTIONED OUR LONG-STANDING
RELATIONSHIPS WITH SCIENTIFIC
AND ADVOCACY COMMUNITIES
PROBABLY HIV/AIDS IS BEST KNOWN
FOR THEIR OTHERS. AND WE HAVE
PRETTY BIG CLINICAL TRIAL
SHOPS, ACROSS MEDICAL OFFICERS
AND PROGRAMS AS YOU CAN
IMAGINE.
REALLY BRIEFLY IN THE LAST FIVE
MINUTES I WILL SAY THE IDEA
HERE IS TO DO A REALLY DEEP
DIVE ON WHAT THE CURRENT
RECOVER CLINICAL TRIALS
LANDSCAPE IS. WHAT IS BEING
DONE? WE KNOW THERE ARE FOUR
TRIALS AND MORE PLANNED. WHAT
CAN WE LEARN FROM THE DESIGN
AND CONDUCT OF THE STUDIES?
THAT WILL DETERMINE WHAT
MODIFICATIONS ARE NEEDED. AND
IF YOU THINK ABOUT TRIAL
ENDPOINT, THE ABILITY TO REACH
ENROLLMENT TARGETS, SITES
PARTICIPATING IN WE WANT
RECOVERY SITE TO PARTICIPATE.
BUT IF WE NEED TO GO BEYOND TO
OTHER NETWORK WE WILL GO TO
OTHER NETWORKS THAT CAN ENROLL
THE MOST APPROPRIATE
PARTICIPANTS. BOTTOM LINE.
WE NEED TO FIGURE OUT OUR
BUDGET AND WE ARE WORKING ON
THAT. AND IF I LESSONS LEARNED
FROM PROTOCOL DESIGN AND LAUNCH
OF THE NEW CLINICAL TRIALS
PROGRAM.
WE ARE ALREADY PLANNING ON
HAVING PERIODIC MEETINGS AS A
FOLLOW-UP TO THE 2 1/2 DAY
MEETING WE JUST HAD. THE
MEETING WAS REALLY I THOUGHT
VERY GOOD; RAISED AS MANY
CHALLENGES AS POTENTIAL
SOLUTIONS. BUT WHAT WE DID THE
MEETING WAS REALLY TO DISCUSS
WHERE WE ARE AT IN OUR
UNDERSTANDING OF THE RESEARCH,
AND CLINICAL NATURE OF LONG
COVID.
SO STATE OF THE SCIENCE. AND
TALK ABOUT HOW DO WE MOVE THIS
FORWARD. WE WILL HAVE PERIODIC
WEBINARS TO SHARE WHAT WE ARE
DOING WITH SCIENTIFIC CLINICAL
AND PATIENT COMMUNITIES, AND
IMPORTANTLY WILL HAVE AN ANNUAL
MEETING NEXT YEAR HOPEFULLY
SOMEPLACE BIGGER, THAN THIS
TIME PLANNED FOR FIVE WEEKS. SO
IT WAS REALLY, REALLY FAST. THE
TEAMWORK REALLY REALLY HARD.
I WANT TO EMPHASIZE THE
ENGAGEMENT. THAT IS CORE OF
WHERE WE ARE AT AT NIAID. THIS
IS NOT JUST A MATTER OF HAVING
A PATIENT REPRESENTATIVE. THIS
IS A MATTER OF HAVING PEOPLE
INVOLVED IN PROTOCOL DESIGN,
PROTOCOL REVIEW. PRESENTING THE
PROTOCOL TO COMMUNITIES AND
GETTING BUY-IN, ASSESSMENT AND
MEANINGFUL CONTRIBUTION IS A
REALLY GOOD EXAMPLE OF WHAT
HAPPENS WHEN YOU DON'T DO THAT.
YOU DESIGN THE PROTOCOL AND I
HAVE BEEN GUILTY OF THIS
MYSELF-- AND NOT AT ALL PERFECT
IN THIS ROUND-- YOU DESIGN ARE
ALL THINKING YOU KNOW WHAT THE
DISEASE LOOKS LIKE AND WHAT IT
IS. YOU DON'T HAVE IT, MAYBE
AND THEN IT TURNS OUT YOU
REALLY WISH YOU HAD TALKED TO
MORE PEOPLE BEFORE YOU DID WHAT
WE DID. AND WE WILL HAVE A
COMMUNITY ENGAGEMENT GROUP,
THIS IS IN FLUX, I DON'T WANT
TO BE TOO SPECIFIC BUT WILL
HAVE THE COMMUNITY ENGAGED IN
ALL WORKING GROUPS IN THE
SCIENTIFIC COMMUNITY.
I THINK I'VE SAID MOST OF THIS.
ONE THING I WILL MENTION IS
THAT, TWO THINGS. ONE WE DO NOT
WANT TO RE-CREATE THE BIO
REPOSITORY THAT RECOVER HAS. IF
WE DO BIO SPECIMENS THAT WILL
BE SPECIFICALLY LINKED TO THE
PURPOSE OF THE TRIAL. IT WILL
BE A NEW VIRAL DEPOSITORY I
THINK MADE AVAILABLE TO OUTSIDE
AND INSIDE RESEARCHERS. AND WE
WILL LINK ALL OF THAT TO THE
CLINICAL DATA, AS WE HAVE DONE
FOR OUR OTHER STUDIES.
THE OTHER IMPORTANT PART ABOUT
TRIAL DESIGNS IS, YOU WANT TO
DO LARGE TRIALS TO LOOK FOR
EFFICACY OF COURSE. BUT WE HAVE
THOSE YET? DO WE HAVE AGENTS
THAT WE CAN SAY, WE WANT TO DO
A 2000 PERSON TRIAL? NOT SO
SURE. WE WILL BE DOING A DEEP
ASSESSMENT OF THE LANDSCAPE.
BUT WE MAY START WITH VERY SOON
I WOULD SAY SMALLER MECHANISM
STUDIES WHERE WE CAN LOOK AT
HYPOTHESES DRIVEN BY SOME OF
THE PATHOBIOLOGY, AND
INCORPORATE BIOMARKERS AND
MEASURES OF WHETHER WE ARE
MAKING AN IMPACT WITH WHATEVER
INNOVATIONS WE ARE TALKING
ABOUT.
I SUSPECT WILL START WITH SOME
OF THOSE. BUT AGAIN THESE ARE
ALL OF THE DISCUSSION.
THIS WAS OUR ORIGINAL TAKE IN
THE ORGANIZATION. I DO WANT TO
DWELL ON THIS BECAUSE AFTER THE
MEETING WE ARE GOING TO CHANGE
IT UP QUITE A LOT. BUT THE
IDEA IS THAT WE HAVE A
SCIENTIFIC OVERSIGHT COMMUNITY,
THAT REALLY DIRECTS THE
SCIENCE. AND THAT IS FED BY
WORKING GROUPS THAT ARE
PROBABLY RELATED TO THINGS LIKE
NEURO MANIFESTATIONS AND
PATHOLOGY, VASTLY DISEASE AND
VIROLOGY. IMPORTANT ALSO GROUP
THAT OVERSEES OPERATIONS, A LOT
OF INTERACTION BETWEEN THOSE
GROUPS.
AND VERY IMPORTANTLY, A PORTAL,
AN OPEN WAY FOR INDUSTRY AND
ANYONE TO SUBMIT INTERVENTION
CANDIDATES. SO WE DEBUTED, OR
PREVIEWED I SHOULD SAY, THE
PORTAL CANDIDATE, SIMILAR TO
WHAT WAS USED IN THE ACT TRIALS
WHERE ANYBODY COULD GO IN AND
PROPOSE AN INTERVENTION--
WHETHER IT'S AN AGENT OR A
DEVICE.
AND THAT WILL BE OUR MAIN WAY
FOR PEOPLE TO GET INTO THIS.
OF COURSE WE ALSO WELCOME
DIRECT CONTACT FROM INDUSTRY.
THERE WERE A NUMBER OF INDUSTRY
FOLKS AT THE MEETING; THAT
ACTUALLY WAS QUITE HELPFUL.
SO JUST AS LAST SLIDE TO
SUMMARIZE A COUPLE OF OTHER
THOUGHTS ABOUT THE WORKSHOP AND
I ACTUALLY GOT A WHOLE SERIES
OF SLIDES I USED YESTERDAY TO
WRAP IT UP. BUT I CAN TALK MORE
ABOUT THOSE IF YOU WANT. BUT TO
GIVE YOU A QUICK SENSE, WE
FILLED THE ROOM. WE COULD NOT
GET A BIGGER ROOM IN TIME. SO
WE HAD OUR MAX OF 180 PEOPLE,
THERE WERE 1200 PEOPLE ONLINE;
WE INTENTIONALLY BROUGHT
TOGETHER PEOPLE FROM RECOVER
PATIENTS OUT OF THE KITS, AND
RESEARCHERS IN HOPEFULLY
EXAMPLE WAS REPORTED IN MY
COMFORTABLE LAST 45 MINUTES.
PATIENTS HAVE TO BE INVOLVED
FROM THE GET-GO AND IN THE
ONGOING FIGHT, SO WE CAN BE
CAMPING FOR WHAT WE ARE DOING.
THAT IS THE ONLY WAY WE'RE
GOING TO GET TRUST WITH THE
COMMUNITY AND GET PEOPLE TO
PARTICIPATE.
WE REALLY NEED TO ESCALATE
URGENCY FOR INFORMED TRIAL
DESIGN USING THE EXISTING BIO
SAMPLES. RIGHT? SO THERE IS A
VERY BIG REPOSITORY THAT COULD
BE LEVERAGED VERY QUICKLY TO
START LOOKING AT BIOMARKERS.
AND I THINK THAT IS SOMETHING
THAT NEEDS TO HAPPEN VERY, VERY
SOON. BECAUSE WE NEED THAT TO
TAKE A LOOK AT THESE DISTINCT
PHENOTYPES, BIO TYPES, AND
THINK ABOUT HOW YOU ARE GOING
TO DESIGN STUDIES, BOTH FOR
PATHOBIOLOGY AND ALSO FOR
INTERVENTIONS.
MANY PEOPLE IN THE AUDIENCE
THOUGHT THAT WE WOULD PROBABLY
ULTIMATELY NEED MULTICOMPONENT
INTERVENTIONS. SO ANTIVIRALS,
ANTI-INFLAMMATORY, --
MODULATORS, YOU NAME IT
METABOLIC ALTERING DRUGS. I
THINK LIKE WE DESIGNED MANY OF
THE HIV THERAPEUTIC TRIALS. WE
HAD COMBINATIONS THAT WERE
GOOD; AND WE GOT NOMINATIONS
THAT WERE BETTER, AND
INDIVIDUAL AGES THAT WERE
BETTER, AND DELIVERY SYSTEMS
THAT WERE BETTER. SO THINKING
ABOUT HOW YOU DESIGN TRIALS TO
START ADVANCING COMPLEX--
SOMETIMES MULTI-MECHANISTIC
REGIMENTS I THINK IS GOING TO
BE REALLY IMPORTANT.
AND THEN THE LAST THING IS, I
THINK YOU KNOW INFECTION
ASSOCIATED CHRONIC WORK
CONDITIONS IS A BIG AREA THAT
WE JUST HAVE TO EMBRACE. YOU
KNOW? NOT JUST AT THE NIH BUT I
PROCESS IT IS BECAUSE YOU SAW
ALL THE ORGAN SYSTEMS AFFECTED
AND ALL THE PATHWAYS THAT MIGHT
BE INVOLVED. YOU SAW THE FACT
THAT MINORITY POPULATIONS-- IF
YOU WANT TO USE THAT TERM OR
UNDERREPRESENTED MINORITIES--
ARE MORE AFFECTED. I MEAN
THERE'S ALMOST NOT AN INSTITUTE
HERE THAT IS NOT POTENTIALLY
AFFECTED BY LONG COVID.
I THINK THAT IS MY LAST SLIDE.
I'M GOING TO STOP THERE AND
STOP SHARING. AND LEFT 10
MINUTES. SORRY I WANTED TO
LEAVE MORE, BUT ENDED GOING
LONGER. SORRY.
I'M GOING TO HAND IT OVER TO
VERONIQUE WHO WILL MODERATE.
>> THANK YOU DR. MARRAZZO. I AM
AN INFECTIOUS CLINICIAN STAFF
AT NIAID AND I WILL RELAY YOUR
QUESTIONS TO DR. MARRAZZO.
THIS AFTERNOON I WILL REMIND
EVERYBODY TO USE THE "SAND LIVE
FEEDBACK" BUTTON ON THE VIDEO
CASCADE TO SEND QUESTIONS TO
DR. MARRAZZO.
DR. MARRAZZO THANK YOU SO MUCH
TALK TODAY, IT IS REALLY
WONDERFUL TO SEE EVERYTHING
THAT IS DONE. ALL THIS
WONDERFUL WORK AND INITIATIVE
TO LEARN ABOUT, AND TO
HOPEFULLY TREAT LONG COVID,
WHICH IS A CONDITION THAT
AFFECTS SO MANY PEOPLE AROUND
THE WORLD.
SO WE HAVE SEVERAL QUESTIONS
COMING IN. THE FIRST QUESTION
FOR YOU IS, WHICH INSTITUTE AT
THE NIH LEADING THE EFFORTS TO
FIND THERAPIES FOR LONG COVID?
>> DR. MARRAZZO: GREAT
QUESTION. I THINK IT IS US
RIGHT NOW. BECAUSE WE ARE
TASKED FOR ALL THE REASONS THAT
I MENTIONED, FOR TRYING TO
STAND UP CLINICAL TRIALS.
AND SO IT IS NOT TO SAY THAT
OTHER ... INSTITUTES AREN'T IN
THE DRUG DEVELOPMENT BUSINESS,
IT MAY TURN OUT THAT A
CARDIOVASCULAR DRUG MIGHT BE A
HUGE WIN IN SOME MANIFESTATIONS
OF LONG COVID. AND MAYBE EVEN
IN PREVENTION.
SO I WOULD SAY WE ARE ALL
INVOLVED. THE POINT IS FOR US
TO TAKE-- TO PROVIDE SORT OF A
FUNNELED, DIRECT PATHWAY SO IT
IS NOT CONFUSING. SO IF YOU
HAVE A DRUG THAT YOU'RE
INTERESTED IN, OR YOU KNOW
SOMEBODY WHO HAS A DRUG, COME
TO US. COME TO THE PORTAL THAT
WE WILL HAVE PROBABLY AFTER
NEXT WEEK OR SO AND WE CAN
FACILITATE WHAT THAT MIGHT LOOK
LIKE.
I WILL SAY TOO, A LOT OF PEOPLE
ASKED AT THE MEETING, WELL ARE
YOU DEVELOPING ANTIVIRAL DRUGS
THAT YOU THINK MIGHT WORK
BETTER THAN PAXLOVID? AND THE
ANSWER IS YEAH, WE HAVE
ANTIVIRAL DRUG DISCOVERY
PROGRAM, AND WITH ALL THE
INFLUENZA STUFF GOING ON, THERE
VERY INTERESTED IN RESPIRATORY
VIRUSES BUT MOST OF THOSE
PRODUCTS ARE IN THE EARLY PHASE
DEVELOPMENT. THERE IS NOTHING
WE CAN PLUCK OUT AND SAY LET'S
LOOK AT THIS FOR LONG COVID. SO
FOR IMMUNOLOGICS IT COULD BE
ANY OF THESE INTRODUCE THE DEAL
WITH SPECIFIC MANIFESTATIONS.
>> GRADE WE HAD ANOTHER
QUESTION SPECIFICALLY ALONG
THOSE LINES. OF THE ONE HAS A
NOVEL DRUG THAT WE THINK MIGHT
BE EFFECTIVE FOR TREATING LONG
COVID, HOW DOES ONE GET IN
TOUCH WITH NIAID? HOW DO WE
FIND OUT? SOUNDS LIKE THERE
WILL BE A PORTAL MADE
AVAILABLE.
>> DR. MARRAZZO: THEY WILL BE A
PORTAL AND YOU ARE WELCOME TO
CONTACT ANY OF US. ONE OF THE
THINGS I COMMITTED TO AT THE
MEETING WAS ESTABLISHING AN
OFFICE WITHIN MY GROUP. SO IT
IS NOT A FORMAL INSTITUTE,
NOTHING LIKE THAT. BUT I WILL
HAVE SOMEONE OVERSEEING THESE
EFFORTS DIRECTLY REPORTING TO
ME IN MY OFFICE. AND WE ARE
WORKING ON THAT, AND THE
LOGISTICS ON THAT.
AND I REALLY WANT THIS TO BE
SEAMLESS; I WANT IT TO BE KIND
OF A PRIORITY FOR OUR OFFICE.
AND I THINK THAT ANY OUTREACH
TO US WILL OBVIOUSLY BE TAKEN
SERIOUSLY.
I WOULD ALSO SAY IF YOU'RE
INTERESTED BE SURE TO KEEP YOUR
EYES OUT. WE WILL DISSEMINATE
WIDELY REPORTED MEETING WHICH I
HOPE WILL BE DONE IN A COUPLE
OF WEEKS.
>> WONDERFUL. SO THE NEXT
QUESTION IS, WILL NIAID
ESTABLISH AN INTRAMURAL GROUP
TO COORDINATE THESE TRIALS? AND
WILL THESE CLINICAL TRIALS GO
THROUGH A REVIEW PROCESS?
>> DR. MARRAZZO: THAT THE
QUESTION WE WILL ESTABLISH A
GROUP SO THE MODEL WE ARE GOING
TO USE IS REALLY WHAT WE HAVE
DONE FOR MANY OF HER CLINICAL
TRIALS, WHICH HAVE TAKEN PLACE
IN THREE BIG DIVISIONS: THE
DIVISION OF MICROBIOLOGY AND
INFECTIOUS DISEASES, ALL OF THE
FLU STUDIES, ALL OF THE STI
STUDIES AND THE MALARIA
STUDIES. MANY OF THOSE HAVE
BEEN DONE THERE. TB. IN THE
OTHER BIG GROUP IS THE DIVISION
OF AIDS. AND THE DIVISION OF
ALLERGY, IMMUNOLOGY AND
TRANSPLANTATION IN THE FOOD
ALLERGY STUDIES.
ALL OF THOSE GROUPS HAVE
RIGOROUS REVIEWS AND WE ALSO
HAVE AN INTERNAL DISCUSSION AS
PART OF THE NETWORK THAT WILL
HAVE THE OVERSIGHT OF THE
CLINICAL TRIALS. SO I THINK WE
WILL BUILD HEAVILY ON THE
MODELS WE USED FOR PREVIOUS
CLINICAL TRIALS.
>> THERE IS A QUESTION ABOUT
THE TIMELINE FOR RECOVER TLC.
WHEN WILL THE TRIALS BEGIN?
WHEN WILL DATA BE AVAILABLE?
AND WILL THE NIH CLINICAL
CENTER BE A TRIAL SITE?
>> DR. MARRAZZO: GOOD QUESTION
AND THINK THERE IS A REASON FOR
THE NIH NOT TO BE A TRIAL SITE.
WE HAVE MANY PARTICIPANTS IN
THE PROGRAM-- GAVE A GREAT
PRESENTATION ABOUT THE STUDY
THAT IS BEING DONE THERE.
ROBERTA DIBIASE (PHONETIC) WAS
THERE TALKING ABOUT GINA
MONTENEGRO'S STUDY WITH KIDS,
AN INCREDIBLE WEALTH OF DATA I
WOULD SAY, ABSOLUTELY
INCLUSIVE, WOULD BE DELIGHTED
TO CONSIDER THAT AGAIN. WE WANT
SITES THAT CAN ENROLL THE MOST
APPROPRIATE PARTICIPANTS AND DO
A GOOD JOB. THAT IS REALLY WHAT
I CARE ABOUT.
THE TIME I IS A LITTLE TRICKY
BECAUSE FIRST OF ALL, IF YOU GO
ONLINE AND LOOK FOR POTENTIAL
INTERVENTION AGENTS ON LONG
COVID, YOU WILL COME UP WITH
ONE OF THE SLIDES THAT ONE OF
THE PRESENTERS SHOWED. WHICH IS
A GIGANTIC LIST OF THINGS THAT
PEOPLE HAVE TRIED. SOMETIMES IN
DESPERATION. SOMETIMES WITH THE
SUPPORT AND INPUT OF THE
COMMUNITY OF PEOPLE WHO HAVE
BEEN USING THESE THINGS.
SO I THINK THE QUESTION IS
GOING TO BE, WE HAVE TO DO IN
THE NEXT COUPLE MONTHS, VERY
DEEP DIVE ON THE LIGHT ESCAPE
OF WHAT PEOPLE ARE DOING, WHAT
THEY ARE FINDING USEFUL, WHAT
MIGHT BE AVAILABLE. IN THE
NEXT THING IS HOW WOULD YOU
DESIGN A DRUG, OR HOW WOULD YOU
LOOK AT AN EXISTING DRUG TO
REPURPOSE? THAT IS ANOTHER
THING WE CAN TALK ABOUT THAT
MIGHT ADDRESS SOME OF HIS
PATHOPHYSIOLOGIC MECHANISMS
WHERE LEARNING ABOUT.
IT IS A LITTLE BIT LIKE YOU ARE
ON THE BALL THAT IS ROLLING;
THERE IS A LOT OF DATA COMING
OUT. THERE IS A WHOLE PANOPLY
OF THINGS THAT PEOPLE ARE
USING, TO REALLY HAVE TO DO OUR
DUE DILIGENCE I THINK AND LOOK
AT THE LANDSCAPE OF
INTERVENTIONS. AND THEN ALSO
THINK PROACTIVELY ABOUT OKAY,
WE HAVE ALL OF THESE. ARE THEY
WORTH STUDYING REALLY? OR DO WE
LOOK AT THESE MECHANISTIC
STUDIES, A COUPLE OF SMALL
ONES, TO PURSUE WHAT WE THINK
MIGHT BE INVALID BIOLOGIC
HYPOTHESIS AND BIOLOGIC
INTERVENTION? THAT IS NOT GOING
TO BE EASY. IT'S GOING TO TAKE
A LOT OF THOUGHT AND A LOT OF
HOMEWORK. SO I DON'T WANT TO
OVERPROMISE. I WOULD LIKE TO
THINK AT LEAST ONE OF THE
MECHANISTIC STUDIES SET UP
EARLY NEXT YEAR. MAYBE FIRST
HALF OF NEXT YEAR. THAT WILL BE
VERY AMBITIOUS. MAYBE ANOTHER
MONTH LATER. AND MAYBE BY 2026
WE ARE READY FOR A LARGE
EFFICACY TRIAL. AGAIN I CANNOT
PROMISE BECAUSE THERE IS SO
MUCH RIDING ON WHAT WE LEARN
NEXT YEAR AND WHAT WE WILL
LEARN WITH THE RECOVER DATA.
THAT IS HOW I WOULD SEE IT.
>> DR. MARRAZZO YOU JUST
MENTIONED PEDIATRIC PATIENTS.
THERE ARE SEVERAL PICTURES
COMING IN FROM THE AUDIENCE
ABOUT WHETHER OR NOT THERE WILL
BE PARALLEL ADULT AND PEDIATRIC
PROTOCOLS OR IF PEDIATRIC
PATIENTS HAVE TO WAIT FOR DATA
TO BE VALIDATED IN ADULTS.
MAYBE YOU COULD COMMENT ON
THAT.
>> DR. MARRAZZO: AGAIN I THINK
I POINTED THAT OUT AS ONE OF
THE THINGS-- THE IN SERIES,
YOUR STUDIES AND YOU GO ALONG
TO GET YOUR DATA, AND NOW WE
ARE GOING TO DO A STUDY... WE
ARE DOING AN AGE DE-ESCALATION
STUDY, STARTING IN OLDER WHERE
WE PROBABLY NEED TO THE
TEENAGERS AND THEN YOU GO DOWN,
THERE ARE SOME STUDIES WE HAVE
TO DO THAT. BUT MY ANSWER IS IT
WILL DEPEND ON THE
INTERVENTION. WHAT I DO NOT
WANT TO SEE IS SETTING
ARTIFICIAL BARS HI AND SAYING
WE ARE GOING TO EXCLUDE PEOPLE
LOW 18, BECAUSE THEY ARE BELOW
18. AND WHEN WE SET UP AN
INTERVENTION AND MAY BE TOTALLY
APPROPRIATE FOR SOMEONE ABOVE
OR EVEN 12 AND ABOUT, OR EVEN
SIX MONTHS AND ABOUT. I DON'T
KNOW SO IT WILL DEPEND ON THE
AGENT.
BUT I DO WANT TO SIGNAL THAT WE
WANT TO BE EXPEDIENT AND SAFE.
WE WANT TO BE INCLUSIVE. BUT WE
WANT TO BE SENSITIVE TO THE
FACT THAT KIDS AREN'T ADULTS.
WE KNOW THAT. BUT WE DO NOT BUY
INTO THE TRADITIONAL MODEL
NECESSARY TAKES A LONG TIME TO
GET THINGS DONE.
>> THANK YOU. SO WE HAVE
ANOTHER QUESTION HERE ABOUT,
ARE THERE ANY LESSONS TO BE
LEARNED FROM CHRONIC FATIGUE?
OR OTHER POST VIRAL SYMPTOMS
THAT COULD BE TAKEN TO STUDY
LONG COVID?
>> DR. MARRAZZO: ABSOLUTELY I
THINK THE BIGGEST LESSONS WE
TALKED ABOUT-- THERE ARE
PROBABLY PAPA BIOLOGIC
MECHANISMS-- UNFORTUNATELY WE
DO NOT HAVE TIME TO GO IN HERE,
PROBABLY BETTER TO GET SOMEBODY
WHO HAS BEEN IN THE FIELD
LONGER THAN I HAVE, AND CAN
REALLY SPEAK TO THOSE THAT ONE
OF THE BIGGEST THINGS WE
LEARNED AT THIS MEETING WAS THE
BARRIER TO PEOPLE PARTICIPATING
IN THE STUDIES-- WE HAVE ONE OF
THESE CONDITIONS, INFECTIOUS
ASSOCIATED CHRONIC CONDITIONS,
LARGELY VERY MUCH CHARACTERIZED
BY FATIGUE. AND SOMETIMES
REDUCED MOBILITY. IT IS
IMPOSSIBLE FOR MANY OF THESE
AFFECTED PEOPLE TO GET TO
CLINICAL TRIAL SITES.
IMPOSSIBLE FOR PEOPLE TO COME
TO A SITE THAT MAY BE REALLY
FAR AWAY. OR ONLY OPEN BETWEEN
9 AND 3 P.M. WE WANT TO GET
SAMPLES BY 3 PM SO WE CAN SHIP
THEM, BLAH BLAH.
AND IMPOSSIBLE FOR PEOPLE WHO
CAN'T LEAVE THE HOUSE, WHETHER
THEY'RE HOMEBOUND OR BEDBOUND
TO PARTICIPATE IN THE STUDY SO
SOMETIMES THE STUDIES GET A
SKEWED VIEW OF THE
FUNCTIONALITY OF PARTICIPANTS
WHO GET IN TRIALS.
SO THE BIGGEST THING I HEARD AT
THE MEETING, WAS TO TRY TO
THINK ABOUT WAYS TO REPRESENT
THE SPECTRUM OF SYMPTOMATIC
SEVERITY IN THESE TRIALS. SO
WE REALLY HAVE TO THINK I THINK
INCLUSIVELY.
WE HAVE BEEN FOCUSED A LITTLE
MORE ON TRYING TO INCLUDE
PEOPLE WITH SEVERE
DISABILITIES. MOSTLY AROUND
MOBILITY. SOMETIMES COGNITIVE
DISABILITIES IN CLINICAL
TRIALS. I THINK THIS IS A
GREAT KIND OF WEDGE TO SORT OF
SAY, THIS IS A PLACE WE REALLY
HAVE TO DO WITH IT.
>> GREAT. DR. MARRAZZO THANK
YOU SO MUCH. UNFORTUNATELY WE
ARE AT THE TOP OF THE HOUR. AND
YOU ARE RIGHT WE COULD KEEP
GOING ON AND ON AND TALKING
ABOUT THIS FOR A LONG TIME.
THANK YOU SO MUCH FOR YOUR
TIME, AND FOR SHARING THIS
WONDERFUL INITIATIVE WITH US.
WE REALLY LOOK FORWARD TO
HEARING ABOUT THE WONDERFUL AND
IMPORTANT INFORMATION THAT WE
LEARNED FROM RECOVER-TLC.
TO OUR AUDIENCE THANK YOU SO
MUCH FOR JOINING US. WILL SEE
YOU AT THE NEXT EXERCISE. HAVE
A GREAT AFTERNOON.
>> BYE-BYE.