>> WELCOME.
THIS IS WIN ARIAS AT THE NIH.
AND YOU ARE MOST WELCOME TO THE
13TH SESSION OF THE 21ST YEAR OF
A COURSE CALLED DEMYSTIFYING
MEDICINE, WHICH SEEKS TO BRIDGE
THE EXCITING DEVELOPMENTS IN
BIOLOGY AND ENGINEERING WITH
MEDICINE.
MANY OF OUR TOPICS HAVE
PARTICULAR INTEREST TO SOMEWHAT
SMALLER GROUPS OF INDIVIDUALS.
BUT TODAY'S TOPIC, CHRONIC
COVID, OR LONG HAUL COVID, IS OF
INTEREST TO EVERYONE.
IN FACT, TO THE WORLD
SO AS I MENTIONED, THIS IS
REALLY A COURSE IN
BRIDGE-BUILDING, AND IN THIS
CASE TODAY, WE ARE BRIDGING THE
ENTIRE AREA THE CHRONIC COVID.
PARTICULARLY I WOULD EMPHASIZE
THE NEUROLOGIC AND THE MENTAL
DISEASE ASPECT OF IT.
AND THAT PUTS 'S WHAT THE TWO
GENTLEMEN ON THE CATWALK ARE
DISCUSSING.
THEY ARE BRIDGING BETWEEN
BROOKLYN AND NEW YORK, AND
LIKEWISE, WE WILL BE BRIDGING TO
LEARN MORE ABOUT CHRONIC COVID
AND WHERE WE STAND.
NOW WHAT IS POST-COVID PROBLEMS
ANYWAY?
AND THIS SLIDE LISTS A BUNCH OF
THEM, AND YOU'RE GOING TO HEAR
MORE DISCUSSION AND DETAIL OF
THEM.
THEY RANGE FROM RESPIRATORY
SHORTNESS OF BREATH/COUGH,
MEMORY, CONCENTRATION, SLEEP
PROBLEMS, CARDIOVASCULAR,
PALPITATIONS, LOSS OF SMELL OR
TASTE, WHICH WAS RECOGNIZED VERY
EARLY IN THE COURSE OF THE
DISEASE.
AND OF COURSE, SUBSTANTIAL
INCREASE IN DEPRESSION AND
ANXIETY, BROUGHT ABOUT BY THE
ISOLATION THAT IS IMPOSED BY THE
VIRAL INFECTION.
AND FEVER AND DIZZINESS.
AND THEN THERE ARE RARE TRUE
ORGAN DAMAGES, WHERE PATHOLOGY
HAS BEEN SHOWN, THE RARE
MULTISYSTEM INFLAMMATORY
SYNDROME, KAWASAKI'S, MAINLY IN
VERY YOUNG CHILDREN AND YOUNG
ADULTS, CARDIOVASCULAR, KIDNEY,
CLOT FORMATION, STROKES, AND THE
GUILLAIN-BARRE SYNDROME.
ALL HAVE OCCURRED, ARE RARE, AND
WHETHER THEY ARE DIRECT RESULTS
OF THE COVID VIRUS INFECTION IS
ONE OF THE TOPICS THAT WILL BE
DISCUSSED TODAY.
AN ARTIST CAPTURED THE ENTIRE
PANORAMA.
THIS IS FROM THE COVER OF "CELL"
MAGAZINE, MARCH 3RD.
IN THE REARVIEW MIRROR AT THE
BOTTOM OF THE SLIDE IS WHAT
WE'VE PASSED.
THAT IS, THE VIRUS.
BUT WHAT'S AHEAD IS A LONG AND
COMPLICATED ROAD, AND IT'S NOT
CLEAR WHEN AND HOW IT REACHES
THE ACTUAL SUNSHINE.
AND IT'S THIS AREA OF
UNCERTAINTY AND CHALLENGE THAT
WILL BE DISCUSSED TODAY, AND WE
ARE MOST FORTUNATE TO HAVE TWO
INDIVIDUALS WHO HAVE PLAYED AND
ARE PLAYING A MAJOR ROLE IN
TRYING TO UNRAVEL THE PROBLEMS
OF CHRONIC COVID, PARTICULARLY
FROM THE STANDPOINT OF NEUROLOGY
AND MENTAL HEALTH.
SO EACH IS A DIRECTOR OF THE
NATIONAL INSTITUTE AND NATIONAL NATIONAL
INSTITUTES OF HEALTH.
OUR FIRST SPEAKER, JOSH GORDON,
HAS HIS DEGREE, M.D. AND PH.D.,
WORKED FOR MANY YEARS AT
COLUMBIA UNIVERSITY AND THE
PSYCHIATRIC INSTITUTE ASSOCIATED
WITH IT, AND CAME IN 2016 TO BE
THE DIRECTOR OF THE NATIONAL
INSTITUTE OF MENTAL HEALTH,
WHICH YOU SHOULD KNOW OVERSEES
OVER $2 BILLION IN RESEARCH.
RESEARCH AND PUBLIC OUTREACH ON
THE PANDEMIC'S EFFECT ON MENTAL
HEALTH.
JOSH IS A MEMBER OF THE NATIONAL
ACADEMY OF MEDICINE, AND HIS OWN
INDIVIDUAL RESEARCH IS IN
APPLYING NEUROSCIENCE TECHNIQUES
FROM IN VIVO IMAGING, BEHAVIORAL
RECORDINGS, OPT THOUGH , USING THESE TO ST UDY
IN PATIENTS SCHIZOPHRENIA,
ANXIETY AND, OF COURSE,
DEPRESSION.
SO DR. GORDON WILL BE OUR FIRST
SPEAKER, AND THEN OUR SECOND
SPEAKER IS WALTER KOROSHETZ, WHO
TRAINED IN NEUROLOGY AND
NEUROSCIENCES LARGELY AT
HARVARD, WHERE HE WAS AT THE
MASSACHUSETTS GENERAL HOSPITAL
FOR MANY YEARS, CAME TO THE NIH
AS DEPUTY DIRECTOR OF THE
NATIONAL INSTITUTE OF NEUROLOGIC
DISEASES, AND IN 2015, HE WAS
MADE THE DIRECTOR.
THAT INSTITUTE OVERSEES IN
EXCESS OF $2.5 BILLION FOR
RESEARCH IN NEUROLOGIC DISEASES.
IT IS ALSO A PRIMARY FUNDER OF
COVID-19 RESEARCH DUE TO
SARS-COV-2 VIRUS, AND ITS EFFECT
ON THE BRAIN AND THE NERVOUS
SYSTEM.
WALTER IS ALSO A MEMBER OF THE
NATIONAL ACADEMY OF MEDICINE,
AND HIS INDIVIDUAL RESEARCH IS
ON EXYITOTOXICITY AS A CAUSE OF
NEURONAL CELL DEATH.
SO DR. GORDON WILL SPEAK FIRST,
HE'LL BE FOLLOWED BY
DR. KOROSHETZ.
WE ENCOURAGE YOU TO SUBMIT
QUESTIONS DURING THESE
PRESENTATIONS, AND THEN THEY
WILL BE DISCUSSED IN A Q & A
PERIOD AT THE CONCLUSION OF
DR. KOROSHETZ' TALK.
SO PLEASE, DR. GORDON.
>> THANKS, WIN.
APPRECIATE THE INTRODUCTION.
AND I WAS LOOKING FORWARD TO
SPEAKING WITH YOU ALL ABOUT
COVID-19 AND MENTAL HEALTH.
AND I TITLED THIS "THE SHORT AND
THE LONG OF IT."
HOPEFULLY IT WILL BE A LITTLE ON
THE SHORTER SIDE
FIRST I HAVE NO DISCLOSURES, AND
THE OBJECTIVES ARE LISTED HERE.
TO UNDERSTAND MENTAL HEALTH
IMPACTS OF THE PANDEMIC AND
UNDERSTAND THE BIDIRECTIONAL
RELATIONSHIP BETWEEN COVID-19
AND MENTAL HEALTH.
AND IF WE'RE GOING TO TALK ABOUT
LONG COVID OR CHRONIC COVID OR
THE POST-ACUTE SEQUELAE OF COVID
INFECTION, IN THE CONTEXT OF
MENTAL ILLNESS, IT'S REALLY
IMPORTANT TO UNDERSTAND THAT
LONG COVID IS NOT TAKING PLACE
IN A VACUUM, IT'S TAKING PLACE
IN THE CONTEXT OF TREMENDOUS
MENTAL HEALTH IMPACTS OF THE
PANDEMIC ON THE GENERAL
POPULATION, AS WELL AS IMPACTS
OF THE PANDEMIC ON THOSE WITH
PRE-EXISTING MENTAL ILLNESSES.
THOSE COMPLICATE OUR ABILITY TO
STUDY THE PERSISTENT MENTAL
HEALTH EFFECTS OF COVID
INFECTION ITSELF.
SO I'LL TAKE YOU THROUGH THOSE
FIRST TWO POINTS BEFORE WE
ACTUALLY GET INTO THE DISCUSSION
OF LONG COVID PER SE.
SO WHAT HAVE BEEN IMPACTS OF THE
PANDEMIC -- FIRST AND FOREMOST
WE KNOW WHAT TO EXPECT IN THE
CONTEXT OF DISASTERS AND OTHER
EMERGENCIES FROM REALLY DECADES
OF RESEARCH.
MOST WHO ARE EXPOSED TO
TRAUMATIC EXPERIENCES WILL HAVE
SOME INITIAL SYMPTOMS, AND FOR
MOST OF THOSE, THOSE SYMPTOMS
WILL IMPROVE WITH TIME.
SOME, THOUGH, WILL HAVE LONG
TERM OR CHRONIC EXPERIENCES WITH
MENTAL ILLNESS IN THE AFTERMATH
OF SUCH AN EMERGENCY.
LOTS OF FACTORS PREDISPOSE
TOWARDS THOSE LONGER TERM
EXPERIENCES INCLUDING SOCIAL
INEQUITIES, DISPARITIES WITH
REGARD TO TRAUMA EXPOSURE
ITSELF, AND SUBSEQUENT MENTAL
HEALTHCARE VULNERABILITY.
BUT ONE OF THE STRONGEST FACTORS
PREDICTING CROW CHRONICITY AND
SEVERITY IS IMMEDIATE EXPOSURE
TO THE TRAUMATIC EVENT.
LET'S SAY YOU HAVE PSYCHIATRIC
SYMPTOMS IN THE AFTERMATH OF
LONG COVID.
IS THAT DUE TO THE TRAUMATIC
EXPERIENCE OF THE INFECTION AND
OF BEING IN THE HOSPITAL AND OF
BEING SEPARATED FROM LOVED ONES?
OR IS IT DUE DIRECTLY TO A
BIOLOGICAL CONSEQUENCE OF THE
INFECTION?
WE'LL TALK MORE ABOUT THAT AS
TIME MOVES ON.
IN ADDITION TO THESE RISK
FACTORS I'VE MENTIONED, THERE
ARE OTHER INDIVIDUAL DIFFERENCES
INCLUDING HISTORY OF PRIOR
TRAUMA OR MENTAL ILLNESS,
ONGOING STRESSORS INCLUDING
OCCUPATIONAL/FINANCIAL STRAIN,
SUBSTANCE ABUSE, BEING FEMALE OR
NON-WHITE, AND HAVING FEW SOCIAL
SUPPORTS.
OF COURSE THESE INDIVIDUAL
DIFFERENCES ALSO ARE
INTERACTING, NUMBER ONE, AND
NUMBER TWO, MAY BE ACTUALLY
REFLECTIVE OF ONE OR MORE OF THE
OTHER ONES.
SO THE POINT HERE IS NOT TO TRY
TO CONVINCE YOU OF INDIVIDUAL
RISK FACTORS, BUT TO SAY THAT
THERE'S NO SINGLE VARIABLE THAT
DETERMINES INDIVIDUAL OUTCOMES
IN THE SETTING OF AN EMERGENCY.
AND IT'S QUITE AN EMERGENCY
WE'VE BEEN FACING OVER THE LAST
TWO YEARS.
I KNOW I DON'T HAVE TO TELL YOU
ALL.
BUT THE REASON WHY WE'RE VIRTUAL
AND NOT IN BUILDING 50 RIGHT NOW
IS SHOWN RIGHT HERE ON THIS
GRAPH, WHICH IS A GRAPH OF THE
DAILY CASES OF COVID OVER THE
LAST TWO YEARS, WITH THE
PROMINENT OMICRON SPIKE RIGHT
THERE IN THE EARLY 2022.
EVEN EARLY IN THE PANDEMIC, IT
WAS RECOGNIZED THAT THE PANDEMIC
AND/OR THE MITIGATION MEASURES
AND THE ECONOMIC IMPACTS HAVE
HAD SUBSTANTIAL EFFECTS ON
MENTAL HEALTH IN THE GENERAL
POPULATION.
THE EARLIEST REPORT WAS IN THE
SUMMER OF 2020, TAKING DATA
THROUGH LATE JUNE OF 2020.
BASICALLY THE FIRST SPRING OF
THE PANDEMIC SHOWING THE
DOUBLING OF THE RATE AT WHICH
U.S. ADULTS REPORTED STRUGGLING
THROUGH MENTAL HEALTH ACROSS A
RANGE OF DIFFERENT FACTORS.
THAT INCREASE PERSISTED AND
ACTUALLY EVEN ROSE THROUGH THE
FALL OF 2020 AND INTO EARLY
2021, WITH APPROXIMATELY 35 TO
40% OF AMERICANS SELF-REPORTING
SYMPTOMS OF AN ANXIETY OR
DEPRESSIVE DISORDER.
THESE ARE SUBSTANTIALLY HIGHER
NUMBERS THAN WE WOULD EXPECT AT
BASELINE.
ANOTHER INDICATION, A LITTLE BIT
HARDER DATA, IS AN INCREASE IN
THE RATES AT WHICH INDIVIDUALS
WERE SEEKING PRESCRIPTION
MEDICATION OR RECEIVING COUNSEL
EGG OR THERAPY FOR MENTAL HEALTH
SYMPTOMS BUT ALL POINT TO THE
TREMENDOUS EFFECTS OF THE
PANDEMIC.
NOW ONE COULD SAY, OH, MAYBE
IT'S JUST MILD OR MODERATE
SYMPTOMS THAT PEOPLE ARE
REPORTING BUT IN FACT ACROSS A
BROAD RANGE OF SEVERITY, YOU'RE
SEEING MORE PEOPLE AFTER COVID
THAN BEFORE COVID REPORTING IN
THIS CASE DEPRESSION SYMPTOMS,
WHETHER THEY BE CLASSIFIED AS
NON-MILD, MODERATE, MODERATELY
SEVERE OR SEVERE.
SO WE'RE SEEING INCREASES EVEN
AT THE SEVERE END OF THE
SPECTRUM.
ONE PIECE OF GOOD NEWS IN THIS
IS THAT WE ARE SEEING WHAT WE
MIGHT EXPECT TO SEE, THAT IS,
CASES -- THE CURRENT CASES IN
RED OF COVID THROUGH THE COURSE
OF THIS CASE, 2020, ROUGHLY
CORRESPOND TO PEAKS AND VALLEYS
IN REPORTS OF ANXIETY AND
DEPRESSION.
SO ON THE ONE HAND, WORSENING
SEVERITY OF THE PANDEMIC,
WORSENED SYMPTOMS IN THE GENERAL
POPULATION.
ON THE OTHER HAND, AS THE
PANDEMIC ABATES, AS PREDICTED WE
CAN EXPECT FOR MOST INDIVIDUALS,
THOSE SYMPTOMS THEMSELVES WILL
ABATE AS WELL.
NOW, THERE ARE SOME SPECIFIC
ISSUES WE'RE MOST CONCERNED
ABOUT WITH ANY PE DICK ANY EPIDEMIC,
POST-TRAUMATIC STRESS DISORDER
AND WE CAN SEE AN INCREASE IN
THE PREVALENCE OF POST-TRAUMATIC
STRESS DISORDER IN THE CORN TEXT CON
DEMIBGS, BE SARS, COVID-19 OR
OTHER PANDEMICS.
AMOUNTING TO A .1 TO .3 FOLD
INCREASE, SO 10 TO 30% HIGHER
RATES OF PTSD IN THE CONTEXT OF
PANDEMICS, AND AS YOU CAN SEE
FROM THIS PARTICULAR SET OF
STUDY, FROM THE META-ANALYSIS,
THAT'S TRUE FOR COVID-19 AS IT
WAS FOR EBOLA AND SARS.
HOW DO WE HELP PREVENT THE ONSET
OF PTSD AND OTHER CHRONIC MENTAL
HEALTH PROBLEMS IN THE CONTEXT
OF PANDEMIC?
A LOT OF IT IS WHAT WE HAVE BEEN
DOING IN THE CONTEXT OF COVID.
WE'VE BEEN TRYING TO MEET THE
IMMEDIATE NEEDS OF PEOPLE FOR
FOOD, HOUSING -- FOR FOOD,
SHELTER AND CLOTHING.
ONE STUDY, FOR EXAMPLE, HAS
SHOWN THAT THOSE IN COMMUNITIES
WHO'VE RECEIVED FREE GROCERIES
OR MEALS COMPARED TO THOSE WHO
DIDN'T RECEIVE FREE GROCERY OR
MEALS HAD LOWER LEVELS OF A
VARIETY OF MENTAL HEALTH
COMPLAINTS.
OTHER THINGS THAT WE CAN DO IS
TO PRACTICE HEALTHY COPING
STRATEGIES, SOMETHING NIMH AND
NIH AND THE CDC HAVE ALL BEEN
ACTIVE IN PROMOTING.
WHETHER THAT BE ENGAGING
SOCIALLY WITH OTHERS, SLEEPING
AND EATING WELL, AND SEEKING
HELP WHEN YOU NEED IT,
PRACTICING HEALTHY COPING
STRATEGIES CAN HELP.
FINDING WAYS TO HELP OTHERS IN
THE CONTEXT OF AN EMERGENCY
PROMOTES A SENSE OF
SELF-EFFICACY, PROMOTES CONNECT
IFNESS AND CAN FORESTALL THE
WORST EFFECTS OF TRAUMATIC
EXPERIENCES.
FLAD TO THE
EXPERIENCES.
THE IMPACT ON INDIVIDUALS WITH
PRE-EXISTING MENTAL ILLNESSES
HAVE, AS WE MIGHT HAVE EXPECTED,
BEEN SIGNIFICANT.
ONE OF THE THINGS THAT WAS
UNEXPECTED OR AT LEAST NOT CLEAR
THAT WE WOULD SEE WAS REVEALED
ACTUALLY BY OUR COLLEAGUE, NORA
VOLKOW, DIRECTOR THE NIDA, AND
OTHERS WHO LOOKED AT ELECTRONIC
HEALTHCARE DATA AND SAW THAT
INDIVIDUALS WITH MENTAL
ILLNESSES HAD INCREASED RATES OF
CONTRACTING COVID-19, OF GETTING
THE INFECTION EARLY ON IN THE
PANDEMIC.
THIS DATA IS FROM I THINK
THROUGH THE SUMMER OF 2020.
THAT INCLUDED DIAGNOSES OF ADHD,
BIPOLAR DISORDER, DEPRESSION AND
SCHIZOPHRENIA.
THE LIKELIHOOD, A TENFOLD
INCREASED RISK IF YOU HAVE A
SERIOUS MENTAL ILLNESS COMPARED
TO IF YOU DON'T.
MOREOVER, IF YOU HAVE A
PSYCHIATRIC DIAGNOSIS, YOU'RE
MORE LIKELY TO DIE FROM COVID
THAN IF YOU DO NOT HAVE A
PSYCHIATRIC DIAGNOSIS, AND
THAT'S ESPECIALLY TRUE FOR
INDIVIDUALS WITH SCHIZOPHRENIA,
WHO HAVE APPROXIMATELY A THREE
FOLD INCREASE IN RISK, EVEN
AFTER YOU ACCOUNT FOR
COMORBIDITIES THAT ARE PRESENT
IN SCHIZOPHRENIA LIKE HEART
FAILURE, MYOCARDIAL INFARCTION
AND DIABETES.
SO EVEN CONTROLLING FOR THESE
DEMOGRAPHIC VARIABLES WHICH
RAISE YOUR RISK FOR DEATH FROM
COVID, YOU HAVE AN INCREASED
LIKELIHOOD OF DEATH IF YOU HAVE
SERIOUS MENTAL ILLNESS LIKE
SCHIZOPHRENIA.
AND THAT ASSOCIATION WITH
MORTALITY HAS BEEN BORNE OUT IN
A META-ANALYSIS COVERING A WIDE
RANGE OF MENTAL ILLNESSES, AND
IT'S ESPECIALLY SEEN IN THE
STUDIES THAT INCLUDED OR FOCUSED
ON SCHIZOPHRENIA ACROSS A WIDE
RANGE OF DIFFERENT LOCALITIES,
WITH AN ODDS RATIO SLIGHTLY LESS
THAN THAT ONE STUDY IN THE U.S.
WOULD SUGGEST OF AROUND NEARLY
2.
THAT ODDS RATIO IS ENHANCED IF
YOU'RE A MEMBER OF A MINORITY
CLASS, WHICH ARE ALREADY AT
INCREASED RISK OF SERIOUS
CONSEQUENCE OF COVID.
FOR EXAMPLE, AFRICAN AMERICANS
WITH SCHIZOPHRENIA HAVE ABOUT A
TWOFOLD INCREASE IN RISK
COMPARED TO WHITES WITH
SCHIZOPHRENIA, OF DYING FROM
COVID IF THEY GET IT.
AND THERE ARE SIMILAR
DISPARITIES IN THE PREVALENCE OF
A WIDE RANGE OF MENTAL HEALTH
SYMPTOMS IN THE CONTEXT OF THE
PANDEMIC, IN THE GENERAL
POPULATION AS WELL, POINTING TO
THE FACT THAT THE PANDEMIC HAS
NOT BEEN KIND, IN FACT, IT'S
BEEN PARTICULARLY BRUTAL ON
MINORITY POPULATIONS IN THE
UNITED STATES.
WHAT ARE WE DOING ABOUT IT?
I CAN TALK A LOT ABOUT THE
RESEARCH THAT NIMH HAS SUPPORTED
BUT I WANTED TO MENTION, ONE,
BECAUSE IT'S SORT OF RELEVANT TO
THE KIND OF INTERVENTIONS WE'RE
HOPING TO TEST IN LONG COVID.
THIS ONE AWARD THAT NIMH GAVE
OUT, IT SEEKS TO UNDERSTAND THE
ROLE OF GETTING MOBILE HEALTH --
MOBILE MENTAL HEALTHCARE TO
INDIVIDUALS AT RISK FOR MENTAL
HEALTH ISSUES IN THE CONTEXT OF
THE COVID-19 PANDEMIC.
AND IN PARTICULAR, IT'S FOCUSED
ON DELIVERING THIS CARE TO
BLACK, LATINX AND AMERICAN
INDIAN INDIVIDUALS.
IT TESTS THIS MOBILE APP THAT
CAN REDUCE ANXIETY AND
DEPRESSIVE SYMPTOMS IN THE
CONTEXT OF COVID-19.
AND THE APP INCLUDES A NUMBER OF
EVIDENCE-BASED APPROACHES TO
TREATING SUCH SYMPTOMS INCLUDING
SYMPTOM MONITORING, EXPOSURE
MANAGEMENT, WHICH IS AIMED AT
POST-TRAUMATIC STRESS DISORDER
LIKE SYMPTOMS, AS WELL AS
EDUCATION ON THE STRESS AND
COPING STRATEGIES.
SO THAT'S JUST A LITTLE ON THE
MENTAL HEALTH EFFECTS OF COVID
ON THE PANDEMIC AND MENTAL
ILLNESSES.
IT COMPLICATES OUR ABILITY TO
LOOK AT THE PERSISTENT MENTAL
HEALTH EFFECTS BUT NONETHELESS
WE CAN DO IT WITH THE RIGHT
CONTROLS.
SO EARLY ON, THIS WAS PUBLISHED
IN 2021 BUT IT WAS ACTUALLY
PRE-PRINT IN THE FALL OF 2020.
EARLY ON IT WAS RECOGNIZED THAT
THERE ARE NEUROLOGIC AND
PSYCHIATRIC OUTCOMES AMONGST
SURVIVORS OF COVID-19 AS LATE AS
SIX MONTHS AFTER THE INITIAL
INFECTION.
NOW, HOW DO YOU LOOK FOR
INCREASED RATES OF MOOD, ANXIETY
OR SIGH TO TICK DISORDERS IN PSYCHOTIC DI SORDERS WHEN
YOU'RE ALSO SEEING INCREASED
RATES IN THE GENERAL POPULATION
AND I CREASED MENTAL HEALTH
CONSEQUENCES IN THE CONTEXT OF
THE TRAUMATIC EXPOSURE?
THE WAY THIS PARTICULAR GROUP
LED BY PAUL HARRISON TRIED TO DO
THAT WAS COMPARE THE RATES OF
SUCH SYMPTOMS IN INDIVIDUALS
HOSPITALIZED FOR COVID-19
COMPARED TO INDIVIDUALS
HOSPITALIZED FOR OTHER
RESPIRATORY TRACT INFECTIONS, SO
OTHER SERIOUS HOSPITALIZED
RESPIRATORY TRACT INFECTIONS
LIKE INFLUENZA AND THE LIKE.
WHAT YOU CAN SEE IS, EVEN FOR
CONTROLLING FOR THOSE WHO HAVE
BEEN EXPOSED TO THE TRAUMA OF A
HOSPITALIZATION FOR A
RESPIRATORY INFECTION, YOU CAN
SEE INCREASED RATES OF MOOD,
ANXIETY OR SIGH TO PSYCHOTIC DISORDERS
IN INDIVIDUALS WHO WERE INFECTED
WITH COVID-19 COMPARED TO
INFECTED WITH OTHER INFECTIOUS
AGENTS CAUSING RESPIRATORY TRACT
INFECTIONS.
ONE CLUE TO THE ETIOLOGY DOES
SUGGEST IT HAS TO DO WITH THE
SEVERITY AND LOCUS OF THAT
ILLNESS.
SO IF YOU LOOK AT THE RATES OF
MOOD, ANXIETY OR SIGH PSYCHOTIC
DISORDER SYMPTOMS AND SEPARATE
INDIVIDUALS WITH COVID-19 NO
INTO COVID-19 NOOPT
A HOSPITALIZED GROUP,
HOSPITALIZED PLUS ENCEPHALOPATHY
GROUP HERE IN THE DARK RED AS
COMPARED TO A HOSPITALIZATION
ALONE OR MATCHED COHORT THAT
DIDN'T RECEIVE -- DIDN'T HAVE
COVID-19 THAT WERE HOSPITALIZED
WITH OR WITHOUT ENCEPHALOPATHY,
YOU CAN SEE THAT WHAT IT SEEMS
TO BE IS THAT COVID-19 PLUS
ENCEPHALOPATHY RAISES YOUR RISK
FOR LONG LASTING PSYCHIATRIC
SYMPTOMS, AND THAT RISK
CONTINUES TO INCREASE THROUGH
THE FIRST SIX MONTHS AFTER
INFECTION WITH COVID-19.
SO IT DOES APPEAR THAT THERE IS
A CONJOINT SEVERITY BY COVID-19
EFFECT WHICH RAISES YOUR RISK
FOR MENTAL ILLNESS SYMPTOMS.
NOW WE CANNOT DEFINITIVELY POINT
TO THE BIOLOGY OF COVID-19 LIKE
THIS, BUT IT DOES STRONGLY
IMPLICATE THE FACT THAT THERE'S
SOMETHING SPECIAL ABOUT COVID-19
COMPARED TO OTHER INFECTIOUS
AGENTS, AND SOMETHING SPECIAL
ABOUT COVID-19 SEVERE ENOUGH TO
INDUCE ENCEPHALOPATHY THAT
RAISES YOUR RISK FOR THESE
DISORDERS.
I'LL JUST POINT OUT THAT THIS IS
NOT THE ONLY STUDY TO SHOW THIS.
THIS IS ANOTHER STUDY LOOKING AT
LARGE NUMBER OF INDIVIDUALS
TREATED FOR COVID-19 IN THE
CONTEXT OF THE VETERANS'
ADMINISTRATION HOSPITAL SYSTEM,
AND YOU CAN SEE INCREASED RISK
OF A WIDE RANGE OF PSYCHIATRIC
SYMPTOMS INCLUDING ANXIETY
DISORDERS, DEPRESSIVE DISORDERS
AND PTSD.
THESE ARE HAZARD RATIOS TO THE
DIAGNOSIS IN THE PRESENCE OF
SUICIDAL IDEATION WITH INCREASE
IN RISK OF ABOUT 30 TO 40%
INCREASES.
ALSO IN THE PRESENCE OF THIS
LARGE STUDY OF ELECTRONIC HEALTH
RECORDS, THEY COULD LOOK AT THE
PRESCRIPTION USE OF
ANTIDEPRESSANTS, THE
PRESCRIPTION USE OR MISUSE OF
OPIOIDS AND OTHER SUBSTANCES,
AND SLEEP DISORDERS IN THAT SAME
POPULATION ALL HAVE INCREASED
RISKS IN THE AFTERMATH OF
COVID-19 FROM THESE EHRs.
NOW HERE WE'RE NOT SHOWING
NECESSARILY CONTROLS RELATIVE TO
OTHER RESPIRATORY TRACT
INFECTIONS BUT WE'RE
DEMONSTRATING IN THE CONTEXT OF
PANDEMIC, IN THOSE WHO HAVE BEEN
INFECTED COMPARED TO THOSE WHO
HAVEN'T, WE'RE SEEING INCREASES
IN RISK FOR A WIDE RANGE OF
PSYCHIATRIC SYMPTOMATOLOGY.
AND THAT'S REFLECTED HERE IN THE
OVERALL DATA FROM THIS STUDY,
SHOWING ABOUT A 50% INCREASE IN
THE LIKELIHOOD OF HAVING ANY
MENTAL HEALTH DIAGNOSIS, ANY
MENTAL HEALTH DIAGNOSIS TREATED
BUT WITH A DRUG OR ANY MENTAL
HEALTH DIAGNOSIS TREATED WITH
EITHER ONE, SORRY, DIAGNOSIS,
DRUG, OR BOTH.
SO WITH THAT, I'M GOING TO TURN
IT OVER TO WALTER WITH THIS
BRIEF INTRODUCTION, AND THAT IS
THAT IN COLLABORATION ACROSS A
NUMBER OF DIFFERENT NIH
INSTITUTES, BUT REALLY LED
WALTER'S
WALTER'S INSTITUTE, THE NIH
RECOVERY INITIATIVES WHICH HE'LL
TELL YOU MORE ABOUT IS SEEKING
TO UNDERSTAND CHRONIC COVID AND
TO DEVELOP INTERVENTIONS THAT
WILL REDUCE ITS IMPACT.
WITH THAT, I'LL TURN IT OVER TO
WALTER.
THANKS FOR LISTENING, AND I'LL
BE HAPPY TO TAKE YOUR QUESTIONS
AT THE END.
>> THANKS SO MUCH, JOSH.
AS JOSH MENTIONED, I'M GOING TO
TALK A LITTLE BIT ABOUT -- MAYBE
IT'S MORE ABOUT WHAT WE DON'T
KNOW ABOUT POST-ACUTE SEQUELAE
OF COVID AS OPPOSE DOLLARS TO
WHAT OPPOSED TO WHAT WE
DO KNOW, AND THEN TALK ABOUT HOW
NIH IS ATTEMPTING TO TRY TO GET
ANSWERS TO SOME OF THESE
QUESTIONS.
SO THE PROBLEM IS THE CONDITION
THAT IS CALLED LONG COVID NOW IS
A SYMPTOMATIC LIST OF THINGS,
AND PEOPLE WHO HAVE THESE
PERSISTENT SYMPTOMS AFTER THE
ACUTE INFECTION TEND TO HAVE
MULTIPLE BUT NOT NECESSARILY ALL
THAT BEGS THE QUESTION OF
WHETHER THERE ARE SUBSETS IN
THIS GROUP OF FOLKS.
THE SYMPTOMS AND THE EFFECT OF
COVID POINT TO POTENTIAL
TROUBLES IN MULTIPLE DIFFERENT
ORGAN SYSTEMS IN THE BODY, SO WE
CAN'T REALLY FOCUS IN ON ANY
ONE.
WE HAVE TO LOOK AT ALL THE ORGAN
SYSTEMS AND HOW THEY MIGHT
CONTRIBUTE TO SYMPTOMS PEOPLE
HAVE AFTER ACUTE COVID
INFECTION.
ALSO I'D POINT OUT THAT WE NEED
TO SET UP TO LOOK AT HOW THE
ACUTE COVID INFECTION, WHICH IS
AFFECTING UP TO 76 MILLION
PEOPLE IN THE U.S., BUT GOING TO
AFFECT THEIR FUTURE HEALTH OVER
TIME, THOSE ARE POTENTIAL
INCREASES OR MAYBE DECREASES
HOPEFULLY IN RARE CONDITIONS OR
COMMON CONDITIONS.
SO A LOT OF QUESTIONS OUT THERE
TO BE STUDIED.
WHAT IS THE PREVALENCE?
WELL, IT KIND OF DEPENDS ON HOW
YOU DEFINE IT AND WHAT YOUR
STUDY IS SET UP TO DO.
THE BEST DATA I COULD SEE IS
FROM
FROM THE U.K. OFFICE FOR
NATIONAL STATISTICS IS TRYING TO
LOOK SERIOUSLY AT WHAT THE LEVEL
OF PREVALENCE AND INCIDENCE IS.
SO IF YOU TRACK SYMPTOMS IN A
GROUP OF PEOPLE AND LOOK FOR
SYMPTOMS THAT ARE PERSISTENT
AFTER 12 WEEKS OF ACUTE
INFECTION, THE DATA YOU GET IS
ABOUT 3% IF YOU'RE DOING A
CAREFUL TRACKING, IF YOU'RE
LOOKING ON JUST HOW PEOPLE
CLASSIFY THEMSELVES, IT GOES UP
TO 11.7%.
IN THE U.K., AMONG THOSE
STUDIED, 5% REPORTED ANY OF THE
12 COMMON SYMPTOMS, 12 TO 16
WEEKS AFTER INFECTION.
HOWEVER, THE PREVALENCE OF THESE
COMMON SYMPTOMS THAT I SHOWED
YOU ON THE PREVIOUS SLIDE IS
3.4% IN THE CONTROL GROUP WHO
NEVER HAD COVID.
SO YOU HAVE TO BE A LITTLE BIT
CAREFUL IN ATTRIBUTING THESE
VERY COMMON SYMPTOMS TO THE
INFECTION ITSELF.
HOWEVER, IF YOU LOOK AT PEOPLE
WHO HAVE CONSISTENTLY SUFFERED
FROM THESE SYMPTOMS IN A
CONTINUOUS PERIOD FOR AT LEAST
12 WEEKS FROM THE INFECTION,
THEN YOU SEE THE INCIDENCE IS 3%
VERSUS 0.5% IN THE CONTROL
GROUP.
SO THIS MIGHT BE THE BEST GOLD
STANDARD DATA WE HAVE SO FAR.
IF YOU GO TO SELF-REPORTED LONG
COVID AND YOU ASK THEM, YOU
KNOW, ARE YOU FEELING WELL OR
NOT, IT GOES UP MUCH HIGHER.
THE DATA FROM THE U.K. SAID THE
PREVALENCE WAS HIGHER IN
FEMALES, HIGHER IN ADULTS 50 TO
69.
SOME STUDIES HAVE SHOWN THAT
MAYBE IT'S HIGHER IN PEOPLE A
LITTLE YOUNGER THAN THIS, IT'S
ALWAYS MIER HIGHER IN PEOPLE WITH
PRE-EXISTING HEALTH CONDITIONS
AND ALWAYS HIGHER IN PEOPLE WHO
HAVE HIGH VIRAL LOAD AT THE TIME
OF INFECTION OR MORE SEVERE
INFECTION.
THIS IS A STUDY FROM THE VETERAN
ADMINISTRATION'S ELECTRONIC
HEALTH RECORDS LOOKING AT
153,000 COVID-POSITIVE SUBJECTS,
5-POINT ,
5.86 MILLION CONTROLS.
WHAT YOU SEE ON THE SCREEN IS
PEOPLE WHO WERE NEVER
HOSPITALIZED, THEIR RISK OF
STROKE, TIA, THIS IS THE
CARDIOVASCULAR SIDE OF THINGS.
THE RED IS PEOPLE WHO WERE IN
THE HOSPITAL, DIDN'T REALLY
REQUIRE ICU LEVEL CARE, AND THE
PURPLE ARE THE PEOPLE WHO
REQUIRED ICU LEVEL CARE.
YOU CAN SEE THAT MANY THINGS,
EVEN IF YOU DIDN'T GO IN THE
HOSPITAL, THERE WAS AN INCREASED
RISK OF THESE
CARDIOVASCULAR/STROKE
COMPLICATIONS AT THIS -- I THINK
THIS WAS OUT BEYOND 30 DAYS
GOING OUT TO ABOUT SIX MONTHS
AFTER THE ACUTE INFECTION.
SO A SIGN HERE THAT SOMETHING'S
GOING ON EVEN IF YOU WEREN'T
HOSPITALIZED, CLEARLY THOSE
PEOPLE IN THE HOSPITAL HAVE
GREATER RISKS FOR
CARDIOVASCULAR.
IN ANEAR ANOTHER STUDY OF HEALTH
RECORDS OUT OF BOSTON, LOOKING
AT 97,000 PEOPLE WHO TESTED
POSITIVE FOR COVID, AND THEN
LOOKING AT WHO DEVELOPED A NEW
DIAGNOSIS IN THEIR ELECTRONIC
HEALTH RECORD STARTING LIKE
THREE MONTHS AFTER THEIR COVID
DIAGNOSIS, THREE TO SIX MONTHS
AFTER THEIR COVID DIAGNOSIS,
THEN THEY ACTUALLY FOLLOWED IT
OUT SIX TO NINE MONTHS, AND THEY
DEVELOPED SCORING THAT GIVES YOU
THE STRENGTH OF THE ASSOCIATION
OF THESE DIFFERENT SYMPTOMS WITH
WHAT THEY CALL A POST-ACUTE
SEQUELAE OF COVID, AND SO THINGS
LIKE ALOPECIA ARE VERY SPECIFIC.
IT'S A STRESS-RELATED RESPONSE,
CHEST PAIN, PALPITATIONS,
PROTEINURIA, AND FATIGUE IS DOWN
HERE, BUT AT THE AFTER 6 TO 9 MONTHS,
IT GOES BACK UP TO BE SECOND
ONLY TO TROUBLE WITH SMELL AND
TASTE.
SO YOU CAN SEE HOW THINGS CHANGE
OVER TIME, BUT THERE IS CLEARLY,
UNFORTUNATELY, IN MOST OF THESE
STUDY, PEOPLE HAVE PERSISTENT
TROUBLE OUT PAST SIX MONTHS
AFTER THE ACUTE INFECTION.
PEOPLE GET BETTER OVER THE FIRST
COUPLE MONTHS, THEN THERE'S A
SLOWING DOWN OF THE IMPROVEMENT
AROUND THAT SIX-MONTH PERIOD.
THAT'S VERY CONCERNING BECAUSE A
LOT OF THESE SYMPTOMS, WHAT WE
SEE IN ADDITION, MYALGIA,
ENCEPHALITIS, CHRONIC FATIGUE
SYNDROME, THOSE PEOPLE OFTEN
PRESENTED WITH SOME TYPE OF A
VIRAL INFECTION AND NEVER GOT
BETTER, BUT THEY CAN BE SICK FOR
DECADES.
SO THAT'S REALLY THE WORST FEAR,
IS THAT THOUSANDS, EVEN A
MILLION PEOPLE COULD GO ON TO
THAT VERY TRAGIC CONDITION
UNLESS WE UNDERSTAND HOW TO
PREVENT THAT OR IF THIS IS
SOMEHOW GOING TO PEETER OUT OVER
A LONGER PERIOD OF TIME.
NOW, WHAT'S AT THE BOTTOM OF
THIS?
WE REALLY DON'T KNOW WHAT THE
BIOLOGICAL DRIVERS ARE.
I TALKED TO YOU ABOUT THREE
MAJOR HYPOTHESES.
ONE IS THAT THERE'S A
DISTURBANCE IN THE IMMUNE SYSTEM
THAT OCCURS DURING COVID, AND
THAT DOESN'T RESET AND THAT
CAUSES PERSISTENT SYMPTOMS.
THE SECOND ONE IS THAT THERE IS
A AUTOIMMUNITY THAT DEVELOPS DUE
TO THE SURGE IN IMMUNE RESPONSE
TO THE VIRUS WITH THE IMMUNE
RESPONSE OVERSPILLING AND
ATTACKING SELF-ANTIGENS SO YOU
GET AN AUTOIMMUNE DISORDER.
THERE ARE SOME INCREASES OF,
SAY, LUPUS AFTER COVID, CLASSIC
AUTOIMMUNE DISORDER, AND THE
LAST ONE, POTENTIAL PERSISTENT
VIRUS IN THE BODY THAT IS
CONTINUING TO STIMULATE THE
IMMUNE SYSTEM, SO YOU STILL HAVE
THOSE SYMPTOMS THAT YOU HAD WHEN
YOU FIRST GOT INFECTED.
SO THIS IS A PAPER THAT RECENTLY
CAME OUT IN "CELL."
THEY LOOKED AT 309 PATIENTS, AND
THEY TRIED TO LOOK AT EVERYTHING
THEY COULD, SINGLE CELL
MULTI-YOE MIX IN THE WHITE
CELLS, PLASMA -- AUTO
ANTIBODIES, AND RNAEMIA, AND
ALSO VIREMIA DUE TO EPSTEIN-BARR
VIRUS.
WHAT THEY FOUND WAS THAT THERE
WERE FOUR -- IN THE ACUTE STAGE,
THERE WERE FOUR THINGS THAT
ANTICIPATED YOU WERE GOING TO
GET POST-ACUTE SEQUELAE OF
COVID.
THOSE WERE TYPE 2 DIABETES, HIGH
RNAEMIA FROM YOUR COVID-19
VIRUS, AND HIGH VIREMIA DUE TO
ACTIVATION OF EPSTEIN-BARR
VIRUS, AND THEN SPECIFIC AUTO
ANTIBODIES.
I JUST WANTED TO MENTION THAT
EPSTEIN-BARR VIRUS IS A VIRUS
THAT INFECTS PRETTY MUCH ALL OF
US, WHEN IT CAUSES AN ILLNESS,
IT'S CALLED INFECTIOUS
MONONUCLEOSIS, MOSTLY IN
TEENAGER, YOUNG 20s WHO GET
THIS INFECTION, BUT PRETTY MUCH
EVERYBODY GETS EPSTEIN-BARR
VIRUS, AND IT IS PERSISTENT IN
THE BODY.
AND WHEN YOU HAVE A MAJOR IMMUNE
CHALLENGE, WHATEVER IS HOLDING
DOWN THE EPSTEIN-BARR VIRUS IN
YOUR BODY LOSES ITS
EFFECTIVENESS AND THE
EPSTEIN-BARR VIRUS STARTS TO
REPLICATE, SO THIS IS SOMETHING
THAT YOU WOULD SEE IN MANY
DIFFERENT IMMUNE INSULTS.
NOW THE PROBLEM WITH THE STUDY
IS THAT EVERYBODY DIDN'T HAVE
THE SAME THING AND THEN THEY
STARTED TO LOOK FOR DIFFERENT
SUBGROUPS OF PATIENTS, AND THEY
DIVIDED IT INTO SYMPTOMS AND
RESPIRATORY NEURO, G.I.
ESTIMATES AND CLAIMED THAT COULD
FIND CERTAIN PATTERNS MORE
ASSOCIATED WITH THE RESPIRATORY
AND THE G.I. AND THE NEURO.
SO THAT, YOU KNOW, THAT REALLY
HAS TO BE VALIDATED.
YOU START TO DROP INTO
SUBGROUP-SPECIFIC
CHARACTERISTICS, YOU RUN INTO
TROUBLE WITH MULTIPLE
COMPARISONS.
SO THIS REALLY HAS TO BE LOOKED
AT.
WHAT THEY FOUND WAS THAT THERE
WAS A PARTICULAR T-CELL PATTERN
IN THOSE PEOPLE WHO DEVELOPED
GASTROINTESTINAL SYMPTOMS IN
THEIR POST-COVID STATE.
THEY FOUND THAT THERE WERE
IMMUNOLOGIC ASSOCIATIONS BETWEEN
DIFFERENT FACTORS, WHETHER THEY
BE CYTOKINES OR T-CELL SUBSETS
OR AUTO ANTIBODIES, AND THOSE
ASSOCIATIONS WERE PRETTY TIGHT
IN THE ACUTE STAGE AND MAYBE AT
THREE MONTHS, BUT THEN THEY
SEPARATED OUT BY SIX MONTHS AND
DIDN'T REALLY HANG TOGETHER
ANYMORE.
SO THE EMPHASIS WAS ON THE IDEA
THAT THE BEST PREDICT TORES OF
WHETHER YOU GET PASC ARE
MEASURES DURING THE ACUTE
INFECTION.
OF COURSE THAT'S A PROBLEM IF WE
DON'T UNDERSTAND THAT RIGHT
AWAY, HOPEFULLY ACUTE INFECTIONS
WILL START DROPPING OUT, BUT
IT'S GOING TO BE A LOT HARDER TO
GO BACKWARDS FROM SOMEBODY WHO'S
SIX MONTHS OUT TO TRY AND FIGURE
OUT WHAT IS THE MAJOR DRIVER.
SO JUST AN EXAMPLE.
THERE'S ANOTHER EXAMPLE, THE
STUDY WAS FROM SWITZERLAND, AND
IT'S A SMALL NUMBER AGAIN, ONLY
175 PATIENTS.
WHAT THEY'RE SHOWING HERE IS
THAT IF YOU GET COVID-19, YOU
GENERALLY ELEVATE YOUR LEVELS OF
IG3, AND THEY GO UP IN MILD
DISEASE, THEY GO UP HIGHER IN
SEVERE DISEASE, WHERE THE GROUPS
THAT DEVELOP -- YOU DON'T SEE
THAT SAME OF IG3.
PATIENTS WHO HAD BOTH HIGH IGM
AND HIGH IG3 WERE LESS LIKELY TO
DEVELOP POST SEQUELAE.
THERE'S AN INTERESTING CUT
DEPENDING ON WHETHER YOUR
IG3 LEVEL WAS LOW OR NOT.
SIMILARLY, THEY LOOK ALMOST
IDENTICAL WHEN YOU LOOK AT
IG3 AND A CUT BETWEEN THOSE WHO
HAVE HIGH I GM LEVELS OR LOW IGM
LEVELS.
THAT COMBINATION SOMEHOW IS
INTERACTING.
AGAIN, THESE KIND OF THINGS HAVE
TO BE VALIDATED AND THEN THE
NUMBERS ARE SMALL AND THE
QUESTION IS, ARE THERE A SUBSET,
YOU CAN SEE THIS TREMENDOUS
OVERLAP HERE PATTERNS.
NEXT ONE IS A PAPER THAT'S NOT
YET PUBLISHED LOOKING AT IL-1
BETA, IL-6, TNF ALPHA.
258 PEOPLE AFTER MOSTLY MILD
INFECTION FROM A TOWN IN
GERMANY, AND POST-ACUTE SEQUELAE
REPORTED IN 40% OF CASES AT SIX
MONTHS, SO THIS IS SELF-REPORTED
NUMBERS.
NOT ONLY FATIGUE, SHORTNESS OF
BREATH, TROUBLE WITH
CONCENTRATION.
BUT THEY LOOKED AT JUST
ANTIBODIES, THE NUMBER OF AUTO
ANTIBODIES, YOU GET A BIG
INCREASE, I THINK IN THE CONTROL
GROUP, IT WAS ZERO.
SO IF YOU HAVE PASC, YOUR CHANCE
OF DEVELOPING AUTO ANTIBODIES
GOES REALLY HIGH, I THINK UP TO
30%.
IF YOU HAVE NO PASC, THEY DIDN'T
REALLY -- IF ANYTHING, WITHOUT
DEVELOPING POST-ACUTE SEQUELAE
HAD A HIGHER CHANCE OF HAVING
AUTO ANTIBODIES THAN THE PEOPLE
WHO ARE PASC.
SO YOU'RE NOT SEEING A
ASSOCIATION THERE WITH WHETHER
YOU HAVE AUTO ANTIBODIES OR NOT,
THAT BEGS THE QUESTION OF
WHETHER SPECIFIC AUTO ANTIBODIES
ARE CAUSING THE TROUBLE, THAT'S
NOT SOMETHING THAT THEY GOT
INTO.
IF YOU LOOK AT THE PROBABILITY
OF PASC WITH DIFFERENT CYTOKINE
LEVELS THEN YOU CAN SEE FAIRLY
SIGNIFICANT ASSOCIATION WITH
HIGH CYTOKINE LEVELS OF TNF
ALPHA, -- A DIFFERENT SUBSET OF
CYTOKINES.
THEY ALSO SAID DEVELOPING --
GETTING A VACCINE AFTER YOU'RE
INFECTED DID NOT AFFECT YOUR
CHANCE OF GETTING PASC.
THERE WAS A STORY THAT PEOPLE
WHO HAVE PASC, THEY GOT
VACCINATED, THEY FELT BETTER.
THERE'S BEEN SOME STUDY THAT
DOESN'T SEEM LIKE A STRONG
EFFECT SIZE, THESE FOLKS DIDN'T
SEE IT AT ALL.
HIGH PERCENTAGE OF THE PEOPLE
WITH COVID-19 HAVE AUTO
ANTIBODIES BUT NOT ASSOCIATED
WITH PASC, BROAD RANGE OF
CYTOKINES DISREGULATED LONG
AFTER INFECTION.
SO THE QUESTION IS, IS THIS
CYTOKINE PATTERN SOMETHING THAT
WOULD MAKE YOU FEEL FATIGUE,
TROUBLE WITH CONCENTRATION?
THAT'S POSSIBLE, BUT NEEDS TO BE
PURSUED FURTHER.
AND THEIR POINT WAS THAT THESE
CYTOKINES ARE BASICALLY COMING
FROM THE MACROPHAGES THAT ARE
BEING ACTIVATED IN THE LUNG
DURING THE ACUTE INFECTION.
THIS IS THE NEXT KIND OF THING
THAT WORRIES ME THE MOST, IS
THAT THERE MAY BE EVIDENCE THAT
THE VIRUS, ALTHOUGH THE ACUTE
INFECTION IS OVER, THE VIRUS IS
STILL HIDING IN YOUR BODY.
SO WE TALKED A LITTLE BIT ABOUT
THAT WITH REGARD TO EBV.
THE QUESTION IS, COULD THAT BE
TRUE WITH COVID-19?
SO THIS STUDY FROM MICHELLE'S
LAB AT ROCKEFELLER BASICALLY DID
INTESTINAL BIOPSIES FROM
ASYMPTOMATIC INDIVIDUALS FOR
FOUR MONTHS AND REVEALED
PERSISTENCE OF NUCLEAR ACIDS
FROM COVID-19 IN 7 OF 14 PEOPLE,
AND THEN THEY LOOKED AT MEMORY B
CELL RESPONSES OVER TIME, AND
THEY SEE THE CHANGES THAT ARE
OCCURRING IN PEOPLE CONSISTENT
WITH CONTINUED ANTIGEN
PERSISTENCE.
SO THIS WAS THE FIRST THING THAT
I'VE SEEN THAT SUGGESTED THAT
THE VIRUS IS STILL PRESENT,
STILL ACTIVE IN THE IMMUNE
SYSTEM.
THESE WERE NOT NECESSARILY PAST
PATIENTS SO IT DOESN'T GET YOU
AT PASC, SO CERTAINLY IF THE
VIRUS IS STILL PRESENT, THAT
THAT'S GOING TO BRING THAT AS A
HIGH DRIVER OF THE SYMPTOMS.
THEN THERE'S THIS PAPER COMING
OUT OF THE NCI GROUP, AUTOPSIES
ON 44 COVID-19 PATIENTS, OVER
SEVEN MONTHS FOLLOWING SYMPTOM
ONSET AND CLAIMING THAT
SARS-COV-2 IS ACTUALLY
EVERYWHERE IN THE BODY, EVEN
THOSE WHO DIED WITH ASYMPTOMATIC
OR MILD INFECTION, AND EVEN AT
LATE TIME PERIODS.
THEY'RE CLAIMING THE REPLICATION
IS PRESENT IN BOTH THE PULMONARY
ANNEX -- HARDER TO SEE LAYERS
BUT THEY CLAIM IT'S STILL THERE
IN MULTIPLE ANATOMIC SITES
INCLUDE THE BRAIN FOR UP TO 230
DAYS, THAT'S THE LATEST THEY
LOOKED, AND THEY SEE --
PATHOLOGY EXCEPT FOR IN THE
LUNG.
SO THIS IS NOT YET PUBLISHED BUT
I THINK IT'S BEEN ACCEPTED, SO
THIS REALLY RAISES THE QUESTION
ABOUT PERSISTENT VIRUS AND, OF
COURSE, IT WOULD LEAD PEOPLE TO
THINK, WELL, IF THAT'S WHAT'S
DRIVING SOME OF THESE SYMPTOMS
AND THAT POTENTIALLY AN
ANTIVIRAL AGENT MAY WORK, THE
VACCINE DOESN'T SEEM TO HAVE THE
EFFECT SIZE, REPEATING
VACCINATION, BUT POTENTIALLY THE
ANTIVIRUS -- IF WE GO INTO THE
NERVOUS SYSTEM, PEOPLE MAY HAVE
SEEN THIS BEFORE, DR. -- LAB
INITIALLY SHOWED THERE'S NOT A
LOT OF VIRUS THAT HE COULD FIND
IN THE NERVE CELLS, BUT THE
VIRUS IS BASICALLY -- ATTACKS
THE ACE 2 RECEPTOR WHICH IS
PRESENT ON ENDOTHELIAL CELLS
THAT LINE THE BLOOD VESSELS, SO
YOU SEE BLOOD VESSEL PATHOLOGY.
YOU SEE LEAKAGE HERE IN GREEN OF
DYES, BLOOD PRODUCTS, BLOOD
PROTEINS LEAKING THROUGH THE
BLOOD-BRAIN BARRIER, WE SEE
BRAIN SUBSTANCE WHICH SHOULDN'T
BE THERE.
WE SEE LOSS OF EXTRACELLULAR
MEMBRANE ALONG BLOOD VESSELS.
THEN YOU SEE INFLAMMATION THAT
STARTS TO SURROUND THESE BLOOD
VESSELS, WHICH YOU WOULD EXPECT
TO SEE IF THERE'S LEAK OF
SUBSTANCES FROM THE BLOODSTREAM
INTO THE BRAIN SUBSTANCE.
AND THEN THERE'S AN INFLAMMATORY
RESPONSE WHICH IS POTENTIALLY A
DRIVER OF SOME OF THE NEUROLOGIC
SYMPTOMS IN THE ACUTE COVID
CASE, SO IF YOU LOOK AT RISK
FACTORS IN THE SPINAL FLUID,
PEOPLE WHO HAVE COGNITIVE
TROUBLE AFTER MILD COVID, AGAIN,
VERY SMALL STUDY, BUT THIS ONE
SHOWED THAT 9 OF 13 MONO CLONL
BANDS IN THE SPINAL FLUID, SO
THEY'RE BANDS OF IMMUNOGLOBULINS
ASSOCIATED WITH PARTICULAR
ANTIGENS, ANTIGENS ARE NOT
DEFINED, BUT IT'S A FAIRLY LOW
PREVALENCE IN NORMAL
INDIVIDUALS.
SO THIS INDICATES SOME TYPE OF
PRODUCTION OF ANTIBODIES IN THE
CENTRAL NERVOUS SYSTEM.
IN STUDIES OF ACUTE COVID CASES,
THERE'S A LOT OF BRAIN INJURY
LIKE WE TALKED ABOUT IN
BLOOD-BRAIN BARRIER BREAK DOWNS
AND WHAT YOU SEE IS A LEAKAGE OF
CERTAIN PROTEINS, NEUROFILAMENT
LIGHT, FIBRILLARY ACIDIC
PROTEIN, AND THESE WERE ELEVATED
IN THE ACUTE PHASE BUT THEY
NORMALIZED BY SIX MONTHS.
AND THEY FOUND NO CORRELATION
BETWEEN SYMPTOMS AND THESE CNS
BIOMARKERS OF LEAKAGE.
BUT THERE IS DEFINITELY LEAKAGE
SO THERE IS EVIDENCE OF CELLULAR
INJURY IN THE ACUTE PHASE WITH
SEVERE ILLNESS.
MAYBE NOT THAT SURPRISING.
OTHER STUDIES LOOKING AT SPINAL
FLUID SHOW T-CELL ACTIVATION IN
THE SPINAL FLUID.
THE CYTOKINE RESPONSE IN THE
CNS, THE T-CELLS PATTERN YOU SEE
IS DIFFERENT THAN WHAT YOU SEE
IN THE BLOOD, SO THERE'S
SOMETHING PARTICULAR GOING ON IN
THE NERVOUS SYSTEM, AND THIS IS
ANOTHER STUDY LOOKING AT THE
INJURY MARKER BUT ALSO CYTOKINES
IN THE SPINAL FLUID OF PATIENTS
WITH NEUROLOGICAL COMPLICATIONS,
ACUTE COVID.
WHAT ARE PROBLEMS, FATIGUE IS
PROBABLY THE MOST COMMON AND THE
MOST DISABLING.
THE OTHER ONE THAT'S DISABLING
IS TROUBLE WITH CONCENTRATION.
SO THIS IS A STUDY FROM THE
U.K., A REALLY LARGE STUDY.
THEY HAVE THESE COMPUTERIZED
TESTS OF WORD SPAN, RARE WORD
DEFINITION, AND THEY TESTED
81,000 PEOPLE AND THEY LOOKED AT
PEOPLE WHO HAD COVID BEFORE
COMPARED TO NORMALS.
WHAT THEY SEE IS THAT THERE IS
SOME DEFICITS THAT YOU CAN
MEASURE AT THIS POPULATION LEVEL
IN PEOPLE WHO HAVE HAD COVID.
IT'S VERY SMALL EFFECT SIZE IF
YOU HAD SYMPTOMS OF COVID BUT
DIDN'T HAVE REALLY TROUBLE WITH
RESPIRATION.
IF YOU HAD SHORTNESS OF BREATH
AND STAYED AT HOME, IT'S A
LITTLE WORSE.
IF YOU NEEDED MEDICAL ASSISTANCE
AT HOME, YOUR SCORE IS ACTUALLY
A LITTLE WORSE THAN THAT.
IF YOU WENT TO A HOSPITAL NOT ON
A VENTILATOR, THEY'RE
SIGNIFICANTLY WORSE, AND THEN ON
A VENTILATOR, THEY'RE THE WORST.
SO THIS IS A LARGE POPULATION
STUDY SHOWING COGNITIVE CHANGES
RELATED TO COVID WHETHER OR NOT
YOU WENT INTO THE HOSPITAL BUT
CERTAINLY THE WORST, MORE SEVERE
ILLNESSES.
THAT THEME HAS BEEN REPEATED
OVER AND OVER AGAIN IN THE
POST-ACUTE SEQUELAE OF COVID.
NOW, IN TERMS OF THE CENTRAL
NERVOUS SYSTEM, WE'RE TALKING
MOSTLY ABOUT FATIGUE, SLEEP
TROUBLES, TROUBLE WITH
CONCENTRATION.
IN THE PERIPHERAL NERVOUS SYSTEM
WE OFTEN TALK ABOUT PAIN AND
DISOUGHT NOME
DISAUTONOMIA.
THOUGHT TO COME TO SMALL NERVE
FIBERS.
THEY EVALUATED A VERY -- THIS IS
NOT AN UNBIASED GROUP.
THESE ARE PEOPLE WHO HAD SOME
KIND OF SYMPTOMS OF LONG COVID,
THAT GOT THEM TO SEE A
PERIPHERAL NERVE DOCTOR.
THEY DID FIND 57% HAD NEUROPATHY
FROM THEIR SYMPTOM CHECKLIST AND
THEIR TESTING WAS SIGNIFICANT
WITH A SMALL FIBER NEUROPATHY.
SO THESE ARE THE NERVE FIBERS
THAT DON'T HAVE MYELIN AROUND
THEM, THEY GO TO THE SKIN.
THEY'RE BASICALLY PAIN FIBERS,
TEMPERATURE FIBERS PRIMARILY.
THE SUGGESTION WAS THAT THIS IS
AN INFECTION TRIGGERED IMMUNE
DYSREGULATION THAT GIVES RISE TO
THE SMALL -- NEWER NEUROPATHY SIMILAR
TO GILLIAN BARRE EXCEPT GILLIAN
BARRE AFFECTS MOSTLY MYELIN, BUT
THERE ARE FORMS OF VERY
AUTOIMMUNE POST INFECTIOUS
CONDITIONS WHERE THE TARGET IS
NOT THE MYELIN, BUT IT'S THE
SMALL FIBERS, AND THAT'S WHAT IT
LOOKS LIKE WE'RE SEEING HERE.
THAT WILL ALSO GIVE YOU
AUTONOMIC TROUBLE.
THERE'S ACTUALLY AN INTERESTING
STUDY THAT WAS PUBLISHED LOOKING
AT THE NERVE FIBERS IN THE
CORNEA.
SO THIS IS SOMETHING THAT
POTENTIALLY COULD BE A GOOD BIO
MARKER WHERE YOU CAN SEE HERE'S
THE NORMAL, HERE'S SOMEBODY WHO
HAD COVID AND HAVING TROUBLE,
AND HERE'S SOMEBODY WHO HAD
COVID AND NOT HAVING TROUBLE,
AND YOU CAN CERTAINLY SEE SEVERE
ABNORMALITY IN THE SMALL NERVE
FIBERS OF THE CORNEA IN THIS
PATIENT, A SMALL
FIBRONEUROPATHY.
THERE'S AN INTERESTING PAPER
THAT CAME OUT THAT GOT A LOT OF
PRESS IN NATURE FROM THE U.K.,
WHERE THEY HAVE A BIOBANK AND
THEY DO MRI SCANS ON PEOPLE IN
THE STUDY, AND THE STUDY STARTED
BEFORE COVID, SO THEY ACTUALLY
HAD MRI SCANS BEFORE COVID AND
AFTER COVID, AND THEY COULD FIND
CHANGES WHICH ARE PRIMARILY
DECREASES IN CORTICAL THICKNESS
IN DIFFERENT AREAS OF BRAIN, AND
MOST OF THEM ARE ASSOCIATED WITH
THE LIMBIC SYSTEM, WHICH IS
SIGNIFICANTLY ASSOCIATED WITH
THE OLFACTORY SYSTEM.
SO PIRIFORM CORTEX -- ALL LIMBIC
SYSTEM AREAS, AND SO THEY SHOW
DEFINITE THINNING OF CORTEX IN
THESE AREAS.
IT'S VERY CLEAR THAT THAT'S THE
CASE.
AND THE QUESTION IS, WHY?
YOU MIGHT ASSUME, WELL, IT'S DUE
TO INFECTION, BUT THERE IS A
CAVEAT HERE, AND THAT IS THAT IF
YOU LOSE YOUR SENSE OF SMELL,
YOU SEE CHANGES IN A LOT OF
THESE SAME REGIONS.
THIS IS A STUDY THAT HAD NOTHING
TO DO WITH COVID, JUST PEOPLE AS
THEY GET OLDER, THEY LOSE THEIR
SENSE OF SMELL, SO THEY DIDN'T
EVEN HAVE BEFORE AND AFTERs.
SO THE SAME THINGS IN THE SAME
AREAS, SAME THING OF CORE TECT,
CLEARLY MUCH MORE ROBUST WHEN
YOU HAVE BEFORE AND AFTER MRI,
SO THE ANSWER TO THE QUESTION
COULD BE, IT HAS NOTHING TO DO
WITH THAT SECTION OF THE BRAIN
AT ALL OR IMMUNE RESPONSE OF THE
BRAIN BR MORE RELATED TO HAVING
LOST YOUR SENSE OF SMELL AND
PLASTICITY [INAUDIBLE].
JUST TO MENTION THAT PEOPLE HAVE
LOOKED AT THE VACCINATION STORY
AND CERTAINLY IF YOU HAVE BEEN
VACCINATED, YOUR CHANCE OF
GETTING POST-ACUTE SCE LAY SEQUELAE OF
COVID IS DECREASED.
SO THAT'S WHAT I WANTED TO JUST
MENTION WHERE WE ARE IN TERMS OF
WHAT THE STUDIES ARE THAT ARE
OUT THERE.
AS YOU CAN SEE, THERE'S LOTS OF
SMALL STUDIES, THEY'RE ALL
PLANNING TO SEE SOME
ASSOCIATIONS, POTENTIALLY
INTERESTING WITH REGARD TO
CAUSATION, BUT NO CAUSATION.
SO THE RECOVERY INITIATIVE IS
ENGINEERED TO KIND OF, AT THE
END OF THE THING, GIVE THE
ANSWERS IF IT'S POSSIBLE, WE'RE
GOING TO GET THEM THROUGH THE
RECOVERY INITIATIVE.
IF THAT -- IF A SMALL STUDY OR
INVESTIGATOR-INITIATED SMALL
GROUP GETS TOGETHER, FIGURES IT
ALL OUT, THAT WOULD BE FINE, WE
CAN CLOSE TO IT DOWN.
BUT THE GUESS IS THAT THIS IS
GOING TO BE A HARD PROBLEM.
AND ONE REASON I THINK IT'S
GOING TO BE A HARD PROBLEM IS
BECAUSE DEALING WITH DEALING
WITH CHRONIC FATIGUE SYNDROME
FOR YEARS, WE HAVEN'T MADE ANY
PROGRESS FOREVER, AND SOME OF
THESE PEOPLE HAVE BEEN BED BOUND
FOR DECADES.
SO THIS GOVERNMENT INITIATIVE IS
FUNDED TO THE TUNE OF
$1.15 BILLION BY CONGRESS.
THE GOAL IS TO UNDERSTAND THE
BIOLOGY UNDERLYING RECOVERY OVER
TIME, UNDERSTANDING RISK
TYPES, -- TO STUDY THE
PATHOGENESIS OVER TIME AND TO
IDENTIFY INTERVENTIONS TO TREAT
AND PREVENT POST-ACUTE SEQUELAE
OF COVID.
IT'S A NATIONAL SCALE TO BE
INCLUSIVE, DIVERSE
PARTICIPATION, AND REALLY BROAD
LOOK AT COVID, NOT TAKING A
PARTICULAR GROUP AND STUDYING
THEM AND FOR GETTING ABOUT SEVEN
OR EIGHT OTHER GROUPS THAT
CONSTITUTE POST-ACUTE SEQUELAE
OF COVID.
AND IT'S A LARGE STUDY WITH 30
HUBS AROUND THE COUNTRY, 15
ADULT COHORTS, TWO PREGNANCY
COHORTS, EIGHT PEDIATRIC
COHORTS, AND IMPORTANTLY WE HAVE
ENGINEERED IN AUTOPSIES ON
PEOPLE WHO HAVE SURVIVED COVID
TO FIND OUT WHAT ARE THE -- WHAT
CAN WE SEE UNDER THE MICROSCOPE
IN PEOPLE WHO ARE STILL
SUFFERING WITH POST-ACUTE
SEQUELAE OF COVID VERSUS THOSE
WHO DON'T?
IF ANYTHING IS GOING TO GIVE US
A QUICK ANSWER, IT GOING TO COME
OUT OF THE AUTOPSY STUDIES.
BUT THE OTHER ONES, THERE'S SO
MUCH TO LOOK AT, WE'RE GOING TO
SEE ASSOCIATIONS, AND THEN WE'RE
GOING TO HAVE TO DRILL DOWN ON
THOSE AND DISCARD THOSE THAT ARE
NOT CAUSATIVE AND REALLY TRY AND
KEEP WORKING UNTIL WE FIND WHAT
ARE THE BIOLOGICAL DRIVERS.
WE'RE ALSO LOOKING AT ELECTRONIC
HEALTH RECORDS, 50 MILLION
PEOPLE, AND THIS IS PARTICULARLY
THE LOOK OVER TIME AT CHANGES IN
PUBLIC HEALTH THAT ARE RELATED
TO THE COVID PANDEMIC.
WE ARE ENROLLING UP TO 40,000
PARTICIPANTS.
1,500 SO FAR, ELECTRONIC HEALTH
RECORD STUDIES ARE GOING, TISSUE
PATHOLOGY, AUTOPSY STUDY.
WE'RE JUST SETTING UP NOW
CLINICAL TRIALS IN PEOPLE WHO
HAVE POST SEQUELAE OF ACUTE
COVID.
NOW THAT THERE'S STILL ACUTE
COVID AROUND, TO TRY TO RECRUIT
PEOPLE WHO ARE ACUTE AND THEN TO
FOLLOW THEM OVER TIME TO SEE
WHAT'S DIFFERENT IN THOSE PEOPLE
WHO RECOVER WELL VERSUS THOSE
WHO DON'T.
THIS IS THE OPPORTUNITY TO DO
THAT, AND THEY SAID HOPEFULLY A
YEAR OR TWO LATER, THE PANDEMIC
WILL BE OVER, YOU'RE NOT GOING
TO GET THAT OPPORTUNITY AGAIN.
AND THE HOPE IS WE CAN GET INTO
CLINICAL TRIALS, I THINK IN THE
BEGINNING THEY'LL BE BASED ON
SYMPTOMATIC THERAPY, LIKE WHAT
DOES IT TAKE TO TREAT THEIR PAIN
OR THEIR AUTONOMIC TROUBLE OR
DEPRESSION OR ANXIETY DISORDERS?
THEY MAY BE JUST LIKE EVERYBODY
ELSE WHO HAS THOSE TROUBLE, THEY
MIGHT BE QUITE UNIQUE.
SO GETTING SYMPTOM ATTENUATION
WOULD BE THE FIRST STEP IN
TRIALS.
BUT THEN IF WE UNDERSTAND SOME
OF THE BIOLOGICAL DRIVERS, FOR
INSTANCE, WE TALKED ABOUT
PERSISTENT VIRUS, THEN
ANTIVIRALS WOULD BE THERAPY
THAT'S DESIGNED TO GET RIGHT AT
THE ROOT CAUSE OF THE TROUBLE.
SO THAT'S WHAT I WANTED TO TALK
ABOUT.
I THINK WE'RE EMBARKING ON AN
UNBELIEVABLY LARGE AND WELL
ENGINEERED STUDY, AND IT
CERTAINLY HAS TAKEN TIME TO SET
IT ALL UP, BUT I THINK IT'S
GOING TO LEAVE NO STONE UNTURNED
AND HOPEFULLY WE GET ANSWERS,
HOPEFULLY SOONER THAN LATER.
SO THANKS VERY MUCH.
>> THANK YOU VERY, VERY MUCH,
BOTH OF YOU, FOR REALLY
STIMULATING AN AND INFORMATIVE
PRESENTATIONS.
WE HAVE A BARRAGE OF QUESTIONS,
AND I'M GOING TO TRY AND
CONDENSE SOME OF THEM.
BUT LET ME BEGIN BY THIS ONE.
ANTIPERHAPS AND PERHAPS YOU WANT TO RESPON D
OR DISCUSS IT AMONGST
YOURSELVES.
SO KIRA SUBMITS A MESSAGE.
SHE SAYS, THIS HAS BEEN
FANTASTIC, THANK YOU!
HOWEVER, IN A CLINICAL SETTING,
IF THE BIOMARKERS ARE
DIMINISHING BY 6 MONTHS AND
EVIDENCE SUGGESTS THAT LONG
COVID SYMPTOMS CAN LAST WELL
BEYOND 6 MONTHS, HOW DO YOU
EVALUATE NEUROLOGIC SYMPTOMS FOR
CAUSE?
FOR EXAMPLE, IF AN ADOLESCENT
PATIENT DEVELOPS SOME RARE
NEUROLOGIC SYMPTOM OR MAIBL A OR MAYBE A
SEIZURE APPROXIMATELY 6 WEEKS
FOLLOWING A MILD COVID
INFECTION, IT WOULD SEEM
PHYSICIANS ARE MORE LIKELY TO
EVALUATE OTHER SOURCES BEFORE
THEY LOOK AT COVID WHEN IT COMES
TO ANY ASPECT OF TREATMENT.
SO ARE THESE SYMPTOMS THEN
TREATED DIFFERENTLY IF COVID IS
THE CAUSE?
AND I GUESS UNDERNEATH IT ALL IS
HOW DO YOU DETERMINE WHETHER
COVID IS THE CAUSE OR RELATED TO
THE OCCURRENCE OF NEUROLOGICAL
SYMPTOMS DURING THIS PERIOD WHEN
THE BIOMARKERS HAVE DIMINISHING
BUT VARIOUS SYMPTOMS NOW APPEAR?
>> I'LL TAKE A STAB AT IT AND
THEN WALTER IF YOU WANT TO ADD
ON.
FIRST YOU HAVE TO DISTINGUISH
BETWEEN STATISTICAL CLINIC
EFFECTS AND THE BIOMARKERS.
SO LET'S TAKE THE CASE THAT YOU
SUGGEST, OR REALLY ANY CASE OF A
SYMPTOM OR A SYNDROME THAT
HAPPENS AFTER COVID.
YOU HAVE TO LOOK AT THE BASE
RATE OF THAT SYMPTOM IN A
SIMILAR CONTROL POPULATION.
THAT'S WHY WE NEED A VERY LARGE
STUDY TO UNDERSTAND WHAT ARE THE
CONSEQUENCES OF COVID
THEREAFTER?
NOW EVEN IF YOU ESTABLISH THAT
THERE'S A HIGHER RATE OF
SEIZURES IN THE SIX MONTHS AFTER
COVID, IT'S QUITE POSSIBLE THAT
IT'S NOT DUE TO COVID, IT'S DUE
TO SOMETHING ELSE, SO THEN YOU
NEED TO DO YOUR TYPICAL
DIFFERENTIAL DIAGNOSIS AS A
CLINICIAN, BUT NONETHELESS, IF
YOU WANT TO KNOW COULD SOMETHING
LIKELY BE CONSEQUENT TO COVID,
WE HAVE TO COMPARE THE RATES OF
THOSE EFFECTS IN AFTERMATH OF
COVID COMPARED TO CONTROL GROUP.
I THINK FOR A LOT OF THESE
THINGS, IT'S GOING TO BE
CHALLENGING ESPECIALLY WITH LOW
BASE RATE CONDITIONS.
AND THE QUESTION IS HOW DO YOU
TREAT IT?
THERE, WALTER -- AS WALTER SAID,
RIGHT NOW, ALL THAT WE CAN DO IS
TREAT THE SYMPTOMS, SO IN THE
CASE OF SEIZURE, YOU'RE GOING TO
TREAT THEM WITH ANTIEPILEPTIC IF
IT'S INDICATED.
AND THAT'S WHAT YOU'RE GOING TO
DO.
BUT IF WE CAN UNDERSTAND THE
DIFFERENCE IN CAUSALITY, THEN WE
WOULD TRY TO TARGET THE
MECHANISM UNDERLYING SEIZURES IN
THE AFTERMATH OF COVID WHICH
MIGHT BE DIFFERENT THAN THE
MECHANISM OF OTHER FORMS OF
EPILEPTIC ACTIVITY IN
ADOLESCENT.
FINALLY WITH REGARD TO THE
BIOMARKERS, I THINK IT'S REALLY
IMPORTANT TO SAY, NUMBER ONE, WE
DO NOT KNOW WHETHER THE
BIOMARKERS WILL BE GONE AFTER
6 MONTHS AT THIS POINT.
WE'RE TALKING ABOUT VERY SMALL
STUDY, WEAR WE'RE TALKING ABOUT
NEUROIMAGING STUDIES WHICH ARE
NOTORIOUSLY CHALLENGING, AND
WE'RE TALKING ABOUT BIOMARKER
STUDIES THAT DON'T LOOK AT TREUL
MECHANISM AT THIS POINT.
SO I THINK IT'S TOO EARLY TO SAY
WHETHER THE BIOMARKERS ARE,
QUOTE-UNQUOTE, DIMINISHING BY
SIX MONTHS, AND THEN IN TERMS OF
THE EVIDENCE SUGGESTING THAT
LONG COVID SYSTEMS CAN PERSIST
PAST 6 MONTHS, AGAIN, WALTER
SHOWED YOU THE DATA.
THEY'RE NOT TERRIBLY CONVINCING.
WE'RE TALKING ABOUT RELATIVELY
LOW RATES OF SYMPTOMS PERSISTING
OUT BEYOND SIX MONTHS IF YOU
LOOK IN CAREFULLY CONTROLLED
STUDIES.
SO ANOTHER REASON WHY WE NEED
THOSE LARGE STUDIES.
SO I THINK THE ANSWER TO ALL
THESE QUESTIONS IS, RIGHT NOW,
YOU TREAT SYMPTOMATICALLY, YOU
TRY TO DO A DIFFERENTIAL
DIAGNOSIS AND IN THE FUTURE,
HOPEFULLY WE'LL UNDERSTAND
SOMETHING ABOUT THE TRUE
PREVALENCE OF THESE CONSEQUENCES
AND OF THEIR MECHANISM.
>> WALTER, DO YOU WANT TO
COMMENT ABOUT THAT?
>> WELL, I THINK IT'S A REALLY
GOOD QUESTION.
I THINK THAT RIGHT NOW, WE'RE
KIND OF LOOKING UNDER THE LAMP
POST SO WE HAVE A LOT OF DATA
FROM ACUTE INFECTION STANDPOINT.
AND SO WHAT WE KNOW IS, WHAT WE
USED TO SAY IN INTENSIVE CARE
RESEARCH, IT ALL BOILS DOWN TO
SICK PEOPLE DON'T DO WELL.
SO I THINK WHAT WE SEE HERE IS
THAT THE WORSE YOUR INFECTION
WAS, IT INCREASES YOUR CHANCES
OF DEVELOPING PERSISTENT TROUBLE
LATER ON, AND THEN THERE ARE
PATTERNS THAT OCCUR IN THE ACUTE
STAGE THAT AGAIN PREDICT
POTENTIALLY -- THESE ARE SMALL
STUDIES NOW, BUT THAT THEY
PREDICT THAT YOU'RE GOING TO
HAVE TROUBLE WITH POST-ACUTE
SEQUELAE OF COVID.
NOW THAT DOESN'T MEAN THAT THOSE
MARKERS ARE ACTUALLY THE CAUSE 6 MONTHS LA TER.
THEY'RE JUST A PATTERN THAT WAS
IDENTIFIED ACUTELY, AND THERE'S
SOME OTHER DRIVER AT THE 6 MONTH
PERIOD.
SO THE OTHER QUESTION IS WHAT
ELSE IS IN THAT PATTERN THAT
DOESN'T GO AWAY, AND THAT'S
GOING TO TAKE SOME TIME.
SO EXAMPLE OF THE SEIZURES, SO
EVERYBODY GETS AUTO ANTIBODIES
AFTER COVID, AND THAT PROBABLY
IS NOT GOING TO BE ASSOCIATED
WITH SEIZURES, BULL IF ONE OF
THOSE AUTO ANTIBODIES IS AN MMDA
RECEPTOR, YOU'RE GOING TO HAVE
SEIZURES AND YOU'RE GOING TO
HAVE PSYCHOSIS.
AND THAT'S BEEN SEEN ALREADY IN
COVID.
SO I WOULD SAY WHAT WE'RE SEEING
NOW IS KIND OF LIKE THE CLOUD
AND YOU HAVE TO KIND OF GET INTO
THE CLOUD AND SEE THE DROPLETS
OF THE MOISTURE, AND GET MORE
DRILLED DOWN INTO WHAT THE
CAUSATION IS.
SO I WOULDN'T THROW IT OUT, BUT
I AGREE WITH THE QUESTION, IT'S
NOT SOLVING OUR PROBLEM.
IT JUST STARTING TO OPEN THE
DOOR TO RESEARCH.
>> THERE'S A COUPLE QUESTIONS
REGARDING WHEN INDIVIDUALS ARE
DIAGNOSED WITH ONE MANIFESTATION
OR ANOTHER OF CHRONIC COVID, ARE
THEY INFECTIOUS?
ARE MANY OF THEM INFECTIOUS?
ARE THEY CARRYING THE VIRUS?
>> WE DON'T THINK THEY'RE
INFECTIOUS, NO.
>> ARE THEY CARRYING THE VIRUS?
>> THE VIRUS COULD BE PRESENT.
THERE MIGHT BE VIRUS PRESENT,
YOU KNOW, IN SOME CELLS IN THE
BODY, THERE'S NO EVIDENCE THAT
PEOPLE ARE INFECTIOUS.
MOST OF THE INFECTION IS COMING
OUT OF RESPIRATORY DROPLETS, AND
THESE PEOPLE DO NOT HAVE ANY
VIRUS IN THEIR RESPIRATORY TRACT
THAT YOU CAN MEASURE COMING OUT.
SO THEY'RE NOT INFECTIOUS.
>> ANOTHER GROUP OF QUESTIONS
CONCERNED WHETHER THE TYPE OF
SYMPTOMATOLOGY ASSOCIATED WITH
CHRONIC COVID HAS BEEN OBSERVED
WITH OTHER CORONA VIRAL
INFECTIONS AND OTHERS HAVE
POINTED OUT THAT THOSE ARE VERY
SIMILAR TO SOME OF THE SYMPTOMS
OF INFECTIOUS MONONUCLEOSIS, AND
ALSO INFLUENZA.
DO YOU WANT TO DISSECT OUT SOME
OF THOSE DIFFERENCES AS TO WHAT
WE KNOW AND DON'T KNOW?
COULD THEY ALL BE PART OF SOME
COMMON UNDERLYING MECHANISM OR
WOULD YOU JUST COMMENT ABOUT
THIS DILEMMA?
>> FROM A MENTAL ILLNESS
PERSPECTIVE, I SORT OF
TELEGRAPHED THAT IN MY
PRESENTATION, RIGHT?
I MEAN, YES, WE SEE INCREASED
RATES OF ANXIETY AND DEPRESSION
AND PSYCHOSIS AFTER
HOSPITALIZATION FOR COVID, BUT
WE SEE THAT ALSO AFTER
HOSPITALIZATION FOR OTHER
RESPIRATORY TRACT INFECTIONS,
AND THERE COULD BE BIOLOGICAL
CAUSES RELATED TO THE
CORONAVIRUS, BUT THERE ALSO ARE
CONTRIBUTORS HAVING TO DO WITH
ICU STAYS WHICH CAUSE -- CAN
CAUSE LONG LASTING MENTAL HEALTH
COMPLICATIONS AS WELL.
SO I THINK A LOT OF THAT IS FROM
MY PERSPECTIVE, THE MENTAL
HEALTH AREA, IS UNKNOWN AT THIS
POINT.
I THINK THE FACT THAT SARS-COV-2
IS NEW, THAT COVID-19 IS A NEW
ILLNESS, RAISES THE POSSIBILITY
THAT IT'S SPECIAL, AND WE NEED
STUDIES TO KNOW HOW SPECIAL AND
HOW DIFFERENT IT REALLY IS FROM
OTHER CORONAVIRUSs.
WALTER, IN TERMS OF LOOKING AT
THE PRESENCE -- THE POTENTIAL
PRESENCE OF THE VIRUS IN THE
BRAIN OR ITS EFFECTS ON BRAIN
CELLS, WHETHER THERE'S DATA FROM
OTHER CORONAVIRUSs?
>> WE DID HAVE THIS INITIAL SARS
EPIDEMIC AND THEN MERS, AND
THOSE WERE SEVERE RESPIRATORY
VIRAL INFECTIONS, AND THOSE
PERSONS WERE AFFECTED FOR MANY
MONTHS OR YEARS.
SIMILAR SYMPTOMS THAT WE HAVE
NOW, SARS COV-2.
SO WE WERE SURPRISED BECAUSE THE
PEOPLE WITH SARS AND MERS HAD --
THEY WERE VERY ILL, IN THE
EXPECTATION, ANYBODY THAT GOES
IN, DEVELOPS ARDS AND IS ON A
RESPIRATOR, THEY'RE LOOKING AT
MANY MONTHS TO YEARS OF RECOVERY
AFTER THAT.
SO THE EXPECTATION WAS THAT,
YEAH, THAT WAS PART AND PARCEL
OF GETTING SO SICK.
THE BIG SURPRISE WITH COVID-19
IS THAT WE'RE SEEING THOSE
SYMPTOMS IN PEOPLE WHO WERE
NEVER IN THE HOSPITAL AND SOME
PEOPLE VERY MILD, SOME PEOPLE
HAVEN'T HAD ANY SYMPTOMS.
SO INITIALLY IN THE HOSPITALS,
THERE WAS A RUSH INTO INTENSIVE
CARE UNITS, THE HOSPITALS THEN
STARTED TO SET UP THESE POST-ICU
CLINICS FOR PEOPLE COMING OUT OF
THE ICUs, AND THE SURPRISE WAS
THAT THEY WERE NEVER EVEN IN THE
HOSPITAL.
SO THAT'S KIND OF THE UNUSUAL
FEATURE TO THIS VIRUS, WHICH I
THINK DR. FAUCI MENTIONED, HE'S
NEVER SEEN A VIRUS WITH THIS
WIDE SPECTRUM OF PHENOTYPES FROM
PEOPLE WHO ARE COMPLETELY NORMAL
TO PEOPLE ON DEATH'S DOORSTEP.
AND THAT'S SEEMINGLY ALSO
OCCURRING WITH THE PERSISTENCE
OF THE SYMPTOMS.
ALTHOUGH AS WE SHOWED MANY
TIMES -- [INAUDIBLE] LONG TERM.
NOW, THE OTHER VIRUS WHICH IS --
IS EPSTEIN-BARR VIRUS, SO
EVERYBODY GETS EPSTEIN-BARR
VIRUS PRETTY MUCH, EVERYBODY
GETS IT, MOST PEOPLE DON'T GET
SICK, SOME PEOPLE GET INFECTIOUS
MONONUCLEOSIS, AND REMEMBER
THOSE FOLKS, YOUNG KIDS, THEY'LL
MISS A WHOLE SEMESTER OF SCHOOL
BECAUSE OF THEIR FATIGUE AND
THEY JUST CAN'T GET BACK TO
STUDYING LIKE THEY DID BEFORE,
MOVING AROUND, AND THEN THEY
START GETTING BETTER, MAYBE EVEN
GO OUT A YEAR FOR SOME PEOPLE.
AND WE HAVE STUDIES LOOKING AT
THOSE FOLKS, SOME OF THOSE
DEVELOP CHRONIC FATIGUE
SYNDROME.
BUT THAT IS THE CLOSEST
PRECEDENT THAT I KNOW OF TO
COVID-19, WHERE IT STANDS
COMPLETELY ASYMPTOMATIC TO
INFECTIOUS PROBLEM THAT LASTS
WITH PERSISTENT SYMPTOMS.
YOU'RE NOT INFECTIOUS AFTER A
WHILE BUT YOU HAVE PERSISTENT
SYMPTOMS THAT CAN GO OUT MANY
MONTHS, AND THEN A SMALL
PROPORTION OF THOSE PEOPLE GO ON
TO MORE CHRONIC TROUBLE.
SO THAT WOULD BE THE PRECEDENT.
THE EPSTEIN-BARR VIRUS IS
PERSISTENT IN YOUR BODY AND YOUR
BRAIN, YOU NEVER ACTUALLY GET
RID OF IT.
>> IS THERE A RELATIONSHIP
BETWEEN CHRONIC COVID AND
VACCINATION STATUS?
>> AS I MENTIONED, IF YOU ARE
VACCINATED, THE CHANCE OF
GETTING SYMPTOMS THAT ARE
PERSISTENT IS MUCH LESS.
THE EVIDENCE THAT THE VACCINE
ACTUALLY MAKES YOU BETTER IF YOU
ALREADY HAD, SAY, LONG COVID,
THAT'S NOT CLEAR.
IT DOESN'T LOOK LIKE A BIG
EFFECT SIZE.
>> THERE HAVE BEEN SEVERAL
QUESTIONS OF PEOPLE WHO HAVE
ASKED ABOUT THE VACCINE, AND
ASKING DOES IT CAUSE PERIPHERAL
NEUROPATHY BY TARGETING THE
SPIKE PROTEIN ON ENDOTHELIAL
CELLS AND DOES IT DAMAGE THE
VASCULATURE?
SO DO YOU WANT TO COMMENT ABOUT
ANY POSSIBLE SUCH TOXICITY OF
THE VACCINES?
>> I THINK THERE HAVE BEEN A FEW
CASES OF GILLIAN BARRE FOLLOWING
THE VACCINE, BUT VERY, VERY,
VERY RARE, AND I DON'T THINK ANY
MORE THAN FOR OTHER VACCINES.
OTHERWISE I DON'T THINK THERE'S
ANY EVIDENCE OF PERIPHERAL NERVE
DAMAGE.
I'M NOT AWARE OF ANY EVIDENCE OF
VESSEL DAMAGE.
THERE ARE -- THERE'S A LOW RATE
OF I THINK IT'S MYOCARDITIS,
RIGHT, IN YOUNG MEN MOSTLY?
VERY LOW RATE.
BUT THAT -- I DON'T KNOW IF
THAT'S BEEN ASCRIBED TO THE
VASCULATURE VERSUS THE MUSCLE
ITSELF.
>> YEAH, I THINK GILLIAN BARRE,
MYOCARDITIS, I THINK THOSE ARE
AUTOIMMUNE REACTIONS, AND SO
WHEN YOU GET THE VACCINE, THE
WHOLE PURPOSE IS TO DEVELOP THIS
IMMUNE RESPONSE TO THE VIRUS,
BUT SOMETIMES, AND WE DON'T
UNDERSTAND WHY, THAT CAN SPILL
OVER TO AFFECT IMMUNE RESPONSE
AGAINST OTHER ANTIGENS IN YOUR
BODY.
SO GILLIAN BARRE IS THE ONE
THAT'S BEST STUDIED AND IT IS --
IT HAS BEEN ASSOCIATED WITH
MULTIPLE DIFFERENT VACCINES.
THERE'S 1H1N1 FLU VACCINE THAT
HAD INCREASED INCIDENCE A COUPLE
YEARS AGO, AND THE STUDIES
FROM THE U.K., AGAIN, SHOW THAT
IN THE VACCINES THAT WERE
DELIVERED TO A VIRUS, THERE WAS
AN INCREASE IN GILLIAN BARRE DUE
TO THE VACCINE.
AND IN THE U.S., SIMILARLY THE
FDA LAST SUMMER PUT OUT A NOTICE
THAT THEY WERE SEEING INCREASED
GILLIAN BARRE IN THE J & J
VACCINE, WHICH IS -- NOBODY'S
SEEN IT IN THE MRNA VACCINES
YET.
BUT IN THE U.K. STUDY, YOUR RISK
OF GETTING GILLIAN BARRE AFTER
VACCINE IS MUCH LESS, FIVE TIMES
LESS THAN IT IS IF YOU GET
COVID.
SO STILL IF YOU DON'T WANT TO
GET GILLIAN VA RAY, THE BEST GILLIAN BARRE , THE BEST
THING TO DO IS STILL GET
VACCINATED.
THERE HAVE BEEN CASES REPORTED
AFTER THE VACCINE OF ABSOLUTELY
EVERY NEUROLOGIC CONDITION
REPORTED AFTER THE VACCINE, AND
IN NONE OF THEM WITH THE
EXCEPTION OF GILLIAN BARRE, HAS
ANYBODY BEEN ABLE TO SHOW WHAT
JOSH WAS SAYING IN THE FIRST
PLACE, YOU KNOW, THAT IT'S OUT
OF THE ORDINARY FOR WHAT WE
WOULD EXPECT O GIVEN THE
INCIDENCE OF THOSE CONDITIONS.
BUT AT THE NIH, THEY ARE SEEING
PATIENTS WHO ARE THE VACCINE WHO
HAVE SYMPTOMS OF USUALLY PAIN,
AND THEY HAVE FOUND SMALL FIBER
NEUROPATHY, IT'S BEEN WELL
MANAGED BY TREATMENT WITH
STEROIDS OR IVIG, BUT THEY DON'T
KNOW IF IT HAS ANYTHING TO DO
WITH THE VACCINE OR NOT.
CAN'T REALLY TELL.
FOR SURE.
THEY'VE LOOKED TO SEE IF THERE
WAS SOME KIND OF ANTIBODY THAT
CROSS-REACTS WITH THE NERVES AND
THE VIRUS.
BUT THEY HAVEN'T SEEN ANY.
SO IT'S HARD TO KNOW IF IT'S
CAUSAL OR IF IT'S COINCIDENTAL.
THE VIRUS ITSELF --
DEMONSTRATED -- [INAUDIBLE].
>> THERE HAVE BEEN SEVERAL
QUESTIONS AS TO WHETHER THERE
ARE ANY ANIMAL MODELS WITH LONG
COVID.
THE POINT BEING THAT WITHOUT AN
ANIMAL MODEL, IT'S GOING TO BE
THAT MUCH MORE DIFFICULT TO
UNDERSTAND WHAT'S GOING ON AND
TO DEVELOP SOME FORMS OF
THERAPY.
SO ARE THERE ANY ANIMAL MODELS?
AND WHAT'S THE STATUS OF THAT
RESEARCH?
>> I DON'T KNOW OF ANY ANIMAL
MODELS WITH LONG COVID.
SOME -- I DON'T KNOW IF ANY HAVE
STUDIED LONG-TERM EFFECTS.
>> JOSH IS RIGHT.
I SUSPECT THERE ARE PEOPLE WHO
ARE SMART ENOUGH TO DO THAT.
THERE WAS A CALL FOR GRANTS IN
THE RECOVERY INITIATIVE TO
UNDERSTAND THE PATHOBIOLOGY OF
LONG COVID, AND THAT INCLUDED A
CALL FOR ANIMAL STUDIES.
BUT THOSE HAVE COME IN AND WE
GOT A LARGE NUMBER OF
APPLICATIONS, AND HOPEFULLY
WE'LL -- I HAVEN'T SEEN THEM
YET, BUT HOPEFULLY THERE WILL BE
A FEW IN THAT SPACE.
I THINK THAT WOULD BE IMPORTANT.
OF COURSE THESE SYMPTOMS THAT
PATIENTS ARE REPORTING ARE A
LITTLE DIFFICULT TO DO HIGH
THROUGHPUT SCREENING IN ANIMALS.
-- TACHYCARDIA SYNDROME, OR
MUSCLE PAIN, SLEEP TROUBLE.
>> I THINK IF WE GO BY ANALOG TO
MENTAL ILLNESSES, I THINK WE
NEED TO HAVE BIOMARKERS THAT WE
CAN HANG OUR HAT ON IN ORDER TO
BE ABLE TO STUDY IN ANIMALS.
I THINK IT'S GOING TO BE REALLY
CHALLENGING TO DO SOME OF THESE
THINGS IN ANIMAL MODEL, UNTIL
YOU KNOW WHAT TO LOOK FOR.
SO FOR EXAMPLE, IF IT'S BORNE
OUT THAT THE SMALL VESSEL
PATHOLOGY IS PART OF IT, OR IF
THE C FIBER NEUROPATHY IS PART
OF IT, THEN WE CAN STUDY, YOU
KNOW, C FIBER NEUROPATHY IN THE
CONTEXT OF COVID INFECTION IN AN
ANIMAL MODEL.
BUT ABSENT SOME OF THOSE PIE
BIOMARKERS, IT'S REALLY HARD TO
TAKE A SYMPTOM-FOCUSED APPROACH.
GLL I THINK WE TOUCHED ON THIS,
BUT THERE HAVE BEEN SEVERAL
SPECIFIC INQUIRIES AS TO WHETHER
PATIENTS WHO HAVE SOME FORM OF
AUTOIMMUNE DISEASE, NEUROLOGICAL
OR NON-NEUROLOGICAL, AN THEN
BECOME INFECTED WITH THE VIRUS,
DO THINGS GET WORSE IN THEIR
UNDERLYING DISEASE OR ARE THESE
TWO NOW UNRELATED?
DO THEY INTERACT WITH ONE
ANOTHER?
DO WE HAVE EXPERIENCE TO COMMENT
ABOUT THAT?
>> IT'S A REALLY GOOD QUESTION
AND I THINK A LOT OF PEOPLE
WORRY ABOUT THIS.
I'VE BEEN FOLLOWING IT FROM THE
NEURO SIDE OF THINGS AND
MULTIPLE SCLEROSIS IS PROBABLY
THE MOST COMMON ONE.
THERE'S DEFINITELY INFORMATION
ON THE BRAIN AND MS AND COVID.
IT'S NOT BEEN -- THE GOOD NEWS
IS THAT WE HAVEN'T SEEN
SOMETHING DRAMATIC.
SOME SUBTLE CHANGES COULD BE
THERE THAT WE HAVEN'T SEEN YET,
BUT NOT SEEING DRAMATIC CHANGES
THERE.
I WOULD SAY, MAYBE DAN KASTNER
COULD TALK ABOUT THIS, BUT THERE
ARE REPORTS THAT -- HOPE I GET
THIS RIGHT -- PEOPLE WHO HAVE
AUTO ANTIBODIES, EVEN IF THEY'RE
ASYMPTOMATIC, THEY HAVE A BIG
CHANGE WHEN THEY GET COVID AND
DEVELOP CONDITIONS THAT ARE NEW,
LIKE LUPUS OR RHEUMATOID
ARTHRITIS.
CERTAINLY DIABETES IS
POTENTIALLY A DIFFERENT STORY,
THAT THERE IS PRETTY -- MOST OF
THE STUDIES ARE SHOWING THAT
PEOPLE -- THAT THERE'S MORE
DIABETES AFTER COVID.
NOT SURE IF THAT'S IMMUNOLOGIC
OR NOT.
BECAUSE IN COVID, THERE'S
INVOLVEMENT OF THE BLOOD VESSELS
THAT PERFUSE THE PANCREAS AND
THERE'S EVIDENCE OF DAMAGE TO
THE PANCREAS.
THERE COULD BE VASCULAR DAMAGE
THAT GETS YOU TO DIABETES.
IT ALSO COMPLICATED BY THE FACT
THAT AS WE SHOWED IN THE
BEGINNING, PEOPLE WITH DIABETES
HAVE MORE SEVERE COVID AND THEY
HAVE MORE TROUBLE WITH
POST-ACUTE SCWEA LAY SCE SCWI LAY.
SEQUELAE.
YOU COULD HAVE PEOPLE WITH
PRE-CLINICAL DIABETES OR
UNDIAGNOSED DIABETES, THEY'RE
GOING TO GET WORSE COVID THAN
OTHERS AND SO IT'S NOT COVID
THAT'S CAUSING THE PROBLEM BUT
IT'S THEIR DIABETES THAT GOT
THEM THE WORSE COVID.
THAT'S THE -- THE AUTOIMMUNE
SIDE.
>> WALTER, THANK YOU FOR RAISING
THAT QUESTION AND ACTUALLY I
DON'T KNOW OF ANY LARGE ENOUGH
STUDIES LOOKING AT THIS.
CERTAINLY IT MAKES THEORETICAL
SENSE ANYWAY TO THINK THAT IF
SOMEBODY HAS ALREADY AT LEAST
SOME EVIDENCE FOR AUTO
ANTIBODIES OR AN AUTOIMMUNE
PROCESS THAT SIMPLY HAVING
THE -- WHATEVER IT MIGHT BE
CALLED -- ADJUVANT EFFECT OF
VIRAL INFECTION COULD DO THAT,
BUT I DON'T KNOW THAT THERE'S
ENOUGH DATA REALLY TO MAKE THAT
CASE AT THIS POINT.
>> EARLIER IN THE COURSE, WALTER
HOLLAND PRESENTED A FASCINATING
STUDIES ON ANTICYTOKINE
PARTICULARLY INTERFERON
ANTIBODIES AS BEING SOMEWHAT
NEGLECTED PATHOGENIC MECHANISMS.
HERE IN THESE STUDIES INCLUDING
THE ONE THAT WALTER REFERRED TO
THAT WAS IN "CELL" AMONGST THOSE
AUTO ANTIBODIES ARE ANTIBODIES
AGAINST SOME OF THE CYTOKINES.
IT'S NOT UNIVERSAL, IT'S NOT
DRAMATICALLY SEPARATING ONE
GROUP FROM THE OTHER.
BUT YOU SORT OF WONDER WHETHER
THERE IS SOME COMMONALITY
INVOLVED IN THOSE AUTO
ANTIBODIES TO PRODUCE THE
DISEASE.
I GUESS THAT'S AN AREA OF
INTENSE RESEARCH NOW, NO?
>> YEAH, NO, I THINK THAT'S VERY
TRUE.
WHAT WE'RE HOPING IS TO COLLECT
BIOSAMPLE FROM TENS OF THANK THANK YOU
THOUSANDS OF PEOPLE AND HAVE
THEM STORED SO THESE KIND OF
THINGS CAN BE EXPLORED AND
HOPEFULLY GIVE US ANSWERS.
MAYBE IF WE DON'T GET IT RIGHT
AWAY, SOME SMART PERSON TWO OR
THREE YEARS FROM NOW WILL GO
BACK AND FIGURE IT OUT.
BUT I THINK PIECING APART WHAT
ARE THE -- WHAT AUTO ANTIBODIES
ARE REALLY DRIVING THE TROUBLE,
WHAT IMMUNE CHANGES ARE REALLY
DRIVING THE TROUBLE ARE -- I
THINK THEY'RE TOUGH QUESTIONS
BECAUSE THERE'S SO MANY -- COVID
IS
HAS SUCH A DRAMATIC EFFECT,
TRYING TO UNDERSTAND WHAT'S
CAUSATIVE GIVEN EVERYTHING
THAT'S GOING ON IS GOING TO BE
DIFFICULT.
THAT'S MAYBE WHERE ANIMAL
STUDIES WILL BE NECESSARY TO DO
THOSE KIND OF INTERVENTIONS.
>> IT SOUNDS LIKE ANOTHER
FRAMINGHAM-TYPE STUDY.
IS THAT WHAT YOU THINK MIGHT BE
USEFUL?
>> I THINK RECOVER IS KIND OF
LIKE A FRAMINGHAM.
THAT'S HOW RECOVER WAS PUT
TOGETHER.
KIND LIKE A FRAMINGHAM STUDY.
3,000 PEOPLE, 50 MILLION
ELECTRONIC HEALTH RECORDS.
SO IT'S A REAL BATTLESHIP TYPE
OF APPROACH TO THE PROBLEM.
BUT THAT'S NOT GOING TO GET YOU
THE KILLER EXPERIMENT THAT SAYS,
YOU KNOW, OH, IT'S THAT AUTO
ANTIBODY THAT'S CAUSING THE
TROUBLE.
IT WILL GET YOU ASSOCIATIONS AND
THEN PEOPLE WILL HAVE TO LOOK AT
THOSE ASSOCIATIONS AND THEN PIG
APART THE PATHWAYS THEY THINK
ARE REALLY DRIVING THE SYMPTOMS
OR PATHOLOGY.
YOU DON'T KNOW WHERE TO START.
YOU HAVE NO CLUE WHAT TO BEGIN
WITH.
BECAUSE I THINK THEY GIVE YOU
[INAUDIBLE] TO DRILL DOWN ON.
>> I THINK IN THE PREVIOUS GREAT
PANDEMICS AND EPIDEMICS
INCLUDING THE
HUNDRED-YEAR-OLD -- WE DIDN'T
KNOW ENOUGH TO SAVE NATISH EUS ANY NATISH ANY TISSUES
OR CELLS.
EVEN IN THE FRAMINGHAM STUDY,
THERE WERE SOME TISSUES THAT
WERE SAVED.
NOBODY WAS INTO DNA AT THAT
POINT WHEN THAT STUDY WAS
STARTED.
SO IF WE'RE GOING TO SAVE
THOUSANDS OF SAMPLES TODAY
BECAUSE WE'RE LOOKING AT
TOMORROW'S SCIENCE AND COMING UP
WITH WHAT MAY BE THE ANSWERS AT
THE MOMENT WE'RE TALKING ABOUT
THE AUTO ANTIBODY, BUT WE DON'T
KNOW WHAT PARTICULARLY THE
SYSTEMS BIOLOGISTS ARE GOING TO
PULL OUT.
ARE THERE PLANS TO ACTUALLY
STORE WHAT WOULD BE SUITABLE
SAMPLES FOR ALMOST ANYTHING THAT
WE CAN IMAGINE IS COMING DOWN
THE PIKE FROM THE STANDPOINT OF
SCIENCE?
>> YEAH, WELL, IT ALL DEPENDS ON
WHAT THE PATIENTS WILL GIVE US.
SO EVERYTHING DEPENDS ON WHAT
PEOPLE WILL DO.
SO I WANT EVERYBODY TO HAVE A --
SPINAL FLUID BUT THAT DIDN'T GO
OVER WELL.
BUT I THINK THEY SHOULD HAVE IT,
BUT IT'S JUST NOT FEASIBLE.
BUT YEAH, THAT'S THE IDEA, IS TO
RECOVER THOSE THREE TIERS OF
INVESTIGATION, AND TIER 1 IS
PRETTY BENIGN BUT IT'S
BURDENSOME.
HERE TOO IS ALSO BURDENSOME
BECAUSE IT'S DRIVEN BY THE
SYMPTOMS, WHAT WE FOUND IS WE
SHOULD HAVE ANTICIPATED THIS,
THAT MOST OF THE PEOPLE HAVE
SEVEN SYMPTOMS SO THEY TRIGGER
THREE OR FOUR DIFFERENT TIER TWO
STUDIES, AND THAT'S WAY TOO
MUCH.
SO WE HAVE TO FIGURE OUT --
ACTUALLY RIGHT NOW WE'RE
FIGURING OUT HOW TO DECREASE THE
BURDEN ON THE PATIENTS, AND THEN
THE TIER THREE STUDIES ARE THE
REALLY DEEP MECHANISTIC ONES.
AND THE IDEA IS, YES, EVERYTHING
WILL BE SAVED, EVERYTHING WE CAN
GET AHOLD OF WILL BE SAVED, AND
I THINK THE BEAUTY IS THAT
WHAT'S HAPPENED WITH THE TOOLS
IN SCIENCE IS THAT SOMETIMES YOU
DON'T NEED TO KNOW WHAT THE TOOL
IS GOING TO BE TO SAVE THE
TISSUE FOR.
I GUESS THE BEST EXAMPLE WE HAVE
FROM THE BRAIN INITIATIVE IS
THAT PEOPLE INVESTIGATING THESE
DIFFERENT CELL TYPES AND DOING
TRANSCRIPTOMICS OUT OF THE
CYTOPLASM AND GETTING PATTERNS
OF RNA THAT -- THE CELL, THEN
SOMEBODY FIGURED OUT YOU CAN GET
THE SAME THING FROM THE NUCLEUS,
AND THE GOOD NEWS ABOUT THE
NUCLEUS IS THAT THE WAY YOU DO
THAT IS YOU PUT THE BRAIN IN A
BLENDER AND AS SOMEBODY SAID,
ANY EXPERIMENT THAT STARTS WHEN
YOU PUT THE BRAIN IN A BLENDER
IS GOING TO BE VERY ROBUST.
SO IF YOU GET STUFF OUT OF THE
FLEW CLEE US AND YOU GET THAT
OUT OF AUTOPSY -- THE NUCLEUS IS
PRETTY HARDY.
SO YOU NEVER KNOW, BUT YEAH,
THROWING THINGS AWAY, IT ALWAYS
COMES BACK TO BITE YOU.
>> JUST LIKE THE LIVER.
YOU CAN'T PUT IT IN A BLENDER.
SO WE HAVE A SERIES OF QUESTIONS
ABOUT FREQUENCIES OF DISEASES,
AND MAYBE BOTH OF YOU WOULD
RESPOND.
FOR EXAMPLE, DOES COVID CAUSE OR
CHANGE THE INCIDENCE OF
MIGRAINE?
WHY IS ADHD A GREATER RISK FOR
COVID?
ARE PEOPLE WHO ARE CHRONICALLY
DISABLED, THEY SEEM TO BE MORE
RESILIENT IN TERMS OF BEING
INFECTED FROM THE DATA THAT WAS
SHOWN.
SO MAYBE, JOSH, DO YOU WANT TO
START WITH THOSE?
>> WELL, LET ME JUST -- THE ADHD
IS THE EASY ONE.
WE DON'T KNOW.
IT'S EASIER TO EXPLAIN -- WELL,
ANY SERIOUS MENTAL ILLNESS,
THOUGH, IS GOING TO IMPACT YOUR
ABILITY TO ADHERE TO MITIGATION
MEASURES.
SO THAT'S ONE POSSIBILITY.
SO IF YOU HAVE SCHIZOPHRENIA OR
DEPRESSION OR ADHD, YOU MAY BE,
FOR DIFFERENT REASONS, LESS
LIKELY TO BE ABLE TO WEAR A MASK
PROPERLY, LESS LIKELY TO
REMEMBER SOCIAL DISTANCING,
MAYBE YOU'RE MUCH MORE LIKELY TO
BE EMPLOYED IN A JOB THAT
DOESN'T PERMIT YOU TO WORK FROM
HOME.
SO YOU ARE MORE LIKELY TO BE
HOMELESS.
SO FOR LOTS OF DIFFERENT
REASONS, YOU MIGHT BE EXPOSED
MORE TO COVID.
THAT DOESN'T EXPLAIN THE
MORTALITY DIFFERENCES, THE
MORTALITY DIFFERENCES, THOUGH,
MAY HAVE SOMETHING TO DO WITH
YOUR LOWER ABILITY TO SEEK CARE
OR TO GET CARE WHEN YOU SEEK IT.
SO THERE'S BOTH SYSTEMIC REASONS
WHY INDIVIDUALS WITH SERIOUS
MENTAL ILLNESS HAVE A HARDER
TIME ACCESSING MEDICAL CARE,
THERE'S ALSO EVIDENCE OF
DISCRIMINATION AGAINST
INDIVIDUALS WITH SERIOUS MENTAL
ILLNESS WHEN THEY BRING UP
MEDICAL COMPLAINTS, THEY ARE
LESS OFTEN TREATED IN AN
EVIDENCE-BASED OR APPROPRIATE
MANNER.
SO FOR ALL THOSE REASONS,
REGARDLESS OF DIAGNOSIS,
INDIVIDUALS WITH A SERIOUS
MENTAL ILLNESS ARE MORE LIKELY
TO EXPERIENCE NEGATIVE OUTCOMES
OF PHYSICAL ILLNESSES.
MAYBE THAT EX-PLAWNS THE EXPLAINS THE
DIFFERENCE OF CONTRACTING COVID
AND DEATH BY COVID.
WE DON'T REALLY KNOW BUT THAT'S
ONE POSSIBILITY.
THE OTHER QUESTION HAD TO DO
WITH PEOPLE WITH DISABILITIES.
I THINK -- I SAW THAT QUESTION
IN THE CHAT EARLIER.
I THINK THE QUESTION WAS, IN
TERMS OF THE MITIGATION
MEASURES, WHICH HAVE PERHAPS
CONTRIBUTED TO THE RISING RATES
OF ANXIETY AND DEPRESSION, MIGHT
WE LEARN SOMETHING ABOUT
RESILIENCE FROM INDIVIDUALS WITH
DISABILITIES WHO ARE SUBJECT
ALMOST ALL THE TIME TO MANY OF
THESE MITIGATION MEASURES, AT
LEAST IN TERMS OF MORE LIKELY TO
EXPERIENCE SOCIAL ISOLATION,
DIFFICULTY LEAVING THEIR HOME
AND PARTICIPATING IN MANY
ASPECTS OF LIFE.
I DON'T KNOW THE DIRECT ANSWER
THE QUESTION IN TERMS OF WHAT WE
CAN LEARN FROM STUDYING SUCH
INDIVIDUALS.
THERE ARE LOTS OF DIFFERENT
REASONS WHY PEOPLE ARE RESILIENT
TO STRESSES, AND TO SPECIFIC
ASPECTS OF THE PANDEMIC, AND WE
ABSOLUTELY ARE STUDYING THOSE
RESILIENCE FACTORS.
SOME OF THEM, WE ALREADY KNEW,
THEY WERE REFLECTED IN THE
EARLIER POINTS OF MY
PRESENTATION.
MANY HAVE TO DO WITH YOUR
ABILITY TO SOCIALLY CONNECT AND
THAT CAN BE DOB EVEN IF DONE EVEN IF YOU ARE
SHUT IN THE HOME.
OTHER RESILIENCE FACTORS INCLUDE
A STRONG
STRONG FAMILY CONNECTIONS,
INCLUDE HAVING BEEN EXPOSED TO
HARDSHIPS IN THE PAST ARCHED
RESPONDING TO THEM AND DEALING
WITH THEM WITH SELF-EFFICACIES,
THEY'VE LEARNED THEY HAVE
SELF-EFFICACY TO COMBAT
CHALLENGES WHEN THEY'RE
CONFRONTED WITH IT.
SO LOTS OF DIFFERENT THINGS THAT
WE CAN LEARN FROM VARIOUS GROUPS
ABOUT RESILIENCE AND WE ARE
DOING THAT IN THE CONTEXT OF THE
PANDEMIC.
THERE WAS A THIRD QUESTION,
MIGRAINES.
I DON'T KNOW ABOUT THAT.
MAYBE WALTER KNOWS ABOUT
MIGRAINES.
>> DO YOU WANT TO COMMENT ON
MIGRAINE?
>> RIGHT.
SO HEADACHE IS ONE OF THE PRETTY
COMMON SYMPTOMS OF PEOPLE WHO
SUFFER FROM LONG COVID, AND
THOSE HEADACHES HAVE -- THEY ARE
MIGRAINOUS IN THEIR
CHARACTERISTICS.
PEOPLE WHO HAVE MIGRAINE TEND TO
HAVE WORSE HEADACHES, WORSENING
OF HEADACHES AFTER COVID, AND SO
I THINK THE ANSWER IS YES, THAT
COVID IN PEOPLE WITH PERSISTENT
SYMPTOMS OF COVID ARE HAVING
MIGRAINE.
THEY GO AWAY TWO OR THREE MONTHS
AFTER THE INFECTION IN MANY
PEOPLE.
MIGRAINE IS SO COMMON, IT'S HARD
TO KNOW IF IT'S WORSENING
PREDISPOSITION VERSUS TRIGGERING
MIGRAINE IN SOMEBODY WHO HAD
NEVER HAD A MIGRAINE.
>> THERE'S AN INTERESTING
QUESTION OF THE ELECTRONIC
HEALTH RECORD.
YOU MENTIONED IN YOUR SLIDE
SOMETHING LIKE 50 MILLION --
ACCESS TO 50 MILLION ELECTRONIC
HEALTH RECORDS.
SO THE QUESTION IS, ARE THOSE IN
THE COUNTRY WHO HAVE GROSSLY
INADEQUATE HEALTHCARE AND
AVAILABILITY OF PUBLIC HEALTH
FACILITIES AND SO FORTH, SO NOW
WE'RE TALKING ABOUT TRULY
UNDERPRIVILEGED, SOME
MINORITIES, UNEMPLOYED, ALL OF
THAT.
ARE THEY INCLUDED IN THE
ELECTRONIC HEALTH RECORDS THAT
ARE IS STUDIED?
AND ARE SOME OF THE DIFFERENCES
THAT MAY BE OBSERVED IN THE
UNITED STATES AND U.K. OR
WESTERN EUROPE OR AUSTRALIA, DUE
TO THE FACT THAT IN THOSE
COUNTRIES, EVERYBODY IS INCLUDED
IN AN ELECTRONIC HEALTH RECORD.
IS THIS AN ISSUE IN ANALYZING
THE RESULTS?
WHAT DO YOU THINK ABOUT THAT?
>> I'M SURE EVERY TOOL THAT YOU
GET TO ASSESS HEALTH HAS ITS
LIMITATIONS AND ITS STRENGTHS.
THE ELECTRONIC HEALTH SYSTEM
RECORD THAT WE ARE WORKING WITH
IS -- ONE IS NC3 WHICH WAS SET
UP BY NCATS AS A COVID
SURVEILLANCE SYSTEM.
NOW WAS THAT WAS SET UP PURPOSEFULLY TO
GET A DIVERSE POPULATION OF
PEOPLE.
AND THE OTHER ONE WE'RE WORKING
WITH IS THE PATIENT-CENTERED OUT
COME RESEARCH INSTITUTE FOR THAT
MEDICAL RECORDS DATABASE, WHICH
AGAIN I THINK IS PRETTY -- IS
LARGE NUMBERS AND HAS PEOPLE
FROM DIVERSE BACKGROUNDS.
NOW THAT BEING SAID, THAT'S
ELECTRONIC HEALTH RECORDS, SO
THEY MIGHT BE THE BEST YOU CAN
DO, BUT STILL THE POINT REMAINS
THAT PEOPLE WERE LOW -- OF LOW
SOCIOECONOMIC STATUS ARE NOT
GETTING THEIR SYMPTOMS INTO THE
ELECTRONIC HEALTH RECORDS PLUS
THEY'RE NOT GETTING GOOD CARE
AND THEY'RE NOT SEEING DOCTORS.
SO WE DON'T HAVE DATA ON VAST
DEMOGRAPHICS.
THEY WERE SET UP PARTICULARLY
NOT TO BE BIASED.
BUT I COULD SAY FROM TALKING TO
THE DOCTORS WHO TAKE CARE OF
PEOPLE IN THE CLINICS, THE
POST-ACUTE SEQUELAE OF COVID
CLINICS, THEY ARE NOT DIVERSE.
IT'S SOMEBODY WHO HAS THE
WHEREWITHAL AND THE MEANS TO
KIND OF BREAK INTO THE
SUBSPECIALTY CLINICS.
MOST OF THEM NOW ARE SO FULL
THAT THEY'RE BOOKED FOR MONTHS
IN ADVANCE, AND SO THE BAR TO
GET THERE, I THINK PUTS PEOPLE
OF LOW SOCIOECONOMIC STATUS AT A
REAL DISADVANTAGE.
SO WE DO HAVE A PROBLEM.
I THINK ON THE RESEARCH SIDE OF
THINGS, WE'RE TRYING TO TAKE
CARE OF IT.
ON THE HEALTHCARE SIDE OF
THINGS, IT'S A REAL PROBLEM.
NOW I KNOW AT HHS, THE PEOPLE
WHO RUN THE FEDERAL -- THE
COMMUNITY HEALTH CLINICS ARE
TRYING TO FOCUS ON PROVIDING
CARE.
I SUSPECT THAT PEOPLE WHO DON'T
FREQUENT PHYSICIANS DON'T GET
ANY TREATMENT AND THEIR SYMPTOMS
ARE NEVER CODED ANYWHERE.
I THINK THERE'S PROBABLY LOTS OF
THOSE FOLKS OUT THERE.
I THINK ONE OF THE STRESSES ON
THE HEALTHCARE SYSTEM.
BECAUSE COVID DID ACTUALLY
PREFERENTIALLY HAVE BIGGER HITS
AGAINST AFRICAN AMERICANS AND
HISPANICS IN THIS COUNTRY WHO
TEND TO COME FROM AREAS OF
COMMONLY LOW SOCIOECONOMIC
STATUS, THAT THAT DISPARITY ON
THE ACUTE SIDE, THEY GOT HIT
WORSE, IS GOING TO FLOW OVER TO
THE CHRONIC SIDE TOO.
AND THAT'S SOMETHING THAT I
THINK THE COUNTRY HAS TO TAKE TO
MIND AND TRY TO --
>> ACTUALLY EVERYTHING -- I I A
GREE WITH EVERYTHING WALTER
SAID.
THERE'S A MISCONCEPTION
INHERENTLY IN THAT QUESTION,
THAT UNDERRESOURCED HEALTHCARE
SETTINGS MIGHT NOT USE
HEALTHCARE RECORDS OR MIGHT NOT
HAVE AS GOOD HEALTHCARE RECORDS.
ACTUALLY THAT IS NOT TRUE.
SO IN FACT, UNDERRESOURCED
HEALTHCARE SETTINGS LIKE
COMMUNITY CLINICS AND MEDICAID
CLINIC, ET CETERA, THE EARLY
ADOPTERS IN THE AGE OF
OBAMACARE.
SO THE PENETRATION OF HEALTHCARE
RECORDS, THE ELECTRONIC
HEALTHCARE RECORDS IS ACTUALLY
LESS WHEN YOU LOOK AT SMALLER
PRIVATE PRACTICES, ET CETERA,
ALTHOUGH EVERYBODY USES THEM
NOW.
SO I DON'T THINK IT'S AN
ELECTRONIC HEALTHCARE ISSUE,
ALTHOUGH IT ABSOLUTELY IS AN
ACCESS TO HEALTHCARE ISSUE, AND
STUDIES LIKE RECOVER HAVE TO
WORK HARD TO RECRUIT OUTSIDE OF
THE NORMAL HEALTHCARE SETTINGS
IN ORDER TO MAKE SURE TO RECRUIT
A REPRESENTATIVE GROUP.
>> VERY INTERESTING.
WE HAVE -- LET'S SEE.
THERE'S -- AH, HERE'S A
QUESTION.
SO JORDAN ASK, HOW LONG DOES
COVID AFFECT LIVER ENZYMES?
DOES IT AFFECT THE LIVER
ENZYMES?
I PERSONALLY WAS NOT AWARE OF
THAT, BUT IS THIS AN ISSUE?
>> FREQUENTLY, YEAH.
FREQUENTLY, 46% OF THE -- COVID
PATIENTS ELEVATED ASTs, 35%
ELEVATED ALTs.
MY UNDERSTANDING, THEY TEND TO
GO DOWN WITHIN WEEKS TO MONTHS
AFTER DISCHARGE.
>> SO THEY GO DOWN RATHER
PROMPTLY.
IS THAT --
>> OVER A MONTH.
>> YEAH.
THERE ARE ALSO A COUPLE OF
QUESTIONS.
DIABETES MELLITUS, TYPE 2, IS
LISTED AS A RISK FACTOR, BOTH IN
SEVERITY AND ALSO IN CHRONIC
LONG HAUL COVID.
WHAT ARE YOUR THOUGHTS ABOUT HOW
DOES THAT WORK?
DO WE UNDERSTAND WHAT THE
UNDERLYING ASSOCIATION MEANS?
IN BIOLOGICAL TERMS,
MECHANISTICALLY?
>> I THINK, AGAIN, THERE'S A LOT
OF POSSIBILITIES.
AND I DON'T THINK I'M THE RIGHT
PERSON TO ANSWER THE QUESTION,
BUT I'LL THROW OUT A COUPLE OF
IDEAS.
ONE IS THAT I UNDERSTAND FAT
TISSUE IS ENRICHED [INAUDIBLE].
ALSO FAT TISSUE IS, IN SOME
INSTANCES, ALMOST LIKE AN
ENDOCRINE ORGAN THAT STIMULATES
ABNORMALITIES THAT AFFECT OTHER
BODY SYSTEMS, SORT OF METABOLIC
SYNDROME.
ONE OF THOSE IS ACTUALLY
INFLAMMATION.
SO THAT OBESITY IS ASSOCIATED
WITH WORSENED IMMUNE RESPONSES
TO A WHOLE BUNCH OF DIFFERENT
CONDITIONS.
AND THEN THERE'S THE DIABETES
ISSUE WHICH COULD BE SEPARATE
FROM OBESITY OR COULD BE ONE OF
THE DRIVERS.
THOSE ARE THE THINGS THAT I
WOULD THROW OUT ON THE TABLE,
BUT I BET YOU THERE'S A
DIABETOLOGIST ON THE CALL WHO
KNOWS THE RIGHT ANSWER.
>> SO JOSH, DO YOU HAVE THOUGHTS
ABOUT THAT?
>> THE OTHER THING WHICH DATA
COULD TELL US, I JUST DON'T KNOW
THE ANSWER TO IT, IS WHETHER THE
ASSOCIATION WITH LONG COVID AND
DIABETES MIGHT HAVE TO DO
WITH -- SORRY, MOI DOG , MY DOG IS
DEMANDING MY ATTENTION -- MIGHT
HAVE TO DO WITH THE LIKELIHOOD
OF MORE SEVERE COVID.
SO I DON'T KNOW WHEN YOU
STRATIFY FOR SEVERITY IF YOU
ALSO SEE THE DIABETES
ASSOCIATION.
>> THERE WAS AN INTERESTING
QUESTION OF WHETHER PEOPLE
INFECTED WITH COVID, THE ACTIVE
DISEASE OR CHRONIC, LOSE THEIR
CIRCADIAN RHYTHMS.
>> I WOULD SAY THAT SLEEP
DISORDERS ARE PRETTY COMMON.
IN POST-ACUTE SEQUELAE OF COVID.
AND I JUST RECALL TALKING TO ONE
DOC WHOSE PATIENT TOLD HIM HE
FORGOT HOW TO SLEEP.
HE WOULD GO TO BED AND HAVE NO
IDEA TO SLEEP, HE WAS UNABLE TO
SLEEP AT ALL.
SO THERE IS DEFINITELY IN SOME
PEOPLE VERY PROFOUND TROUBLE
WITH SLEEP.
AND I THINK ALSO THE PAPER IN
"CELL" CLAIMED THAT THERE WERE
PROTEINS -- PROTEINS THAT THEY
FOUND AN ABNORMAL PATTERN IN, IN
PARTICULAR NEUROLOGIC PASC, SO I
THINK THAT'S SOMETHING TO
PURSUE.
AND OF COURSE, YOU KNOW, IF
YOU'RE NOT SLEEPING, THE FATIGUE
IS GOING TO BE COMPOUNDED
DRAMATICALLY, AND IF YOU'RE
FATIGUED, THEN YOUR
CONCENTRATION IS GOING TO BE
AFFECTED.
SOME PEOPLE, MAYBE SOLVING THEIR
SLEEP PROBLEM MAY BE VERY
BENEFICIAL.
>> SO I GUESS THE LAST QUESTION
WE MIGHT ASK IS, HOW SHOULD WE
PREPARE FOR THE NEXT POST
PANDEMIC?
>> IN MY MIND, THE MOST
IMPORTANT THINGS WE CAN DO ARE
TO REALLY UNDERSTAND TWO
PHENOMENON THAT HAVE NOTHING
DIRECTLY TO DO WITH LONG COVID,
RIGHT?
ONE OF THEM IS, WHAT MITIGATION
MEASURES WORK, AND WA DON'T, AND
WHAT'S THE RELATIVE COST BENEFIT
OF THOSE MITIGATION MEASURES?
I THINK THERE WERE A LOT OF
DIFFERENT EXPERIMENTS IN THE
UNITED STATES ALONG THOSE LINES,
AND WE HOPE TO LEARN SOMETHING
FROM THOSE VARIANTS IN
MITIGATION MEASURES AND THEIR
ADHERENCE AS WELL AS THE EFFECTS
OF THOSE MITIGATION MEASURES ON
THINGS LIKE ECONOMIC EFFECTS ON
SCHOOL, ET CETERA.
SO ALREADY WE'VE LEARNED SOME
THINGS, BUT I THINK THAT'S ONE
THAT WILL HELP US PREPARE A LOT
FOR THE NEXT PANDEMIC.
THE SECOND THING WHICH ALSO
DOESN'T HAVE MUCH TO DO WITH IT
IS TRYING TO -- OH, IT JUST
FLIPPED OUT OF MY HEAD SO I'M
GOING TO HAND IT OVER TO WALTER
AND MAYBE IT WILL COME BACK WHEN
WALTER TRIES TO STAB IT IN THE
ANSWER.
>> I THINK FROM THE NIH POINT OF
VIEW, HAVING BEEN INVOLVED IN
THE -- IN THE BEST OF ALL
POSSIBLE WORLDS, THE RESEARCH
THAT NIH HAS FUNDED WOULD SIGN A
COMPACT SAYING IN THE CASE OF A
PANDEMIC, WE'RE ALL GOING TO BE
PANDEMIC RESEARCHERS AND WE'RE
GOING TO TAKE DIRECTION FROM THE
TOP DOWN AND WE'RE ALL GOING TO
DO IT LOCK-STEP.
AND THEN THINGS COULD REALLY
MOVE QUICKLY.
BUT THE WAY IT -- IT WAS QUICKER
THAN ANYTHING ELSE WE EVER DID,
BUT IT TOOK MONTHS TO GET
CONTRACTS SIGNED, THERE WERE
PEOPLE DOING MULTIPLE DIFFERENT
TRIALS, SOME OF THEM NIH FUNDED,
SOME INDUSTRY FUNDED, SOME
HOSPITAL FUNDED, AND I'M NOT
SURE THAT THAT WAS -- OUR SYSTEM
IS NOT BUILT TO RESPOND ON A
DIME TO GET A BIG HEALTH PROBLEM
LIKE WE GOT HIT WITH.
SO IF WE WANT TO LEARN A LESSON,
I THINK WE'D HAVE TO ORGANIZE
OURSELVES TO JUMP INTO A
DIFFERENT MODE OF ACTIVITY IN
THE CASE OF A PANDEMIC, AND THAT
WOULD -- YOU CAN'T DO THAT ON
THE FLY.
YOU'VE GOT TO BE PREPARED FOR
THAT, GET IT ALL SET AND
HOPEFULLY YOU NEVER HAVE TO
TRIGGER IT, BUT YOU HAVE TO TEST
THE SYSTEM, MAKE SURE IT'S
WORKING, HAVE ALL THE CONTRACTS,
EVERYBODY SIGNED ON, AND THERE'S
GOT TO BE A PENALTY IF YOU DON'T
PLAY BALL.
SO THAT'S WHAT -- A LOT OF THE
PEOPLE WHO HAVE BEEN INVOLVED IN
ACUTE TRIALS ARE TALKING ABOUT
THAT.
THAT WAS SOMETHING WE SHOULD GET
READY TO DO FOR THE NEXT
PANDEMIC, ON THE RESEARCH SIDE
OF THINGS.
>> VERY GOOD.
JOSH, DO YOU HAVE ANY ADDITIONAL
COMMENT?
>> I THINK THE OTHER THING WE
ALSO HAVE TO LEARN ABOUT IS HOW
TO COMMUNICATE OUR SCIENCE MORE
EFFECTIVELY IN A PUBLIC
HEALTH-RELEVANT WAY.
>> WELL, LISTEN, ON BEHALF OF
MANY, MANY, MANY PEOPLE WHO HAVE
LISTENED AND I'M SURE LEARNED AS
I HAVE, WE WANT TO THANK BOTH OF
YOU.
YOU'RE VERY BUSY PEOPLE, WE
FULLY UNDERSTAND AND APPRECIATE
VERY MUCH YOUR SHARING, YOUR
EXPERIENCE AND INFORMATION.
AND I THINK IT'S EXTRAORDINARY
THAT THIS IS PROBABLY -- IT IS,
I THINK, THE FIRST PANDEMIC,
WELL, MAYBE HIV WAS THE FIRST IN
THE MODERN ERA, WHERE THERE'S
THIS INCREDIBLE INVESTMENT IN
COMBINED COLLABORATIVE ACTIVITY,
A LOT OF BRIDGE-BUILDING GOING
ON, NOT ONLY BETWEEN DISCIPLINES
BUT BETWEEN COUNTRIES, BETWEEN
HEALTH SYSTEMS, SO THIS HAS BEEN
AN EXTRAORDINARY PRESENTATION
AND ON BEHALF OF EVERYONE, THANK
YOU.
THANK YOU VERY MUCH.
>> THANKS FOR HAVING US.
>> IT'S A PLEASURE.
THANK YOU.