I WAS HAVING DÉJÀ VU IN MY
EARLIER DAYS AS AN HIV ACTIVIST
WATCHING THIS HAPPEN TO MY
FRIENDS WITH HIV.
DURING THE 10 WEEKS SENSE MY
DIAGNOSIS I RECEIVED A CRASH
COURSE ON THE HISTORY OF THE
DISEASE OF ME, THE STIGMA AND
DISCRIMINATION I PREPARED MYSELF
TO FACE.
THE FACT THERE WAS NO FDA
APPROVED DRUG, NO SOCIAL
SERVICES AND NO COORDINATED
HEALTH CARE AND REALIZED QUICKLY
HOW SCREWED WE ALL WERE.
I'M GOING FAST FORWARD TO NOW
AND I HAD ME AND LONG COVID AND
HELPED PASS STATE LEGISLATION IN
NEW YORK, I'VE DEVELOPED ME
CLINICAL EDUCATION COURSES AND
I'VE ALSO PROTESTED AGAINST
ANYONE WHO GOT IN OUR WAY AND
SPECIFICALLY LOOKING AT.
YOU SHOWED UP AT COLUMBIA
UNIVERSITY ONE DAY.
I WAS NOT HAVING THAT IN BACK
YARD.
RIGHT NOW I'M ON IVIG EVERY FOUR
WEEKS AND TAKING NALTREXON AND
WANING MYSELF OFF SOMBALTA AND
TAKING SOMETHING FOR SLEEP AND
STARTED CORTIZONE.
THESE TREATMENTS HELPED ME AND
KNOW HOW LUCKY I AM TO HAVE
ACCESS.
NOT EVERYONE CAN GET ACCESS TO
THESE TREATMENTS, CAN TOLERATE
THEM OR EVEN RESPOND TO THEM.
YOU KNOW, IN 2016 I WAS SURE MY
PARENTS WERE GOING TO BURY ME BY
THE END OF THE YEAR.
I WAS SO SICK.
I LITERALLY THOUGHT I WAS DYING.
I HAD NEVER BEEN THAT SICK IN MY
LIFE.
I'M GRATEFUL THAT MY SYMPTOMS
ARE NOT AS SEVERE AS THEY WERE
BACK THEN.
IT HORRIBLE.
I WOULD LAY IN BED AND CRY.
MY CURRENT TREATMENT NOT
APERFECT TREATMENT PLAN BUT IT'S
GIVEN ME SOME OF MY LIFE BACK.
I'M STILL WAITING FOR MY BRAIN
TO COME CAN BACK.
PEOPLE NEED TREATMENT OPTIONS.
WHEN I SAY PEOPLE, I MEAN ALL
PEOPLE NEED TREATMENT OPTIONS.
EVERY SINGLE PERSON WHO HAS THIS
DISEASE.
A FEW WEEKS AGO I POSTED A
MESSAGE ON SOCIAL MEDIA THE
MESSAGE SAID AND I'LL QUOTE,
I'VE BEEN INVITED TO SPEAK AT
THE NIH DECEMBER MEETING.
WHAT WOULD YOU WANT EARLY CAREER
SCIENTISTS AND MEDICAL STUDENTS
TO LOOK AND I RECEIVED RESPONSE
TO THE QUESTION AND 18,600
RESPONSE TO THE POST.
I'LL SHARE A FEW THAT STOOD OUT
TO ME.
THE MOST PREVALENT ISSUE
ADDRESSED IN THAT POST REVOLVED
AROUND PEM, POST EXERTION
MALAISE AND PATHOPHYSIOLOGY AND
RESPONDENTS EMPHASIZED THE
IMPORTANCE OF RECOGNIZING AND
STUDYING PEM IN ANY RESEARCH.
THEY STRESS THE NEED TO STOP
ADVOCATING EXERCISE FOR THOSE
EXPERIENCING PEM AS IT
EXACERBATES SYMPTOMS AND THE
IMPACT ON PEOPLE WITH ME.
THE SECOND THING BROUGHT UP WE
THE URGENT NEED FOR RESEARCH ON
TREATMENTS.
THE URGENCY FOR INCREASED
RESEARCH EFFORTS AND ACCELERATED
METHODOLOGIES TO FIND TREATMENT
WAS A SIGNIFICANT THING.
RESPONDENTS HIGHLIGHTED THE NEED
TO SPEED UP RESEARCH DUE TO THE
LONG STANDING LACK OF EFFECTIVE
TREATMENTS.
AND ONE PERSON WROTE, QUOTE, ADD
AN ARM TO THE LONG COVID STUDY
BEING CONDUCTED BY THE NIH.
WE ASKED FOR THIS MANY TIMES AND
THEY SAID NO.
IT'S INHUMANE TO EXCLUDE US.
AND THE THIRD THEME WAS THE NEED
FOR A NECESSARY PARADIGM SHIFT
IN HEALTH CARE AND THE
IMPORTANCE OF COMMUNITY
INVOLVEMENT EMERGED PROMINENTLY.
MANY ADVOCATED FOR ACKNOWLEDGING
OUR EXPERTISE IN DEVELOPMENT OF
SYMPTOMS OF CARE.
WE ARE THE EXPERTS AFTER ALL.
ALSO THEY STRESS THE NEED FOR
FRESH PERSPECTIVES AND OVERHAUL
AT HOW HEALTH CARE PROFESSIONALS
APPROACH THE DISEASE.
ONE PERSON WROTE, QUOTE, THEY
SHOULDN'T BE AFRAID TO TRY
OFF-LABEL MEDS IF NEEDED.
THERE MAY BE SECONDARY AFFECTS
BUT WE CAN'T STAND THE
SUFFERING.
I'M GOING TO LET YOU SIT WITH
THAT FOR A MINUTE.
BEFORE I CLOSE I WANT TO MENTION
TWO MORE THINGS.
ANY RELATED STIGMA IS CAUSING
HARM.
PEOPLE DON'T BELIEVE US WHEN WE
SAY WE'RE SICK AND PEOPLE MAKE
FUN OF US AND MISPERCEPTIONS
EXIST.
YESTERDAY SOMEONE ON SOCIAL
MEDIA QUESTIONED WHY THERE
WEREN'T PEOPLE WITH SEVERE
DISEASE SHARING THEIR LIVED
EXPERIENCE AT THIS MEETING WHEN
I SAW PEOPLE WITH SEVERE DISEASE
SHARING THEIR STORIES.
LIVING WITH SEVERE DISEASE IS
NOT ONE SIZE FITS ALL.
PEOPLE WITH SEVERE DISEASE IS
NOT A MONOLITH AND MUST STOP
STIGMATIZING EACH OTHER BY
MAKING JUDGMENTS AND ASSUMPTIONS
ABOUT EACH OTHER'S HEALTH AND
LIVED EXPERIENCE.
IT'S NOT FAIR AND IT NEEDS TO
STOP.
I PROMISE I'M WRAPPING UP NOW.
I TURNED 56 YEARS OLD TWO MONTHS
AGO.
IN MY DAY JOB I WORK ON HIV AND
HIV POLICY TO IMPROVE THE LIVES
OF PEOPLE AGING WITH HIV.
THOSE 50 AND OLDER AND THOSE
LIFE TIME SURVIVORS WHO HAVE
BEEN LIVING WITH IT IS SINCE
BIRTH.
THIS JOB I THINK ABOUT SOCIAL
SERVICES, HEALTH CARE SYSTEMS,
THE OLDER AMERICANS ACT, FEDERAL
AGENCIES THAT CAN BE DOING A
BETTER JOB AND RESEARCH THAT IS
BEING DONE OR COULD BE DONE TO
LOOK AT WHAT HAPPENS TO THE BODY
WHEN A PERSON AGES WITH HIV.
HOW DOES HIV IMPACT AGING AND
VICE VERSA.
DOES IT ACCELERATE IT,
COMPLICATE IT?
WHY DO MY FRIENDS WITH HIV HAVE
SO MANY COMORBIDITIES AND AGE
YOUNGER THAN ONE WOULD EXPECT.
THERE'S A COHORT OF PEOPLE WITH
ME WHO GOT SICK IN THE 1980s AND
1990s.
IN THE PRIME OF THEIR LIFE.
THEY'RE OLDER NOW, MUCH OLDER.
THEY HAVE WAITED DECADES FOR
SCIENTIFIC DISCOVERY.
THEY DREAMED OF A DAY WHEN THERE
WOULD BE A MAJOR ANNOUNCEMENT
SHARING A TREATMENT BEEN
DISCOVERED TO TAKE AWAY THE
SUFFERING OF THIS DISEASE.
THEY KEEP WAITING AND WAITING
YEAR AFTER YEAR MISSING MORE AND
MORE OF THEIR LIFE WITH EACH
PASSING DAY.
SO YOU MAY COME TO THIS MEETING
A COMMITMENT TO ATTEND TO PAY
ATTENTION, TO NETWORK, TO EXPAND
YOUR KNOWLEDGE, TO LEARN A NEW
SKILL.
YOU TRAVELED FROM YOUR HOME
WHERE YOU LOGGED IN VIA ZOOM.
SO WHETHER IT WAS A 30 MINUTE
COMMUTE OR TWO MINUTE COMMUTE OR
HOURS TRAVELED BY AIR LANE --
AIRPLANE I HAVE A QUESTION FOR
YOU.
WHAT ARE YOU GOING DO DIFFERENT
THAN WHAT YOU'RE DOING TODAY TO
MAKE THE DREAM OF A MAJOR
DISCOVERY IN TREATMENT COME TRUE
FOR THE FOLKS WHO HAVE BEEN
WAITING DECADES AND DECADES AND
DECADES.
WE'RE ALL DEPENDING ON YOU.
THANK YOU.
>> THANK YOU, TERRI.
>> IT'S MY PLEASURE TO INTRODUCE
THE MODERATOR FOR THE NEXT
NUMBER OF TALKS DR. ALAIN MOREAU
WHO HAS BEEN A TREMENDOUS
COLLEAGUE AND PARTNER FROM
MONTREAL AND EXPERT IN LONG
COVID AND ME/CFS AND THE VERY
END OF THIS LONGER SESSION HE'LL
TELL US ABOUT HIS WORK BUT FIRST
WILL HELP MOVE THINGS ALONG.
THANK YOU.
>> THANK YOU, JOE.
GOOD MORNING, EVERYONE.
IT'S MY EXTREME PLEASURE TO BE
THE MODERATOR OF THIS SESSION
THIS MORNING.
SO, I WOULD LIKE TO INTRODUCE
OUR SECOND SPEAKER, DR. CINDY
BATEMAN USING RECOVER TO
UNDERSTAND ME/CFS AND LONG
COVID.
CINDY.
>> THANK YOU FOR THE OPPORTUNITY
TO COME SHARE SOME RESEARCH WITH
YOU.
I'LL TALK ABOUT USING RECOVER
ADULT STUDY DATA TO ANALYZE THE
NUMBER OF PEOPLE WITH ME/CFS.
AS BACKGROUND, THE BATEMAN HORN
CENTER I HELPED FORM IS A
NONPROFIT ORGANIZATION IN SALT
LAKE CITY THAT FOCUSES ON
CLINICAL CARE FACILITATION OF
RESEARCH AND DISSEMINATION OF
EDUCATIONAL RESOURCES.
PRIMARILY WE USED TO DO HEAVY
WORK WITH FIBROMYALGIA AND HAD A
FOCUS ON ME/CFS AND NOW
EXTENDING TO LONG COVID AND THE
GOAL IS TO COMPARE LONG COVID
WHICH IS AN EARLY VIRAL ILLNESS
TO ME/CFS A LONG-STANDING
ILLNESS GENERALLY KNOWN TO BE A
POST-VIRAL CLINICIAN.
WE WANTED TO LEARN ABOUT THE
CLINICAL PRESENTATION AND
DETERMINE WHAT WAS CAUSING IT
AND DETERMINING IF UNDERSTANDING
LONG COVID CAN IMPROVE ME/CFS
DIAGNOSIS AND TREATMENT.
BECAUSE OF THIS GOAL AND OUR
AWARENESS OF LONG COVID IN 2021
WE INVITED MORE THAN 100 LONG
COVID PATIENTS TO BATEMAN HORN
CENTER CLINIC FOR EVALUATION
BASED ON CERTAIN CHARACTERISTICS
BY SCREENING QUESTIONNAIRE.
THEY WERE NOT HOSPITALIZED AND
REQUIRES -- AND CANDIDATE TO BE
A NOBEL LAUREATE.
THAT MEANS WE'RE GOING TO SPEAK
RAPIDLY AND THE COMMITTEE DOES
NOT HAVE TIME TO REVERSE THEIR
DECISIONS.
[TECHNICAL DIFFICULTIES]
-- THEY MET THE CRITERIA FOR
POST-COVID ME/CFS AND THEY WERE
ME/CFS LIKE WHO DIDN'T MEET THE
FUEL CRITERIA FOR ME/CFS AND
THERE WAS A GROUP THAT HAD NO
SYMPTOMS.
I WANT TO POINT OUT THAT GROUP 2
THEY WERE PEOPLE ACUTE INFECTED,
THAT MEANS WHEN THEY WERE
ENROLLED IT HAD ONLY BEEN 30
DAYS SINCE THEIR INFECTION AT
THE TIME THEY WERE ENROLLED IN
THE STUDY AND THEN THE
POST-ACUTE INFECTED WHO HAD
LONGER PERIOD OF TIME SINCE
THEY'VE BEEN SICK WITH COVID
WHEN THEY WERE ENROLLED.
IN THE UNINFECTED GROUPS WE'LL
CALL THEM GROUPS 5, 6, 7, 8 AND
PRE-EXISTING ME/CFS AND SAY MORE
BECAUSE I WON'T GO INTO THEM
MUCH, 1.5% AND A GROUP THAT MET
CRITERIA AFTER ENROLLING 2.8%.
GROUP 7 WAS THE ME/CFS-LIKE 41%
AND GROUP 8 WAS THOSE WITH NO
ME/CFS SYMPTOMS 54.6%.
A LITTLE BIT SURPRISING BUT IT'S
VERY MESSY.
SO MANY PEOPLE HAVE BEEN EXPOSED
TO COVID THROUGHOUT THIS TIME.
SO LET ME GO INTO A LITTLE MORE
DETAIL.
OF THOSE 10,711 INFECTED
PARTICIPANTS THAT WERE STUDIED
INFECTED ARM HAVE BEEN SIX MORE
THAN SIX MONTHS.
GROUP 1 WAS THOSE WITH
PRE-EXISTING ME/CFS WHO ALSO GOT
INFECTED AND THAT WAS 1.7% OF
THE TOTAL PARTICIPANTS.
BUT GROUP 2 IS THE GROUP WE'RE
MOST INTERESTED IN.
THE PEOPLE WHO MET CRITERIA FOR
POST-COVID ME/CFS AND THAT
EQUALLED 9.5% OF PARTICIPANTS
WHO MET ME/CFS CRITERIA MORE
THAN SIX MONTHS FOLLOWING THE
SARS COV2 INFECTION.
THIS MAY SEEM DISAPPOINTING TO
SOME PEOPLE BUT REMEMBER IT'S
NOT A GROUP OF PATIENTS WHO GO
TO A CLINIC -- A LONG COVID
CLINIC.
IT'S NOT A POPULATION-BASED
CLINIC BUT SOMEWHERE IN BETWEEN.
WE'LL SEE DIFFERENT NUMBERS.
GROUP 3 IS IMPORTANT ALSO.
THIS IS A VERY LARGE GROUP, 56%
OF PATIENTS WHO MET AT LEAST ONE
OF THE ME/CFS CRITERIA AND MANY
OF THEM MET MORE BUT THEY HAD TO
MEET ALL THE CRITERIA TO GET
INTO GROUP 2.
AND THEN THERE WAS A GROUP 33%
WHO REALLY NEVER MET ANY OF THE
CRITERIA.
THIS SLIDE IS REALLY TO
HIGHLIGHT THE APPROXIMATION OF
INCIDENT CASES.
SO OF THOSE -- IF YOU LOOK ON
THE LEFT SIDE, THOSE WHO HAD
BEEN LESS THAN 30 DAYS SINCE
THEIR INFECTION WHEN THEY
ENROLLED IN THE STUDY, 3.5% MET
ME/CFS CRITERIA.
SO THESE ARE PEOPLE VERY EARLY
IN THE COURSE OF THEIR DISEASE,
3.5% MET CRITERIA DURING THAT
FIRST YEAR AND OF THOSE WHO HAD
BEEN SICK WITH SYMPTOMS MORE
THAN 30 DAYS WAS MORE THAN 13.2%
THAT MET ME/CFS CRITERIA AND YOU
SEE THE FOUR CATEGORIES ACROSS.
THIS IS A COMPARISON TO THE
UNINFECTED GROUP DOWN AT THE
BOTTOM THAT WE TALKED ABOUT
WHERE 2.8% OF PATIENTS ENDED UP
MEETING ME/CFS CRITERIA BASED ON
THESE CRITERIA.
SO I WANT TO JUST PAUSE AND
REFLECT BACK ON A RECENT PAPER
THAT WAS IN JAMA.
A VERY IMPORTANT PAPER I THINK
THAT LOOKED AT SYMPTOMS AND
SYMPTOM PRESENTATION IN THE
RECOVER ADULT COHORT.
THEY LOOKED AT 9,764 SUBJECTS
SICK AT LEAST SIX MONTHS SINCE
ACUTE COVID AND THEY IDENTIFIED
AND THERE WAS REFERENCE FOR
THIS -- I WON'T GO TOO MUCH INTO
THE PAPER BUT IDENTIFIED THE
MOST DISTINGUISHING SYMPTOMS
THAT SEPARATED PEOPLE WHO HAD
HAD SARS COV2 AND THERE WAS A
LIST OF 12 WEIGHTED.
I DON'T KNOW IF YOU REMEMBER,
LOSS OF SMELL WAS THE TOP AND
EIGHT POINTS FOR LOSS OF SMELL
AND IT WENT DOWN.
IF YOU HAD A SCORE OF 12 THEY
CALLED YOU POST-ACUTE SEQUELAE
COVID.
AS DEFINED IN THE STUDY.
OF THOSE WHO MET PASC CRITERIA
IN THE PAPER, THE MOST COMMON
SYMPTOMS WERE POST-EXERTIONAL
MALAISE, FATIGUE, BRAIN FOG,
DIZZY , G.I. SYMPTOMS AND
PALPITATIONS.
JUST POKE THOSE INTO YOUR BRAIN
AND ALSO FROM THIS PAPER AND
PEOPLE HAVE SEEN THIS BEFORE.
THEY DID A CLUSTER ANALYSIS OF
THOSE PEOPLE WHO MET CRITERIA.
CLUSTER 1 WAS LOSS OR CHANGE OF
SMELL OR TASTE AND THOSE WITH
POST-EXERTIONAL MALAISE AND
FATIGUE AND CLUSTER 3 WAS BRAIN
FOG.
100% HAD BRAIN FOG IN THAT
CLUSTER AND POST-EXERTIONAL
MALAISE AND FATIGUE AND CLUSTER
4 REALLY SICK PEOPLE WE MAY
RECOGNIZE WITH FATIGUE,
DIZZINESS, BRAIN FOG AND G.I.
AND PALPITATIONS.
THAT FOURTH COLUMN HAS THE DARK
BANDS BECAUSE THEY GET DARKER
THE HIGHER THE PERCENT.
THERE WERE APPROXIMATELY 2,031
IN THE PASC GROUP AND ROUGHLY A
FOURTH OF EACH PATIENT BUT THERE
WERE 562 WHO MET THE CLUSTER
FOUR OF THE 2000 PATIENTS.
SO BACK TO OUR RESULTS.
AND THIS IS THE SAME SLIDE I
SHOWED YOU BUT WE TOOK THE PASC
CRITERIA AND APPLIED THEM TO OUR
GROUP OF PATIENTS WHO MET THE
I.O.M. CRITERIA FOR ME/CFS TO
SEE WHAT THE OVERLAP WAS.
SO THAT IS GROUP 2 AND I ADDED
THE NEW OBSERVATION IN RED.
SO THOSE PEOPLE WHO HAD
POST-COVID ME/CFS MEETING THE
IOM CRITERIA, 84% OF THOSE
PEOPLE MET THE DEFINITION IT
FROM THE MAY PAPER.
YOU CAN WRAP YOUR MIND ABOUT
THAT AND I'LL BEND YOUR MIND A
LITTLE BIT MORE HERE.
YOU HAVE TO READ THE PAPER.
SOMETIMES THE PAPERS ARE
COMPLICATED AND YOU HAVE TO TAKE
SOME TIME TO READ THEM.
BUT LET ME WALK YOU THROUGH
THIS.
SO THE FIRST PIE CHART, THIS IS
FROM FIGURE 2 IN THE PAPER.
THE FIRST PIE CHART IS THAT
GROUP 2.
THESE ARE THE PEOPLE THAT WE
DEFINED AS HAVING POST-COVID
ME/CFS BASED ON THE CRITERIA AND
THE PIE CHART IS HOW OFTEN DID
THEY FALL INTO THE CLUSTERS.
SO CLUSTER 1 IS MEETING THE PASC
CRITERIA FROM THE JAMA PAPER.
LIGHT BLUE IS CLUSTER 1 AND NEXT
IS CLUSTER 2 AND MEDIUM BLUE IS
CLUSTER 3 AND THE DARK BLUE AREA
IS CLUSTER 4.
THE VERY LIGHT GROUP IS NOT
MEETING THE PASC SCORE OF 12.
THEN THERE'S A GROUP OF MISSING
DATA.
CAN SEE BY FAR AND THIS IS THE
SAME NUMBER THAT WAS IN THE
SLIDE BEFORE ABOUT 84% OF PEOPLE
WE DEFINED AS HAVING ME/CFS
BASED ON THE I.O.M. CRITERIA MET
THE PASC CRITERIA.
NOW, IF YOU LOOK AT B, B IS
GROUP 3.
THIS IS THE PEOPLE WHO WERE
ME/CFS LIKE ON OUR APPLICATION
OF THE I.O.M. CRITERIA AND YOU
CAN SEE ABOUT A FOURTH OF THEM
MET PASC CRITERIA IS ALL.
SO THE BLUE ONES.
IT'S EVENLY SPREAD OUT WHICH
CLUSTER THEY FELL INTO.
BY FAR THE MAJORITY OF PEOPLE IN
THAT ME/CFS-LIKE GROUP DID NOT
HAVE A PASC SCORE OF MORE THAN
12 BASED ON THE JAMA PAPER.
THE LAST ONE IS REALLY OF ALL
THE PEOPLE WHO MET PASC CRITERIA
IN OUR STUDY, WHAT GROUPS DID
THEY FALL INTO AND THE LARGEST
PIECE OF ME/CFS-LIKE.
THE LIGHT BLUE AND THE SLIVER OF
DARK BLUE IS THOSE WITH
PREEXISTING ME/CFS THE NEXT
MEDIUM BLUE ARE THOSE WHO
DEVELOP POST-COVID ME/CFS BASED
ON OUR I.O.M. APPLICATION
CRITERIA.
SOME HAD A SCORE OF 12 OR
GREATER AND MARK INCREASE AMONG
SARS COVID RECOVER ADULT
PARTICIPANTS AND THE CONCLUSION
OF THE PAPER IS ME/CFS IS A
SEQUELAE OF SARS COV2 AND SHOULD
BE INCLUDED IN TRIALS AND
RECOVER PROVIDES WHAT WE'VE
ALWAYS SUSPECTED AND ASSUMED
THAT RECOVER PROVIDES THE
OPPORTUNITY TO STUDY THE BIOLOGY
MECHANISMS AND NATURAL HISTORY
OF POST-VIRAL ME/CFS AND
ME/CFS-LIKE POST-VIRAL ILLNESS
AND WE DON'T KNOW HOW MANY OF
THOSE PEOPLE WILL GO ON TO
DEVELOP ALL THE FULL CRITERIA
FOR THE I.O.M. CRITERIA FOR
ME/CFS.
WE ALL HOPE THE STUDY LONG COVID
CAN BRING US CLOSER TO
UNDERSTANDING THE CAUSE AND
UNDERLYING PATHOPHYSIOLOGY OF
ME/CFS, IDENTIFY BIOMARKERS AND
DIAGNOSTIC TESTS AND USE THE
INFORMATION TO MOVE TOWARD A
TREATMENT TRIALS FOR LONG COVID
AND ME/CFS.
SO THANK YOU TO SUSAN AND THE
TEAM AT THE UNIVERSITY OF UTAH
AND ALL THE MANY RECOVER AUTHOR
WHO'S CONTRIBUTED THEIR TWO BITS
TO THE PAPER AND WE ARE FINGERS
CROSSED WE CAN GET THIS
PUBLISHED.
THANK YOU.
>> WE HAVE TIME FOR A FEW
QUESTIONS.
PLEASE COME UP TO THE MIC.
>> DO YOU HAVE ANY SENSE TO WHAT
THE RISK IS IS WITH DIFFERENT
VARIANTS?
DOES THAT CHANGE?
>> UM, WE DIDN'T LOOK AT THAT
BUT THE INCIDENT GROUP WERE
REALLY PEOPLE LATER PROBABLY
MORE LIKELY TO BE VACCINATED AND
POST-OMICRON.
IT'S HARD TO COMPARE OVER TIME
PERIODS IN COVID AND WE'D HAVE
TO DIG A LOT DEEPER TO BE ABLE
TO DO THAT.
>> YOU COULD USE SEROLOGY FOR
THAT.
>> SORRY?
>> YOU CAN USE SEROLOGY FOR
THAT.
>> HONESTLY WE HAD A BIT OF A
TIME GETTING HOLD OF THE RECOVER
DATA AND WE MIGHT HAVE AN EVEN
HARDER TIME GETTING HOLD OF THE
SAMPLES BUT IT'S DEFINITELY
POSSIBLE AND IT MIGHT COME OUT
IN A RECOVER STUDY.
>> HI, MY NAME IS BRYN CONRAD AN
UNDERGRADUATE RESEARCHER WITH
VASSAR COLLEGE.
I HAD A QUESTION ON CRITERIA FOR
ME/CFS BECAUSE I KNOW THERE'S A
LOT OF DIFFERENT METHODS OF
DIAGNOSING ME WITH DIFFERENT
CRITERIA AND SOME PEOPLE FIT
INTO ONE CATEGORY AND WONDERING
WHAT LED YOU AND YOUR TEAM TO
CHOOSE THE I.O.M. CRITERIA
VERSUS A CANADIAN CONSENSUS AND
CDC AND HOW THEY COMPARE.
>> THAT'S A GOOD QUESTION.
I LIKE THE I.O.M. CRITERIA AS A
CLINICIAN BECAUSE THEY'RE
SCREENING CRITERIA AND THE FIRST
STEP IN TRYING TO UNDERSTAND.
THEY'RE THE CORE PRESENTING
SYMPTOMS.
THEY'RE NOT ALL THE SYMPTOMS,
RIGHT, BUT THE CORE COMMON
SYMPTOMS AND THIS ISEE -- THIS S
EVIDENCE BASED IN THE STUDY AND
THE RECOVER PROTOCOL HAD ALREADY
BEEN DESIGN AND IMPLEMENTED IN
THE DATA GATHERED.
AND DIDN'T PUT IN SPECIFIC
QUESTIONS TO DETERMINE IF PEOPLE
MET ME/CFS CRITERIA.
AND THE CRITERIA WERE THE
CLOSEST WE COULD COME TO
APPROXIMATING THE I.O.M.
CRITERIA AND WOULD HAVE BEEN
CLOSE TO IMPOSSIBLE TO TRY TO
USE CANADIAN CRITERIA OR ONE OF
THE OTHER MORE COMPLICATED
CRITERIAS FOR THIS PURPOSE.
BUT EVERY PERSON SHOULD BE
TRACKED AND STUDIED AND HAVE
MANY END CASE DEFINITIONS
APPLIED TO THEM INCLUDING ALL
THE OTHER COMORBIDITIES DONE.
>> THANK YOU.
>> MY PLEASURE TO INTRODUCE OUR
THIRD SPEAKER DR. NANCY CLI MASS
FROM NOVA SOUTHEASTERN
UNIVERSITY AND PRESENT COVID-19
UNDERSTANDING THE POST-VIRAL
PHASE COVID UPP.
>> IT'S AN HONOR TO REPRESENT
THIS AMAZING GROUP THAT HAS
ASSEMBLED TO TRY TO PUT THE
STUDY UP AND GET NICE DATA.
IT'S A GREAT OPPORTUNITY TO IN
INVOLVED IN THIS GROUP AND OUR
GODSEND IN TRYING TO GET THE
NEUROCOGNITIVE THERAPY TO WORK
AND THE OUTSTANDING TEAM AT THE
CDC UNDER THE LEADERSHIP OF GENE
BERTOLI.
WE DON'T HAVE ANY CONFLICTS.
SO THE OBJECTIVE OF THE STUDY IS
A LITTLE DIFFERENT.
IT WAS TO UNDERSTAND WHERE THE
ME/CFS AND LONG COVID OVERLAP
AND WHERE THEY DIFFER.
THAT'S THE BASIC OBJECTIVE.
WE HAD A TREMENDOUS ADVANTAGE.
I KNOW YOU UNDERSTAND NOW IT'S
HARD TO DO PROSPECTIVE ME/CFS
STUDIES THAT DON'T HAVE THE
CONFOUND OF COVID INFECTION.
IT'S HARD TO FIND NON-COVID
TRIGGERED ME/CFS NOW THAT WE
DON'T HAVE VERY GOOD TESTING.
PEOPLE AREN'T BOTHERING TO TEST
FOR COVID AND THEY'RE ASSUMING
ALL THEIR INFECTIONS ARE COVID
SO IT'S JUST A DIFFICULT TIME TO
DO A PROSPECTIVE STUDY.
WE WERE SO LUCKY WE HAD JUST
COMPLETED THIS GREAT BIG STUDY
WITH THE CDC WITH SEVEN SITES
AND THERE'S A GREAT GROUP OF
PEOPLE THAT DID THIS STUDY AND
WE LOOKED AT THE DATA SET AND
PROCEEDED TO DO COMPARABLES AND
THERE'S A PHENOTYPING COMPONENT
TO IT.
I DON'T NEED TO TELL YOU COVID
IS VERY FREQUENT AND THE RATE OF
COVID INFECTION IS IS TOPPING
77% LIFE TIME COVID, 19
INFECTION IN THE U.S.
AND SO YOU HEARD PEOPLE TALKING
SO MUCH OVER THE PAST TWO DAYS
ABOUT THE IMPORTANCE OF BEING
THOROUGH IN OUR INFORMATION AND
TRYING TO DEVELOP
DEMOGRAPHICALLY REPRESENTED
COHORT.
THAT WAS A CHALLENGE OF OUR
STU
STUDY.
WE ARE IN SOUTH FLORIDA AND
PREDOMINANTLY HISPANIC COMMUNITY
AND LOOKING FOR DEMOGRAPHICALLY
RICH SETS AS IT TURNED OUT TO
BE.
THE STUDY HAS A DATA SET OF 47
PATIENTS CHARACTERIZED IN WEB
BASED AND ONSITE STUDY AND 14
PAPERS HAVE -- 12 OR 14 FROM THE
DATA SET I THINK YOU SAW AN
E-MAIL COME THROUGH THERE'S A
RELATIONSHIP NOW WITH THE CDC
AND THE NIH DATA AND BIO
REPOSITORY TO DIRECT IT FOR A
BROADER GROUP OF INVESTIGATORS.
LONG COVID AS YOU'VE HEARD BY
MULTIPLE INVESTIGATORS IS
COMPLICATED.
IT HAS A HOST OF SYMPTOMS.
MANY SYMPTOMS ARE OVERLAPPING
BUT BY FAR THE MOST COMMON
SYMPTOM IS FATIGUE.
AND IT CASE DEFINITION ISSUES
AND THERE WAS THE FIRST ONE THAT
WAS WIDELY ACCEPT THE WORLD
HEALTH ORGANIZATION CASE
DEFINITION IT HAD BEEN PUBLISHED
AND NOW THERE'S A NASEM LARGE
CASE DEFINITION EVIDENCE-BASED
CASE DEFINITION EFFORT UNDERWAY.
SO WE HAD TO DECIDE HOW WE WERE
GOING TO APPROACH THIS WITH THE
COMPLICATION OF NOT KNOWING
EXACTLY HOW TO DEFINE THE
ILLNESS.
THE RECRUITMENT IS SOUTH FLORIDA
RECRUITMENT WHICH FOR US IS WEST
PALM BEACH DOWN TO THE END OF
THE KEYS.
AND THE PEOPLE IN THE STUDY THAT
ARE ENROLLED ARE RECOVERED AND
UNRECOVERED AND WE HAVE TO HAVE
A TEST NOT AN ASSUMPTION.
AND THE RECOVER GROUP HAS TO
HAVE NO NEW SYMPTOMS OR CHANGE
IN OLD SYSTEMS THAT HAVE
PERSISTED BEYOND THE RECOVERY
PERIOD AND UNRECOVERED HAS TO
HAVE PERSISTENT FATIGUE IN
SYMPTOMS THREE MONTHS AFTER
INFECTION.
THE COMPARATIVE GROUP IS THE M
CAM COHORT WAS NOT RECRUITED BY
CASE DEFINITION.
IT WAS RECRUITED BY HAVING SEVEN
WELL REGARDED EXPERTS PICK FROM
THEIR CLINIC THEY WERE SURE HAD
ME/CFS.
IT WAS A DIFFERENT WAY TO GO
EXPERT CONSENSUS ON WHO HAD
ME/CFS.
THE EXCLUSION CRITERIA WERE
BASICALLY ORGAN DAMAGE FROM
ACUTE COVID AND THE CRITERIA AND
THE COMMON DATA ELEMENTS
RECOMMENDATION FOR UNDERSTANDING
HOW TO GO FORWARD WITH
EXCLUSIONS AND ME/CFS RELATED
RESEARCH.
IT'S A PROSPECTIVE STUDY.
IT HAS -- I WON'T GO INTO THE
RECRUITMENT STRUGGLES AND IT'S
BEEN EDUCATIONAL FOR ME TO LEARN
HOW TO RECRUIT THE COHORT.
BASICALLY THERE'S A LONGITUDINAL
COMPONENT WITH ASSESSMENT UP TO
THREE YEARS ON A PLATFORM THAT
LOOKS AT ALL THE DOMAINS OF
ILLNESS.
AND THE RECOVER FROM THAT GROUP
AND THIS IS GOING TO BE A BROAD
GROUP DEFINED BY FATIGUE PLUS
ONE SYMPTOMS.
IT'S A BROAD GROUP AND THEN FROM
THAT WE PICK PEOPLE WHO HAVE A
PROMISE 29 SCORE THAT PUTS THEM
IN THE MODERATE TO SEVERELY ILL
AND PUTS THEM IN THE PHENOTYPING
STUDY.
THE LONGITUDE YAL COHORT HAS A
LOT OF QUESTIONS.
THESE ARE ALL FROM THE COMMON
DATA ELEMENTS IMPRESSIVE FRANKLY
BECAUSE THEY'RE ALSO FROM THE
MCAM STUDY WHICH PROCEEDED THE
COMMON DATA ELEMENT DECISIONS
THEY WERE BASED ON THE
EVIDENCE-BASED DATA SET.
IT ALSO HAS COVID RELATED THINGS
AND AN IMPORTANT SET OF
QUESTIONS AND THE PATIENT OWN
PER SECTION OF OF THEIR
TRAJECTORY.
SOCIAL DETERMINATES OF HEALTH
AND SOMETHING WE TEND TO EXCLUDE
IN OUR ME/CFS AND SHOULD BE
INCLUDED.
YOU CAN SEE THE EXAM AND THE
LEAN TEST AND COGSTATE BATTERY
AND AN AUSTRALIAN GROUP
DEVELOPED THIS AND IT'S BEEN A
LABOR OF LOVE TO MAKE SURE WE
CLOSELY ALIGN TO THE MCAM STUDY.
BIOMARKERS, MUCH OF THIS IS
BATCHED WORK.
I WON'T SHARE THE BIOMARKER WORK
TODAY AND YOU CAN SEE THE IMMUNE
MARKERS AND THE CYTOKINE
PLATFORM THAT'S INTENSIVE AND
SEROLOGIC MARKERS AND DAMAGE
STRESS MARKERS AND MICROBIAL
TRANS LOCATION AND PERMEABILITY
MARKERS.
A LOT OF YOU HEARD ABOUT
YESTERDAY IN THE ME/CFS
LITERATURE SO WE'LL HAVE
COMPARABLE DATA.
SO RECRUITMENT.
THIS HAS BEEN SUCH A BUGABOO.
THAT'S A SCIENCE WORD.
WE STARTED THE STUDY WITH THE
FLORIDA DEPARTMENT OF HEALTH AND
WHEN WE WENT TO PULL IT OFF
LOGISTICALLY IT FELL APART.
WE GET TO DO THAT PERFECT DESIGN
WE HAD INTENDED.
IT TURNED OUT TO BE A GOOD THING
AS TIME EVOLVED NO ONE'S
REPORTING RESULT TO THE PUBLIC
HEALTH DEPARTMENT ANYMORE AND
WOULD HAVE MISSED THE NEW YORK
CASES AND WOULD HAVE ONLY BEEN
ABLE TO GET INTO THE ONLY 2022
AND BEFORE CASES BUT AT THE TIME
IT WAS HEARTBREAKING.
WE CAME UP WITH A PLAN AND
ENGAGED THE LARGEST MENTAL
HEALTH SYSTEMS IN THE COUNTIES
AND ASKED THEM TO HELP US FIND
THE STUDY SUBJECTS.
I'LL BELABOR THIS BECAUSE WE
DON'T HAVE DEMOGRAPHICALLY
REPRESENTED DATA EXCEPT IN THE
POPULATION-BASED STUDIES BY THE
DEPAUL GROUP AND CDC IN THIS
COUNTRY.
WE HAVE LIMITED DEMOGRAPHICALLY
REPRESENTATIVE DATA.
AS YOU HEARD FROM OUR LIVED
EXPERIENCE FOLKS.
WE STARTED OFF WITH THIS IS
GOING TO BE EASY.
WE'LL MAKE A CONTRACT WITH THE
HOSPITALS.
THAT WAS HYSTERICAL.
STOP ME RIGHT THERE.
THEN THEY'LL GO OUT AND SEND
E-MAILS TO ALL THESE PEOPLE AND
PEOPLE WILL READ THEIR E-MAILS.
THAT WAS REALLY HYSTERICAL.
THAT WAS JUST A HYSTERICAL
ASSUMPTION THEY'LL CLICK AND GET
IN.
IN THE END WE HAD TO KEEP ON AT
IT UNTIL WE FOUND WAYS TO REACH
PEOPLE.
SO RECRUITING THROUGH THE LARGE
HOSPITAL SYSTEMS, BAPTIST HEALTH
IN MIAMI-DADE AND JACKSON AND
BROWARD HEALTH IN Ft. LAUDERDALE
AND WE HAVE APPOINTMENTS AND
DR. PALACIO HAS A LARGE COVID
CLINIC.
WE WENT FROM THERE.
667 PEOPLE WENT TO OUR SITE.
THAT'S GREAT.
200 READ SOMETHING THERE AND
CLICKED THE CONSENT WHICH IS
AMAZING BECAUSE MOST OF THOSE
ACTUALLY STAYED IN THE STUDY.
IF WE LOOK AT THE DEMOGRAPHICS
THEY'RE FANTASTIC.
JUST FANTASTIC.
16% NON-HISPANIC BLACK.
23% NON-HISPANIC WHITE AND THEN
56% HISPANIC IS REALLY
REPRESENTATIVE COHORT EXACTLY
WHAT WE WERE TRYING TO ACHIEVE.
WE'LL TAKE THAT.
IT WAS HARD.
STUDENTS HAD TO DO THE TEXT FROM
BEHIND THE FIRE WALLS WHICH WAS
CHALLENGING AND WE GOT ANOTHER
BUMP IN RECRUITMENT.
FIRST THE V.A. HEALTH SYSTEM
WOULD NOT LET US E-MAIL OR TEXT.
WE HAD TO TALK TO THE PATIENTS
AND BECAUSE WE'RE PROVIDERS WE
WERE ALLOWED TO AND REACHED OUT
TO MORE THAN 1700 PEOPLE.
THAT WAS OUR BEST RECRUITMENT.
WE GOT MORE PEOPLE TO BE
INCLINED.
ADVOCACY GROUPS SENT E-MAILS
THAT SAID IF YOU'RE IN THE
HEALTH CARE SYSTEMS YOU'RELY
ELIGIBLE FOR OUR STUDY.
YOU SHOULD GO TO OUR SITE AND
HAVE A QR CODE AND THAT HELPED.
WE GOT ANOTHER BUMP FROM THAT.
.
THEN FINALLY, JUST IN THE LAST
MONTH, WE WENT TO TWO HUGE
EMPLOYERS NOVA AND UNIVERSITY OF
MIAMI.
THEY'RE NOT PEOPLE WHO WERE
NECESSARILY COVID POSITIVE.
THAT WOULD BE EVERYBODY.
55,000 PEOPLE RECEIVED AN E-MAIL
AND NOT THAT MANY CLICKS.
BUT THE PEOPLE THAT CLICKED WERE
A BETTER RATE OF ENROLLMENT.
SO IT'S BEEN INTERESTING.
IT'S BEEN A CHALLENGE.
THE STUDY ITSELF ALSO HAD TO
CHANGE OVER TIME TO ACKNOWLEDGE
THE CHANGING KNOWLEDGE OF WHAT
IT MEANT TO HAVE COVID.
SO WE DESIGN A STUDY THREE YEARS
AGO WE WERE TRYING TO CATCH
PEOPLE WITHIN FIRST SIX MONTHS
OF POST-INFECTION.
THAT WAS A GREAT CONCEPT BUT
WHEN WE ACTIVATED THE STUDY IT
WAS AT THE BEGINNING OF OMICRON
AND WE WERE GOING TO MISS ALL
THE INFORMATION AND IMPORTANT
INFORMATION THAT WOULD MAKE OUR
STUDY GENERALIZABLE FROM EARLY
COHORTS.
HALF OUR COHORTS WAS ENROLLED
WITHIN SIX MONTHS OF ILLNESS AND
ROUGHLY HALF AT THIS POINT IS
BASICALLY ALL COMERS THAT HAVE
LONG COVID OR RECOVERED.
THERE WAS A SERIES OF BUMPS IN
OUR RECRUITMENT AS WE CHANGED
THE CRITERIA.
AGAIN, I'M EXCEEDINGLY PROUD OF
HOW THIS COHORT REPRESENTS AGES,
SEXES AND RACES.
IT'S AN EXCELLENT REPRESENTATION
OF OUR COMMUNITY.
THAT'S FANTASTIC.
THE SYMPTOMS AND WE HAD A
BROADER FATIGUE PLUS 1 SYSTEM
CRITERIA VERSUS AN EXPERT GROUP
OF ME/CFS DOCTORS THINKING YOU
HAVE THIS DISEASE.
ON THE MCAM COHORT LOOK
CIRCUMSTANCE AND MORE
SYMPTOMATIC THAN OUR COHORT
WHICH IS BROADER.
AGAIN, YOU'LL SEE FATIGUE IS THE
MOST COMMON AND POST-EXERTIONAL
FATIGUE IS EXCEEDINGLY COMMON IN
THE COVID GROUP AS WELL THE
OTHER SYMPTOMS OF ME/CFS.
THIS IS ALSO TRUE IN THE
SELF-REPORT OF COGNITIVE
FUNCTIONING AND THEIR PROMISE 29
WHICH IS LIKE THE SF36 SCORE OF
FUNCTION.
BOTH SOCIAL AND PHYSICAL.
WHEN YOU TRY TO COMPARE SOME OF
THIS TO THE MCAM STUDY AND WE'RE
HALFWAY THROUGH OUR RECRUITMENT
BUT YOU CAN SEE THIS IS COMPARED
TO THE PUBLISHED MCAM DATA THAT
THE COVID RECOVERED IS THE
HEALTHY GROUP IS THE BOTTOM LINE
THERE AND COVID UP IS THE MIDDLE
LINE AND THEN THE WHITE LINE IS
THE MCAM COHORT.
YOU CAN SEE THE PHYSICAL
FUNCTIONING SCORE ON BETWEEN THE
UNRECOVERED COVID PATIENTS AND
THE MCAM PATIENTS IS PRETTY
CLOSE.
THERE WASN'T A GOOD COGNITIVE
DATA SET TO COMPARE IN THE MCAM.
WE DIDN'T SEUSS THE SAME
ASSESSMENT TOOL BUT THE SOCIAL
PARTICIPATION ON THE PREMISE 29
COMPARISON THE MCAM IS A LITTLE
WORSE.
AND SOME OF THIS ISN'T READY FOR
PUBLICATION BUT I KNOW YOU GUYS
WANTED TO HEAR SOMETHING AND THE
DIASTOLIC DYSFUNCTION AND IT'S
NOT WELL PUBLISHED.
IT'S IN A COUPLE PAPERS BUT YOU
DON'T SEE IT AS SOMETHING WE
TALK A LOT ABOUT BUT WHEN THE
AFTERNOON GROUP WAS TALKING
ABOUT HYPOXIA AND PRE-LOAD
FAILURE, DIASTOLIC DYSFUNCTION
IS HAPPENING IN THE ATRIUM WHEN
IT'S FILLING SO MAY OR MAY NOT
BE EXACTLY PERFECT FOR PRE-LOAD
FAILURE AND BASICALLY SHOWING IN
THE UNRECOVERED GROUP ALMOST
HALF OF THE SUBJECTS THAT HAVE
GOTTEN THEIR ECO DATA HAVE
DIASTOLIC DYSFUNCTION AND IT'S
AN INTERESTING MARKER AND SPEAKS
TO A COMMONALITY BETWEEN LONG
COVID AND ME/CFS.
AND THE STUDY IS ONE YOU CAN DO
IN THE CLINIC AND HAVE PEOPLE
LEAN AGAINST THE WALL AND DO
BLOOD PRESSURE AND PULSE FOR 10
MINUTES AND TRY TO USE THIS IN
OUR STUDIES AND HAVE THE DATA IN
THE MCAM STUDY.
YOU SEE 20 OF THE PATIENTS OF 21
PHENOTYPING PATIENTS HAVE A
POSITIVE BUT YOU ALSO SEE A
FAIRLY HIGH NUMBER IN THE
RECOVER GROUP.
THE TEST IS NOT THAT GREAT A
DISCRIMINATOR.
THE TILT TABLE SAY BETTER
MEASURE FOR DYSOMONIA AND I DID
IT FOR THE PULSE OF 20 AND IF I
USED 20 I PICKED MORE UP IN THE
RECOVERED GROUP.
NEXT WAS AN ANALYSIS TO SEE IF
WE CAN CLUSTER THE POSTCOVID
UNRECOVERED PEOPLE INTO CLASSES.
THIS IS DONE A TRADITIONAL WAY
WITH THE LATENT CLASSIFICATION
STRATEGY.
WE LOOKED AT THESE PROSPECTIVES
FROM THE LONGITUDINAL COHORTS
BASELINE ASSESSMENT AND LOOKED
AT SOCIAL DETERMINATES OF HEALTH
AND VARIOUS SYMPTOMS AND THE
DEMOGRAPHICS THEN COMORBIDITIES
AND TRIED TO BREAK IT OUT AND
THE METHOD AND THIS IS THE
ANALYSIS FRESH OFF THE PRESS AND
INTERIM AND LOOK AT STATISTICS
AND DO THE BIVARIANT LABEL AND
SUMMARY STATISTICS SHOWS NO REAL
DIFFERENCE FROM RECOVERED AND
UNRECOVERED IN DEMOGRAPHICS
EXCEPT COMORBIDITY.
THAT'S NOT A SURPRISE.
WHEN YOU GO INTO THE
MULTI-VARIANT YOU'LL SEE THE
SYMPTOMS ARE WORSE IN THE
UNRECOVERED VERSUS RECOVERED
WITH THE EXCEPTION OF ANXIETY
AND THE FINANCIAL HARDSHIP AND
FOOD INSECURE WAS WELL BALANCED
BETWEEN THE CONTROL GROUP AND
THE SICK GROUP.
SO WE DIDN'T PICK UP IN A
MULTIVARIABLE REGRESSION A
DIFFERENCE IN SOCIAL
DETERMINATES OF HEALTH.
HOWEVER, WHEN WE DO THE LATENT
PROFILE ANALYSIS AND CLUSTER
INTO THREE GROUPS YOU'LL SEE
THERE'S A HEALTHY MODERATE AND
SICKEST GROUP AND THIS BREAK
DOWN AND HERE YOU START SEEING
SOME DEMOGRAPHIC DIFFERENCES AND
THE SOCIAL DETERMINATES OF
HEALTH BEING A FACTOR IN THE WAY
THESE THINGS CLUSTERED.
SO THE SICKEST GROUP WAS
HISPANIC MALE AND FINANCIALLY
INSECURE AND OLDER.
THE OLDER GROUP WAS PROMINENTLY
FEMALE AND THE IN THE SOUTH
FLORIDA COHORT AND HISPANIC
FEMALE OLDER MIDDLE AGE.
FOOD INSECURE AND THE HEALTHIEST
GROUP WAS THE NON-HISPANIC
WHITES AND YOUNGER AND ALSO HAVE
FOOD INSECURITY AND THE
COMORBIDITIES VARIED BY AMOUNT.
AND STRUGGLED ON RECRUITMENT
CAUSED A SPINOFF OF QUALITATIVE
STUDY.
THIS IS DR. PALACIO'S BABY AND
WITH THE CDC INVESTIGATORS AND
BASICALLY WAS A QUALITATIVE
STUDY WHERE YOU INTERVIEWED
PATIENTS THAT DECLINED TO BE IN
OUR STUDY AND ASKED THEM
QUESTIONS ABOUT WHAT WOULD HAVE
MADE THAT MORE LIKELY AND WHY
DID THEY DECLINE.
YOU'LL SEE THE BARRIERS THE
BIGGEST BARRIERS WERE LONG COVID
PERCEPTIONS, PATIENT'S OWN
UNDERSTANDING OF WHAT LONG COVID
IS AND THEIR OWN WILLINGNESS TO
EMBRACE THAT MIGHT BE THEIR
ILLNESS AND THEN UNCERTAINLY
ABOUT THE INSTITUTIONS OF
SKEPTICISM ABOUT WHETHER OR NOT
THEY COULD TRUST US AND THEIR
OWN PERSONAL PRIORITIES.
THEY INFORMED US ABOUT MESSAGING
AND WE CHANGED OUR MESSAGING
BASED ON THIS AND THE IACFS
WORKSHOP WE DID LAST SUMMER
WHERE WE HAD FEEDBACK FROM
ME/CFS PEOPLE WHAT WOULD HAVE
BROUGHT THEM IN IF WE CHANGE THE
WAY WE WERE REACHING OUT AND SO
THERE WAS QUITE A BIT OF LESSONS
LEARNED IN THE QUALITATIVE STUDY
THAT WAS HELPFUL AND YOU SEE THE
SKEPTICISM AND UNDERSTANDING OF
THE ILLNESS AND DISTRUST BEING A
REASON WHY THEY DIDN'T
PARTICIPATE AND THE PATIENTS WHO
SAID THEY'D PARTICIPATED THE
THING THAT BROUGHT THEM IN THE
BEST WAS IF THEIR OWN DOCTOR
ASKED THEM OR SOMEBODY THEY KNEW
ASKED THEM TO BE IN SO THAT
BUSINESS OF BEING ABLE TO CLICK
AN E-MAIL FROM A STRANGER VERSUS
HAVING SOMEONE YOU KNEW.
WE SENT THE E-MAIL IN MY
UNIVERSITY FIRST FROM THE DEAN
OF RESEARCH AND THE SECOND ONE
FROM ME, MY NAME WAS THERE AND I
GOT 450 OUT OF OFFICE MESSAGES
IN LESS THAN FIVE MINUTES.
THAT WAS FUN.
WE HAD FAR MORE PEOPLE OPEN ON
THE E-MAIL BECAUSE I'D BEEN
AROUND THE UNIVERSITY LONGER AND
KNOW WHO I AM AND I TALK A LOT.
CONCLUSIONS, THE CLINICAL
PRESENTATION OF LONG COVID AND
ME/CFS IS SIMILAR.
EFFORTS TO REPRESENT THE COHORT
HAS BEEN SUCCESSFUL WHICH IS
EXCITING IF SLOW.
WE'VE LEARNED A LOT AS WE'VE
WENT ALONG.
SO FAR WE'VE SEEN NO DIFFERENCES
IN GENERAL BETWEEN AGE, SEX AND
RACE BY SYMPTOMS BUT THE LATENT
CLASS ANALYSIS ALLOWED US TO SEE
THERE ARE GROUPINGS AND THERE'S
CONCERN THE HISPANIC MEN AND
WOMEN ARE GROUPING INTO THE MORE
SEVERE ILL GROUP AND FOOD AND
HOUSING INSECURITY WEIGHT IN THE
PREDICTORS OF SEVERITY.
THE PHENOTYPING STUDY IS
UNDERWAY AND GOING WELL AND
IDENTIFIED DYSFUNCTION AS A
CONCERN.
THIS WILL CONTINUE.
WE HAVE QUITE A BIT MORE DATA TO
GO IN THE STUDY.
AND MAYBE A LITTLE BIT MORE AND
THE QUALITATIVE STUDIES WERE
HELPFUL AND HELPED US DEVELOP
MORE EFFECTIVE TOOLS AND FINALLY
THE STUDY WILL KEEP ON GOING AND
WE'LL GET IT DONE, BY GOSH.
THANK YOU VERY MUCH.
>> WE HAVE TIME FOR ONE OR TWO
QUESTION.
>> AND I'M CURIOUS IF THE STUDY
YOU'VE BEEN ABLE TO INCLUDE
BILIRUBIN OR BODY TEMPERATURE.
>> THERE WAS A STUDY WE PROPOSED
YEARS AGO AND WE CAN EVOLVE THE
STUDY AND CHANGE THE PLATFORM AS
LONG AS WE CAN AFFORD TO DO IT
WITHIN OUR BUDGET.
WE HAVE OUR STORIED SAMPLES THAT
ARE EXTREMELY WELL CARED FOR AND
STORED IN A WAY WE CAN DO THAT
TYPE OF THING IN BACHZ AT THE
END.
I'D LOVE TO HEAR.
WE CAN TALK ABOUT WHAT'S
IMPORTANT AND KNOW WHAT IT IS
BUT I ALSO KNOW THE OXIDATIVE
STRESS MARKERS SHOULD BE
INCLUDED AND WE HAVE A COLLEAGUE
IN OUR GROUP THAT IS AN EXPERT
IN THAT THAT.
I THINK WE'LL BE ENGAGING HIM.
>> AND DO YOU KNOW IF THE
SAMPLES INCLUDE VENUS AND
ARTERIAL BLOOD.
>> THERE'S AN ECHO ON THE
STABLE.
I'M SORRY.
WE DO NOT HAVE ARTERIAL BLOOD
SAMPLE.
I'M SORRY.
THAT WOULD HAVE KILLED
RECRUITMENT.
>> OUR NEXT SPEAKER IS PROFESSOR
MAUREEN HANSON FROM CORNELL
UNIVERSITY AND PRESENT ON ME/CFS
AND LONG COVID SIMILARITIES AND
DIFFERENCES.
MAUREEN.
>> THANKS.
SO I'M GOING TO GIVE A BIT OF A
DIFFERENT TALK AND IT'S
DIFFERENT THAN MY USUAL KIND OF
TALK.
I'LL HAVE LESS DATA TO SHOW YOU
AND WANT TO GIVE HISTORICAL
BACKGROUND I THINK IS QUITE
RELEVANT ESPECIALLY IN THE DAYS
OF COVID.
SO WHAT ARE SOME MAJOR
SIMILARITIES OF ME/CFS AND LONG
COVID?
BOTH ARE CAUSED BY VIRUSES.
NOT EVERYBODY WILL BELIEVE ME
BUT I BELIEVE THEY'RE BOTH
CAUSED BY VIRUSES.
AND THE VIRUSS INSIDE THEM CAN
CAUSE OUTBREAKS AND PANDEMICS
AND THE PRE-2020 OUTBREAKS WERE
LIKELY CAUSED BY ENTEROVIRUSES
AND POLIO CAUSED AN EPIDEMIC IN
THE PAST AND SARS COV2 IS A PLUS
STRAND RNA VIRUS.
A LOT OF PEOPLE ARE UNAWARE OF
HOW MUCH EVIDENCE THERE IS THAT
ENTEROVIRUS CAUSED PAST
OUTBREAKS OF ME/CFS.
THESE FOUR BOOKS HERE THAT I'M
SHOWING ON THE EDGES DOCUMENT
THE ENTERO INVOLVEMENT OF
ME/CFS AND YOU CAN'T READ THEM
WITHOUT THINKING THEY CAUSED IT
HIT AN OSLER'S WEB MEASURED THE
OUTBREAKS AND I'M SHOWING A LIST
OF THE MANY OUTBREAKS DOCUMENT
ED.
ONE TIME I WAS AT A CONFERENCE
AND HAD A PATIENT SAY I GOT
ME/CFS ON A SCHOOL TRIP TO CHINA
IN THE MID-80s AND A LOT OF OUR
GROUP BECAME ILL.
WE SAW A CHINESE DOCTOR WHO
IMMEDIATELY DIAGNOSED US BECAUSE
THEY WERE HAVING AN OUTBREAK OF
ME/CFS IN THE TOWN.
INCIDENTALLY IF THAT PERSON IS
LISTENING, I'D LIKE TO YOU GET
IN TOUCH WITH ME.
A NUMBER OF THE OUTBREAKS
OCCURRED AT THE SAME TIME OF
POLIO OUTBREAKS.
THE 1934 OUTBREAK IN A LOS
ANGELES HOSPITAL AND 1946
ICELAND OUTBREAK AND 1949
AUSTRALIAN OUTBREAK.
THE FIRST POLIO VACCINE BECAME
AWARE IN 1964 BUT THE POLIO
VIRUS WAS STILL CIRCULATING AND
SOME REMEMBER GETTING A SHUG
CUBE WITH A PINK DOT ON IT THAT
WAS THE ORAL VACCINE.
POLIO WAS ERADICATED IN THE '70
IN THE U.S. BUT WE HAVE SOME
CASES NOW.
MANY OCCURRED WHEN POLIO WAS
STILL CIRCULATING ALL THE ONES
ON THE RIGHT.
WHY DID ME/CFS OUTBREAKS OCCUR
AT THE SAME TIME AS POLIO
OUTBREAKS?
THE POSSIBLE EXPLANATION IS THE
POLIO IS SPREAD BY CONTAMINATED
WATER AND THE FECAL/ORAL ROUTE.
I REMEMBER NOT BEING ALLOWED TO
GO TO THE SWIMMING POOL BECAUSE
I MIGHT GET POLIO.
OTHER ENTEROVIRUSES ARE FOUND IN
CONTAMINATED WATER AND IT COULD
HAVE BEEN CONTAMINATED WITH
VIRUSS AND THERE'S A
COINCIDENCE.
HOWEVER, IT'S ALSO POSSIBLE
BECAUSE ENTEROVIRUSES CAN
RECOMBINE MAYBE THE OUTBREAKS
THEN CALLED TYPICAL POLIO WAS A
RECOMBINATION VIRUS AND WITHOUT
SAMPLE WE'LL NEVER KNOW WHAT
VIRUS CAUSED THEM.
ONE THING THAT'S INTERESTING IS
SOME OF THE EARLY ME OUTBREAKS
COINCIDED WITH SOMETHING CALLED
BORNHOLM DISEASE AND KNOWN TO BE
CAUSED BY COX B ENTEROVIRUSES OR
COX A AND CAUSES LOW PAIN IN THE
CHEST AND ATTACKS THAT ARE
CRIPPLING AND TACHYCARDIA AND
RASHES AND SOMETIMES CAUSES
DISSEMINATED INTRAVASCULAR
COAGULATION, DIC AND YOU CAN
PLEAD -- BLEED FROM THAT AND YOU
CAN GET BLOOD CLOTS IF FACTOR 5
IS HIGH.
YOU CAN SEE STUDIES DESCRIBED
HERE.
THAT'S A COMMONALITY THAT
COAGULATION DISTURBANCES HAVE
BEEN DETECTED IN LONG COVID AND
ME/CFS.
THIS WORK IS LARGELY DONE BY THE
LAB IN SOUTH AFRICA.
IT'S INTERESTING PAPERS SHOWING
HYP
HYPERCOAGUABILITY AND IN THE
NEXT TALK YOU MAY HEAR SOMETHING
ABOUT PLATELETS.
ONE THING THAT HER LAB DID FIND
IS AND TWO CLINICIANS SAW
PATIENT AND TESTIFIED THERE WAS
A FIVE TO EIGHTFOLD INCREMENT
WORLDWIDE BETWEEN 1980 AND 1989.
I'M SHOWING THE LIST OF THE
OUTBREAKS DURING THAT PERIOD OF
TIME.
AND THEN FROM HILARY JOHNSON'S
BOOK OSLER'S WEB SHE TURNED UP
INFORMATION FROM A DISABILITY
INSURANCE COMPANY SHOWING THAT
CLAIMS FOR DISABILITY CAUSED BY
WHAT WAS THEN CALLED CHRONIC
FATIGUE SYNDROME INCREASED 500%
FROM 1989 TO 1993.
THIS WAS A BIGGER INCREASE THAN
AN OTHER CATEGORY OF DISABILITY.
WHAT HAPPENED IN THE MID 80s I
BELIEVE WAS A HIDDEN PANDEMIC.
TO EMPHASIZE THIS WAS A
PANDEMIC, I WANT TO TELL YOU
MORE INFORMATION FROM OSLER'S
WEB AND SHE FOUND AN EMPLOYEE AT
CDC TO INTERVIEW WHEN SHE
VISITED CDC AND FOND OUT IN 1999
THERE WERE 1,000 CALLS PER MONTH
ABOUT CHRONIC FATIGUE SYNDROME
BEING RECEIVED AT CDC AND THIS
OUTNUMBERED CALLS ABOUT AIDS AT
THE TIME.
IN 1990 THE CDC WAS RECEIVING
OVER 7,000 CALLS A MONTH AND A
HUNDRED LETTERS A DAY AND THEY
HAD TO HIRE A FULL-TIME EMPLOYEE
TO CONTACT THESE PEOPLE SAYING
THERE WAS NO EVIDENCE ME/CFS WAS
CONTAGIOUS AND A SMALL NUMBER OF
PATIENTS HAD MODEST IMMUNE
DIFFERENCES.
THIS IS UNFORTUNATE GIVEN IF
THESE OUTBREAKS HAD BEEN
INVESTIGATED PROPERLY THEN WE
WOULD KNOW MORE TODAY.
WHY WERE ALL THESE OUTBREAKS IN
THE 1980s AND WHAT WOULD RESULT
IN THESE OUTBREAKS?
WE NEED TO REMEMBER IN THE 1980s
OUTBREAKS OCCURRED AT THE SAME
TIME AIDS WAS UNCONTROLLED.
THIS SOMETHING NOTED BY A LOT OF
THE PHYSICIANS SUCH AS DAN
PETERSON WHO PRESIDED OVER ONE
OF THE OUTBREAKS AND DURING THE
SAME PERIOD THE OUTBREAKS WERE
OCCURRING THERE WAS A SEVERELY
IMMUNOCOMPROMISED POPULATION IN
THE U.S.
WHAT COULD BE THE CONSEQUENCE
AND ENTEROVIRUS HAVE HIGHER
MUTATION RATES THAN CORONAVIRUS
AND WE HEAR ALMOST DAILY ABOUT
SOME NEW VARIANT OF THE
CORONAVIRUS BECAUSE THERE'S SO
MANY PEOPLE INFECTED OUT THERE
GENERATING NEW VARIANTS BUT
ENTEROVIRUSES ALSO HAVE THE
PROPENSITY TO MUTATE AND A
GREATER PROPENSIPROPENSITY, ACT.
THE CURRENT ESTIMATES OF
IMMUNOCOMPROMISE VARY 9% TO 18%
AND MANY ARE IMMUNOCOMPROMISED
DUE TO MEDICATION OR DISEASE AND
ONE DOCUMENTED IMMUNOCOMPROMISED
PATIENTS ARE INCUBATING SARS
COV2 AND CREATING VARIANTS AND
COVID-19 CAN RESULT IN A WEAK
IMMUNE RESPONSE.
I THINK AND THIS IS JUST AN
OPINION, LIKE THE ORIGINAL SARS
COV2 THE 1980s OUTBREAK ENT
ENTEROVIRUS IS NO LONGER
CIRCULATING AND THE SPORADIC
CASES WE'RE SEEING NOW ARE
RISING FROM AN OCCASIONAL
VARIANT INFECTS A SUSCEPTIBLE
INDIVIDUAL.
WHAT'S INTERESTING AND SCARY IS
THE CONDITIONS ARE NOW FAVORABLE
FOR EMERGENCE OF NOVEL VARIANTS
THAT CAN INSIGHT BUT HOW WILL WE
DETECT THESE ME/CFS OUTBREAKS?
WE RIGHT NOW CANNOT DISTINGUISH
ME/CFS FROM LONG COVID UNLESS
THE PERSON OBVIOUSLY HAS LOVES
SENSE OF SMELL OR TASTE.
-- LOST SENSE OF SMELL OR TASTE.
THE PERSISTENCE OF DNA VIRUS IS
IS WELL KNOWN.
SARS COV2 PERSISTS LONG AFTER
THE ACUTE INFECTION.
WE HAD A CONVINCING TALK
DESCRIBING SOME OF THE
INFORMATION THOUGH THERE'S
CONTROVERSY ABOUT PERSISTENCE
AND TWO PAPERS INDICATE SARS
COV2 CAN BE FOUND TO PERSIST
AFTER A LONG PERIOD OF TIME.
SO A QUESTION ARISES DO
ENTEROVIRUS PERSIST IN
INDIVIDUALS WITH ME/CFS?
THERE'S EVIDENCE THAT IT DOES
PERSIST IN SOME INDIVIDUALS.
WE DON'T KNOW HOW MANY
INDIVIDUALS WITH ME/CFS HAVE
PERSISTENT VIRUS BUT I BELIEVE
THERE'S EVIDENCE AT LEAST SOME
INDIVIDUALS DO.
ENTEROVIRUSES CAN BE STUDIED IN
PEOPLE WITH CARDIO MYOPATHY AND
TYPE 1 DIABETES AND THEY CAN BE
STUDIED AND MAINTAINED IN CELL
CULTURE FOR LONG PERIOD OF TIME.
THE ADAPTATIONS OF THE VIRUS
THAT ALLOW IT TO DO THIS ARE
REASONABLY WELL KNOWN AND HAVE
AN ALTERATION IN THEIR
TRANSLATED REGION ALLOWS THEM TO
PERSIST.
SO I'LL MENTION ONE STUDIO IN
WHICH ENTEROVIRAL SEQUENCES WERE
DETECTED IN MUSCLE.
THOUGH THE PCR HADN'T BEEN
AROUND A LONG TIME THEY GOT
SEQUENCES.
THIS IS CALLED CFS PATIENTS
REFERRED TO A HOSPITAL IN THE
U.K. OVER A 10 YEAR PERIOD AND
10 OF THE 48 MUSCLE BIOPSIES HAD
A SEQUENCE IDENTICAL COX B
STRAIN ISOLATED IN 1949.
THREE CONSEQUENCES ARE IDENTICAL
TO COXSACKIE B AND IT TELLS ME
IT'S NOT JUST CONTAMINATION AND
THEY GOT DIFFERENT -- THEY
DETECTED DIFFERENT SEQUENCES IN
THE PATIENTS.
IF YOU WANT TO LEARN MORE ABOUT
THIS, I SUGGEST YOU SEE MY TALK
IN THE CHRONIC INFECTIONS NIH
ROAD MAP WEBINAR SERIES NOT YET
RELEASED BUT SHOULD BE IN THE
NEXT WEEKS AND WILL SEE MORE
DOUGH TAILED INFORMATION ABOUT
ENTEROVIRUSES.
I WOULD LIKE TO HIGHLIGHT ONE
PAPER DONE BY A LAB BECAUSE IN
THE LATER DAYS HE'S DONE THE
MOST RECENT STUDIES OF ENT
ENTEROV
ENTEROVIRUSES.
THE ONE PAPER PUBLISHED IN 2008
AMAZE LIG HE WAS ABLE TO GET A
LARGE NUMBER OF UPPER G.I.
ENDOSSCOPIES DONE TO GET HOLD OF
STOM
STOMACH BIOPSIES AND DOING THE
MONOCLONAL ANTIBODY 135 OF THE
165 SAMPLE WERE POSITIVE AND
ONLY 31 CONTROL BUT NOTICE SOME
CONTROLS ACTUALLY HAD GASTRIC
DISEASE.
SO WHEN I REREAD THIS PAPER LAST
WEEK IN PREPARATION FOR THE TALK
I REALIZED HE MENTIONED THEY HAD
GOTTEN RNA SEQUENCES FROM THE
VIRUS AND HE STILL HAD THEM THE
DATABASE WAS SMALLER THAN IT IS
NOW.
I GOT SEQUENCES FROM HIM AND
USED BLAST TO SEE WHAT THEY WERE
AND MY RECENT BLAST OF THIS 156
NUCLEOTIDE UTR SEQUENCE SHOWED
98% IDENTICAL TO ECO VIRUS 18
AND ALSO TO ECHO VIRUS 6.
IT DOESN'T MEAN THEY WERE 18 OR
6 BECAUSE WITH SUCH A SHORT
SEQUENCE IF WE HAD MORE IT MAY
BE A DIFFERENT ENTEROVIRUS BUT
CLEARLY IT'S AN ENTERO VIRUS
SEQUENCE THERE.
SO NEXT THING I'D LIKE TO TALK
ABOUT IS THE FACT THAT BOTH SARS
COV2 AND ENTEROVIRUSES CAUSE
ASYMPTOMATIC INFECTIONS AS THE
EXAMPLE FROM THE NEW YORK TIMES
AND THERE'S A REFERENCE TO A
SCIENTIFIC PAPER ABOUT IT.
MOST THE 15 TO 30 MILLION
ENTEROVIRUSES MENTIONED ON THE
CDC WEBSITE ANNUALLY ON THE
U.S. ARE ASYMPTOMATIC OR MILD.
YOU MAY THINK YOU HAD A COLD FOR
A DAY.
SO LONG COVID FOLLOWING
ASYMPTOMATIC INFECTION SUGGESTS
TO ME THE ONSET OF ME/CFS MAY
NOT BE DUE TO SOME COINCIDENTAL
MENTAL TRAUMA OR ENVIRONMENTAL
EXPOSURE BUT COULD RESULT FROM
AN ENTEROVIRAL INFECTION AND
WHEN YOU'RE TRYING TO FIGURE OUT
WHY I GOT SICK, YOU MAY THINK,
OH, I WAS IN THE CAR ACCIDENT
BUT YOU MAY HAVE HAD AN
ASYMPTOMATIC INFECTION AND
STRESS CAN IMPAIR IMMUNE
RESPONSE AND COULD PLAY A ROLE
IN THE DEVELOPMENT OF ME/CFS
FOLLOWING AN INFECTION.
YOU HAVE AN INFECTION AND LOST
YOUR JOB OR SOMETHING HAPPENED
AND THE STRESS COULD INCREASE
YOUR CHANCES.
AND I'D LIKE TO A THOUGHT
EXPERIMENT FROM A CORONAVIRUS
OUTBREAK.
THERE'S FOUR COMMON COLD
CORONAVIRUSES PROBABLY ALL OF US
HAVE HAD.
SUPPOSE INSTEAD OF SARS COV2
INFECTING THE WORLD IN 2020 A
COMMON COLD CORONAVIRUS MUTATED
AND RESULTED IN INFECTIONS THAT
LED TO LONG COVID.
WELL, THE INITIAL INFECTION
WOULD BE ASYMPTOMATIC OR MILD
JUST A LITTLE COLD OR FLU-LIKE
ILLNESS AND PEOPLE WOULDN'T BE
HOSPITALIZED OR DYING AND THEN
WHAT WOULD HAPPEN?
PEOPLE WOULDN'T KNOW WHAT CAUSED
THEIR PERSISTENT ILLNESS AND NOT
BE BELIEVED UNTIL THEY HAD A
PSYCHOLOGICAL ILLNESS AND
THOUGHT TO BE FAKING TO AVOID
WORK OR SCHOOL.
DOESN'T THAT SOUND FAMILIAR?
IT'S TELLING US THE MOST LIKELY
CAUSE OF THE SPORADIC CASES OF
ME IS AN INDIVIDUAL WITH A
VARIANT NOT AN EXOTIC VIRUS OUT
THERE.
NOW, OFTEN PEOPLE SAY THEY GOT
THEIR ME/CFS FROM SOME HERPES
VIRUS INFECTION OR FOLLOWING
THAT AND REACTIVATION OF HERPES
VIRUS OCCURS IN LONG COVID AND
ME/CFS.
I WAS SHOWING A FEW PAPERS ABOUT
LONG COVID AND I WANTED TO
HIGHLIGHT THE PAPER DONE
INVESTIGATING THE INCLINE
VILLAGE OUTBREAK PRESIDED OVER
BY DAN PETER SSON I THINK IT'S E
BEST INVESTIGATION OF THAT
OUTBREAK IN THAT TIME PERIOD AND
ALREADY IN 1992 THIS GROUP WAS
ABLE TO SEE THERE WAS
REACTIVATION OF HPV6 AND THAT'S
BEEN SEEN SINCE THEN AS WELL.
AND I THINK AND THIS IS
SPECULATION AND MY OPINION I
THINK HERPES VIRUS ACCOMPLICES
IN LONG COVID BUT I DON'T THINK
THE EPIDEMIOLOGY OF OUTBREAKS IS
NOT CONSISTENT WITH THE
EPIDEMIOLOGY OF INFECTIONS AND
EBV OR OTHER HERPES VIRUSES AND
WHETHER THEY'RE INCITED BY THEM
RECEIVED WITHOUT ANY CASE OF
ME/CFS IS UNKNOWN AND THE ACTIVE
HERPES VIRUS MAY MAKE AN
INDIVIDUAL MORE SUSCEPTIBLE TO
ANOTHER VIRUS.
YOU GET MONOAND ARE FATIGUED FOR
A MONTH AND DON'T KNOW IT'S
ANYTHING UNUSUAL AND THEN BEGIN
TO REALIZE IT'S BAD.
I'M STILL SICK WITH MY MONO.
NOW I HAVE ME/CFS.
IT'S TRUE CONTINUED EXPRESSION
OF HERPES VIRUS PROTEINS DUE TO
ESCAPE FROM THE CONTROL COULD BE
CONTRIBUTING TO LONG COVID AND
PATHOPHYSIOLOGY AND IT'S
IMPORTANT TO KNOW ABOUT HERPES
VIRUS INFECTIONS AND THEIR ROLE
IN ME/CFS.
AND IN LONG COVID.
PATIENT SYMPTOMS ARE DIVERSE AND
A POST-DOCTORAL ASSOCIATE IN MY
LAB DID CLUSTERING OF PATIENTS
AND IDENTIFIED FOUR CLUSTERS.
THIS WORK IS UNPUBLISHED BUT
PRESENTED ON A POSTER YOU CAN
SEE AT LUNCH TIME AND THE AUTHOR
WILL BE AROUND AND SHE WAS ABLE
TO SEE THERE WERE FOUR CLUSTERS
AND THERE WAS LOWER ME/CFS
SEVERITY ACCORDING TO HAVING
HIGHER FS36 AND LOWER WAKING
TIME AND SEVERITY SCALE FOR
POST-EXERTIONAL MALAISE AND SORE
THROAT AND MIALGIA AND IT WOULD
BE GOOD TO EXTEND THIS TIE
LARGER BATCH.
WE DID THIS AND YOU SAW THIS
SAME CHART FROM CINDY BATEMAN
THIS MORNING AND IT SHOWS
THERE'S THESE FOUR CLUSTERS.
I THINK WHAT IS AN IMPORTANT
POINT ABOUT THE FOUR CLUSTERS IS
THAT THIS PASC STUDIO
DEMONSTRATES THE SINGLE VIRUS
TYPE CAN GIVE RISE TO A
POST-VIRAL ILLNESS POPULATION
THAT HAS DIVERSE SYMPTOMS.
THERE'S A DIVERSITY IN THE
PATIENT GROUP.
PEOPLE SOMETIMES SAY IT COULD BE
EASIER TO STUDY LONG COVID
BECAUSE THEY'RE ALL UNIFORM.
IT'S NOT THE CASE.
IN FACT, THE OTHER POINT I'D
LIKE TO MAKE IS PRE-2020 ME/CFS
MAY HAVE BEEN CAUSED BY A SINGLE
VIRUS TYPE RATHER THAN BY
MULTIPLE VIRUS.
IT'S AN OFTEN BEEN CLAIMED TO
EXPLAIN THE DIFFERENCE IN ME/CFS
SUB GROUPS THEY DO EXIST IN
TERMS OF SYMPTOMS AND ALSO IN
TERMS OF SOME OF THE MOLECULAR
AND BIO CHEMICAL AND
PHYSIOLOGICAL DATA WE HAVE.
CAN STUDY OF PRE-2020 ME/CFS BE
REPLACED BY STUDIES MUCH LONG
COVID PATIENTS THAT FULFILL THE
2015 CRITERIA?
WELL, THE COMMONALITY OF MANY
SYMPTOMS WE'VE BEEN HEARING
ABOUT SUGGEST THERE ARE COMMON
DISRUPTIVE PATHWAYS THAT CAN
LEAD TO A SYMPTOM.
THIS COULD RESULT FROM THE
ME/CFS AGENTS AS WELL AS SARS
COV2 AND IF YOU HAVE AN
INTERVENTION AT THIS POINT IN
THE COMMON DISRUPTED PATHWAY,
THEN THAT'S GOING TO BENEFIT
BOTH ME/CFS AND LONG COVID.
SUPPOSE INSTEAD HAVE YOU AN
INTERVENTION THAT CAN AFFECT
THIS EARLIER PART.
WHAT LEADS TO THAT COMMON
DISRUPTED PATHWAY.
AND AN EXAMPLE OF SUCH AN
INTERVENTION THAT CAN BENEFIT
ONLY LONG COVID IS TREATMENT OF
A PERSISTENT LONG COVID
INFECTION WITH A SARS COV2 DRUG
AND AN INTERESTING STUDY WHERE
THREE PEOPLE WERE CURED
RECEIVING AN ANTIMONOCLONAL
ANTIBODY THAT AFFECTED THEIR
INCITING VIRUS.
IF THERE'S CHRONIC INFECTION
MAINTAINING AN ME/CFS STATUS WE
NEED TO HAVE DRUGS THAT WILL
CURE US OF THAT ENTEROVIRUS
INFECTION OR OTHER INFECTION.
ALSO, IT'S QUITE POSSIBLE
THERE'S AN AUTO ANTIBODY OR
PATHOGENIC ANTIBODIES INVOLVED
AND MAY RESULT FROM MOLECULAR
AGENTS WILL BE DIFFERENT IN LONG
COVID VERSUS ME/CFS FOR EXAMPLE,
ENTEROVIRUS AND SARS COV2 DON'T
SHARE SEQUENCE AMOL GY.
THERE COULD BE DIFFERENT
ANTIBODIES RESULTING FROM THE
TWO AND YOU MAY NEED DIFFERENT
INTERVENTIONS.
OF COURSE THERE'S ALSO THE
POSSIBILITY THERE'S DIFFERENT
DISRUPTED PATHWAYS THAT OCCUR IN
ME/CFS VERSUS SARS COV2.
FOR EXAMPLE, THERE'S LOTS OF
WAYS OF GETTING A HEADACHE.
THERE CAN BE DIFFERENT PATHWAYS
TO GET A HEADACHE.
WE NEED TO STUDY BOTH ME/CFS AND
SARS COV2 TO UNDERSTAND THE
COMMON DISRUPTED PATHWAYS AND
ARE THERE ANY DIFFERENT
DISRUPTED PATHWAYS.
SO WHAT ARE SOME DIFFERENCES
BETWEEN LONG COVID AND ME/CFS?
PEOPLE TEND TO EMPHASIZE THE
SIMILARITIES BECAUSE IT'S VERY
STRIKING.
THEY ARE NOT INCITED BY THE SAME
VIRUS AND THE VIRUS THAT
ULTIMATELY LEADS TO LONG COVID
IS A LOT MORE DEADLY THAN THE
ONES LEADING TO ME/CFS WHICH
NORMALLY CAUSE MILD FLU-LIKE
ILLNESS.
THE VIRUS CAUSING LONG COVID
MUTATES LESS OFTEN THAN
ENTEROVIRUSES.
THERE ARE SOME LONG COVID
SYMPTOMS YOU DON'T SEE IN
EMPHASIS AND FOREMOST ARE THE
LOSS OF SENSE OF SMELL OR TASTE.
THERE'S COAGULABILITY AND
CORTISOL WAS STUDIED AND THERE'S
LONG COVID AND CONTROLS WHO
RECOVERED AND DON'T HAVE
CORTISOL AND WE DON'T SEE A
DIFFERENCE AS IN ANY ME/CFS
PUBLISHED IN 2022 PAPER.
THE DATA'S AVAILABLE AND
SUPPLEMENTARY DATA IN THE PAPER.
SO THIS ACTUALLY BRINGS THE
POINT THAT WE NEED TO BE DOING
STUDIES OF ME/CFS AND LONG COVID
AT THE SAME TIME SO WE CAN
USE -- WE DIDN'T USE THE SAME
PROTOCOL FOR ISOLATING THE BLOOD
FOR DOING THE ASSAY.
WE NEED TO DO DIRECT COMPARISONS
IN ORDER TO KNOW WHETHER THERE
ARE DIFFERENCES OR SIMILARITIES.
THIS IS CERTAINLY SUGGESTIVE
THERE'S A DIFFERENCE HERE.
AND ALSO A PAPER THAT GOT A LOT
OF PRESS WAS FOR LOW LEVELS OF
SEROTONIN OBSERVED IN LONG
COVID.
AGAIN, YOU SEE ON THE RIGHT IS
THE PASC LEVEL OF SEROTONIN AND
THE RECOVERED PEOPLE HAVE HIGHER
SEROTONIN AND THE ACUTE CASES
HAVE LOW SEROTONIN ALSO.
WHEN WE ASSAYED OUR PATIENT
COHORT WE DID NOT SEE
DIFFERENCES IN SEROTONIN LEVEL
AND NEED TO MAKE DIRECT
COMPARISONS.
IN THE LAST MINUTE OR SO I'D
LIKE TO MENTION ONE OTHER MAJOR
DIFFERENCE BETWEEN LONG COVID
AND ME/CFS.
THIS IS THAT MAJOR DIFFERENCE.
THERE'S MORE MONEY AVAILABLE FOR
STUDYING LONG COVID THAN ABE
ME/CFS.
IN 2021 WE RECEIVED $13 MILLION
FROM NIH.
NOW, NIH DIDN'T HAVE A BILLION
DOLLARS LYING AROUND TO DEVOTE
TO PASC IT WAS GIVEN TO NIH BY
CONGRESS BECAUSE OF THE URGENCY
OF STUDYING THIS.
MOST ARE WELL AWARE OF THE UNDER
FUNDING OF ME/CFS RELATIVE TO
THE BURDEN OF ILLNESS AND ONE
BURDEN IS AIDS.
IT OVERSHADOWED AIDS IN THE '80s
AND STILL OVERSHADOWING ME/CFS.
THERE'S 1.2 MILLION INDIVIDUALS
LIVING WITH HIV IN THE U.S. AND
OVER 3 MILLION BARELY LIVING
WITH ME/CFS IN THE U.S.
WHAT'S PARTICULARLY CRITICAL IS
IT'S POSSIBLE THE FUTURE FUNDING
FOR PASC IS IS NOW GOING TO
DISAPPEAR AND WHAT I WOULD LIKE
TO SAY TO THE ADVOCATES AND
PATIENTS AND MEMBERS OF THE
ADVOCACY ORGANIZATIONS IS WE
NEED AN INITIATIVE FOR
POST-ACUTE INFECTION DISEASE
SYNDR
SYNDROME.
THERE NEEDS TO BE A NEW
INITIATIVE TO STUDIES THESE
ILLNESSES TO RESTORE THEIR
HEALTH.
I'D LIKE TO END WITH THESE
ACKNOWLEDGEMENTS.
THANK YOU.
WE HAVE TIME FOR ONE OR TWO
QUESTIONS.
PLEASE GO UP TO THE MIC.
>> WE TALK ABOUT THIS ON THE WAY
HOME BUT I'D LIKE MORE ANSWERS
FROM THE AUDIENCE.
THINKING ABOUT INFECTIONS,
MICROBACTERIA NEVER GO AWAY
THOUGH WE CALL IT CURED FROM
T.B.
STA
STAPHAUREUS INFECTIONS YOU'RE
STILL COLONIZED WITH IT
AFTERWARDS AND WONDERING IF
THERE'S ANY KNOWLEDGE ABOUT
MAYBE WHEN YOU GET A VIRUS IT
NEVER LEAVES YOUR BODY.
THIS IS WHAT WE'RE SEEING.
I'M CURIOUS IF THERE'S
INFORMATION ABOUT WHAT PEOPLE
KNOW ABOUT THAT.
>> I ONLY KNOW ABOUT ENTEROVIRUS
AND SARS COV2.
I DON'T KNOW ABOUT OTHER VIRUSES
AND OF COURSE THERE'S
CONTROVERSY ON WHAT CHRONIC LYME
IS.
SO -- I CAN'T ANSWER THAT
QUESTION.
I DON'T KNOW ABOUT OTHER
VIRUSES.
>> THANK YOU FOR YOUR TALK.
I HAVE COMMENTS FROM YOUR WEB
PEOPLE ONLINE.
ONE IS AN OBSERVATION THAT A
PARTICULAR PATIENT WHO HAS NOTED
THE IMPACT OF NUTRITION ON THEIR
JOURNEY AND MAKE THE CONNECTION
YOU WERE SAYING WHAT'S
DIFFERENCE ABOUT THE 1980s CASES
AND THEY JUST WANT TO BRING UP
THAT'S WHEN THE SWITCH TO HIGH
FRUCTOSE CORN SYRUP AND FOOD
STUFFS OCCURRED.
THAT'S A COMMENT NOT A QUESTION.
>> MAYBE PEOPLE ON ZOOM CAN'T
HEAR THAT NUTRITION COULD HAVE
BEEN DIFFERENT IN THE 1980s.
>> THE OTHER IS TWO SEPARATE
FOLKS ONLINE HAVE ASKED ABOUT
THE CONNECTIONS BETWEEN WHAT YOU
PRESENTED FOR ENTEROVIRUSES AND
MICROBIOME CHANGES AND IF YOU
HAVE ANY THOUGHTS ABOUT THAT
SINCE WE SAW DATA ABOUT
MICROBIOME CHANGES.
>> THE QUESTION IS IS THERE
RELATIONSHIP BETWEEN THE
ALTERATIONS OF PEOPLE SEE IN THE
GUT MICROBIOME AND WHAT I'VE
BEEN TALKING ABOUT ENTER YO --
ENTEROVIRUSES.
THEY ARE CALLED THAT BECAUSE
THEY GO TO YOUR GUT AND START
THE INFECTION.
WE DON'T KNOW WHETHER IN FACT IN
YOUR GUT YOU STILL HAVE
ENTEROVIRUSES IF YOU HAVE ME/CFS
AND THAT COULD BE EXAMINED.
THAT COULD BE A CONNECTION.
>> I'M FROM U.C. SAN DIEGO.
CAN ENTEROVIRAL INFECTION OF
ANIMAL CAUSE A FATIGUE SYMPTOM
IN ANIMALS OR PHENOTYPE?
>> I COULDN'T HEAR -- YOU SAID
SOMETHING ABOUT ENTEROVIRUS
INFECTION IN ANIMALS DO WHAT?
>> INDUCE FATIGUE PHENOTYPE IN
ANIMALS?
>> SO DO ANIMALS GET FATIGUED BY
ENTEROVIRUSES?
PEOPLE HAVE BEEN STUDYING IN
MICE.
I DON'T KNOW DETAILS ON THAT
DATA WHETHER THEY CAN RUN LESS
ON THEIR WHEELS BUT IT'S
PROBABLY KNOWN.
I JUST DON'T KNOW THAT DATA.
>> HAVE YOU INCLUDED THE
HOMOGEASE BILIRUBIN -- DID YOU
HEAR?
[INDISCERNIBLE]
>> THE HEME OXYGENASE AND THE
BYPRODUCT ARE BILIRUBIN AND SOME
HAVE BEEN IDENTIFIED AS ELEVATE
AND ASKED IF YOU LOOKED AT THAT
AND SEEN THAT?
>> I COULDN'T HEAR THAT REALLY
BUT I PROBABLY WOULDN'T KNOW THE
ANSWER EVEN IF I DID.
>> THANK YOU.
>> THANK YOU VERY MUCH, MAUREEN.
>> SO I THINK WE HAVE AN
EXCEPTIONAL MORNING.
PLEASE JOIN ME FOR A BIG ROUND
OF APPLAUSE FOR OUR SPEAKERS
THIS MORNING.
NOW IT'S TIME FOR THE BREAK
WE'LL COME BACK AT 11:00.
THANK YOU.
-- THE REASON IT'S IMPORTANT IS
WE NEED TO MATCH THE SEQUENCING
DATA BACK TO THE CELL OF ORIGIN
AND THE BAR CODE LETS US DO
THAT.
THE PLATFORM WE USED IS CALLED A
10X PLATFORM OR EVERY INDIVIDUAL
PROFILE MANY THOUSANDS IMMUNE
CELLS AND WE DETECT THOUSANDS OF
GENES.
WE CAN DO THIS ONLY WITH A FEW
HUNDRED MICROLITERS SO IT'S AN
EFFICIENT WAY OF USING VALUABLE
SAMPLES.
THIS IS A SIMPLE CARTOON OF WHAT
THE DATA LOOKS LIKE.
LOOK AT THE UNDERLYING
SEQUENCES.
THE DNA CONSEQUENCE TELLS YOU
THAT GENE WAS EXPRESSED IN A
CELL AND BECAUSE WE ALSO ALSO
SEQUENCE THE CELL BAR CODE WE
KNOW IT WAS EXPRESSED IN A
PARTICULAR BAR CODE AND CAN PARS
OUT FROM THOUSANDS OF CELLS FROM
EACH DIFFERENT BAR CODES.
THIS IS THE DATA SET.
WE HAVE 15 BILLION TOTAL
SEQUENCING READS AND CORRESPONDS
TO HALF A MILLION CELL
TRANSCRIPTOMES SPLIT BETWEEN
ME/CFS AND CONTROL COHORT.
THE DIAGRAM YOU'RE LOOKING AT IS
CALLED THE U-MAP.
A COMMON WAY OF REPRESENTING THE
DATA EACH DOT IS THE
TRANSCRIPTOME OF ONE CELL AND IF
THE CELLS ARE CLOSE TO EACH
OTHER IT MEANS THEY'RE HIGHLY
CONGRUENT THE SOFTWARE THEN
GATHERS HIGHLY CONCORDANT
TRANSCRIPTOMES AND CALLS THEM
CLUSTER AND WHAT'S COLORED AND
NUMBERED.
THE CLUSTERS WILL CORRESPOND TO
PARTICULAR CELL TYPES.
THIS WAS A HUGE TEAM EFFORT
START FROM THE CLINICIANS, THE
CLINICAL CORPS, THE PROJECT
COORDINATOR AND CORNELL AND A
LOT OF MOLECULAR BIOLOGY AND
SEQUENCING AND A COMPUTATIONAL
BIOLOGISTS THAT DID THE ANALYSIS
I GET TO TALK ABOUT.
BEFORE THE BIOLOGY A BIT OF
QUALITY CONTROL DATA WHICH IS
IMPORTANT FOR THE STUDIES.
THESE ARE COMMON QC METRICS FOR
DATA.
THE NUMBER OF GENES YOU DETECT
PER CELL AND THE NUMBER OF mRNA
AND PERCENT MITOCHONDRIAL
CONTAMINATION PARSED FROM THE
FOUR GROUPS.
THE CONTROL COHORTS AT BASELINE
AND THEN THE ME/CFS INDIVIDUALS
AT BASELINE AND ALL WE NEED TO
GET FROM THIS IS THE METRICS ARE
EQUIVALENT ACROSS THE FOUR
GROUPS WHICH IS IMPORTANT.
YOU CAN'T GENERATE ALL THE DATA
AT ONE TIME AND HAVE TO SPLIT IT
INTO BATCHES.
AGAIN THIS LOOKS GOOD.
WE HAVE TO PUT BIOLOGICAL LABELS
ON THE CLUSTERS.
WE LOOK AT DIAGNOSTIC MARKER
GENES KNOWN TO BE EXPRESSED IN
IMMUNE CELLS AND COME UP WITH A
FINAL MAP TO PLACE BIOLOGICAL
LABELS ON THE CLUSTERS.
AND IF WE SPLIT IT INTO ME/CFS
AND LOOK ESSENTIALLY IDENTICAL
AND SO THE DIFFERENCES WE'RE
GOING TO LOOK AT ARE MORE
SUBTLE.
AND WE SEE SOME SUBTLE CHANGES.
THE DATA IS SHOWING YOU ANTIGEN
EXPERIENCED CD8 T CELLS ARE
SLIGHTLY DEPLETED IN THESE
PATIENTS BUT SUBTLE, OTHERS ARE
DIFFERENT AND WE DON'T THINK
THEY'RE MAJOR FEATURES OF THE
IMMUNE SYSTEM.
THEY'RE QUITE SMALL DIFFERENCES.
YOU CAN SEE THE INDIVIDUAL
VARIATION EXCEEDS THE DIFFERENCE
BETWEEN THE GROUPS.
WHAT WE WANTED TO DO WITH THE
DATA WAS TO LOOK AT EACH CLUSTER
AND COMPARE THE GENE EXPRESSION
PROFILE BETWEEN PATIENTS AND THE
CONTROLS AND COUNT UP HOW MANY
GENES ARE DYSREGULATED ACROSS
EACH IMMUNE CELL TYPE AND THIS
IS THE RESULT WE GET.
THE RED BARS ARE NUMBERS OF
DYSREGULATED GENES AT BASELINE
COMPARING ME/CFS TO CONTROL.
THE PURPLE IS POSTPOST AND THE
OTHER COMPARES CONTROLS BETWEEN
THE TWO TIME POINTS.
THERE'S A FEW GENERAL
CONCLUSIONS FROM THIS.
THE FIRST IS YOU HAVE A LARGE
SUBSET OF MONOCYTES THE MOST
DYSREGULATED TYPE IN THIS ASSAY.
THE OTHER CLEAR CONCLUSION FROM
THIS IS THERE'S BROAD
DYSREGULATION ACROSS IMMUNE
TYPES.
THESE ARE T CELL SUBSETS.
FOR NOW I'LL FOCUS ON MONOCYTES.
THEY DO A LOT OF THINGS AS DO
IMMUNE CELLS.
THEY'RE INVOLVED IN PHAGOCYTOSIS
AND ANTIGEN PRESENTATION AND
CYTOKINE PRODUCTION AND SOURCE
OF MACROPHAGES AND THEY GO INTO
THE TISSUE IN RESPONSE TO
STIMULI AND DIFFERENTIATE TO
MACROPHAGES AND THEY CAN DO
DIFFERENT THINGS.
THEY CAN BE INVOLVED IN WOUND
REPAIR, HEALING BUT THEY CAN
ALSO BE PRO-INFLAMMATORY.
I'LL MENTION THERE'S THERE'S
ASSOCIATION WITH INFLAMMATORY
AND AUTO IMMUNITY.
WHAT DO WE SEE WHEN BETWEEN THE
CONTROLS AND ME/CFS INDIVIDUALS?
AND WE INTERSECT THE WHOLE
CHANGE WITH EXTERNALLY CURATED
SETS OF GENES.
THAT'S WHAT IS SHOWN ON THE Y
AXIS CALLED GENE SET ENRICHMENT
ANALYSIS AND THE DOTS ON THE FAR
RIGHT OF THE PLOT ARE SETS OF
GENES UPREGULATED IN ME/CFS.
AND THE MONONUCLEAR CELL
MIGRATION AND LEUKOCYTE
MIGRATION AND ACTIVATION ARE THE
PATHWAYS REQUIRED FOR MONOOCYTE
TO RESPOND, GO TO TISSUE AND
BECOME MACROPHAGES.
BUT THE GENES ARE UP REGULATED
IN ME/CFS.
THE FIRST TWO HERE ARE
SELF-SERVICE PROTEINS CRITICAL
F
FOR MONOSITES TO -- MONOCYTE TO
GET INTO TISSUE AND LOWER LEVELS
ARE REQUIRED FOR IT TO BECOME A
MACROPHAGE AND THE CCL4 IS A
CHEMO ATTRACT ANT THAT BRINGS
MONOCYTES TO TISSUE.
THE FIRST FOUR ARE A SERIES OF
PRO AND INFLAMMATORY RECEPTORS.
THOSE ARE DIFFERENTLY REGULATED
AND THE FINAL ONE WHICH IS
IMPORTANT IS CCL4 PROBABLY MORE
UPREGULATED POST-CPET.
WHEN WE PUT IT TOGETHER THE
HYPOTHESIS WE HAVE NOW IS SOME
PART HAS WILL ELEVATE D TISSUES
AND WE'LL LOOK IN TISSUE BIOPSY
AN LOOK AT GENOMICS AND ANALYSES
THAT GIVE MORE SUPPORT TO THIS
HYPOTHESIS.
FIRST THING WE DID WAS DECIDED
TO MOVE FROM SINGLE CELL RNA SEQ
AND USED MONOCYTES AND THE THIS
IS A PRINCIPLE COMPONENT AND THE
YELLOW DOTS ARE CONTROLS.
THEY'RE TIGHTLY CLUSTERED AND
DISTINCT AND FROM THE ME/CFS
INDIVIDUALS AND THEY'RE MORE
DISPERSED.
SUGGESTING HETEROGENEITY AND
THAT WILL BE A FEATURE LATER IN
THE TALK.
WE CAN LOOK AT THE CONTROL AND
ME/CFS COHORTS YOU SEE
SIGNALLING MOLECULES THAT PUSH
MONOCYTE TO GO TO TISSUE AND THE
TOP IS CFS2 A KEY PLAYER IN
ACTIVATING IMMUNE CELLS
INCLUDING IN THE MONOCYTE
MACROPHAGE AND WE DON'T PICK IT
UP FOR TECHNICAL REASONS BUT
ANOTHER WAY TO VALIDATE THIS
USING THE ORTHOGONAL APPROACH
AND THE SAMPLES USED ARE
DISTINCT FROM THOSE USED IN THE
SINGLE CELL.
IT'S INDEPENDENT VALIDATION.
WE MOVED BEYOND VALIDATING THE
DYSREGULATION USING
TRANSCRIPTOME AND THIS IS
PROTEOMICS FROM CONTROL AND
CLASSICAL MONOCYTES AND WHEN
ENRICHMENT ANALYSIS ON THE
CHANGES IN THE PROTEOME YOU SEE
TERMS SUGGESTIVE OF
INAPPROPRIATE ACTIVATION OF M
MONOC
MONOCY
MONOCYTES.
SO, I MENTIONED WE SEE MORE
TRANSCRIPTOME FROM CONTROLS AND
I'LL SPEND TIME TALK ABOUT THAT
BECAUSE I THINK WE FOUND
INTERESTING WAYS TO LOOK AT
THAT.
THE IDEA WE EXPLORED IS MAYBE IN
CONTROLS THERE'S A UNIFORM
POPULATION OF MONOCYTES THE
YELLOW CELLS AND IN PATIENT AS A
VARIABLE NUMBER OF RELATIVELY
NORMAL YELLOW MONOCYTES AND THE
DYSREGULATEDMONEYCYTESS --
MONOCYTES AND THE IDEA FOR THE
HYPOTHESIS AND EXECUTING GOES TO
HANYA IN MY LAB.
SHE USED POSITIVE UNLABELLED
LEARNING THAT IMPLEMENT THE
CARTOON ON THE LEFT AND YOU CAN
SEE THE REAL DATA FOR CLASSICAL
MONOCYTES AND IN THE CONTROLS
YOU HAVE THE SEA OF YELLOW DOTS,
NOR
NORMAL MONOCYTES AND SEVERELY
PERTURBED MONOCYTES AND NOW
SPLIT IT IN INDIVIDUAL ME/CFS
INDIVIDUALS AND WHAT YOU CAN SEE
I THINK IS SOME INDIVIDUALS
MOSTLY HAVE BLUE CELLS THE
DYSREGULATED PREDICTIVE DISEASE
CELLS AND SOME STILL HAVE THE
CELLS BUT AT LOWER FREQUENCIES.
THIS IS THE OTHER SIDE OF THE
COIN.
THIS IS THE CONTROL COHORT.
YOU SEE NO BLUE CELLS THEY'RE
ALL PREDICTED NORMAL.
THIS IS SUMMARIZING THE SAME
DATA AND AN EASIER WAY TO LOOK
AT IT.
WE BUILT THE CLASSIFIER
INDEPENDENTLY FROM THE DETE
DATA AND CORRELATION OF THE
PERCENTAGE OF DISEASE AND
PREDICTED MONOCYTES.
YOU SEE'S CONGRUENT.
IT'S STABLE AT BASELINE AND AT
THE EARLY STAGES OF
POST-EXERTIONAL MALAISE.
THERE'S A STRONG CORRELATION.
THIS CLASSIFIER IS ABLE TO PICK
OUT INDIVIDUALS WITH MORE SEVERE
SYMPTOMS BASED ON THE PERCENTAGE
OF THEIR MONOCYTES PREDICTED AS
DISEASE.
THIS IS ALSO AN IMPORTANT WAY OF
LOOKING AT THIS.
THIS INDEX I WON'T TRY TO
PRONOU
PRONOUNCE, IF YOU SPLIT DATA
ACCORDING TO DIFFERENT CRITERIA
AND THE Y AXIS YOU ASK HOW MUCH
INFORMATION ARE YOU GETTING BY
SPLITTING THE DATA.
HOW WELL ARE YOU DISTINGUISHING
TWO SETS.
FROM THE BOTTOM UP, IF YOU SPLIT
ALL THE SINGLE CELL
TRANSCRIPTOMES YOU GET A CERTAIN
AMOUNT OF INFORMATION.
IF YOU SPLIT THE SAME DATA BY
INDIVIDUAL OF ORE ORIGIN YOU GET
MORE INFORMATION AND THIS IS THE
HUGE CONFOUNDING EFFECT WE GET
IN THE HUMAN POPULATION.
THERE'S HUMAN INTERINDIVIDUAL
VARIATION NOT RELATED TO DISEASE
STATE.
THE NEXT UP IS SEX.
IF YOU SPLIT BY FEMALE AND MALE
MORE PARTITIONING.
MALE AND FEMALE MONOCYTES ARE
DIFFERENT AND IF WE PARTITION BY
THE PREDICTIVE DISEASE CELLS AND
NORMAL CELLS YOU GET THE MOST
INFORMATION.
THERE'S INFORMATION THERE WE CAN
EXTRACT THAT WILL HOPEFULLY TELL
US SOMETHING ABOUT THE DISEASE.
THAT'S WHAT I'LL SHOW YOU ON THE
NEXT SLIDE.
WE TOOK THEM INTO SIX GROUP,
MALE AND FEMALE AND THEN WHETHER
THERE'S PREDICTIVE DISEASE CELLS
AND LOOKED AT THAT IN PRINCIPLE
COMPONENT SPACE.
YOU SEE DISEASE DISPARITY FROM
THE MALES ALL THE WAY TO THE
CONTROL AND YOU GET THE SAME
IDEA BUT FOR THE FEMALE.
WE CAN ASK WHAT ARE THE GENES
DRIVING THOSE PRINCIPLE
COMPONENT AXES AND
DISTINGUISHING THE CELL
IDENTITIES.
THAT'S WHAT'S PLOTTED HERE AND
I'LL POINT OUT CCL4 I MENTIONED
EARLIER AND CCL4L2 ARE AMONG THE
TOP GENES DRIVING THE DIFFERENCE
FOR MALES AND FEMALES.
WE TOOK EACH INDIVIDUAL ME/CFS
AND COMPARED GENE EXPRESSION
PROGRAMS BETWEEN THEM AND
AGGREGATED THAT ACROSS ALL THE
INDIVIDUALS.
THE REASON WE DID THIS IS
BECAUSE BY DOING THE
DIFFERENTIAL EXPRESSION ANALYSIS
AT THE INDIVIDUAL LEVEL YOU
NORMALIZE A WAY NORMAL HUMAN
INDIVIDUAL DIFFERENCE THE
CONFOUNDING VARIABLE.
THIS DISTILLS DOWN TO THE PUREST
SIGNAL DRIVING WHAT WE'RE
LOOKING AT HERE.
THE TOP PLAYERS ARE FAMILIAR.
CCL4 AND L2.
THEY'RE UP IN THE PREDICTIVE
DISEASE CELL AND ONE
INTERESTING, ATF3 TOWARDS THE
BOTTOM IT'S DOWN REGULATED IN
THE PREDICTED DISEASE CELL.
IT'S A TRANSCRIPTIONAL REGULATOR
AND REPRESSOR THAT DAMPENS A
PROINFLAMMATORY RESPONSE.
THET PREDICTIVE DISEASE CELLS
YOU LOST THE DAMPENING OF THE
PROINFLAMMATORY RESPONSE.
IT'S EASY TO IMAGINE PUSHING
THAT UP WOULD BIAS THE MONOCYTES
TO BECOMING MORE INFLAMMATORY
FAC -- MACROPHAGES AS THEY GET
IN THE TISSUE.
I TOLD YOU ABOUT THE RESEARCH ON
THE IMMUNE CELL AND WE HAVE
HIGH-QUALITY TRANSCRIPTOME IC
DATA ACROSS IMMUNE CELLS.
THIS IS A DATA SET FOR LONG
COVID BECAUSE WE HAVE SUCH NICE
QUANTITATIVE INFORMATION ACROSS
SO MANY CELLS IT SHOULD BE EASY
TO COMPARE HIS EQUIVALENT DATA
SETS ONE AVAILABLE FOR LONG
COVID.
I'VE SHOWN YOU DATA THAT
SUGGESTS THE CLASSICAL MONOCYTE
DYSREGULATION IS AN IMPORTANT
ASPECT OF ME/CFS BIOLOGY AND THE
INCREASED MIGRATION TO TISSUES
WHERE THEY DIFFERENTIATE TO
MACRO FATHPHAGES AND A SUBSET O
CELLS.
THIS IS WE STARTED TAPPING THE
FIRST.
WE REPEATED THE ANALYSIS AND
ASKED A DIFFERENT QUESTION.
INSTEAD OF GENE EXPRESSION
BETWEEN PATIENTS AND CONTROLS,
WE FIRST CALCULATED THE CHANGE
IN GENE EXPRESSION THE CPAT
ELICIT AND COMPARED THE CHANGES
IN GENE EXPRESSION BETWEEN THE
HEALTHY COHORT AND ME/CFS
INDIVIDUAL AND THE IDEA IS TO
HONE ON GENE EXPRESSION WITH
POST-EXERTIONAL MALAISE.
THE BIGGEST SIGNATURE BY FAR IS
IN PLATELETS.
IT'S ALMOST THE ONLY SIGNATURE
WE SEE WHEN WE DO THE ANALYSIS
IN THIS WAY.
THE MAJOR FUNCTION IS TO FORM
CLOTS.
THEY'RE NUCLEUS FREE AND THE
TRANSCRIPTOME WE'RE TALKING
ABOUT IS DERIVED FROM THE PARENT
CELLS MEGAKARE YYOCYTES AND
PLATELET DERIVED CLOTS ARE IN
LONG COVID AND TO SOME EXTENT IN
ME/CFS.
WHAT DO WE SEE?
WE SEE TWO THINGS.
AT BASELINE THE CORE GENES
TRANSCRIPTS REQUIRED FOR
PLATELET ACTIVATION, COAGULATION
AND IMMIGRATION, THOSE GENES ARE
DEPRESSED.
THEY'RE AT LOWER LEVELS.
THEN AFTER CPET THE SIGNAL WHICH
IS STRONG DISAPPEARS I THINK THE
POPULATION BECAUSE THEY CAN'T
GENERATE A NEW TRANSCRIPTOME.
THEY'RE CELL DERIVED PARTICLES.
THE WAY WE THINK OF THIS IS A
POPULATION OF DEFECTIVE
PLATELETS AT BASELINE.
YOU TRIGGER POST-EXERTIONAL
MALAISE AND SOMETHING CHANGES
AND THE PLATELET NO LONGER
VISIBLE TO THE ASSAY AND YOU NOW
HAVE A RELATIVELY NORMAL
POPULATION OF PLATELETS.
PERHAPS, POST-EXERTIONAL MALAISE
IS TRIGGERS MORE CLOT FORMATION.
WE USED CONVENTIONAL RNA SEQ AND
IN THE PROCESS OF USING
PROTEOMICS WHICH IS A BETTER WAY
TO DO THIS.
QUICKLY THEN THE LAST 30
SECONDS, WE NOW VERY INTERESTED
IN T CELL DYSREGULATION IN
ME/CFS.
WE'VE TAKEN OUR ATLAS AND THAT
GIVES HIGHER RESOLUTION TO LOOK
AT THE T CELLS AND HERE'S
THERE'S A CLUSTER WHERE TCF7 IS
UPREGULATION AND THE LATE STAGE
CD8s IS A HALLMARK OF PROGENITOR
CELLS TO AN EXHAUSTED STATE.
THIS IS SUGGESTING EXHAUSTION
AND THIS RESULT AND OTHERS
MOTIVATED MY LAB TO LOOKING AT
CD8 T CELL EXHAUSTION AND A PLUG
FOR JESSICA'S TALK YESTERDAY SHE
USED AND DAVID IN MY LAB WAS A
POSTER HERE IS TAKING THE SINGLE
CELL DATA AND LAYERING ON
ADDITIONAL GENOMIC DATA SETS TO
LOOK FOR SIGNATURES OF
EXHAUSTION AND THE CYTOMETRY
GIVE EVIDENCE OF EXHAUSTION LIKE
STATE IN ME/CFS OR CD8s.
SWEE THIS PROMINENT FEE
THE GENES SUGGESTED THE TISSUE
HOMING AND WHERE THE MONOCYTES
ARE BECOMING PROINFLAMMATORY
MACROPHAGES IN TISSUE.
I DIDN'T SHOW YOU THIS DATA BUT
YOU CAN ALSO MINE THE SINGLE
CELL DATA AND THERE'S
INTERESTING OBSERVATION THE
PLATELETS ARE CHANGING AND
LEADING TO MICROPLOT FORMATION
AND THIS IS OUR FUNDERS AND THIS
IS DONE IN COLLABORATION WITH
TWO OTHER LABS IN CORNELL AND A
GROUP FOR THE SINGLE CELL RNA
SEQ AND AIL STOP THERE.
THANKS.
-- I'LL STOP THERE.
THANKS.I'LL STOP THERE.
THANKS.
>> WE HAVE TIME FOR A FEW
QUESTI
QUESTIONS IF YOU WANT TO COME UP
TO THE MIC.
DON'T BE SHY.
WE DID A GREAT JOB THIS MORNING.
>> QUICK QUESTION.
RATHER THEN PLATELETS BEING
CONSUMED CAN THEY BE DILUTED OUT
FROM BEING RELEASED FROM
SEQUESTERED AREAS.
>> WOW, IT REALLY IS HARD TO
HEAR UP HERE.
>> NANCY'S QUESTION IS WHAT'S
GOING ON WITH THE PLATELETS
RATHER THAN BEING CONSUMED THEY
COULD BE SEQUESTERED.
THAT'S POSSIBLE.
IT'S POSSIBLE THERE'S AN INFLUX
OF PLATELETS.
THE SAMPLES ARE PLASMA AND CDMC.
AND THERE'S PROTEOMICS.
WE'LL REPEAT THESE APPROACH
USING PLATELETS THAT HAVE NEVER
BEEN FROZEN AND THAT ALLOWS YOU
TO BE CONFIDENT THERE'S
PLATELETS IN CIRCULATION BUT
DOES NOT SPEAK TO YOUR QUESTION
ABOUT SEQUESTRATION.
WE'RE THINKING ABOUT THESE
THINGS.
>> SINCE YOU WERE DOING SINGLE
CELL ANALYSIS IT'S PROBABLY NOT
REALISTIC TO LOOK AT OTHER
COMPARATORS SINCE YOU SWITCHED
TO MORE CONVENTIONAL DID YOU
LOOK HOW UNIQUE IS THIS
MECHANISM DO YOU THINK OR IS IT
GOING CROSS TO OTHER COMPLEX
DISEASES?
>> GREAT QUESTION.
THE QUESTION IS USING EITHER THE
SINGLE CELL DATA OR OTHER DATA
SETS, THIS SIGNATURE OF
DISRESOLUTION IN MONOCYTES IS IT
SPECIFIC TO ME/CFS OR DO YOU SEE
SIMILAR SIGNATURES ELSEWHERE?
WE STARTED DOING THAT AND LOOKED
AT SOME CONDITIONS.
>> THANK YOU.
>> IT GIVES ME PLEASURE TO
INTRODUCE DR. ALAIN MOREAU
TALKING ABOUT CONTRIBUTIONS OF
EPIGENETICS IN ME/CFS AND LONG
COVID PATHOGENESIS.
>> HERE ARE MY DISCLOSURES
FUNDING MY RESEARCH ON ME/CFS
AND LONG COVID AS WELL.
I SPOKE ABOUT THE EPIGENETICS
AND EPIGENOMICS SO YOU CAN
LISTEN TO THE WEBINAR AND HAVE
MORE DETAILS BUT IT'S CLEAR THAT
WE ARE WELL AWARE THERE ARE SOME
COMPONENTS IN ME/CFS AS
IDENTIFIED IN THE PEDIGREE.
IT'S A U.K. FAMILY YOU CAN SEE
OVER THREE GENERATIONS.
YOU SEE THE KIDS ARE SUFFERING
FROM ME/CFS.
IT'S A UNIQUE OUTSTANDING FAMILY
AND I THINK WE CAN LEARN A LOT
BY COLLECTING AND TESTING THOSE
FAMILIES.
IF YOU'RE AWARE OF SUCH
FAMILIES, PLEASE LET ME KNOW.
BUT ON THE OTHER A LOT OF
UNRELATED CASES WHEN WE QUESTION
THEM WE ALWAYS GET AN ANSWER,
YES, I HAVE A COUSIN OR UNCLE
HAVING ME/CFS OR SOMETHING
SIMILAR CONDITION WE SUSPECT
EPIGENETICS IS A STRONGER
CONTRIBUTOR IN RESPONSE TO A
VIRAL INFECTION, DRAMATIC
CONDITION, BACTERIA LIKE CHRONIC
LYME DISEASE.
THOSE EXPOSURES WHICH INCLUDE
NOT ONLY VIRUS BUT HEAVY METALS,
ARSENIC CAN BE EXCELLENT
TRIGGERS THAT RESULT IN ME/CFS
OVER TIME.
IT DOESN'T MEAN EPIGENETICS IS
NOT BLACK AND WHITE SITUATION.
THEY MAY HAVE EPIGENETICS AND
CROSS TALK WITH SOME
DISPOSITION.
GENETICALLY WE THINK AND HAVE
EVIDENCE EPIGENETICS MIGHT HAVE
A STRONGER CONTRIBUTION THAN
GENETIC ESPECIALLY ON THE
POPULATION AT LARGE.
WHAT DO WE KNOW AND IN TERMS OF
DNA THIS IS A DATABASE.
EVERY SINGLE CELL IN YOUR BODY
HAS THE SAME INFORMATION.
WE HAVE ABOUT 22,000 GENES.
THE DNA CELL TYPE IS THE MUSCLE
CELLS OR BRAIN CELLS OR BLOOD
CELLS WOULD BE AN ACTIVATION OF
SOME TRANSCRIPT THAT LEADS TO
MESSENGER RNA AND HAVE OVER
140,000 TRANSCRIPT NOT IN SINGLE
CELLS.
THIS IS OVER ALL POSSIBLE
TRANSCRIPT.
IT'S MORE COMMON TO HAVE AROUND
12,000 DIFFERENT TRANSCRIPT IN A
CELL SPECIFIC TYPE AS ANDREW
PRESENTS SO SUPPORTING THAT.
AND THESE MESSENGER RNA WILL
RELATE A CODE THAT WILL PRODUCE
AT THE END OF THE DECODING IN
THE MACHINERY INSIDE THE CELLS
IN THE FUNCTIONAL PRODUCT WE
CALL PROTEIN.
IN THE PROTEIN WE HAVE 100,000
PROTEINS.
THERE COULD BE MORE.
IF YOU CONSIDER THE CLEAVAGE AND
IT WILL CHANGE THE PROPERTIES OF
THE PROTEIN ALSO LOCALIZATION SO
THAT CAN BE IMPORTANT AND
PROTEIN THAT'S AT THE WRONG
PLACE, WRONG QUANTITY WILL LEAD
TO SOME DISORDER.
WE HAVE THE NON-CODING RNA.
THERE'S DIFFERENT TYPES.
I DON'T HAVE TIME TO REVIEW ALL
OF THEM BUT WE HAVE MICRORNA AND
YOU SEE THE NUMBER IS VERY LOW
OR REDUCED COMPARED TO THE OTHER
NUMBERS I GAVE YOU.
AND THOSE MICRORNA NORMALLY
OFTEN ATTACH IN THE REGION OF
MESSENGER RNA AND BY DOING THIS
WILL ATTRACT THE COMPLEX THIS IS
WHAT YOU CAN SEE ON THE CARTOON
WILL PREVENT ACCESS TO THE
MACHINERY AND WILL REDUCE THE
PRODUCTION OF PROTEIN.
SO WHICH IS ALSO INTERESTING SO
FURTHER ADD A LAIR OF COMPLEXITY
AND ONE SINGLE mRNA CAN TARGET
UP TO 200 GENES AND ONE GENE CAN
BE TARGETED BY MORE THAN ONE
SINGLE MICRORNA.
YOU MAY HAVE AMPLIFICATION OF
THE PHENOMENON.
THEY'RE MORE OFTEN USED IN
MOLECULAR MEDICINE AS A
BIOMARKER AND YOU CAN STAGE
CANCER TUMORS AND PREDICT
RESPONSE I THINK MAUREEN
MENTIONED THAT I'M DOING THAT TO
REVEAL WHAT IS GOING ON IN THE
PATIENT.
PAM IS THE HALLMARK AND INVOLVED
IN LONG COVID AND OTHER
CONDITIONS INCLUDING
FIBROMYALGIA.
WE THINK IT'S A MEASUREMENT AT
BASELINE AND 90 MINUTES AFTER
THE STRESS ACTIVATION THAT LEADS
TO PAM WE CAN REVEAL GOOD DAY,
BAD DAY BECAUSE IT'S DIFFICULT
TO SEND A CLINICAL NURSE AT HOME
WHEN WE RECEIVE A CALL.
I DON'T HAVE THIS YET IN FACT
NOBODY HAS IT AT THAT LEVEL SO
WE APPLIED A STANDARDIZED PROVE
VASION MANEUVER WHICH IS
RELATIVELY SAFE.
WE DID OVER 500 CASES SINCE 2015
AND NEVER HAD TO CALL 9-1-1 TO
HOSPITALIZE A PATIENT OUTSIDE OF
TREATMENT THOUGH WE INDUCED PAM
WHICH MEANS THE PARTICIPANTS
WILL BE SICKER DURING A FEW
HOURS UP TO A FEW DAYS BUT
NORMALLY FIVE DAYS LATER THEY'RE
GOING BACK TO THE BASELINE
VALUES OR CONDITION.
HERE YOU CAN SEE THE INFLATABLE
COUGH WE'RE USING AND THEY
RECEIVED THE MESSAGE DURING THE
90 MINUTES AND THE STIMULATION
IS THAT EVERY PARTICIPANT IS HIS
OWN CONTROL.
WE DON'T NEED TO CARE IF THEY'RE
TAKING NINE DIFFERENT
MEDICATIONS, SUPPLEMENTS,
WHATEVER, WE CONTROL FOR THAT
BECAUSE EACH PARTICIPANT IS ITS
OWN CONTROL.
WE SAW DIFFERENCE FROM THE
PARTICIPANTS AS WELL AS THOSE
SUFFERING THAT ALLOWED US TO
HAVE A BETTER UNDERSTANDING AND
COLLECTING DIFFERENT BIOLOGICAL
FLUIDS, MORNING URINE AND PLASMA
AND PBMCs AND USING THE SCEN
THAT ALLOWED US TO MONITOR THE
HEART RHYTHM AS WELL AS
RESPIRATORY RATE AN USING THE
VEST DURING THE NIGHT TO USE
FURTHER CHARACTERIZE ADVANCES
AND WE DID THAT AND NORMALLY
WE'RE DOING FIVE DAYS LATER AT
BASELINE BUT WE CAN DO TEST
AFTER TREATMENT TO SEE WHAT IS
HAPPENING.
I GOT A QUESTION ON THE GENTLE
COUGH ORE OVER THE TWO DAYS AND
THEY TESTED SICK PATIENT WHO
RARELY PARTICIPATE IN CLINICAL
TRIAL BECAUSE THEY CANNOT WALK
IN OR DO CPAC FOR A SINGLE DAY
SO WE TEST SICK PEOPLE AND 85%
ARE PEOPLE TESTING AT HOME.
ALL THE MACHINE ARE PORTABLE
MACHINE AND THE NURSES GO DOWN.
WHEN WE INDUCE WE SEE CHANGES AS
WELL AS AN EXAMPLE WHERE WE
MEASURE THE GOOD MARKER OF
FATIGUE INDUCED 90 MINUTES AFTER
RECEIVING THE MASSAGE.
THEY'RE MORE FATIGUED AND
IMPAIRMENT AFTER THE 90 MINUTE
STIMULATION.
WE CAN MEASURE THE WHOLE BODY
USING OUR STUDY DESIGN.
WE PUBLISHED IN 2020 THE FIRST
PAPER IN SCIENTIFIC REPORT WHERE
WE WERE ABLE TO GENERATE THE
PROFILE THAT LED US TO HAVE A
PANEL A PANEL OF 11 CIRCULATING
MICRORNA YOU CAN SEE IN THE
LIGHT BLUE HERE AND YOU SEE THIS
IS A PATHWAY GRAPHIC GENERATED
BY THE SOFTWARE AND LOOK AT
MENTAL FATIGUE AND FATIGUE OF
MUSCLE.
ALL BIOLOGICAL PROCESSES THAT
ARE QUITE RELEVANT FOR ME/CFS
PATIENT MOREOVER BECAUSE WE CAN
COMPARE THE VARIATION AFTER 90
MINUTES OF STIMULATION WE WERE
ABLE TO CLASSIFY THEM IN FOUR
CLUSTER IN OUR REVISED
CLASSIFICATION AND LEARNED SOME
SYMPTOMS IN CLUSTER 3 AND WE
FIND MORE PEOPLE SEVERELY
AFFECTED BY BRAIN FOG AND OTHER
COGNITIVE IMPAIRMENT AND THIS IS
IMPORTANT FOR THE PATIENT AND
PHYSICIANS GIVING CARE AND
TRYING TO FIND SOLUTIONS FOR
THOSE PATIENTS.
OF YOU CAN SEE 92 PATIENTS WITH
DIAGNOSIS WE APPLY OUR TEST TO
SEE IF IT WAS TRUE YOU REALIZE
THIS WAS A GAME CHANGER
CLINICALLY SPEAKING AND WHEN YOU
TRY TO ANALYZE MORE OF THE
POPULATION BECAUSE FM THOUGH
THERE'S OVERLAPPING SYMPTOMS
THEY'RE NOT ME AND BEING ME/FM
IS SICKER THAN ME AND WE SAW THE
CLASSIFICATION WAS THE RIGHT
ONE.
SO IF YOU'RE INTERESTED YOU CAN
READ THIS PAPER BUT WE HAVE A
DIFFERENT PROFILE BETWEEN EVENTS
AND THE MICRORNA ARE LOW OPPOSED
TO HIGH AND WHEN YOU HAVE BOTH
YOU HAVE A SCORE AS ILLUSTRATING
PANEL A AND B FOR TWO OF THE 11
MICRORNA.
CAN WE USE THE MICRO RNA TO
PREDICT A RESPONSE IN DIFFERENT
PATIENTS AND GROUPS THE ANSWER
IS YES.
THIS IS A TARGET FOR THE GENES
IF YOU HAVE A HIGH LEVEL OF
CIRCULATING MICRO RNA IT WILL
DISAPPEAR OR BE REDUCED WHICH
MEANS 75% OF THE PATIENT WON'T
RESPOND TO WHAT WE PREDICT AND
AS YOU MAY KNOW FROM PAPERS
SHOWING THE GENES ABOUT 25%
CONSIDERED GOOD RESPONDER.
WE ARE QUITE IN THE SAME
BALLPARK AS EXPECTED TO DO THAT.
SO I'M NOT SAYING THAT CAN
REPLACE A CLINICAL TRIAL BUT
THIS IS A GOOD START TO
INTRODUCE PRECISION MEDICINE FOR
ME.
WE DECIDED TO EXPLORE WHETHER
THEY CAN CONTRIBUTE TO THE
TRANSITION OF LONG COVID TO
ME/CFS AND AS YOU KNOW AND WELL
COVERED THIS MORNING BY OUR
LEADING CLINICIANS, THAT THERE'S
SOME SERIOUS OVERLAP BETWEEN THE
SYMPTOMS UNIQUE TO LONG COVID
AND THE 11 MICRO RNA ARE
INFECTED WITH COVID AND GENES
AFFECTED BY COVID ARE CLEARED BY
SOME OF OUR mRNA AND GAVE US THE
IDEA TO USE THE PANEL TO
STRATIFY LONG COVID AND SEE WHAT
IS HAPPENING.
CAN WE RECOGNIZE ME/CFS AND
CONDITIONS.
THIS IS WHAT WE HAVE DONE.
THERE'S A POSTER BY ONE OF MY
STUDENTS IF YOU ARE INTERESTED
ABOUT MORE DETAILS BUT USING
LONG COVID SYMPTOMS NAIVE TO
TREATMENT AND VACCINATION WE
COLLECTED LONG COVID FOLLOWING
THE FIRST WAVE OF THE COVID-19
WHICH MEANS THIS IS THE ORIGINAL
STRAIN NOT OMICRON OR DELTA.
WITH WERE ABLE TO CLASSIFY USING
THE MICRORNA IN SIX CLUSTERS AND
ONE ENDED UP AS ME AND WE
FURTHER STRATIFIED THEM USING
THE STRESS TEST IN DIFFERENT
CLUSTERS I JUST EXPLAINED TO
YOU.
WE WERE ABLE TO SOME ARE FM AND
THEY WERE FURTHER STRATIFIED AS
SEVERE OR MODERATE USING AN A
DIFFERENT GROUP OF PATIENT.
AND ABLE TO SPLIT INTO TWO
ADDITIONAL SUB GROUPS.
ONE WITH RESPIRATORY ILLNESSES
LOOKING LIKE COPD AND WE HAVE
MARKERS FOUND OR ASSOCIATED WITH
SEVERE COPD AND ANOTHER GROUP WE
CALL NEUROLOGICAL IMPAIRMENTS
AND A GROUP CALLED SEVERE
ALLERGY.
WE'LL GIVE YOU AN EXAMPLE TO
COMPARE PRE PANDEMIC ME VERSUS
LONG COVID ME AS WE QUALIFY AND
ALSO LONG COVID AGAINST THE
CONTROL WE COLLECT PRIOR TO THE
PANDEMIC.
CAN SEE IT'S HARD OR ALMOST
IMPOSSIBLE TO DISCRIMINATE BASED
ON QUESTIONNAIRE OR BASIC
INFORMATION THE PREPANDEMIC ME
OR ME/FM USING THE QUESTIONNAIRE
AS IT IS.
WE SAW ME LONG COVID AND DON'T
KNOW THE MEANING.
THE BIG DIFFERENCE IS THE RECENT
INFECTION SITUATION IN THE LONG
COVID THAT MIGHT EXPLAIN THAT WE
ALSO HAVE THE SUB GROUP IN LONG
COVID AND THIS IS THE EXAMPLE
WITH THE ME.
ADDITIONAL GENOME WIDE
PROFILING.
WE REPEAT THE SAME EXPERIMENT WE
HAVE DONE A LONG TIME BEFORE THE
PREPANDEMIC ME TO FIND OUT IF WE
HAVE ADDITIONAL PROFILES OR NEW
PATTERN SPECIFICALLY ASSOCIATED
WITH LONG COVID AND WHAT WE
GATHER HERE.
YOU CAN SEE THE MICROmRNA AND A
BUNCH OF NEW ONES IN LIGHT BLUE.
WHAT IS INTERESTING IS THE NEW
ONE MORE SPECIFICALLY ASSOCIATED
WITH LONG COVID ME TARGETING THE
VERY SAME GENES FOR THE MAJORITY
OF THEM.
THIS IS NOVEL.
IF YOU'RE ASKING WHY A DIFFERENT
VIRUS MAY END UP WITH THE SAME
PHENOTYPE, THIS IS ONE POSSIBLE
MECHANISM THAT DIFFERENT
ACTIVATION OR ELEVATION OF MICRO
mRNA LEADS TO THE SAME RESULT
BY TARGETING THE SAME GENES AND
PATHWAYS.
SO WE'RE STILL DIGGING.
THIS IS THE FIRST IN THE WORLD
TO PRESENT THIS RESULT AND I
WOULD BE VERY HAPPY TO SHARE
THAT DATA WITH WHOEVER IS
INTERESTED.
WE LOOKED AT DIFFERENT MARKERS.
NOT MUCH DIFFERENT WHEN YOU
COMPARE IT WITH LONG COVID ME.
WE LOOKED FOR FGF21 AND PA 1
INVOLVED IN MICRO BLOOD CLOTTING
SO VERY RELEVANT.
WE LOOKED AT THE MECHANISMS
WE'LL FURTHER DISCUSS AND ONE OF
MY STUDENTS PRESENTED A POSTER
AND WE JUST OBSERVED MORE
ELEVATION IN LONG COVID COMPARED
TO PREPANDEMIC AND THAT CAN
SIMPLY REFLECT THE LONG COVID.
AND INTERESTINGLY ENOUGH WHEN WE
DO THIS STRATIFICATION YOU CAN
SEE PANEL A HERE FOR INSTANCE WE
HAVE A STRONG ELEVATION OF ME.
WHICH IS ALSO THE SAME WITH THE
LONG COVID.
AGAIN, THE WAY WE CAN RECOGNIZE
AMONGST LONG COVID WHO IS ME CAN
GUIDE US TO UNDERSTAND SOME
DIFFERENCES OR SIMILARITIES AND
AS EXPLAINED YESTERDAY BY DRA
PRESENTER PLAYED A ROLE IN THE
IMMUNE RESPONSE TOWARDS THE
ACTIVATION OF K CELLS AND IF YOU
HAVE TOO MUCH SOLUBLE MICA
YOU'LL HAVE IMMUNE EVASION WHICH
CAN BE PROBLEMATIC AND BRINGS IN
INSTANCE OF THE IMMUNE RESPONSE
AND THE CELL ONE OF THESE
PROTEIN SP1 CAN INHIBIT THE
LIGANDS AND THIS IS INTRIGUING
AND WE SAW THE LONG COVID AND
YOU CAN SEE PANEL C AND D WHEN
WE LOOK ABOUT THE MANTLE SCORES.
THERE'S A NEGATIVE CORRELATION
WITH PRE-PANDEMIC ME AND
POSITIVE CORRELATION IN THE LONG
COVID ME.
WE DON'T KNOW EXACTLY WHY.
WE KNOW IN ME ELEVATION WITH THE
SEVERITY OF THE SYMPTOM AND YOU
CAN SEE IN PANEL E AND
INTERESTINGLY PANEL F WHEN WE
LOOK OVER TIME SO LONG COVID
POST-INFECTION AND OVER A YEARS
YOU SEE A DECLINE OF SOLUBLE
MICA CIRCULATING LEVELS.
IS IT DUE TO MICRO RNA?
WE DON'T KNOW.
IS IT SOME SARS COV2 POSSIBLY.
WE SUPPORT THE VIEW OF MAUREEN
JUST EXPLAINED AND HAVE THOSE
RESULTS.
WE'RE STILL EXPLORING THE
MEANING OF SUCH REDUCTION AT
LEAST FOR LONG COVID PATIENTS.
SAME WITH THE MARKERS AND
SIMILARITY BETWEEN LONG COVID
AND ME.
WE LOOK AT FGF21 AND IN CASE WE
SAW STRONG ELEVATION IN PRE
PANDEMIC LONG FM AND LONG COVID
CLASSIFIED AS ME PLUS FM.
I DON'T THINK IT'S JUST PURE
LUCK.
I THINK IT'S JUST THE FACT TO
SHOWCASE THE CAPACITY OF THE
TEST TO DISCRIMINATE THE
DIFFERENT SUB GROUP AND THE
PANEL B IS WORK WHERE DURING THE
ACUTE PHASE IT WAS THE HIGHEST
SEPARATING MARKER IN THE
AFFECTED CELL BY SARS COV2.
AGAIN, THERE'S A CONNECTION
BETWEEN THE CONTRIBUTION OF
FGF21.
PANEL C, D AND E RELATE TO
PREPANDEMIC ME/CFS AND WE
INVESTIGATE A LOT OF FGF21 AND
LOOK AT EXTREME LOW AND NORMAL
VALUES AND THE CIRCULATING FGF1
IS ASSOCIATED WITH SEVERITY AS
THE SEVERITY SEEMS TO BE
ASSOCIATED WITH ELEVATION OF THE
CIRCULATING FGF21.
THE GOOD NEWS IS PATIENT ON LOW
DOSE NALTREXONE COULD EXPLAIN
THE PATIENT MAY BENEFIT FROM LOW
DOSE NALTREXONE AND MAY
TRANSLATE FOR ME/CFS LONG COVID
AND HIGH LEVEL OF FGF21.
THESE ARE UNDER REVIEW AND WE
WERE ABLE TO STRATIFY PATIENT
USING OUR STRESS TEST AND TESTED
THEM THREE MONTHS LATER AND A
THIRD VISIT SIX MONTHS LATER.
WITH COLLECT BLOOD AND SALIVA
A
AND WE LOOKED AT THE EPITHELIAL
CELLS IN THE SALIVA TO
UNDERSTAND WHAT IS HAPPENING AND
IF WE CAN IDENTIFY ANOTHER LAYER
OF EPIGENETIC INFORMATION.
WE WERE ABLE TO DISCRIMINATE
BETWEEN LONG AND SHORT COVID.
THE CONTROL WE COLLECT BEFORE
THE PANDEMIC.
YOU CAN SEE IN TERMS OF THE
HEALTH QUESTIONNAIRE IN PANEL A,
B, C, D AND F THE SHORT COVID
BEHAVED MORE OR LESS EXACTLY
LIKE THE HEALTHY CONTROL WHICH
USING PRINCIPLE COMPONENT
ANALYSIS.
PANEL G WE WERE ABLE TO SPLIT
THE LONG AND SHORT COVID.
LONG COVID IS PINK AND THE SHORT
COVID IN GREEN AND THAT GIVES US
ALSO A HEAT MAP YOU CAN SEE WITH
DIFFERENCE CPG MARKERS AT VERY
DIFFERENT SIGNATURE BETWEEN LONG
COVID AND SHORT COVID THOUGH
BOTH GROUP HAD BEEN EXPOSED TO
THE SAME SARS COV2 VIRUS AT THAT
TIME.
AND WE PUSHED IT FURTHER BY
STRATIFYING LONG COVID AS SEVERE
LC1 AND MODERATE PATIENT WE WERE
ABLE TO SPLIT THEM USING THE Q
SCORE.
WE APPLIED THE STRESS TEST AND
MEASURED THE SEVERITY OF THE
PEN.
THE LC1 WAS OVER 20 AND THE LC2
HAS BELOW 20 AND WE HAD A
COMPLETELY DIFFERENT PROFILE.
YOU CAN SEE THE IN THE HEAT MAP
AND WERE ABLE TO DISCRIMINATE
AND HAVE A DISTINCT SIGNATURE
USING THE PBMCs AS WELL AS THE
SALIVA AND WHAT IS INTERESTING
IS WHEN YOU LOOK AT THE TIME
FRAME AND A 18 TO 20 MONTHS POST
INFECTION THEY'RE NOT
PROGRESSING.
HAVE YOU A BAD CLINICAL OUTCOME
OPPOSED TO THE GROUP 2 WHERE
HAVE YOU A SIGNIFICANT
IMPROVEMENT IN TERMS OF THE
TOTAL SEVERITY.
THIS IS VERY IMPORTANT IF WE CAN
USE THE PROFILE AT THE EARLY
STAGE OF LONG COVID WE MAY
PREDICT WHO HAS BETTER CHAINS TO
RESPOND AND THE BIOMARKER ARE
TARGETS WE CAN PREVENT THE
LONG-TERM SEQUELAE BY CAPTURING
THE TARGET AND MAKE' DIFFERENCE
BETWEEN WHO IS WHO IN TERM OF
LONG COVID AND TO ASSESS THE
CLINICAL TRAJECTORIES.
YOU CAN SEE ONE OF THE CPG
MARKER IS ASSOCIATED WITH DDR1
GENES AND THAT GENE WE CAN
MEASURE IN THE PLASMA AND YOU
CAN SEE THE ELEVATE IS
SIGNIFICANT FOR THE SEVERE LONG
COVID COMPARED TO LC2 OR SHORT
COVID AND SOLUBLE DDR1 IS ALSO
IMPORTANT BECAUSE IT CAN BE
CLEAVED.
I TOLD YOU WE HAVE A HIGHER
ELEVATION IN THIS IN COVID AND
PLASMA DDR1 IS CORRELATED
NEGATIVELY IN AGING POPULATION.
THERE'S A GOOD PAPER AND WE
MEASURED AND THE DIFFERENT
DEMAND IN THE LONG COVID AND YOU
CAN SEE ON PANEL C OR TABLE C,
WE SEE BOTH GROUPS ARE DIFFERENT
THAN THE SHORT COVID WHICH IS
NORMAL.
SOME CAN IMPROVE THE LONG COVID.
THIS IS THIS IS AN EXAMPLE OF
WHAT WE CAN DO TOGETHER AND USE
PRECISION MEDICINE TO CHANGE THE
COURSE OF ME/CFS AND LONG COVID
AND THIS IS AN EXAMPLE THAT LONG
COVID MAY INFLUENCE THE RESEARCH
ON ME/CFS AS WELL.
I'M FINISHING WITH THE LAST TWO
SLIDES BY QUOTING YOGA BERRA.
KEEP TRYING, STAY HUMBLE AND
TRUST YOUR INSTINCT AND ACT.
WE'RE ACTING TOGETHER AND WHEN
YOU COME TO A FORK IN THE ROAD,
TAKE IT.
IT'S TIME TO BUILD A ROAD MAP TO
SHIFT TO CLARITY AND MORE
IMPORTANTLY AND I WANT TO
SUPPORT THE PHASE THAT WE NEED
PATIENT AND I'D LIKE TO
ACKNOWLEDGE THE CONTRIBUTORS AND
THE I HAVE A TEAM WORKING WITH
COLLABORATORS AND THANK YOU VERY
MUCH FOR YOUR ATTENTION.
>> WE ARE COVERING THE OMICS AND
AS PART OF T ZERO AND THE STRESS
TEST WE IDENTIFY THIS BIOMARKER
NUMBER ONE IN RESPONSE TO THE
DRASTIC REDUCTION IN HAVE MORE
IN THE STRESS TEST AND YOU TRY
TO NEUTRALIZE AND AND WE LOOK AT
THE RED BLOOD CELL DEFORMITY AND
THEY'RE MORE RIGID AND THE MORE
RIGID IT WILL BREAK AND WE SEE
THE RIDGE IS DECREASED AFTER THE
STRESS TEST.
ALL IN ALL WE'RE GOING IN THE
RIGHT DIRECTION IT SEEMS AS PART
OF THE DIFFERENT MECHANISM
TRIGGERED WE HAVE THIS CHANGE
ALTERATION
>> YOU SEE WHAT IS HIGHLY
OPERATIVE IN YOUR RESEARCH AND
IT DIGESTED THE PROTEIN AND
REDUCES THE AMYLOID BETA
PATHOLOGY.
HAVE YOU CHECKED THAT AVENUE.
>> THE CHANGE BETWEEN ADAPTEN
AND IT'S INVOLVED IN THE
CLEAVAGE AND FILL AMOAMFILAMENT.
WE DID NOT LOOK AT THEM PER SE
BUT HAVE A GROUP OR SUBSET OF
PATIENT HIGH LEVEL OF SOLUBLE
ADAPTENS AND THAT CONDITION IS
NOT GOOD.
WE TRIED TO BRING THEY WILL DOWN
AND THE ONE THAT IS SULE USUAL
ARE HIGH IN SOLUBLE AMIC
IMPAIRING THE IMMUNE SYSTEM AS
WELL.
AND WE HAVE PATIENT WITH VERY
LOW SOLUBLE ADAPT GENS AND WE
TRIED TO BRING THEM AT THE
NORMAL LEVEL AND HAD SUCCESS AND
WE'RE LOOKING AT THE SIDE AND
DID NOT CHECK THE FACTORS
SPECIFICALLY AS YOU MENTIONED.
>> THANK YOU.
SO WE'VE REACHED OUR LUNCH
BREAK.
I WANTED TO ASK IF THE SPEAKERS
FOR THE AFTERNOON HAVE NOT YET
DELIVERED THEIR PRESENTATIONS TO
GIVE THEM TO THE A/V BOOTH
DURING LUNCH TO MAKE THE
AFTERNOON MORE SEAMLESS.
THE LUNCHES SOME ARE BEEN
PROVIDED FOR NETWORKING BY OPEN
MEDICINE FOUNDATION IN THE FAS
TERRACE.
IF YOU GO OUT THE DOORS GO DOWN
TO THE COFFEE SHOP ESSENTIALLY
AND TURN RIGHT AND WE WILL
RECONVENE AT 1:00.
THANK YOU.
>> GOOD AFTERNOON.
WE'RE GOING TO CONTINUE WITH OUR
PROGRAM.
THIS AFTERNOON AS WE DID
YESTERDAY WE'RE GOING TO HAVE
SOME PRESENTATIONS FROM THE
EARLY CAREER INVESTIGATOR
CONFERENCE WHICH HAPPENED MONDAY
SO WE'RE EXCITED TO HAVE THREE
SPEAKERS AND WE'RE GOING TO
START WITH HANNAH BUES FROM MGH
HARVARD.
I APOLOGIZE IF I BUTCHERED YOUR
NAME USING PET TO ASSESS
NEUROINFLAMMATION IN PASC AND
ME/CFS.
6:
>> I'M HANNAH BUES A CLINICAL
RESEARCHER AT MASSACHUSETTS
GENERAL HOSPITAL AND TALK ABOUT
AN ONGOING STUDY TO ASSESS
NEUROINFLAMMATION IN PASC AND
ME/CFS.
AS A BRIEF INTRODUCTION TO THE
STUDY WE HAVE TWO STUDY COHORT.
WE'RE LOOKING AT BOTH PASC AND
ME/CFS AND USE THE INTERNATIONAL
CONSENSUS IN OUR SCREENING AND
FOR PASC WE'RE TRYING TO CAST A
WIDER NET BUT STILL CAPTURE THE
ME LIKE DIVERSE SYMPTOM
PRESENTATION.
WE USE THE ICC BUT REQUIRE OME
THEY ENDORSE ONE SYMPTOM FROM
EACH SYMPTOM CLUSTER.
S IS THE SYMPTOMSLIKE FLU LIKE
SYMPTOMS AND ACCOUNTING SYMPTOMS
OVERLAP WITH THE GENERAL
SICKNESS RESPONSE.
HOW YOUR BRAIN REACTS TO YOUR
BODY BEING SICK.
WE'RE INTERESTED IN LOOKING AT
NEUROINFLAMMATION.
WE ASSESS USING PET CANNING WITH
THE LIGAND AND INVESTIGATE
POTENTIAL ROOT CAUSES BY
INTEGRATING OTHER MEASURES.
JUST TO INTRODUCE YOU TO WHAT
OUR PET SCAN LOOKS LIKE.
WE USE A DUEL SCANNER ACQUIRING
POSITRON EMISSION TOMOGRAPHY AND
MRI DATA AT THE SAME TIME
SIMULTANEOUSLY.
PBR28 BINDS TO THE TRANS LOCAT
ER PROTEIN ACTIVATED BY IMMUNE
CELLS AND ACTIVATED BY PATHOGENS
OR DAMAGE AND IT'S USED TO STUDY
INFLAMMATION AND AFFECT GLIAL
CELL DENSITY OR INFILTRATION OF
IMMUNE CELLS.
CAN AND WE HAVE PRE PRINTS IN
PASC CELLS.
METHODS FOR THIS PARTICULAR
STUDY WE TOOK THE FIRST 12
PATIENTS WE SCANNED WITH PASC
AND AGAIN ALL THESE PATIENTS
ENDORSED AFTER LEAST ONE SYMPTOM
FROM EACH CLUSTER OF THE ICC.
THESE PATIENTS GOT SICK EARLY IN
THE PANDEMIC SO PREOMICRON
VARIANT AND MOST WERE PREVACCINE
WHEN THEY ORIGINAL BY GOT SICK.
THEY WERE UNVACCINATED NOT
BECAUSE THEY CHOSE NOT TO BE BUT
BECAUSE IT WAS IT WAS AVAILABLE.
WE HAD 10 FEMALE AND 12 MALE
FEMALES WITH PASC.
WE COMPARED THEM TO A SET OF 43
CONTROLS WITH NO HISTORY OF
COVID-19 AND SOME REQUIRED
PREPANDEMIC AND OTHERS RECEIVED
A NEGATIVE ANTIBODY TEST.
AND WE USED SEX AS COVARIANT AND
A GENOTYPE AND THE CEREBELLUM
WAS USED TO NORMALIZE THE PET
SIGNAL.
GETTING TO THE RESULTS I'M GOING
TO BREAK THESE UP.
SO HERE WE SEE A HEAT MAP OF THE
AREAS IN THE BRAIN IN WHICH PASC
SHOWED MORE PET SIGNAL, MORE
TSVO AND MORE NEURAL
INFLAMMATION VERSUS CONTROLS.
IN PARTICULAR WE FOUND IT AT THE
LINING OF THE VENTRICLES AS WELL
AS REGIONS OF THE BRAIN DENSELY
VASCULARIZED SUCH AS THE
CINGULATE CORTEX.
HERE'S A BOX PLOT
REPRESENTATION.
YOU SEE WHOLE BRAIN ON THE LEFT
AND THE CORPUS COL OS UM AND WE
LOOKED ACROSS REGIONS.
SO CONSIDERING A FEW THINGS.
CONSIDERING THE FACT THAT
COVID-19 SEEMS TO BE AN
INFECTION THAT DRIVES PROBLEMS
FROM THE VASCULATURE AND WE SAW
VASCULARIZED REGIONS DID OUR PET
SIGNAL CORRELATE WITH THE
VASCULAR DISEASE MEASURE AND WE
TOOK PERIPHERAL BLOOD BEFORE THE
SCAN AND MEASURED ALL PART OF
THE VASCULAR DISEASE PANEL TO
SEE IF THEY CORRELATED WITH PET
SIGNAL.
IN THE PAST PATIENTS THEY DID.
WHERE WE SAW GREATER LEVELS WE
ALSO SAW INCREASED PBR28 SIGNAL.
THE REST OF THE PANEL HAD PRETTY
HIGH SIGNIFICANT CORRELATIONS.
SOME ONGOING WORK WE HAVE GOING
ON IN OUR STUDY IS CONTINUED
SCANNING OF PATIENTS WITH
PRE-COVID ME/CFS AND HEALTHY
CONTROL.
WE'RE DOING ANALYSIS OF FMRI
DATA WITH THE PET DATA AND ALSO
DOING FURTHER INVESTIGATION INTO
ROOT CAUSES USING PERIL RAL
BLOOD AND SALIVA.
ONE OF THE THINGS WE'RE LOOKING
AT IS ANALYSES OF LIVE
PERIPHERAL BLOOD COLLECTED
BEFORE THE CAN.
MY COLLEAGUE COLLECTS A TUBE OF
BLOOD AND ANALYZES IT IN REAL
TIME AND LOOKING AT THE BEHAVIOR
OF NEUTROPHILS THE WHITE CELLS
WHICH ARE THE FIRST IMMUNE
RESPONDERS OF THE SYSTEM.
AND USES MICROFLUIDICS.
THERE'S A SLIDE WHERE IN THE
ANALYSIS YOU CAN SEE THE
NEUTROPHILS THROUGH THE MAZE.
THAT'S WHAT SPONTANEOUS
MIGRATION IS.
HOW FAR AND LAST FROM THE
NEUTROPHILS SWIMMING.
IN LONG COVID THEY SWIM A LOT
COMPARED TO HEALTHY CONTROLS.
ANOTHER THING WE LOOK AT IS
PHAGOC
PHAGOCYTOSIS AND THERE'S A
PATTERN EMERGING THERE SEEMS TO
BE A SPLIT PARTICULARLY AMONG
COVID AND IT SEEMS PHAGOCYTOSIS
LOWER IN SOME CONTROLS AND A
QUESTION WHY WE'RE SEEING THAT.
ANOTHER THING WE LOOK AT IS
NETOSIS AND RELEASE THEIR OWN
DNA TO TRAP PATHOGENS.
SO IT'S A LEVEL OF EXTRA
CELLULAR DNA WHICH IS HOW WE
QUANTIFY NETS AND YOU CAN SEE
THAT IS INCREASED IN ME/CFS AND
LONG COVID.
WE ALSO LOOK AT PMA STIMULATED
NETOSIS.
IT'S SOMETHING USED TO MIMIC THE
BEHAVIORS OF BACTERIA.
SO FAR NO SIGNIFICANT DIFFERENCE
BUT SOMETHING IS POPPING UP IN
LONG COVID AND IT'S TOO SOON TO
BUT A PATTERN MAY BE EMERGING IN
ME/CFS AS WELL.
I WANTED TO FINISH OFF WITH SOME
OPEN QUESTIONS.
CONSIDERING THAT THE TOPIC OF
THE CONVERSATION IS LEARNING
FROM LONG COVID.
THOSE QUESTIONS ARE WHAT CAN WE
LEARN ABOUT ME/CFS FROM LONG
COVID AND THIS IS PRESENT
LOOKING AT THE DATA I JUST SAW
HOWEVER, THE CORRELATION WITH
THE VASCULAR DISEASE MEASURES
CONSIDERING COVID-19 IS A
PATHOGEN THAT PARTICULARLY
DRIVES PROBLEMS WITH THE
VASCULATURE.
WE'RE NOT TOTALLY SURE WE'RE
GOING TO SEE THAT IN ME/CFS IN
GENERAL BUT WE'LL CERTAINLY
LOOK.
AND I WANTED TO FINISH OFF WITH
SOME ACKNOWLEDGEMENTS TO MY
COLLEAGUES AND OUR STUDY
PARTICIPANTS.
WE COULDN'T DO THIS WITHOUT THEM
AND APPRECIATE THEM COMING IN
AND PARTICIPATING.
THANK YOU VERY MUCH.
>> OUR NEXT SPEAKER IS NICHOLAS
HAMPILOS FROM WEILL CORNELL
TALKING ABOUT THE EFFECT OF
PHYSICAL EXERTION ON CNS AND
OXIDATIVE STRESS ON METABOLISM
IN ME/CFS.
>> THANK YOU, DR. GREEN.
I'D LIKE TO FIRST THANK YOU FOR
THE OPPORTUNITY TO PRESENT HERE
TODAY AND THE NIH FOR HOSTING.
MY NAME'S NICHOLAS HAMPILOS A
FELLOW IN THE LABORATORY FOR
ADVANCED RESEARCH HEADED BY MY
VI AND I'M GOING TO PRESENT
ENTITLED EFFECT OF PHYSICAL
EXERTION ON CNS OXIDATIVE STRESS
AND METABOLISM IN ME/CFS.
ONE OF THE KEY AND HALLMARK
FEATURES OF ME/CFS IS CALLED
POST-EXERTIONAL MALAISE AND IT'S
A STATE IN WHICH PHYSICAL OR
MENTAL EXERTION KANSASER -- CAN
MAKE ME/CFS WORSE AND OFFER
COUNSELLING AND DEVELOPING MORE
EVIDENCE-BASED TREATMENTS.
WE USED PROTON MAGNETIC SPECK
TROSY
AND HAVE SHOWN PEOPLE HAVE A
SIGNIFICANT DEFINITION COMPARED
TO HEALTHY CONTROLS AND WE
REPLICATED THIS IN SEVERAL
STUDIES.
AND OXIDATIVE STRESS WITH FREE
OXYGEN AND NITROGEN FREE RAD
KALDZ AND THIS IS THE MOST
ABUNDANT AND THE DEFICIT IS
SUPPORTIVE OF OXIDATIVE STRESS.
WE'VE ALSO SHOWN IN THE BRAIN
AND VENTRICLES PEOPLE WITH
ME/CFS HAVE AN ELEVATION OF
LACTATE.
THIS IS SUGGESTIVE OF ABNORMAL
GLYCOLYTIC METABOLISM AND THIS
STUDY HAD THE POSSIBILITY OF
SHEDDING LIGHT ON THE
PATHOPHYSIOLOGY AND HOW THE
EXERTION AFFECTS THE METABOLITE
LEVELS AND SERVED AS THE
RATIONALE FOR THE STUDY.
THE OBJECTIVE WAS TO INVESTIGATE
A CARDIO PULMONARY EXERCISE TEST
IN PEOPLE WITH ME/CFS AND
HEALTHY PROPERTIES USING THIS
SPECTROSCOPY AND COMPARED TO
HEALTHY PARTICIPANTS BEFORE AND
24 HOURS AFTER CPET.
AND WE ALSO HYPOTHESIZED THAT
BRAIN METABOLITES WOULD
INCREASE AND WE USED THE
CANADIAN CONSENSUS CRITERIA AND
OUR CPET WAS DONE WITH EXERCISE
TESTING.
THERE'S TWO CPETs PERFORMED.
THIS IS PART OF THE CORNELL
COLLABORATIVE CENTER AND WE WERE
INTERESTED IN THE EFFECT OF A
SINGLE CPET.
YOU CAN SEE THE IMAGE DEPICTING
AN MRI PERFORMED THE CPET ON THE
SAME DAY AND 24 HOURS LATER WE
PERFORMED A SECOND SPECTROSCOPY
AND LOOKED FOR CHANGES IN
METABOLITES.
WE RECORDED GLUTEITHION IN THE
OCC IN THE TOP LEFT OF THE
FIGURE AND LOOKED AT THE IRON
ENRICHED PART OF THE GRAIN AND
WANTED TO SEE IF THERE WAS A
DEFICIT.
WE FOUND A DEFICIT BEFORE AND 24
HOURS AFTER CPET COMPARED TO
HEALTHY CONTROLS AND AND
EXERCISE HAD NO EFFECT ON
METABOLITE IN GLUTATHIONE AND
METABOLITE AFTER THE CPET.
WE DIDN'T SEE DIFFERENCE IN
GLUTATHIONE BETWEEN THE TWO
GROUPS BEFORE AND 24 HOURS AFTER
THE CPET.
WITH DIDN'T SEE AFFECT ON CPET
GLUTATHIONE LEVELS IN THIS AREA
AS WELL AND WITH THE LACTATE
LEVELS OF THE VENTRICLE WE
COLLABORATED OUR PRIOR FINDINGS
IN PEOPLE BEFORE AND 24 HOURS
WITH P VALUES OF .003 AND .005
AND DIDN'T SEE IT 24 HOURS POST
CPET.
WE WERE INTERESTED IN EXAMINING
FOR POTENTIAL RELATIONSHIPS
BETWEEN THE CPET PARAMETERS IN
PARTICULAR VO2 MAX AND THE
THRESHOLD AS WELL AS WITH
PRECPET NEURO METABOLITE LEVELS
AND SEE STATISTICALLY
SIGNIFICANT DIFFERENCE IN
LEVELS.
WHAT CAN WE DRAW PERFECT THE
STUDY?
WE CORROBORATED OUR FINDING OF
GLUTATHIONE AND LOOKING AT OX
DATIVE STRESS AND ABNORMAL
METABOLISM IN THIS CONDITION.
WE DID NOT SEE A DIFFERENCE IN
THE LEVELS AND THERE'S POTENTIAL
EXPLANATIONS INCLUDING THE
REGION MAY HAVE SIMILAR LEVELS
OF OXIDATIVE STRESS IN BOTH
GROUPS AND IT'S IRON ENRICHED
AND IRON IS A SUBSTRATE IN THE
REACTION WHICH IS AN IMPORTANT
SOURCE OF ERADICATING FREE
RADICALS AND WE DIDN'T SEE
EFFECT OF CPET ON GLUTATHIONE
AND LACTATE WITH THE KNOWING
EFFECT OF EXERTION IN PATIENTS
AND WHY DIDN'T WE SEE AN EFFECT
IT MAY WELL BE THAT EXERCISE
DOES NOT ALTER THE METABOLITES
OPPOSED TO A DIRECT CHALLENGE TO
THE BRAIN WITH THE ACTIVATION
PARADIGM AND MORE LIKELY LEVELS
COULD HAVE BEEN NORMALIZED
DURING THE FIRST AND SECOND
SPECTROSCOPY AND CHANGES COULD
HAVE OCCURRED AFTER THE EXERCISE
TEST AND NORMALIZED BEFORE THE
SECOND SPECTROSCOPY WAS
PERFORMED AND THE LITERATURE
SUPPORTS THIS IN EXERCISE AND
MEASURIING GLUTATHIONE AND
LACTATE AND AN INCREASE IN
LACTATE SHOWN IN THE BOTTLE
FIGURES.
THE STUDIES WERE PERFORMED
BETWEEN THE FIRST MASS SP
SPECTROSCOPY AND I'D LIKE TO
THANK THOSE WHO CONTRIBUTED.
AND THE DIVISION OF BIO
STATISTIC AND THE WEILL CORNELL
MEDICINE CLINICAL AND
TRANSLATIONAL SCIENCE CENTER AND
BIG THANKS TO THE NIH FOR THEIR
SUPPORT IN FUNDING THE
MULTICENTER GRANT.
THESE ARE MY REFERENCES AND
THANK YOU FOR YOUR ATTENTION.
>> THANK YOU.
YOU CAN SEE WE HAVE AN
OUTSTANDING CONFERENCE ON MONDAY
REPRESENTED BY SIX SPEAKERS OVER
THE TWO DAYS AND THE FINAL
SPEAKER FROM THE EARLY CAREER
INVESTIGATOR IS DR. XIANG XU
FROM MOUNT SINAI TELLING US
ABOUT STRUCTURAL AND OX GEN
METABOLIC MAG KNELTIC RESONANCE
IMAGING OF LONG-COVID AND
ME/CFS.
>> THANK YOU.
WE KNOW UP TO HALF THE PEOPLE
AFFECTED BY LONG COVID MEET
CRITERIA AND WE LEARNED UP TO
9.5% OF PEOPLE AFFECTED WITH
COVID FITS THE CRITERIA.
SO THAT'S THE OVERLAP AN WE'RE
GOING TO CALL THIS GROUP PASS
ME/CFS GROUP.
THEY ARE SIMILAR TO THE CLASSIC
ME/CFS GROUP BECAUSE THEY BOTH
FULFILL THE DIAGNOSTIC CRITERIA
BUT THEY'RE DIFFERENT IN THAT
THEY SHARE THE SAME INFECTIOUS
TRIGGER WHICH IS COVID AND THEY
GENERALLY HAVE SHORTER DISEASE
DURATION.
SO THE AIM OF OUR STUDY IS TO
COMPARE THE SIMILARITIES AND
DIFFERENCES IN BRAIN ANATOMY AND
METABOLISM BETWEEN THE PASC AND
THE NON-PASC AND ME/CFS PATIENTS
TOGETHER WITH HEALTHY CONTROLS
USING MAGNETIC RESONANCE
IMAGING.
THIS IS OUR STUDY DESIGN.
WE SCREENED OR PATIENTS THE PASC
AND NON-PASC ME/CFS S HAVE TO
FULFILL THE 1994 CASE DEFINITION
AND FOR THE PASC PATIENT GROUP
THEY HAVE TO HAVE A CONFIRMED
POSITIVE COVID TEST AND THEIR
SYMPTOM HAPPENED AFTER THE COVID
INFECTION AND LASTED FOR AT
LEAST SIX MONTHS.
DURING THEIR COVID INFECTION
THEY SHOULDN'T HAVE NEUROLOGICAL
SYMPTOMS OR REQUIRE OXYGEN OR
CPAP.
AND AFTER THE SCREENING WE
INVITE THEM TO OUR FACILITY TO
DO AN MRI SCAN AND THEN WE
EVALUATE THEIR SYMPTOM BURDEN BY
QUESTIONNAIRES.
MORE DETAILS ABOUT THE MRI SO
LABELLED IN BLUE ARE THE
STRUCTURAL ANATOMICAL SCANS AND
IN PINK THE MORE ADVANCED MRI
AIMED AT MEASURING THE BLOOD
FLOW AND THE SYMPTOM BURDEN WAS
ASSESSED BY SF36 AND
MULTIDIMENSIONAL INVENTORY AND
CORRELATE THE SYMPTOM BURDEN TO
THE MRI DERIVED METRICS.
HERE'S OUR STUDY DEMOGRAPHIC AND
THIS IS AN ONGOING STUDY.
WE STILL HAVE A RELATIVELY SMALL
SAMPLE SIZE.
FIRST LET'S LOOK AT THE
STRUCTURAL MRI.
OUR NEURAL RADIOLOGIST
CATEGORIZED THE FINDING TOO THE
FOLLOWING DOMAINS.
SO SOME OF THOSE WERE CHOSEN TO
BE RELATED TO ACUTE COVID
INFECTION AND THE ABNORMALITIES
AND AS WE CAN SEE ACROSS THE
COHORT WE DIDN'T OBSERVE AN
INCREASE IN THE NUMBER OF
INCIDENTS ACROSS THE GROUPS.
THERE'S SEVERAL FACTORS.
IT'S NOT SPECIFIC.
SO THEN WE TENDED TO THINK THE
STANDARD STRUCTURAL QUALITATIVE
MRI ARE NOT VERY INFORMATIVE FOR
NON-PASC VERSUS PASC ME/CFS.
NEXT LET'S LOOK AT THE
PHYSIOLOGICAL MRI.
FOR THIS WE APPLIED A NOVEL
SEQUENCE CALLED T2 TAGGING AND
PERFORMED THE TRUST MRI IN THE
MAJOR DRAINING VESSEL OF THE
BRAIN.
THIS GIVES US THE VENOUS
OXYGENATION OF THE ENTIRE BRAIN
AND ALSO MEASURE THE ARTERIAL
OXYGENATION THE YA USING THE
PULSE OXIMETER DURING COVID AND
THE DIFFERENCE IS HOW MUCH
OXYGEN IS EXTRACTED BY THE BRAIN
AND OES.
THIS IS AN EXAMPLE OF TRUST MRI
BEING USED IN A POST-ACUTE
SEQUELAE OF COVID.
BACK THEN THEY CALLED IT PCS,
POST-ACUTE COVID SYNDROME.
IN THIS PRELIMINARY STUDY THEY
FIND THE PCS PATIENT HAS
SIGNIFICANTLY LOWER VENOUS
OXYGENATION COMPARED TO CONTROLS
AND THEY'RE CORRELATED WITH THE
SCORE WHICH IS A MEASURE OF
FUNCTIONAL MOBILITY.
HERE ARE OUR RESULTS.
HERE FIRST I WANT TO BRING OUR
ATTENTION TO THE HEALTHY CONTROL
GROUP LABELLED IN HC.
YOU CAN CAN SEE ALL THE DATA
POINTS ARE QUITE CLUSTERED.
OUR MEASUREMENT IS ROBUST.
THE PATIENT GROUPS THE DATA
LOOKS A LOT MORE HETEROGENOUS.
WHEN WE USE THE PAIR WISE
COMPARISON THE PASC GROUP HAS
SIGNIFICANTLY LOWER OXYGENATION
VENOUS OXYGENATION COMPARED TO
THE HEALTHY CONTROL AS WELL AS
THE NON-PASC GROUP.
THERE'S THE AMOUNT OF MOLECULES
CONSUMED AND THE ABSOLUTE
MEASURE.
IT'S AN IMPORTANT MARKER FOR
BRAIN FUNCTION AND IT'S
REMARKABLY WELL CONSERVED IN
NORMAL CONDITIONS.
WE TALKED ABOUT THIS YESTERDAY
IF THE EXTRACTION FRACTION IS
ELEVATED IT'S TYPICALLY
ACCOMPANIED BY A REDUCED FLOW TO
HAVE A CONSERVED CMRO2 AND IT'S
CALCULATED WITH TIME FLOW AND
EXTRACTION FRACTION AND WANTED
TO SEE IF THERE WAS REDUCTION IN
CEREBRAL BLOOD FLOW AND USED
MEASURING THE MRI AND THE FOUR
MAJOR FEEDING ARTERIES TO THE
BRAIN.
AND HERE'S OUR CBF MEASUREMENT.
AND THE PASC PATIENT HAS
ELEVATED CMR2 WITH THE GROUP
TRENDING SIGNIFICANCE AND OUR
SYMPTOM MEASUREMENT AND BOTH
PATIENT GROUPS HAVE SEVERE
IMPAIRMENT IN TERMS OF PHYSICAL
FUNCTION AND ARE BASICALLY OUT
OF CHART USING THE FATIGUE
MEASURES.
HERE SHOWS GENERAL FATIGUE AS AN
EXAMPLE THAT THEY ARE HEEDING
THE TEST.
LASTLY WE CORRELATED THE
OXYGENATION TO THE PARTICULAR
MEASURES AND SEE THE PHYSICAL
FUNCTION SCORE IS POSITIVELY
CORAL
CORRELATED WITH THE LEVEL.
THAT'S OUR FINDING TO SUMMARIZE
EVERYTHING.
FIRST QUALITATIVE ANATOMICAL MRI
DOES NOT SHOW STRUCTURAL
DIFFERENCES BETWEEN PASC AND
HEALTHY CONTROLS AND COMPARED TO
THE HEALTHY CONTROLS PASC
PATIENT ARE CHARACTERIZED BY
LOWER VENOUS OX OXYGENATION AND
HIGHER EXTRACTION TO THEIR BRAIN
AND THIS PHYSICAL ABNORMALITY IS
DUE TO BRAIN OXYGEN CONSUMPTION
RATHER THAN LOWER BLOOD SUPPLY.
THE FUNCTION IS POSITIVELY
CORRELATED WITH VENOUS
OXYGENATION AND GENERAL FATIGUE
IS NEGATIVELY CORRELATED WITH
VENOUS OXYGENATION.
THE POINT I WANT TO MAKE IS THAT
COMPARED TO THE STRUCTURAL
CHANGES WE MOSTLY FREQUENTLY
LOOK AT ALTERNATIONS IN
METABOLIC PARAMETERS MAY BE MORE
SENSITIVE IMAGING BIOMARKERS.
WITH THAT HERE'S MY
ACKNOWLEDGEMENTS.
THE STUDY WAS SUPPORTED BY THE
NIH AND WE'RE GRATEFUL FOR OUR
RESEARCH PARTICIPANT WHO JOINED
OUR STUDY AND OUR MRI
TECHNOLOGIST AND COLLEAGUES AT
THE BIOMEDICAL ENGINEERING
INSTITUTE AND THANK YOU ALL FOR
YOUR ATTENTION.
>> THANK YOU.
OUR NEXT SESSION IS TITLED
NEUROLOGY OF LONG COVID AND
ME/CFS AND ACTUALLY TRANSITIONS
NICELY FROM OUR PREVIOUS
SPEAKERS.
THE FIRST TALK WILL BE FROM
DR. JARED YOUNGER WHO'S WORK HAS
BEEN MENTIONED IN THE CONFERENCE
FROM UNIVERSITY OF ALABAMA
BIRMINGHAM AND BY ZOOM.
HIS TITLE IS BRAIN INFLAMMATION
AND ME/CFS HOW WE MEASURE IT AND
HOW WE MIGHT TREAT IT.
>> THANKS.
I WANT TO MAKE SURE EVERYONE CAN
HEAR ME.
SOUND GOOD?
ALL RIGHT.
I'M GOING ASSUME THAT'S GOOD
UNLESS SOMETHING FLAGS ME AND
SAYS WE NEED TO FIX SOMETHING.
I AM AN EXPERIMENTAL PSYCHO
PHYSIOLOGIST BY TRAINING AND DO
HUMAN STUDIES ONLY AND BASICALLY
WATCH THE BASIC SCIENCE WORK AND
ANIMAL MODEL WORK AND WHEN I SEE
SOMETHING EXCITING I TRY TO
FIGURE OUT THE BEST WAY TO TEST
THAT IN HUMANS.
I DO HIGH RISK STUDIES AND MY
TOPIC OF INTEREST IS BRAIN
INFLAMMATION.
I'LL TALK ABOUT PHARMACEUTICALS
THAT DON'T USE AND MY GRANT
FUNDING IS FROM DOD, NIH AND
FIBROMYALGIA SYNDROME FOUNDATION
AND U.K. AND ALL MY PROJECTS ARE
ME/CFS, FIBROMYALGIA AND SOME IS
APPLICABLE TO LONG COVID BUT
DON'T HAVE A LOT OF LONG COVID
DATA BECAUSE WHEN THE GRANTS
CAME OUT I WAS SO BUSY TRYING TO
GET MY STUDIES BACK ON TRACK
AFTER THE LONG SHUT DOWN THAT IT
JUST TOOK UP ALL MY TIME AND I
COULDN'T DEVELOP MYSELF TO ANY
OTHER PROJECT.
I HAVE A LITTLE BIT BUT NOT A
LOT OF LONG COVID STUFF.
AS I SAID, EVERYTHING IS GOING
TO BE CENTERED ON BRAIN
INFLAMMATION AND I'M GOING TO
START WITH A QUICK OVERVIEW OF
WHAT BRAIN INFLAMMATION MEANS
AND GET US ALL ON THE SAME PAGE
AND THEN TALK ABOUT NEUROIMAGING
WORK AND THEN TALK ABOUT
TREATMENTS.
THINGS THAT CAN TARGET THE BRAIN
INFLAMMATION AND WE'LL HEAR
TALKS ON IMAGING AND THERE'S
GOING TO BE AREAS OF EVERY LAP.
I WANT TO DE-EMPHASIZE THAT AND
NEXT YEAR ADD MORE FINISHED
PROJECTS.
WE'LL HAVE A LOT OF RESULT TO
LOOK AT IN 2024.
I WANT TO SPEND MOST MY TIME
TALKING ABOUT TREATMENTS RATHER
THAN IMAGING THIS TIME.
SO THIS IS WHAT WE'RE TARGETING.
THESE ARE THE MICROGLIA YOU
HEARD MENTIONED MULTIPLE TIMES
AND THE GREEN ARE THE MICROGLIA
AND THE BLUE ARE DOPAMINERGIC
NEURONS AND THE MICROGLIA ARE
EVE
EVERYWHERE THERE'S NEURONS ON A
ONE TO ONE RATIO AND THERE'S
LITTLE MAGENTA SPOTS WHERE
MICROGLIA REACHED OUT AND
TOUCHING THE NEURONS AND CAN
SENSE THE STATE OF THE NEURONS
AND AFFECT NEURONAL FUNCTION AS
WELL.
THEY'RE VERY INVOLVED IN ALL
PROCESSES IN THE BRAIN.
AND INTERFERING AND PLAYING A
ROLE IN THE PROCESSES OF THE
BRAIN.
AND IT SHOWS THE MICROGLIA STATE
AND WHAT THEY PRODUCE.
THE MICROGLIA ARE TYPICALLY IN
AN ARRESTING STATE AND MOVING
AROUND LOOKING FOR ISSUES.
THEY CAN ALSO ADOPT AN
INFLAMMATORY STATE USUALLY
CALLED AN ACTIVATED STATE AND
THIS IS WHEN THEY'RE IN THEIR
FIGHTING STANCE AND PRODUCING
ALL THESE PRO-INFLAMMATORY
CYTOKINES THAT MAKE US FEEL
HORRIBLE AND PROBABLY PRODUCING
SYMPTOMS OF ME/CFS AND CAN ADOPT
AN ANTI-INFLAMMATORY STATE IN
GREEN AND THEN PRODUCE
ANTI-INFLAMMATORY CYTOKINES TO
REDUCE INFLAMMATION IN THE BRAIN
AND GET THINGS BACK NORMAL AND
MICROGLIA CAN MORE QUICKLY
SOMETIMES IN SECONDS.
IN THE PRIME STATE IT LOOKS LIKE
A NORMAL SITE AND PROTEINS THAT
ALLOW THE PRESENTATION OF
ANTIGENS TO OTHER CELLS AND
BASICALLY MEANS THEY'RE PRIMING
UP EVERYTHING THE ASTROCYTES AND
T CELLS IN THE BODY AND PRIME
EVERYTHING FOR AN INFLAMMATORY
RESPONSE.
THEY LOOK BASICALLY NORMAL AND
IN THAT PRIME STATE THEY CAN
INVITE T CELL TO GET THROUGH THE
BLOOD BRAIN BARRIER AND CAUSE
MORE INFLAMMATION.
THAT'S A STATE YOU DO NOT WANT
YOUR MICROGLIA IN LONG TERM AND
IT CAN CAUSE PROBLEMS.
OUR GOAL FOR ME/CFS IS TO GET
THE MICROGLIA BACK TO THE
RESTING STATE.
WHY ARE YOUR MICROGLIA
SENSITIZED.
THERE'S LOTS OF REASONS.
THIS IS ONE EXAMPLE.
ADIPOSE TISSUE IS GENERALLY NOT
INFLAMMATORY BUT WHEN AS THE TOO
MUCH WHITE ADIPOSE TISSUE IT
BECOMES VERY INFLAMMATORY AND
THAT INFLAMMATION IN THE BODY
AND READY ENTERS THE CENTRAL
NERVOUS SYSTEM AND CAUSES
INFLAMMATION IN THE BRAIN.
WHAT HAPPENS WHEN YOU HAVE A LOT
OF WHITE ADIPOSE TISSUE YOUR
LEPTIN LEVELS GO UP AND YOU GET
RESISTANCE AND TO THE
HYPOTHALAMUS STOPS RESPONDING
AND YOU FEEL HUNGRY THOUGH YOU
SHOULD HAVE HAD ENOUGH FOOD BUT
DON'T GET THAT SIGNAL TO TURN
OFF YOUR HUNGER.
THE PROBLEM IS YOUR HYPOTHALAMUS
BECOMES RESISTANT TO THE LEPTIN
AND THE MICROGLIA DON'T BECOME
SENSITIZED AND AS THE LEPTIN
RISES THEY START TO ADOPT AN
INFLAMMATORY STATE.
THAT'S ONE WAY WHAT'S GOING ON
IN THE BODY CAN AFFECT WHAT THE
MICROGLIA ARE DOING AND
SOMETHING AS SIMPLE AS WHITE
ADIPOSE TISSUE CAN TO
INFLAMMATION IN THE BRAIN.
ANY PERIPHERAL INFLAMMATION
STATE CAN CAUSE MICROGLIA
PRIMING AND ALTERED GUT
MICROGLIA AND NORMAL AGING
CAUSES MICROGLIA TO BE
SENSITIZED AND SLEEP APNEA CAN
DO THAT AND TOXIC EXPOSURES,
CERTAIN MEDICATIONS CAN DO THAT
AND OPIOID ANALGESICS ARE THE
BEST EXAMPLE.
CHRONIC STRESS AND OF COURSE THE
IMMUNE HITS VIRAL OR BACTERIAL
ESPECIALLY IF YOU HAVE A
SEQUENCE OF IMMUNE HITS TOO
CLOSE TOGETHER OR A STRONG
IMMUNE HIT THAT ESPECIALLY
SOMETHING INFILTRATED THE BRAIN
CAN MAKE THEM INTO THE PRIME
STATE AND READY TO GO TO
ACTIVATED STATE WITH MINIMAL
PROVOCATION AND SOMETHING YOUR
BODY'S DOING LIKE JUST EXERTING
YOURSELF A LITTLE BIT AND THE
MICROGLIA SENSITIZED INTERPRET
THAT AS A NEW PATHOGEN EXPOSURE.
I BELIEVE THAT'S WHAT'S GOING ON
WITH THE CNS.
WE DO COMPLEX IMAGING PROTOCOLS
SIMILAR TO OTHERS WE ADJUST
HEARD.
WE INJECT PEOPLE WITH ENDOTOXIN
AND SCAN THEM BEFORE AND AFTER
TO SEE IN THE ABNORMALITIES ARE
RESPONDING TO IMMUNE TRIGGERS.
I WON'T TALK ABOUT THAT THIS
TIME.
YOU PROBABLY SAW THE WORK ON THE
LEUKOCYTE INFILTRATION OF THE
BRAIN AND THAT'S GOING TO BE
VERY INTERESTING BECAUSE AGAIN
THESE MICROGLIA HAVE THE ABILITY
TO PULL THESE T CELLS IN AND
WE'D LOVE TO SEE THAT IF IT'S
HAPPENING AND WE'LL PERFORM
RESULTS NEXT YEAR ON THIS AND
GET HEADS UP ON THE TYPES OF
THINGS WE'RE WORKING ON BUT
THERE'S ONLY TWO I WANT TO
MENTION IN PARTICULAR TODAY
BECAUSE I WANT TO MOVE TO THE
TREATMENTS.
AND ACTUALLY BOTH OF THESE
YOU'VE ALREADY BEEN NOTIFIED ARE
BIG DEALS.
WE JUST HEARD ABOUT THESE.
IT'S NICE WE'RE GETTING
CONVERGING EVIDENCE.
THE FIRST IS USING PET TO LOOK
AT ACTIVATED MICROGLIA.
YOU HEARD HOW THAT HAP JNZ WE
HAVE TSPO LIGANDS WHEN MICROGLIA
ARE ACTIVATED THEY THE PET
LIGAND GOES THERE AND IF WE SEE
A LOT OF SIGNAL WE KNOW THE
MICROGLIA ARE ACTIVATED.
THIS IS A STUDY IN FIBROMYALGIA
AND I WANTED TO SHOW YOU HALF
THE BRAIN SHOWED ACTIVATED
MICROGLIA I HAVEN'T TRIED TO DO
MORE ADVANCED CASE DEFINITION
AND THE SAMPLE IS SMALL LIKE
15-15.
I DON'T KNOW HOW MANY WOULD MEET
THE CRITERIA BUT ENOUGH TO TELL
US WHEN WE FIND IN MICROGLIA
THERE'S A GOOD CHANCE WE'LL SEE
THAT IN A PURE ME/CFS SAMPLE AND
THAT'S LIKELY THE CASE.
MICHELLE JAMES SPEAKING NEXT
WILL PROBABLY PRESENT MORE DATA
THAT'S THE CASE.
WE HAVE A STUDY FUNDED BY NINDS
IT'S 20 HEALTHY CONTROLS AND 9
ME/CFS RUN AND THREE ALL
SCREENED AND READY TO GO AND
THAT IS THREE HEALTHY CONTROLS
AND ONE READY TO GO.
WE'RE NOT TOO FAR FROM FINISHING
THE ME/CFS BUT WE NEED MORE THIL
CONTROLS BEFORE WE FINISH.
I BELIEVE WE'LL HAVE THAT
FINISHED IN 2024 AND IF OUR
RESULTS AGREE WITH WHAT YOU JUST
TALKED ABOUT, AND MICHELLE
JAMES' STUFF WHICH WE'LL ALL
AGREE WE'LL HAVE POWERFUL
EVIDENCE THE MICROGLIA IS IN AN
AGITATED INFLAMED STATE AND IT'S
IMPORTANT TO KNOW.
THE SECOND PART IS THE LACTATE
IN THE BRAIN WHICH ALSO YOU JUST
HEARD ABOUT AND THAT'S BECAUSE
THE LACTATE IS REALLY SUPER
IMPORTANT AND SO MANY STUDIES
INCLUDING OUR STUDIES HAVE FOUND
LACTATE ALL THROUGHOUT THE BRAIN
IN ME/CFS.
THIS IS A CRITICAL PART OF THE
PATHOPHYSIOLOGY AND OF THE
DISEASE.
SO WHAT WE DO YOU'VE HEARD ABOUT
THIS AS WELL, WE DO MAGNETIC
RESONANCE SPECTROSCOPY AND A
SEQUENCE THAT ALLOWS US TO LOOK
THROUGHOUT THE BRIN AND GET LOTS
OF MEASUREMENTS AND WE'RE
LOOKING FOR PEAKS OF LACTATE
AMONG OTHER THINGS BUT I ONLY
WANT TO MENTION THE LACTATE
RIGHT NOW.
WE'RE FINDING IN OUR SAMPLE.
I PUBLISHED LACTATE BEFORE AND
WE FIND MORE LACTATE THROUGHOUT
THE BRAIN AND ME/CFS THAN
HEALTHY CONTROLS AND RUNNING A
LARGER VERSION OF THAT STUDY.
THE LACTATE AS DISCUSSED BEFORE
IT'S AN ALTERNATIVE METABOLIC
PATHWAY AND YOU MAY SWITCH TO
LACTATE FOR ENERGY.
WHY WOULD THAT HAPPEN?
IT'S LIKELY NEURAL OR BRAIN
INFLAMMATION.
THERE'S SO MUCH DEMAND TO FEED
THOSE PROCESSES THAT THERE NEEDS
TO BE AN ALTERNATIVE ENERGY
PROCESS.
THAT'S WHAT WE THINK IS
HAPPENING.
I WANT TO SHOW THIS BRIEFLY.
I SHOWED THIS THREE MONTHS AGO
AT THE NIH WEBINAR AND WE'RE
FINDING THERE ARE NOT EVERY
PATIENT SHOWS STRANGE ELEVATIONS
OF LACTATE BUT THERE'S A
SUBGROUP OF THE ME/CFS
PARTICIPANTS THAT DO SHOW CLEAR
ABNORMAL ELEVATIONS IN LACTATE.
I NEED TO DO A LOT OF WORK ON
THESE DATA AND NEED TO RUN MORE
SUBJECTS AS WELL BUT IT'S
LOOKING VERY INTERESTING.
SO AGAIN, THE LACTATE IS SUPER
IMPORTANT SO WHEN YOU COMBINE
THE PET LOOKING AT THE MICROGLIA
AND THEY'RE BOTH SHOWING THE
SAME THING WE HAVE CLEAR
EVIDENCE THAT THERE'S BRAIN
INFLAMMATION AND I THINK THERE'S
ALMOST NO DOUBT ABOUT THAT NOW.
I DON'T KNOW IF OTHERS WOULD
DISAGREE BUT THE EVIDENCE IS SO
STRONG AND WITH AN A LITTLE BIT
MORE DATA I THINK WE'LL HAVE IT
LOCKED DOWN AND WELL DECIDED.
AND THERE'S ONE MAJOR
ALTERNATIVE AND THAT IS
INADEQUATE BLOOD FLOW TO THE
BRAIN DUE TO VASCULAR PROBLEM.
WE HAVE TO CONTROL FOR THAT.
THAT'S A VERY PLAUSIBLE
HYPOTHESIS OF ME/CFS THERE'S NOT
ENOUGH OXYGEN TO THE BRAIN AND
WE EXCITE THE HYDROGEN ATOMS AND
MEASURE THEM AT THE BRAIN AND
READ HOW FAST THE BLOOD'S
FLOWING THROUGH THE BRAIN AND IF
THERE'S NOT ENOUGH BLOOD OR
OXYGEN GETTING TO THE BRAIN OR
SOME PIECE OF THE BRAIN AND IN
ME/CFS IF THERE WAS A PATHOLOGY
WE WOULD EXPECT NOT ENOUGH BLOOD
FLOW.
THIS IS NOT MY IMAGE.
THIS IS A HYPOFOCAL PROFUSION
AND THE BLUE MEANS NOT ENOUGH
BLOOD OR OX GEN REACHING THE
AREA.
WHAT WE ARE DOING I DON'T EXPECT
TO SEE OR RARELY SEE THIS IT
WILL BE DISTRIBUTED THROUGHOUT
MOST OF THE BRAIN WE'LL FIND OUT
SOON.
I WAS HOPING TO HAVE NEW ASL
DATA PHOR YOU.
WE HAVE 50 CONTROLS AND WE'RE
NOT ABLE TO GET THAT THROUGH THE
PIPELINE AND PROCESS IN TIME.
IT WILL PROBABLY BE A FEW MORE
WEEKS AND HAVE AN ANSWER WHETHER
ME/CFS SHOWS HYPERPROFUSION
USING OUR SPIN LABELLING.
IF WE FIND A DIFFERENCE AND YOU
HEARD REASONS WHY WE MIGHT, IF
WE SHOWED OUR GROUPS IN THE
SCANNER SHOW HYPERPROFUSION IT
WILL BE HUGE SUPPORT NOR
HYPOTHESIS THERE'S AN OX GEN OR
BLOOD FLOW PROBLEM.
IF WE DON'T FIND AN ABNORMALITY
IT WILL MAKE IT INCONCLUSIVE.
THERE'S REASON TO BELIEVE THE
PARTICIPANTS WOULD HAVE TO BE
SITTING OR STANDING IN ORDER FOR
THAT PROFUSION PROBLEM TO
MANIFEST.
SO IF I DON'T SEE ANYTHING
ABNORMAL, I WILL PROBABLY GOING
FORWARD ADD A TASK TO OUR
SCANNER SIMILAR TO THINGS YOU
HEARD BEFORE THE LAST COUPLE
DAYS WHERE WE'LL DO THE ASL, IT
ONLY TAKES ABOUT SIX MINUTES AND
PULL THEM FROM THE SCANNER AND
USE AN ORTHOSTATIC TOLERANCE
TEST MAYBE LASTS ABOUT FIVE
MINUTES AND PUT THEM BACK IN THE
SCANNER AND SEE IF WE'VE
PROVOKED HYPERPROFUSION AND IF
WE FIND THAT IT WILL BE
INCREDIBLE ESPECIALLY IF IT'S
SOMETHING THAT DOESN'T AFFECT
HEALTHY CONTROLS BUT DOES AFFECT
ME/CFS.
WE'LL SEE WHAT WE CAN DO QUICKLY
BY THE SCANNER TO DO IT AND PUT
IT BACK IN AND SEE IF THAT'S
PART OF THE ME/CFS.
AS MOST OF YOU KNOW, LABS, HUMAN
CLINICAL LABS HAVE CYCLES.
SOME YEARS WE'RE WRITING GRANTS
AND PAPERS THE WHOLE YEAR.
SOME YEARS WE'RE JUST COLLECTING
DATA LIKE CRAZY GOING AS FAST AS
WE CAN AND SOME YEARS ANSWERING
QUESTIONS AND NEXT YEAR IS
FORTUNATELY ONE OF THOSE
ANALYZING AND GETTING RESULTS
AND THOSE ARE MY FAVORITE YEARS
SO I'M EXCITE ABOUT 204.
FINALLY SOME OF THE PROJECT
THREE AND FIVE YEARS LONG AND
YOU WAIT UNTIL THE END AND
FINALLY GET TO FIND OUT WHAT
HAPPENS AND THERE'S GOING TO BE
A LOT OF THAT NEXT YEAR.
I GUESS STAY TUNED.
SOME TREATMENTS.
I HOPE THERE'S A HUGE PUSH ON
GETTING CLINICAL TRIALS GOING.
THERE'S A SEF SIT AND WE NEED TO
REMEDY THAT.
IF YOU'VE WATCHED MY TALKS
PREVIOUSLY I HAVE A LONG AND
GROWING LIST OF POTENTIAL
TREATMENTS THAT WOULD LOVE TO
SEE TESTED IN ME/CFS.
EIGHT YEARS AGO IT WAS 20 AND
THEN NOW IT'S PROBABLY AT 100.
I'M NOT EVEN GOING TO SHOW THE
SLIDE BECAUSE IT'S TWO SLIDES.
AND DRILL DOWN ON THE THINGS
THAT GET PRIORITIZED.
SOME OF THE DRUGS OR TREATMENT
OPTIONS ARE GOING TO DEPEND ON
WHAT I SEE WITH THE RESULTS OVER
THE NEXT YEAR.
WE SEE LEUKOCYTE PENETRATION OF
THE BRAIN WE MAY LOOK AT MORE
POPULATION DEPLETERS OR
ALTERNATIVES OR SOMETHING THAT
REPAIRS BLOOD BRAIN BARRIER.
IF WE SEE PROBLEMS WITH CEREBRAL
PROFUSION WE MAY LOOK AT
METHYLINE BLUE SHOWING TO CALM
MICROGLIA AND BLOOD FLOW.
WE'LL SEE WHAT THE DATA LOOKS
LIKE AND IF THAT LEADS TO
PARTICULAR TREATMENT OPTION.
HOWEVER, THERE ARE TWO TREAT
TREATMENTS I BELIEVE WE SHOULD
TEST NOW REGARDLESS OF HOW THE
TESTS TURN OUT.
AS THE TWO DRUGS HAVE SUCH A
GOOD CHANCE OF REDUCING
MICROGLIA EXCITABILITY IN A
BENEFICIAL WAY I THINK WE NEED
TO TEST THEM RIGHT NOW.
SOME OF YOU PROBABLY KNOW WHAT
I'M GOING SUGGEST OR REQUEST BUT
I'LL GO OVER IT ANY WAY.
I'LL ONLY TALK ABOUT TWO.
THE FIRST IS NALTREXONE.
IT'S AN OPIOID ANTAGONIST
CLASSICALLY AND THERE'S
ENDOGENOUS OPIOID RECEPTORS AND
HAVE NATURAL PAIN KILLING
CHEMICALS AND THEY'RE LEGAL
OPIOIDS LIKE OXYCODONE AND
ILLEGAL OPIOIDS LIKE HEROIN AND
THEY'LL TAKE NALTREXONE BLOCKS
ENDOGENOUS AND YOUR OWN
ENDOGENOUS PAIN CONTROL SYSTEMS.
THERE'S DOWN SIDE BUT SUPER
EFFECTIVE AND IT'S INCREDIBLY
IMPORTANT OF A DRUG.
RECENTLY THERE'S LOTUS
NALTREXONE.
INSTEAD OF 50 OR 100 MILLIGRAMS
A DAY IT'S BETWEEN 1 AND 5
MILLIGRAMS A DAY.
MOST OF YOU KNOW THIS.
THE REASON WHY IT WORKS IS
BECAUSE NALTREXONE ANTAGONIZES
TWO TARGETS.
ONE THE OPIOID I JUST MENTIONED
AND THE OTHER IS THE RECEPTOR 4
ON MICROGLIA AND WHEN YOU
ANTAGONIZE IT ON MICROGLIA YOU
SHUT OFF THE FLOW OF
PRO-INFLAMMATORY AGENTS FROM THE
MICROGLIA AND THIS WILL EASE
FATIGUE AND PAIN AND COGNITIVE
ISSUES AMONG OTHERS.
I'VE BEEN SHOWING -- I HAD TO
LOOK UP THE DATE YESTERDAY AND
IT'S BEEN SINCE 2009 SINCE I'VE
BEEN PUBLISHING WITH LOTUS
NALTREXONE AND EFFECTIVE IN FIBE
REMYALGIA BUT NOT USED IN
ME/CFS.
THERE'S BEEN NOT BEEN A
PUBLISHED CLINICAL TRIAL FOR
ME/CFS AND WHAT I DID LAST NIGHT
IS I TOOK THE LAST STUDY I DID
WHICH WAS 2014 IN 30
FIBROMYALGIA PATIENTS AND A 4.5
MILLIGRAMS A DAY AND 50% OF THE
FM PATIENTS HAD A CLINICALLY
SIGNIFICANT REACTION TO THE
NALTREXONE AND HAD A REDUCTION
OF THEIR SYMPTOMS.
50% IS GREAT.
THEY HAD A MUCH OR VERY MUCH
IMPROVED STATE AND THE LDN OVER
PLACEBO AND I TOOK THE DATA SET
AND FOUND AND DUG IT UP THROUGH
MY HARD DRIVE AND WENT THROUGH
THE RECORDS AND WAS ABLE TOFIDE
THE PARTICIPANTS WHO ALSO MEET
THE CRITERIA FOR AND LAST
ENTITLE I LOOKED AT THEIR
FATIGUE.
THERE WAS A REDUCTION IN THEIR
FATIGUE FROM 0 TO 100 FROM
BASELINE TO LOTUS NALTREXONE AND
SIGNIFICANT COMPARED TO PLACEBO.
THE REASON THE P VALUES ARE SO
HIGH IS BECAUSE I DID DAILY
SYMPTOM REPORTS.
IT'S AN ACROSS-SECTIONAL TRIAL
WHERE HALF HAD BETTER THAN 25%
REDUCTION OF THEIR FATIGUE.
THIS IS A LOW ESTIMATE AND I
TOOK ALL THE DATA AND THIS ALSO
INCLUDES THE FIRST FEW DAYS WHEN
THE REDUCTION OF SYMPTOMS IS NOT
THAT IMPRESSIVE AND ALL THE
STUFF IN THE MIDDLE.
HAD I THE FATIGUE WOULD HAVE
BEEN 32% OR 35% ON AVERAGE AND
THAT DOES MEET CLINICAL
SIGNIFICANCE.
I THINK OF 30% REDUCTION AS
CLINICALLY SIGNIFICANT AND THE
SCORE OF VERY MUCH IMPROVED OR
MUCH IMPROVED AND WHAT WE'RE
TARGETING FOR.
IT WASN'T A STUDY DESIGNED FOR
ME/CFS AND ENOUGH TO SAY WE HAVE
TO DO A PROPER CLINICAL TRIAL OF
LOTUS NALTREXONE.
NOW, WHENEVER I GIVE A TALK
USUALLY THE DAY BEFORE I DO A
LITERATURE SEARCH AND MAKE SURE
THERE ISN'T SOME GROUNDBREAKING
NEW DATA THAT CONFLICTS WITH
WHAT I'M TALKING ABOUT.
LAST NIGHT I DID THE LIT REVIEW
AND FOUND A GROUNDBREAKING NEW
STUDIED THAT CONFLICTS WITH WHAT
I'M SAYING SO I NEED TO TALK IT
ABOUT BRIEFLY.
I DON'T KNOW IF IT'S BEEN
DISCUSSED.
I DIDN'T HEAR IT MENTIONED AND
APOLOGIZE IF IT WAS AND THERE
WAS A PAPER PUBLISHED LAST WEEK
ON LOTUS NALTREXONE.
99 PEOPLE FROM DENMARK USING 6
MILLIGRAMS A DAY FOR 12 WEEKS
FOR FIBROMYALGIA.
THEY DID A PARALLEL GROUP.
HALF WITH PLACEBO AND HALF LDN
AND USED A DOSAGE HIGHER THAN
WHAT I'VE USED 6 MILLIGRAMS IS
NOT THAT DIFFERENT FROM WHAT I
TEST.
ANYWAY, THEY DID NOT FIND
STATISTICAL DIFFERENCE BETWEEN
THEIR GROUP AND PLACEBO GROUP
AND THERE'S A HUGE DEAL MADE OUT
OF THIS.
I STILL NEED TIME TO SCRUTINIZE
THE PAPER AND LOOKED WELL DONE
AND THE DECISIONS LOOK WELL AND
I DON'T DOUBT THE QUALITY OF
THEIR DATA OR STATISTICS.
THERE WAS A COMPANION COMMENTARY
THAT WENT WITH IT I BELIEVE WENT
TOO FAR.
I'LL TELL YOU WHY.
YOU CAN FIND THE COMMENTARY IN
LANCET IT SAID IT'S A
RESOUNDINGLY NEGATIVE TRIAL FOR
LDN AND TELL YOU WHY I DON'T
THINK THAT'S TRUE ANDY DON'T
THINK THE STUDY SHOULD DISSUADE
US FROM RUNNING LDN AND THE
EDITORIAL SAID PHYSICIANS SHOULD
STOP PRESCRIBING LDN AND THERE'S
STRONG EVIDENCE WE SHOULD NOT
GIVE IN TO ANY PATIENTS OR
PATIENTS UNLESS THEY'RE ALREADY
ON IT.
YOU SHOULD NOT PRESCRIBE IT TO
ANY NEW PATIENTS.
I STRONGLY DISAGREE AND BELIEVE
THE PHYSICIANS AT THE CONFERENCE
I BELIEVE THEY WOULD STRONGLY
DISAGREE WITH THAT AS WELL.
I HAVE PLENTY OF PHYSICIANS THAT
WOULD THINK IT'S NOT GOOD ADVICE
BECAUSE THE DRUG IS SO HELPFUL
FOR A LOT OF PEOPLE.
THE REASON WHY I DON'T LIKE
THEIR CONCLUSIONS IN
INTERPRETING THE STUDY, FIRST,
THIS STUDY 48% OF THE
FIBROMYALGIA PATIENTS HAD A
CLINICALLY SIGNIFICANT REDUCTION
IN THEIR SYMPTOMS ALMOST HALF.
THAT'S ALMOST EXACTLY WHAT I'VE
ALWAYS FOUND.
THEY GOT 48%, IN MY STUDY I HAD
50%.
VERY SIMILAR IN TERMS OF EFFECT
SIZE.
THE DIFFERENCE IS THEY DID A
PARALLEL GROUP STUDY WHICH YOU
NEED A LOT OF PEOPLE TO HAVE THE
STATISTICAL SENSITIVITY TO FIND
AN EFFECT.
THAT'S WHY FDA TRIALS THAT USE
PARALLEL GROUPS HAVE 100, 200,
300, 400 PEOPLE.
HAD THEY RUN 40 TO 60 MORE
PEOPLE THEY WOULD HAVE HAD
STATISTICAL DIFFERENCE.
THAT'S MY INTERPRETATION.
TAKE A LOOK AND LET ME KNOW WHAT
YOU THINK.
THE DATA LOOKED FINE TO ME AND I
DO NOT THINK IT SHOULD STOP US
FROM LOOKING AT LDN.
I JUST SAW THIS LAST NIGHT AND
THOUGHT THIS IS GOING TO BE A
BIG DEAL BECAUSE PEOPLE ARE
GOING TO SEE THE TITLE AND THE
COMMENTARY AND GO OH, LDN'S
DEAD.
WE SHOULDN'T TRY IT.
I'VE TALKED TO OVER 1,000 PEOPLE
OVER THE LAST 10 YEARS AND IT
WOULD BE BAD TO GIVE UP ON LDM
RIGHT NOW.
ONE THING THE COMMENTARY SAID I
AGREE WITH IS WE NEED TO RUN
FINALLY A PROPERLY POWERED
ADEQUATE SAMPLE SIZE, CLINICAL
TRIAL OF LDN.
WE NEED THAT TO ANSWER THE
QUESTIONS TIMELY.
I'VE GONE ON ABOUT THAT LONG
ENOUGH AND ALMOST OUT OF TIME SO
WE HAVE TO KEEP GOING.
NOW, REAL QUICK THERE'S ANOTHER
DRUG I'D LOVE TO SEE USED IN
HUMANS.
THAT'S BECAUSE AS EFFECTIVE AS I
BELIEVE LDN IS THERE'S A
HINDRANCE AND THAT'S THE OPIOID
BLOCKADE.
IF YOU START TO GET ABOVE 6
MILLIGRAMS YOU BLOCK THE OPIOID
UP SO MUCH YOU CAN START TO
CAUSE SYMPTOMS FOR AN
INDIVIDUAL.
YOU DON'T WANT TO BLOCK THE
OPIOID SYSTEM OUR BLOCKED THE
EUPHORIA, PAIN CONTROL SYSTEMS.
I DON'T THINK IT'S HELPFUL AND
KEEPING US RESTRICTED IN THIS
REALLY TIGHT RANGE.
WE NEED A WAY TO REMOVE THE
CEILING AND THERE'S A WAY TO DO
THAT.
THIS IS CALL DEXTRONE NALTREXONE
IDENTICAL TO THE NALTREXONE WE
TAKE EXCEPT A FLIPPED IMAGE AND
SAME MOLECULAR FORMULA AND ATOMS
IT AFFECT THE RECEPTORS
DIFFERENT AND WHEN YOU TAKE IT
COMMERCIALLY YOU'RE TAKING LEGAL
NALTREXONE AND DEXTRONE
NALTREXONE HAS ONE IMPORTANT
EXCEPTION IT DOESN'T INTERFERE
WITH THE RECEPTORS.
WE CAN RAMP UP THE DOSE AND HAVE
A MORE POWERFUL EFFECT ON THE
MICROGLIA AND THIS IS ONLY
SHOWING LEGAL NALTREXONE HAVE
THE SAME EFFECT BY DOSAGE ON THE
PRODUCTION OF INFLAMMATORY
CHEMICALS FROM MICROGLIA AND
THEY BOTH SUPPRESS MICROGLIA AND
DOESN'T BLOCK THE OPIOID
RECEPTORS.
WE'LL HAVE TO SYNTHESIZE THIS
AND WILL HAVE TO DO FDA TRIALS
TO GET THIS IN HUMANS.
IT WOULD PROBABLY COST $1.5
BILLION TO DO BUT WORTH PUTTING
MONEY INTO.
THERE'S ONE HUGE CAVEAT TO ALL
THIS WORK.
WE CAN SEE BRAIN INFLAMMATION.
WE HAVE TO BE CAREFUL TO KNOW IS
THE BRAIN INFLAMMATION THE
PROBLEM OR IS THE BRAIN
INFLAMMATION TRYING TO SOLVE THE
PROBLEM?
WE HAVE TO CONSIDER WHERE IS
BRAIN INFLAMMATION IN THE ENTIRE
PATHOLOGICAL PROCESS.
I'M PUSHING FOR CLINICAL TRIALS.
WE NEED TO HAVE AN AGREED SET
OF CRITERIA AND DEFINE SAM SIZE
AND COMMON OUTCOMES AND CASE
CRITERIA AND HAVE EVERYONE USE
THE BASIC SAME PLAN TO COMPARE
AND CONTRAST THE DIFFERENT
TRIALS.
I WOULD LOVE TO SEE THAT HAPPEN.
THAT'S IT MY NEW YEAR'S
RESOLUTION IS TO DO A LOT OF
VIDEOS SO MY YOUTUBE PAGE IS
YOUNGER LAB YOU CAN LOOK AT ANY
TIME AND PROMISE MY NEW YEAR'S
RESOLUTION IS TO TRY TO DO A
VIDEO EVERY TWO WEEKS.
I TRIED BEFORE AND FAILED
MISERABLY AND HOPE THIS TIME I
CAN STICK IT TO AND GET THE
INFORMATION OUT AND I'LL STOP
THERE AND THANK YOU FOR YOUR
TIME AND LISTENING.
>> IT GIVES A PERSON AN
INFECTION BUT YOU DON'T WANT TO
SPREAD OF INFECTION OR SEPSIS OR
SOMETHING AND WE'VE ONLY DONE
THIS IN HALF THE MEAN CRITERIA
FOR CHRONIC FATIGUE SYNDROME.
WHEN YOU GIVE A LOW LEVEL
ANTIGEN TO A HEALTHY CONTROL AND
THE BRAIN DOESN'T REACT AND THEY
DON'T FEEL ANYTHING AND THEY
REACT ABNORMALLY.
THERE'S A HUGE INCREASE OF
LEPTIN AND SUPPRESSION OF OTHER
CHEMICALS AND THE MICROGLIA ARE
BE ACTIVATED AND THE SUPPRESSION
SUGGESTIONS THE BREAKS ON
MICROGLIA AREN'T THERE.
IN FIBROMYALGIA WE SCAN THE
BRAIN AND FINDING THERE'S NOT AN
INFLAMMATORY RESPONSE IN THE
HEALTHY CONTROLLED BRAIN BUT IN
FIBROMYALGIA THERE'S A LARGE
INFLAMMATORY RESPONSE TO A SUPER
LOW TRIGGER.
THAT'S THE BEST WE HAVE IN TERMS
OF LOOKING AT THIS.
>> LPS WOULD MIMIC A BACTERIAL
NOT VIRAL INFECTION.
LET'S DO A VIRAL INFECTION.
>> YOU CAN DO THAT WITH THE
VACCINE MAYBE.
>> NO.
PEOPLE COME TO THE HOSPITAL ALL
THE TIME WITH VIRAL INFECTION.
>> IT'S AN INTERESTING APPROACH.
WE HAVE THE SCANNER SCHEDULE.
IF SOMEONE'S SICK WE CAN SAY THE
SCANNER'S AVAILABLE AND BRING IT
OVER.
THAT CAN BE DONE.
A COLLEAGUE THAT BRINGS IN SKITS
FR
FREN -- SCHIZOPHRENIC REACTION
WE CAN SCREEN.
>> THE NEXT SPEAKER BEFORE WE
MOVE TO THE PANEL DISCUSSION IS
DR. MICHELLE JAMES FROM STANFORD
TALKING ABOUT ILLUMINATING WHOLE
BODY RESPONSES USING PET KEEPING
ON OUR THEME.
>> HELLO, EVERYONE.
THANK YOU FOR THE OPPORTUNITY TO
BE HERE AND SHARE DATA WITH YOU
ALL.
A LITTLE OVERVIEW WHAT I'LL BE
SPEAKING ABOUT.
I'LL GIVE BACKGROUND OF THE PET
IMAGING BIOMARKERS US AND OTHER
GROUPS ARE EXPLORING OR LOOKING
OR INFLAMMATION EXPANDING ON PET
IMAGING OF INFLAMMATION AND SHOW
OUR PRELIMINARY DATA AND INSIGHT
FROM PET MRI STUDY IN ME/CFS AND
THEN I'LL LOOKING FORWARD TO
HIGHLIGHTING SOME OF THE NEWER
PET TRACES BEING DEVELOPED IN MY
LAB FOR IMAGING DIFFERENT KINDS
OF IMMUNE CELLS AND I'LL WRAP UP
WITH CONCLUSIONS AS WELL.
LIKE WHAT YOU'VE SEEN FROM
HANNAH'S PRESENTATION AND
DR. YOUNGER'S PRESENTATION WE'RE
MOTIVATED TO TRY TO SHED LIGHT
ON NEURAL INFLAMMATION IN THE
MOLECULAR LEVEL AT ME/CFS TO
INFORMATION MORE ABOUT THE
SPATIAL TEMPORAL DYNAMICS AND
ULTIMATELY WE'D LOVE TO BE ABLE
TO USE ONE OF THOSE APPROACHES
IN CLINICAL TRIALS OF NEW DRUGS
LIKE WHAT DR. YOUNGER WAS
TALKING ABOUT TO DETECT IF
SOMEBODY'S RESPONDING OR NOT
MORE RAPIDLY.
SO AS YOU'VE SEEN AND HEARD
THERE'S LOTS OF TECHNIQUES FOR
MEASURING INFLAMMATORY
BIOMARKERS.
SOME ARE IN BLOOD AND YOU'VE
SEEN GREAT TALKS LOOKING AT
VARIOUS MARKERS OF IMMUNE CELLS
AND THE FUNCTIONAL PHENOTYPES
AND BLOOD AND CSF IS ANOTHER
OPTION AND USE STRUCTURAL
IMAGING FOR BRAIN TUMORS AND
STROKES AND THINGS LIKE THAT AND
THE BASIC STATE OF THE ART
CHANGES IS YOU LOOK AT
STRUCTURAL CHANGES ALONE THAN
MORE FUNCTIONAL CHANGES.
AND POST MORTEM ANALYSES ARE
HELPFUL AND CAN PROVIDE SPECIFIC
INFORMATION ABOUT BIOMARKERS OR
IMMUNE CELLS AND THEN IN A
SPATIAL MANNER.
THAT'S GREAT BUT IT'S OBVIOUSLY
TOO LATE.
WE'D LIKE TO BE ABLE TO LOOK AT
THIS KIND OF INFORMATION IN A
LIVING SUBJECT.
THAT'S WHY MOLECULAR IMAGING
COMES IN AND USING TOMOGRAPHY
AND WHAT A LOVE ABOUT PET IS
IT'S SENSITIVE.
YOU CAN LOOK AT DIFFERENT
MOLECULAR CHANGES OF THE NANO
MOLAR AM AND LOOKING AT SMALL
CHANGES WHICH GIVES ME HOPE
WE'LL BE ABLE TO DETECT CHANGES
AT EARLY STAGE FOR INSTANCE.
WHAT ARE SOME OF THE BIOMARKERS
PEOPLE ARE LOOKING AT?
THE RED LABEL THE RADIO CHEMISTS
AROUND THE WORLD TRY TO MAKE PET
TRACERS FOR.
HAVE YOU YOUR MICROGLIA AND
ASTROCYTES AND A COLLEGIATE THE
UNIVERSITY OF MICHIGAN JUST MADE
A NICE PET TRACER LOOKING AT THE
ACTIVITY OF MAOB THAT COULD BE
OF INTEREST TO PEOPLE TRANSLATED
TO THE CLINIC.
WE HAVE PERIPHERAL IMMUNE CELLS
SO YOUR MYELOID CELLS THAT MAY
INFILTRATE THE CNS AND YOU ARE
HAVE A RANGE OF MARKERS.
YOUR ADAPTIVE IMMUNE CELLS, T
CELLS AND B CELLS.
I'LL TALK ABOUT SOME OF THOSE
MARKERS AND PET TRACERS IN A
BIT.
AND LOOK AT CYTOKINE SIGNALLING
OR OXIDATIVE STRESS AND THERE'S
BEEN PET TRACERS.
AND WE HAVE A NICE TOOLBOX OF
PET IMAGING AGENTS TO LOOK AT
DIFFERENT IMMUNE CELLS AND
LOOKING AT SOME OF THESE IN THE
CONTEXT OF CANCER OR OTHER
DISEASES.
I THINK WE CAN APPLY THEM TO
DISEASES LIKE ME/CFS AND TSPO
AND I'LL TALK WITH THE RESULTS
OF OUR PET IMAGING IN A MINUTE.
YOU CAN SEE THERE'S A NUMBER OF
CELL TYPES.
IT'S PREDOMINANTLY ON YOUR
ACTIVATED MYELOID CELLS.
DEPENDING ON THE CONTEXT IT
COULD BE MORE EXPRESSED ON
ASTROCYTES AND CERTAINLY
EXPRESSED AT HIGH LEVEL ON
ENDOTHELIAL CELLS AND ALSO
CANCER.
WITH NEED TO BE CAREFUL THOUGH
IT'S A USEFUL MARKER AND HAVE
MARKERS MORE SPECIFIC FOR
MACROPHAGES AND I WANT TO FLAG I
WON'T HAVE TIME IT TALK ABOUT
THE T CELL IMAGING AGENTS BUT IF
YOU LOOK AT THE TABLE IT'S A
NICE COUPLE OF TRACERS DOWN THE
LINE.
ONE THAT'S GREAT FOR LOOKING AT
CD 8 T CELLS AND A LINEAGE
MARKER ADAM WU DEVELOPED FROM
UCLA AND THE TOP TRACER THERE IS
AVAILABLE FOR CLINICAL USING.
IF PEOPLE ARE INTERESTED IN
IMAGING T CELLS IT COULD BE A
GOOD ONE.
AND THERE'S IMAGING AGENTS
LOOKING AT T CELL ACTIVATION.
AND THERE'S INTERESTING PROTEIN
ON THE MITOCHONDRIAL MEMBRANE.
IT REACTS WITH REACTIVE OXYGEN
SPECIES AND HAS REGULATION OF
MITOCHONDRIA.
IT'S SUPPRESSED ON DIFFERENT
TISSUES SO KEEP THAT IN MIND.
IT BECOMES ELEVATED IN THE KWON
TEXT OF INFLAMMATION.
PEOPLE THOUGHT IT COULD SERVE AS
THIS DIAGNOSTIC SENSOR OF
INFLAMMATION AND WHY IT STARTED
TO BE INVESTIGATED.
THERE'S A NUMBER OF PET TRACERS
FOR THAT AND I'M GOING TO SHARE
ABOUT WHAT WE'RE DOING OUR
ULTIMATE GOAL I HAD MENTIONED
BEFORE IS TO SPECIFICALLY TRACK
AND MONITOR INFLAMMATION IN VIVO
WITH THE ULTIMATE GOAL OF USING
IT FOR THERAPEUTIC DRUG TRIALS.
WE'RE COMPARING ME/CFS FOR
CONTROLS WITH AGE, SEX AND
GENOTYPING EVERYONE AND
COLLECTING BLOOD AND SALIVA AND
WOULD LIKE TO BE ABLE TO
CORRELATE OUR FINDINGS WITH
FLUID BASED BIOMARKERS OF
INFECTION ULTIMATELY.
WE'RE LOOKING AT MODERATE TO
SEVERE ME/CFS AND THIS IS NICE
TO HAVE BOTH HANNAH AND OTHERS
WORKING ON THE SAME THING TO
MOVE THE FIELD FORWARD AND
HERE'S IMAGES WE'VE BEEN
ACQUIRING.
THESE ARE SOME OF THE FEMALE
IMAGES.
YOU CAN SEE VISUALLY WE'RE
GETTING THIS INCREASED UPTAKE OR
SIGNAL IN THE THALAMUS AND PONDS
AND CORTICAL REGIONS COMPARED TO
THE HEALTHY AND SOME MALE IMAGES
LOOKED A LITTLE BIT DIFFERENT TO
ME IN THE AMOUNT OF UPTAKE AND
THEY'RE ALL SEX DIFFERENCES IN
TSPO SO THEY'RE IMPORTANT TO
CONSIDER.
WHAT IS INTERESTING TO ME WHEN I
LOOKED AT ALL THE IMAGES WE'VE
ACQUIRED SO FAR IS WE KEPT
SEEING THE SIGNAL OUTSIDE THE
BRAIN.
IT'S THE CAROTID GLANDS.
THE SALIVARY GLANDS AND FOUND
THERE'S AN INCREASED NUMBER OF
CELLS THAT ARE IN THE SALIVARY
GLANDS.
AND WE'RE PROBABLY SEEING THEM
HERE WHICH IS VERY INTERESTING
AND I THOUGHT WHAT ELSE ARE WE
MISSING?
SO I WANTED TO AT THAT POINT SEE
IF WE COULD DO A WHOLE BODY SCAN
AND BECAUSE IT'S A CARBON 11
TRACER PEOPLE LAUGHED AT ME
THEY'RE LIKE YOU'RE GOING TO DO
A WHOLE BODY SCAN?
WE DON'T HAVE A WHOLE BODY
SCANNER AT STANFORD THEY'RE JUST
COMING ONLINE AND I THOUGHT WE
CAN TRY AND SEE WHAT WE CAN SEE.
SOMEONE HAS BEEN INJECTED WITH A
RADIO TRACER IT'S THROUGHOUT THE
BODY SO WHY NOT TRY TO CAPTURE
THE INFORMATION.
I JUMPED IN THE SCANNER.
THIS IS ME.
I THOUGHT I SHOULD TRY IT FIRST
AND MAKE SURE IT'S WORTH DOING
BEFORE PUTTING A PATIENT THROUGH
IT AND IT WAS GOOD TO UNDERSTAND
WHAT WE'RE ASKING PATIENTS TO DO
PEOPLE WITH ME/CFS HAVE LIGHT
AND SOUND SENSITIVITY SO WE'VE
TRIED TO DECREASE ALL THOSE
THINGS TO MAKE IT MORE
COMFORTABLE.
SO THESE ARE THE WHOLE BODY PET
MRI SCANS AND WE'RE SEEING
SIGNAL IN THE HEART AND LIVER
AND GUT.
AND WE STARTED WITH GREAT
FUNDING FROM NINDS TO DO WHOLE
BODY SCANS AND SEE VISUALLY FROM
THE SCANS YOU CAN SEE THE BONE
MARROW LIGHTING UP AND THE
MUSCLES.
THAT SURPRISED ME HOW MUCH THE
MUSCLES LIGHT UP COMPARED TO THE
QUIET MUSCLES IN THE CONTROL
THESE ARE ALL SEX AND GENOTYPED
MATCHED.
THE SCANNER IS PROBABLY NOT AS
GOOD BE BECAUSE OF THE CARBON 11
BUT WE'RE GETTING A MORE
SENSITIVE SCANNER SOON AND WE'LL
BE COLLECTING MORE IMAGES AND
SEEING MORE INSIGHT BUT THE SAME
PATTERN OF MUSCLE UPTAKE AND
BONE MARROW UPTAKE.
THE UPPER THIGH AND TRICEP IT
SEEMS THERE'S TWO SUBSETS HERE
AND IN THE SMALL COHORT WE HAVE
SO FAR.
TAKE IT WITH A GRAIN OF SALT.
WE'RE TRYING TO SHOW THE DATA.
WE'RE EXCITE D WE'RE NOT SEEING
IT IN THE THIGH SO FAR BUT
SEEING IT MORE IN THE TRICEP.
BONE MARROW.
THAT'S SOMETHING WE'RE SEEING IN
FEMALES SO FAR.
WE'LL BE ANALYZING EVERYTHING IN
MORE REGIONS SOON.
WE WANT TO LOOK AT SPLEEN AND
THE GUT AND LUNGS.
OTHER AREAS IF PEOPLE HAVE OTHER
THOUGHTS PLEASE LET ME KNOW AND
WE HAVE COLLABORATORS THAT WANT
TO USE MACHINE LEARNING AND A.I.
BECAUSE THERE'S THINGS WE COULD
BE MISSING.
WE WANT TO INCREASE OUR PATIENT
POPULATION BY A BUILT.
WE'RE UP TO SIX MATCHED PAYERS
AND HAVE THE SEVENTH ABOUT TO
HAPPEN IN JANUARY.
AND WE WANT TO EXTRACT
MEANINGFUL INFORMATION.
IN PARALLEL WE'RE LOOKING AT
MORE SPECIFIC BIOMARKERS OF
INFLAMMATION.
IT'S EXPRESSED IN OTHER CELL
TYPES AND WHAT HAS BEEN USEFUL
AND CONTINUES TO BE TREATFUL IN
SHEDDING LIGHT IN INFLAMMATION
THE SIGNAL MAY BE MURKY AT
TIMES.
IF WE WANT SOMETHING SENSITIVE
TO GIVE THE EARLIEST INDICATOR
IF SOMEBODY'S RESPONDING TO A
THERAPY OR NOT WE WANT SOMETHING
CLEAN.
AND WE'RE LOOKING AT THIS RIGHT
NOW AND GETTING INTERESTING
RESULTS.
THIS IS FROM THE LAB RNA SEQ
DATA SET IN HUMAN BRAIN AND YOU
CAN SEE BY LOOKING AT THE
DIFFERENT CELL TYPES AND THE
EXPRESSION OF TSPO IT DOES SEEM
TO BE MORE SPECIFIC FOR YOUR
MICROGLIA AND MACROPHAGES.
GPR84 IS UPREGULATED IN THE
CONTEXT OF MALADAPTIVE
INFLAMMATION AND WE TOOK
MACROPHAGES AND LOOKED AT THE
EXPRESSION OF GPR84 AFTER
STIMULATING THE CELLS WITH LPS
AND WE SAW THE TSPO DOESN'T GET
UPREGULATED AND THAT'S WHAT
PEOPLE HAVE SEEN WITH THE PET
SCANS AND OTHER TESTS DOING ON
TSPO IS THE NUMBER OF RECEPTORS
DON'T GO UPPER CELLS.
THERE'S MORE CELLS EXPRESSING
TSPO AND HERE THE NUMBER OF GPR
RECEPTORS GO UPPER CELL AND
WOULD BE MORE CELLS EXPRESSING
GPR84.
THAT'S EXCITING BECAUSE WE MAY
GET A BETTER SIGNAL TO
BACKGROUND.
WE'VE MADE TWO TRACERS COMPARING
THEM.
SO WE'VE DONE A LOT OF CELL
BINDING STUDIES USING CELLS THAT
EXPRESS HUMAN GPR84 AND GET GOOD
BINDING.
THIS GETS WASHED OUT AND 24
HOURS LATER WE DO IMAGING AND
SCORE THE MICE IN TERMS OF THEIR
SEVERITY AND SEPSIS SYMPTOMS AND
SEE HIGHER UPTAKE COMPARED TO
THE CONTROLS AND SEVERE SEPTIC
MICE WE SEE MORE UPTAKE.
IT SEEMS TO CORRELATE AND
CORRESPOND TO DISEASE SEVERITY
OR INFLAMMATION SEVERITY.
THEN WE CONFIRM SPECIFICITY BY
DOING ORDER RADRADIOGRAPHY AND S
CORRESPONDS WITH THE LITERATURE
WITH RNA LOOKING AT GPR84 IN THE
MOUSE MODEL.
AND LOOKING TO DETECT
UPREGULATION AND I'M SHOWING
WITH THE TRAITORS WE'RE DETECT
ING A NINE-FOLD INCREASE IN THE
HUMAN DERIVED MACROPHAGES AND
WE'RE ABLE TO BLOCK THE SNAM
OVER 50% WHICH IS GREAT.
IT CAN BEING QUICKER THAN A
THERAPEUTIC BECAUSE THE BARRIER
TO GET THE APPROVAL IS LOWER
BECAUSE YOU'RE ONLY INJECTING A
VERY LOW AMOUNT THAT SHOULD NOT
BE PHARMACO LOGICALLY ACTIVE.
AND WE'LL COMPARE TRACES IN
NON-HUMAN PRIMATES AND CELLS AN
TISSUE.
IF ANYONE HAS ANY TISSUE SAMPLES
FROM ME/CFS WHETHER MUSCLE OR
BRIN OR ANYTHING, WOULD LOVE TO
COLLABORATE AND SEE IF WE COULD
TEST OUR NEW PET TRACERS TO SEE
IF THEY'LL BE ABLE TO
DIFFERENTIATE BETWEEN ME/CFS AND
CONTROL.
I WANTED TO HIGHLIGHT TWO OTHER
MARKERS AND PET TRACE ERS AND W
MADE AN ANTIBODY BASED PET
TRACER.
AND THE ANTIBODY HAS BEEN
AMAZING.
IT'S CHANGED MY MIND ABOUT
ANTIBODY IMAGING ACTUALLY.
YOU'LL SEE FROM THE IMAGES THAT
YOU CAN SEE THE LOW SIGNAL.
JUST THE RED SIGNAL IN THE HEART
AND DESCENDING AORTA IS
INDICATIVE OF WHERE AN ANTIBODY
WOULD GO AND HANGING OUT IN THE
BLOOD POOL AND YOU MOVE TO THE
PRE-E.A.
THE MICE LOOK NORMAL AND WALKING
AROUND THE CAGE AND COATS ARE
SHINY BUT THEY'RE ABOUT TO GET
SICK.
THEIR PET SCAN WOULD KNOW THAT
BECAUSE YOU CAN SEE THE SPLEEN
IS LIGHTING UP AND BONE MARROW
AND LUMBAR SPINAL CORD LIGHTING.
.
VERY CLEAR AND THE REGION WHERE
WE INDUCE INFLAMMATION IN THE
CHEST.
THAT IS CLEAR AND AS THE MICE
BECOME PARALYZED THEY GET
PARALYSIS IT'S AWFUL.
WE DO SEE THAT SIGNAL CREEPING
UP THE SPINAL CORD AND REALLY
PLOGE OUT IN THE BONE MARROW AND
SPLEEN AND SEE THE PERIPHERAL
CELLS THE MACROPHAGES AND SEE
THEM TRAFFICKING IN THE SPINAL
CORD AND UP TOWARDS THE BRAIN.
IF YOU COMPARE THAT WITH A PET
OF THE SAME MICE BELOW YOU CAN'T
REALLY TELL WHAT'S GOING ON WITH
THE TSPO BECAUSE THERE'S TSPO
EXPRESSED THROUGHOUT THE BODY
AND OBSCURES OUR ABILITY TO GET
THE SPINAL CORD AND LOOK AT
REMITTING EAA AND YOU'RE LOOKING
AT THE SPINAL CORD AND NAIVE
SIGNAL IN THE SPINAL CORD AND
FIRST WAVE OF DISEASE YOU SEE
THE SIGNAL LIGHT UP IN THE
SPINAL CORD.
REMISSION, THAT SIGNAL GOES WAY.
THE RELAPSE, THE SIGNAL COMES
BACK AND BELOW YOU SEE WE'VE
TAKEN NO SIGNAL IN THE SPINAL
CORD OR REMISSION AND TRACKS
WITH DISEASE SEVERITY.
THIS IS THE SITUATION WHERE WE
ARE LOOKING AT ALL EAE MICE
BEFORE THERAPY.
THE ONE IN THE MIDDLE AND SEE
THE SIGNAL IN THE SPINAL CORD
AND KNEE WITH THE BONE MARROW
AND THEN WE TREAT THEM WHICH
STOPS THE IMMUNE CELLS FROM
LEAVING THE SPLEEN AND LYMPH
NODES AND SEE THE SIGNAL
DISAPPEAR.
THIS IS REALLY CLEAR RESPONSE AT
THE MOLECULAR LEVEL A WEEK AFTER
GIVING THE DRUG HOPE WE CAN DO
SOMETHING LIKE THIS IN A
CLINICAL TRIAL.
WE ALSO LOOK AT HUMAN TISSUE.
WE WORK WITH THE PATHOLOGY
DEPARTMENT CLOSELY AT STANFORD.
THESE WERE LESIONS FRESH LESIONS
AND TREATMENT NAIVE, HARD TO
COME BY THAT KIND OF TISSUE AND
WE SHOWED TERM ONE IN THE BOTTOM
RIGHT IN THE BROWN STRAINING IS
HIGHLY EXPRESSED.
THERE'S TERM 1 POSITIVE CELLS IN
THE LESIONS COMPARED TO THE
IMAGE ABOVE WHICH IS A NON-MS
REGION OF THE BRAIN.
IT'S NOT JUST A GOOD BIOMARKER
FOR MICE BUT SEEMS TO BE
RELEVANT IN THE CLINICAL
SETTING.
LASTLY I WANTED TO HIGHLIGHT THE
B CELL IMAGING WORK WE'VE BEEN
DOING.
THIS IS SIMILAR WHERE WE'RE
DOING IT IN AN MS AND EA MODEL
AND WOULD LOVE TO TRY THIS IF WE
HAVE MOUSE MODEL FOR ME/CFS.
I KNOW THAT'S A QUESTION BEING
RAISED A LOT.
ULTIMATELY YOU CAN MOVE TO THE
CLINIC QUICKLY.
HOPEFULLY WE CAN DO THAT.
HERE WE'RE USING AN ANTI-B CELL
THERAPY.
I KNOW JARRED MENTIONED
RETOXIMAB AND THIS IS A
TREATMENT AND UNTREATED MOUSE
AND YOU CAN SEE HERE THE CLASSIC
B CELL RESERVOIRS AND THE SPLEEN
IS HIGH SIGNAL.
HAVE YOU LYMPH NODES AND BONE
MARROW.
ALL LIGHTING UP WHERE YOU WOULD
THINK THERE'S B CELLS.
WE TREATED A SET OF MICE YOU
THINK BRAIN SIGNAL IS GONE AND
LYMPH NODES THIS MOUSE MUST BE
BETTER.
UNFORTUNATELY THEY'RE ALL STILL
PARALYZED.
THEY WERE NOT BETTER AND WE
COULD NOT REPRODUCE THE
LITERATURE.
PEOPLE SAID THE TREATMENTS HAVE
WORKED I TOLD MY GRAD STUDENT
LET'S NOT GET PERTURBED BUT HAVE
A LOOK CLOSER AT WHAT MIGHT BE
GOING ON.
I SAID LET'S HAVE A LOOK AT THE
FLOOR.
SO SPLEEN WERE DEPLETED THE B
CELLS COMPLETELY.
THEY'RE GONE.
BUT IF WE LOOK AT THE BRAIN AND
SPINAL CORD WE SEE INDEED THERE
ARE CD POSITIVE B CELLS AND HAVE
BEEN AS EFFECTIVE IN AT LEE
ELIMINATING THOSE IN THE AREAS
WHICH WE HAVEN'T BEEN ABLE TO
SEE IN THE LIVING SUBJECT.
THE STANDARD OF CARE IS TAKING
BLOOD MEASUREMENTS BUT WHAT
ABOUT IN THE BRAIN AND SPINAL
CORD?
WE DON'T HAVE A WAY TO LOOK AT
THAT AND HOPING THE PET
STRATEGIES COULD PROVIDE A
MEANS.
THIS IS STAINING SHOWING WE'RE
PRETTY GOOD AT DEPLETING B CELLS
IN THE MENINGES.
AND THERE'S STILL SOME IN THE
PARENCHYMAL AND IT CAN PERMIT
INNATE ACTIVATION IN THE WHOLE
BODY OF ME/CFS.
WE'RE IN THE EARLY STAGES AND
WHAT WE'RE SEEING IS QUITE
ENCOURAGING BECAUSE WHERE IT'S
SEEING AREAS WE DIDN'T KNOW
BEFORE WE ARE LIGHTING UP WITH
THE ACTIVATED MACROPHAGES.
SO THAT IS STAGING FOR THAT AND
HOPEFULLY WE'LL HAVE MORE TO
REPORT NEXT YEAR AND IF YOU WANT
TO ENROLL IN THE STUDY CONTACT
ME.
WE'RE ALSO INTERESTED AND
MOTIVATED BY OUR NEW PET TRACERS
AND THE SPECIFICITY AND
SELECTIVITY WE MAY BE ABLE TO
GET THE SIGNAL TO NOISE THAT MAY
BE BETTER THAN WHAT WE CURRENTLY
DO.
WE'RE ABOUT TO TRANSLATE THOSE
NEXT YEAR.
AND THESE ALL COULD BE EXPLORED
IN THE CONTEXT OF ME/CFS
ULTIMATELY.
WE'RE CONTINUING OUR WORK.
ONE QUESTION I WOULD LOVE TO ASK
THE COMMUNITY AND LOVE TO SPEAK
TO PEOPLE ON NEW SPECIFIC
TARGETS WE COULD MAKE PET
TRACERS FOR IMMUNE TARGETS
COMING OUT IN THE PROTEOMIC DATA
SETS AND I'M HERE AND WILLING.
WOULD LOVE TO TALK WITH YOU ALL
ABOUT OTHER TARGETS THAT MAY BE
MORE SPECIFIC FOR ME/CFS.
I WANT TO END WITH MY
ACKNOWLEDG
ACKNOWLEDGEMENTS.
HUGE SHOUT OUT TO MEGAN BELL WHO
TIRELESSLY WORKS ON RECRUITMENT
AND OTHERS WHO WORKED HARD ON
THE PROJECT.
MANY HAVE HELPED ADVICE AND
THANK YOU FOR LISTENING.
>> IF I CAN HAVE THE PANEL
MEMBERS COME UP WHILE MICHELLE
ANSWERS QUESTIONS, WE'LL DOUBLE
DIP HERE.
>> I WAS INTRIGUED BY THE FACT
HAVE YOU A HARDER TIME CLEARING
THE T CELLS IN THE TISSUES THAN
SPLEEN AND FITS WELL WITH THE
WORK" CD19 CAR OF ITs AND LUPUS
WHERE IT'S HAD AN INCREDIBLE
THAN THE ANTIBODY ITSELF
THERAPEUTICALLY.
IT MAY BE INTERESTING TO USE IN
THE CAR T WHICH I THINK WILL BE
WILDLY AVAILABLE ESPECIALLY FOR
MICE.
>> I AGREE AND WHAT WE'RE
LOOKING AT NEUROLOGICAL DISEASES
AND WE'RE MONITORING.
THANK YOU.
>> THANK YOU MICHELLE FOR
MULTITASKING TOO.
FOR THE LAST TWO SESSIONS OF THE
MEETING THE FINAL SESSION WILL
BE CLOSING THOUGHTS AND SUMMARY
FROM DR. KOMAROFF WHO OFFERED TO
DO THAT FOR US AN HAS DONE IT IN
THE PAST AND WE ALL LOOK FORWARD
TO THAT.
BEFORE WE GET TO TONY'S THOUGHTS
ABOUT CRYSTALLIZING WHAT HE SEES
AND SUMMARIZES I THOUGHT IT
WOULD BE GOOD TO GIVE OUR
SPEAKERS AT LEAST SOME OF OUR
SPEAKERS FROM TODAY A CHANCE TO
TALK ABOUT WHAT THEY'VE THOUGHT
ABOUT SINCE THE MEETING STARTED
AND WHAT HITS HOME KEEPING IN
MIND THAT AND PRESENT THE STATE
OF THE ART RESEARCH AND TRYING
TO HIGHLIGHT WHERE THAT'S
MATCHING TO PANEL WAYS THAT WE
BETTER UNDERSTAND AND CAN
POTENTIALLY BE MEASURED AS
BIOMARKERS AND EVEN MORE SO AS
TREATMENTS KNOWING IT'S A
SLIDING SCALE BUT WE'D BE
INTERESTED IN YOUR OPINIONS.
WE HEARD ABOUT ONGOING TRIALS
THAT AREN'T BE CURRENTLY
SUPPORTED BY NIH BUT BY OTHER
PARTNERS SOME HAVE COLLABORATED
WITH.
IT'D BE GREAT TO GET YOUR
THOUGHTS.
WE CAN START WITH YOU.
WE'RE LOOKING ACROSS DIFFERENT
SYMPTOMS AND SEEM TO BE
CONNECTED AND ANSWERS STARTING
TO COME FORWARD AND I WANT TO
SAY MAUREEN HAS CHALLENGED US
AND I THINK WE HAVE TO ANSWER
THAT CHALLENGE.
I THINK SHE'S MADE GOOD POINTS
AND THEY'RE ANSWERABLE POINTS.
I HAVE THE PERSPECTIVE OF BEING
OLD IN THE FIELD.
AND A GROUP FOUNDED MUSCLE
BIOPSY AND RETRACTED IT BECAUSE
THEY HADN'T.
ESTABLISHED THE CONTROL AND SOUR
THE FIELD.
IT WAS A VALID PATH TO GO DOWN.
I THOUGHT A SINGLE GROUP'S
EXPERIENCE AND THAT IS ECHOED IN
THE FIELD FAR TOO OFTEN.
JARRED CONVERSATION ABOUT THE
LVN PAPER THAT CONTRADICTS HIS
OWN PREMISES IN THE EARLIER
PAPERS IS JUST THE POINT THAT
HAS TO BE MADE.
THERE ARE SOME VERY UNDERPOWERED
STUDIES THAT HAVE DRIVEN OUR
BELIEFS ABOUT WHAT'S GOING ON.
FINALLY IN THE LAST CENTERS AND
WITH GROUP COMING IN AND THE
LONG COVID FOCUS WELL POWER ED
STUDIES ARE COMING OUT THAT ARE
KNOCKING THE COBWEBS OUT OF THE
WAYS WE'VE BEEN THINKING AND
IT'S TIME TO STAND UP AND PAY
ATTENTION TO THESE DATA SETS.
>> I LOVE HOW COLLABORATIVE
EVERYONE IS IN THE FIELD.
IT'S WELCOMING AND I'VE ENJOYED
THE TALKED AND IT FIELD LIKE
WE'RE PRIMED AND IN AN ABOUT WAY
TO PUSH FORWARD MULTIPLE AREAS.
I WAS ASKED TO GIVE A WEBINAR
THE OTHER DAY AND WANTED TO
CAPTURE EVERYTHING AND SURPRISED
THERE WAS ONLY TWO PET IMAGING
STUDIES PUBLISHED FOR MECHGS AND
THAT STRUCK ME AS A WIDE OPEN
SPACE AND IT'S NICE TO SEE OTHER
GROUPS HERE PRESENTING.
JARRED IN THE MGH GROUP.
IT'S ONE AREA WHERE I THINK WE
CAN START TO SHED LIGHT.
OBVIOUSLY I'M BIASSED BUT IT'S
ASTOUNDING WE HAVEN'T DONE AS
MANY IMAGING STUDIES NOT JUST
PET BUT OTHER ONES TO REALLY
HELP SHED INSIGHTS ON MULTIPLE
LEVELS.
I'D LIKE TO LEARN WHAT WE CAN
DRAW INFORMATION COMING AT THE
SAME PROBLEM FROM DIFFERENT WAYS
I THINK THERE'S A QUESTION HERE.
MY LAB IS MAKE MOUSE MODEL ON
POST-EXERTIONAL MALAISE AND WE
HAVE AN OPPORTUNITY TO DO THE
HISTO LOGICAL ANALYSIS IN THE
MICE AND WE HAVE A COUPLE
FINDING IN THE MODEL SHOW A
PATHOLOGY.
WHEN WE DO SOME MUSCLE HISTO
LOGIC WE DIDN'T SEE ANY T CELL
INFILTRATION NEITHER CD4 NOR CD
8 T CELLS BUT ONLY MACRO PHAGE
ACTIVATION AND THEY HAVE A
PHENOTYPE.
THEY EXPRESS A LOT OF CD40.
MOST HAVE AN ENLARGED SPLEEN
ALMOST TWICE THE SIZE AS REGULAR
WILD TYPE MOUSE.
>> MAYBE YOU GUYS CAN TALK ABOUT
THIS OFFLINE.
>> WE CAN TALK MORE.
>> I FOUND YOUR PRESENTATION
VERY INTERESTING AND ALIGNS WITH
MY FINDINGS.
>> GREAT.
>> WE CAN DISCUSS ON THAT.
>> LET'S TALK MORE.
WOULD LOVE TO HEAR THAT.
THANK YOU.
THANK YOU FOR RAISING THAT.
ONE THING WE SHOULD KEEP IN MIND
AND MIND IS THE FACT WE'RE
TRYING TO REPOSITION DRUGS AND
THE EFFICACY ON THE PATIENT IS
NOT DUE TO THE DEFLATION OF THE
LYMPHOCYTE.
WE HAVE TREATMENT BEFORE AND
AFTER AND SAME WITH DR. YOUNG
THEY PRESENT THE EFFECT IS NOT
TRUE AND THE RECEPTOR AND I JUST
SHOWED YOU THIS MORNING THAT THE
OF NALTREXONE IS GOING POSSIBLY
THROUGH FGF21.
WE NEED TO KEEP THE OPPORTUNITY
TO LOOK AT THE OFF TARGET AFFECT
AND LOOK AT BIOMARKERS.
I'M OPEN FOR COLLABORATION ON
THE FAVORITE MOLECULE AND CAN
ACHIEVE THAT BECAUSE AT THE END
OF THE DAY IT'S COMPLEX AND
OFTEN WE'RE PLAYING WITH
MOLECULES SO KNOWN WE DON'T
THINK THEY EXERT THE TARGETED
EFFECT BUT THE TRUE NATURE OF
THE EFFICACY IS IN A NARROW SET
OF BIOMARKER WE NEGLECT TO LOOK
AT BECAUSE WE NEGLECT TO LOOK AT
SUCH POSSIBILITY.
WE DON'T WE LOOK AT THE
POSSIBILITIES.
>> TWO COMMENTS.
THE FIRST IS AT LEAST FROM WHERE
I SIT THE MOMENTUM AND THE
RESEARCH PROGRESS IS NIGHT AN
DAY WHERE WE ARE NOW TO WHERE WE
WERE WHEN WE HAD THE MEETING
FOUR YEARS AGO.
THAT'S REALLY IMPORTANT TO
ACKNOWLEDGE.
AND THE SECOND IS I FEEL THERE'S
BEEN SO MUCH PROGRESS AND I
AGREE IT'S A COLLABORATIVE GROUP
BUT I THINK THERE'S AN
OPPORTUNITY AND NEED FOR
RIGOROUS INTEGRATIVE ANALYSIS
AND CROSSING SOME VERY
COMPLICATED DATA SETS THAT ARE
NOT OFTEN MELDED TOGETHER
CAREFULLY AND I THINK THAT'S
GOING TO BE AN IMPORTANT, I
THINK, NEXT PHASE IN RESEARCH IN
THIS FIELD.
I'LL LEAVE IT AT THAT.
>> SOW I'D LICK -- LIKE TO
COMMENT THE NAME CHRONIC FATIGUE
SYNDROME DOES NOT SERVE THE
PATIENTS WELL.
IT'S A TERRIBLE NAME.
IN 1955 WHEN THERE WAS THE
OUTBREAK THERE WAS A BRILLIANT
DOCTOR WHO CAME UP WITH THE NAME
MYALGIC ENCEPHALOMYELITIS AND
IT'S A MOUTHFUL BUT WHAT I'M
HEARING FROM THE AFTERNOON NEURO
IMAGING TALK IS WHY CAN'T WE USE
ENCEPHALOMYELITIS MEANING
INFLAMMATION OF THE BRAIN AND
SPINAL CORD AND WHEN CAN WE USE
THE NAME ME INSTEAD OF ME/CFS.
THAT'S MY MAIN COMMENT.
>> LONG AS WE'RE BEING
REVOLUTIONARY THERE WAS A
RECOMMENDATION AND WE'VE ALL
WANTED TO DROP THE OTHER HALF
FOR A WHILE AND I THINK THERE'S
CONSENSUS.
I DON'T KNOW WHY WE JUST DON'T
DO IT SO WHEN YOU SUBMIT YOUR
PAPERS DROP THE OTHER HALF.
I WANT TO BE A LITTLE OUT THERE
AND CHALLENGE MY COLLEAGUES HERE
IN THE MEDIA BUSINESS TO SAY ARE
WE READY FOR MEDIATED SUB
GROUPING ENOUGH TO DO TARGETED
THERAPY MEDIATORS?
I VOTE YES AND OUR FOCUS OUR
DRIVE SHOULD BE TO GET THESE
TRANSLATIONAL RESEARCH PROJECTS
OUT AND DONE.
AND WE NEED A MECHANISM.
THE TOOL EXIST AND FOR
CLINICIANS AND USE THEM
PROSPECTIVELY THAN TO DO WHAT
I'LL CALLING.
AND IF YOU FAIL, FAIL, FAIL,
INVEST MILLIONS WOULD BE
DIFFICULT TO FURTHER ATTRACT BIO
TECH TO WORK WITH A COMPLEX
DISEASE AND IF WE HAVE BETTER
PLANNING AND I KNOW IT'S URGENT
BUT WE HAVE THE TOOLS.
NOT ONLY ME BUT THE GROUP
IMPLEMENT THE TOOLS IN THE
DESIGN OF A CLINICAL TRIAL,
BETTER SELECTION OF PATIENTS NOR
BETTER DRUG AT THE BEST
TREATMENT.
THIS IS PRECISION MEDICINE AND
WHAT WE NEED AND CAN MAKE A
DIFFERENCE WITH THE PROOF OF
CONCEPT WITH ME.
>> NOW'S YOUR CHANCE TO TALK
ABOUT THE DATA REPOSITORY.
>> I'LL TAKE THAT OPPORTUNITY.
NANCY MENTIONED FIVE YEARS AGO
WHEN WE START THE COLLABORATIVE
RESEARCH CENTERS WITH THE NIH
PROGRAM NINDS FUNDED THE DATA
MANAGEMENT COORDINATING CENTER
AND ONE OF THE PROJECTS THEY
WORKED ON TO HELP GET TO SOME OF
THE INTEGRATION WAS THE ME/CFS
PROJECT AND WERE ON THE TERRACE
TODAY IF PEOPLE WANTED TO SEE
IT.
THE IDEA IS EVENTUALLY THERE'LL
BE ENOUGH DATA TO TAKE OUT AND
ANALYZE BECAUSE UP TO THIS POINT
MOST THE COHORT HAVE BEEN HARD
TO SUMMARIZE AND THE
DEMOGRAPHICS AREN'T
REPRESENTATIVE OF THE
COMMUNITIES THEY NEED TO AND
PERHAPS OVER TIME WE CAN ENRICH
AS WE PULL IT IN AND LARGER
RECOVER EFFORTS IF THEY'RE
RELEVANT THOUGH THEY'RE
COLLECTED FOR A DIFFERENT
PURPOSE.
>> THEY'RE DEMOGRAPHICALLY
DIFFERENT.
>> IT'S A SHAMELESS PLUG FAND TE
SEARCH TO THE PLATFORM FOR
FIND
FINDING.
I THINK TONY'S REMEMBER ALSO.
IF THERE ARE ONLY FINAL THOUGHTS
FROM THE PANEL?
THANK YOU VERY MUCH.
>> FIRST, I'D LIKE TO THANK THE
PANEL DISCUSSION AND GIVE THEIR
THOUGHTS AFTER THEY PARTICIPATED
IN THE LAST TWO DAYS OF THE
CONFERENCE AND TO CLOSE OUT THE
CONFERENCE WE ARE FORTUNATE TO
HAVE DR. TONY KOMAROFF WHOSE
WORK WAS PRESENTED ON THE SLIDE
EARLIER GIVE A SUMMARY AND
CLOSING THOUGHTS.
HOW FAR WE'VE COME AND FUTURE
DIRECTIONS.
PROFESSOR AT HARVARD AND SENIOR
PHYSICIAN AT BRIGHAM AND WOMEN'S
HOSPITAL.
>> THANK YOU.
CAN EVERYONE HEAR ME?
GOOD.
I'VE HAD TROUBLE HEARING FOLKS.
SO THANKS FOR HAVING ME THOUGH
I'M DAUNTED BY THE CHALLENGE
BECAUSE THERE'S A LOT OF FIELDS
WHOSE WORK WAS REPRESENTED HERE
AND I'M NOT AN EXPERT ON ANY ONE
OF THOSE FIELDS BUT WHAT I'LL
TRY TO DO IS PUT THIS
PRESENTATION IN THE WEBINAR
SERIES NINDS HAS ORGANIZED AND
THE PRIOR LITERATURE INTO A
CONTEXT.
DISCLOSURES, I HAVE NOTHING TO
DISCLOSE.
TOPICS I WANT TO DISCUSS IS HOW
WHAT YOU HEARD OVER THE LAST TWO
DAYS FITS OR DOESN'T WITH WHAT
HAS BEEN PUBLISHED IN THE PAST.
AND WHAT IS EMERGING IN THE PATH
OF PHYSIOLOGY OF ME/CFS AND LONG
COVID AND PROPOSE A HYPOTHESIS
ABOUT HOW THE WIDE VARIETY OF
DIFFERENT ABNORMALITIES BEING
REPORTED IN THE CONDITIONS MIGHT
EFFECT EACH OTHER AND MIGHT HAVE
A COMMON CAUSE.
AND RESEARCH QUESTIONS THAT
SEEMED IMPORTANT TO ME.
WHEN THE ILLNESSES WERE YOUNG
THERE WERE PEOPLE WHO
UNDERSTANDABLY SAID THE PATIENTS
HAVE SYMPTOMS BUT IS THERE
ANYTHING REALLY WRONG BIO
LOGICALLY?
THAT WAS A FAIR QUESTION YEARS
AGO FOR ME/CFS AND TWO AND THREE
YEARS AGO FOR LONG COVID BUT NOW
I THINK IT'S NOT.
NOW IT'S CLEAR THAT AS YOU'VE
HEARD THERE'S MULTIPLE
DIFFERENCE OBJECTIVE MEASURABLE
BIOLOGICAL ABNORMALITIES NOT
JUST ONE-OFF REPORTS BUT THAT
HAVE BEEN REPLICATED REPEATEDLY
BY DIFFERENT LABS, STUDYING
DIFFERENT GROUPS OF PATIENTS
WITH THESE ILLNESSES.
I THINK MY OWN VIEW IS ME/CFS IS
UNLIKELY TO BE CAUSED BY SINGLE
NOVEL INFECTIOUS AGENT.
INSTEAD I THINK IT INVOLVES A
DYSFUNCTIONAL RESPONSE
IMMUNOLOGIC METABOLIC TO
INFECTION OR INJURY.
COULD THERE BE A NOVEL AGENT
THAT EX PLAINS SOME OF THE
CASES.
YES.
THERE COULD BE WELL KNOWN AGENTS
LIKE THE HERPES VIRUSES THAT
STAND FOR A FRACTION OF THE
CASES, YES, BUT A SING --
SINGLE NOVEL AGENT EXPLAINING
ALL THE CASES, UNLIKELY.
THE BIOLOGICAL ABNORMALITIES
BEING REPORTED IN BOTH THE
AUTONOMIC SYSTEM AND NUCLEIC
ACID AND ANTIGEN AND
ABNORMALITIES OF THE GUT
MICROBIOME THAT TRIGGER
METABOLIC REACTION.
METABOLISM SPECIFICALLY DEFICITS
IN ENERGY PRODUCTION AND REDOX
IMBALANCE AND FINALLY
ABNORMALITIES IN THE
CARDIOVASCULAR AND PULMONARY
SYSTEM.
I'M GOING SUMMARIZE ALL THESE
ABNORMALITIES GOING RAPIDLY
THROUGH THEM AND MAKING A WHOLE
SERIES OF ASSERTIONS THAT THE
TIME WON'T ALLOW ME TO PRESENT
DATA TO SUPPORT SO TAKE WHAT I
SAY AND LOOK AT A SOURCE
DOCUMENT AND PURPORTING TO FIND
OR NOT FIND THE ABNORMALITIES
ARE CITED EXPLICITLY.
I'LL GIVE YOU A SENSE OF WHAT
ABNORMALITIES HAVE BEEN REPORTED
BY MANY GROUPS AND WHICH HAVE
HAD NEGATIVE REPORTS TO GET A
SENSE OF THE PREPONDERANCE OF
THE EVIDENCE ON THAT PARTICULAR
ABNORMALITY OF EITHER OF THE TWO
DISEASES.
HERE'S THE FIRST SLIDE.
NEUROLOGIC ABNORMALITIES AND
EACH I'LL SLOW A BIG X MEANS
THERE ARE LOTS OF REPLICATED
REPORTS.
SMALL X MEANS THE POSITIVE
OUTWEIGH THE NEGATIVE REPORTS
BUT IT'S NOT A SLAM DUNK.
IT'S NOT ABSOLUTELY SOLIDLY
ESTABLISHED.
THIS BIG Xs MEAN LOTS OF
EVIDENCE AND LITTLE Xs MEAN
LITTLE EVIDENCE.
TAKE ONE EXAMPLE.
COGNITIVE DEFICITS, BRAIN FOG.
ONE OF THE FUNDAMENTAL PROBLEMS
OF BOTH ILLNESSES.
WHAT DO WE KNOW ABOUT THEM FROM
THE LITERATURE AND HOW MANY
STUDIES BEAR ON IT?
THERE'S MORE THAN 24 BUT 24 GOOD
STUDIES DEMONSTRATING COGNITIVE
DEFICITS PRIMARILY IN THE
ATTENTION AND REACTION TIME.
THESE DEFICITS WORSEN AFTER BOTH
PHYSICAL AND COGNITIVE CHALLENGE
S AN THEY'RE NOT EXPLAINED BY A
COMBINANT MOOD DISORDERS AND TWO
STUDIES SHOW THERE'S NEGATIVE
STUDIES AND ASSERT IT'S
REPRESENTATIVE OF THE BALANCES
OF THE EVIDENCE OF ALL THE BIG
Xs WE'LL BE LOOKING AT.
BESIDES COGNITIVE AND
NEUROVASCULAR ABNORMALITIES AND
ANTIBODIES AGAINST NEURAL
TARGETS AND COGNITIVE
ABNORMALITIES AND THE NERVOUS
SYSTEM AND THOUGH THE LITERATURE
HAS ARTICLES CHALLENGING THE
SPECIFICITY OF THE AUTO ANTIBODY
ASSAYS.
THERE'S A HYPOMETABOLIC STATE IN
THE BRAIN, GRAY AND WHITE MATTER
ABNORMALITIYIES ON IMAGING AND
SMALL FIBER NEURO ON --
NEUROPATHY AND YOU HEARD THAT
FROM DR. JAMES AND YOUNGER AND
BUES AND OTHERS.
HERE'S AN EARLY STUDY USING A
LIGAND AGAINST A MOLECULE IN THE
MICROGLIAL CELLS AND ASTROCYTES
WITH INFLAMMATION WITH COMPARED
TO HEALTHY CONTROLS AND THE
TRACER WOULD BE REGARDED AS
OUTDATED BUT STILL PROVOCATIVE.
AND A STUDY IN LONG COVID
PATIENTS SHOWING NEURAL
INFLAMMATORY WITH A DIFFERENT
LIGAND IN MULTIPLE DIFFERENT
AREAS OF THE BRAIN.
AND HERE IN FIBROMYALGIA.
EVIDENCE OF NEURAL INFLAMMATION
IN THAT CLINICALLY SIMILAR
CONDITION AND THE DEGREE OF
INFLAMMATION CORRELATED WITH THE
SEVERITY OF FATIGUE AND OTHER
SYMPTOMS.
A CORRELATION BETWEEN A
BIOMARKER AND THE SEVERITY OF
THE SYMPTOM.
IMMUNOLOGIC ABNORMALITIES
DECREASE NATURE KILLER CELL
FUNCTION AND ABNORMALCYTE -- AC
NORMAL CYTOKINE ANTIBODIES AND
RATES OF APOTOSIS AND HLA
ASSOCIATIONS.
AND WITH THE NEUROLOGIC
ABNORMALITIES MANY ARE BEING
REPORTED IN LONG COVID.
THE IMMUNOLOGIC MEASURES OF
INFLAMMATION TEND TO BE WORSE IN
FEMALES.
I'M THINKING OF THE FINDINGS
REPORTED BY MARK DAVIS AND
OTHERS THERE'S A GENDER
PHYSIOLOGY DIFFERENCE IN
MULTIPLE TYPES OF MEASURES THAT
IS VERY IMPORTANT TO PURSUE
PARTICULARLY GIVEN THE FACT THAT
THESE ILLNESSES ARE BEING FOUND
TWO OR THREE TIMES MORE OFTEN IN
WOMEN THAN IN MEN.
AND METABOLIC ABNORMALITIES
DIMINISHED ATP PRODUCTION FROM
OXYGEN, GLUCOSE, FATTY ACIDS AND
AMINO ACIDS.
AND YOU HEARD SOME DETAILED
INFORMATION ABOUT THAT AT THE
CONFERENCE.
REDOX IMBALANCE.
YOU HEARD ABOUT SOME OF THE
EVIDENCE OF REDOX IMBALANCE IN
IMMUNE CELL SUBSETS.
AND HYPOMETABOLIC STATE IN THE
BLOOD AND BRAIN AND AGAIN ALL
THESE ARE NOW BEING REPORTED IN
PEOPLE WITH LONG COVID.
CARDIO PULMONARY ABNORMALITIES
AND DIMINISHED EXERCISE CAPACITY
AND ENDOTHELIAL DYSFUNCTION AND
PLATELET NUMBERS IN THEIR
CHEMISTRY.
AND AGAIN MANY OF THESE NOW
BEING REPORTED IN LONG COVID.
ENDOTHELIAL DYSFUNCTION YOU
HEARD EVIDENCE OF PLATELET
AGGREGATION ABNORMALITIES
FOLLOWS FROM DYSFUNCTION AND
ENDOTHELIAL DYSFUNCTION AND
BEING FOUND AS SHOWED IN THE
SLIDE PRIMARILY IN THE BRAIN
STEM AND MORE BROADLY THROUGHOUT
THE BRAIN.
FINALLY LOW GRADE GUT
INFLAMMATION DUE TO DIFFERENCES
OR ABNORMALITIES IN THE
MICROBIOME AND I'D SUMMARIZE THE
RESULTS PRESENTED HERE AND
PREVIOUSLY AS THE FOLLOWING.
REDUCE NUMBERS OF BACTERIA
PRODUCING ANTI-INFLAMMATORY
MOLECULES PARTICULARLY BUTYRATE
AND ACETATE THAT CORRELATE
STRONG WITH THE FATIGUE.
ANOTHER BIOMARKER THAT
CORRELATES WITH THE SYMPTOM.
REDUCED LEVELS OF THE MOLECULES
IN STOOL AND PLASMA SO NOT ONLY
ARE THE BACTERIAL SPECIES THAT
MAKE A PARTICULAR MOLECULE
DIMINISHED IN NUMBER BUT THAT
MOLECULE LEVELS ARE DIMINISHED
IN PLASMA AND STOOL AS YOU WOULD
EXPECT.
THE DYSBIOSIS SEEMS TO WANE OVER
THE YEARS BUT IS FOLLOWED BY
LONG LASTING METABOLIC CHANGES
PARTICULARLY IN LIPIDS.
SO WITH MICROBIOME STUDIES AS
WITH IMMUNOLOGIC AND METABOLIC
STUDIES WHEN IN THE COURSE OF
EFCSS YOU STUDY PATIENTS REALLY
AFFECTS THE RESULTS.
THERE'S DIFFERENCES IN PEOPLE
WHO HAVE BEEN ILL FOR THREE TO
FOUR YEARS FROM THOSE WHO HAVE
BEEN ILL MUCH LONGER.
A SEMI ACUTE PROCESS BECOMES
VERY CHRONIC.
THE RESULTING GUT INFLAMMATION
ALLOWS BACTERIAL PRODUCTS AND
ORGANISMS TO ENTER THE SYSTEMIC
INFLAMMATION POSSIBLY CAUSING
SYSTEMIC INFLAMMATION AND NEURAL
INFLAMMATION.
DR. HANSON'S GROUP FIRST
REPORTED THIS AND THE FINDINGS
HAVE BEEN REPLICATED IN MULTIPLE
COHORT OF ME/CFS.
TO MY KNOWLEDGE THE GUT MICROBUY
HOME HAS NOT -- GUT MICROBIOME
HAS NOT BEEN AGGRESSIVELY
STUDIED IN LONG COVID AND 20, 30
YEARS AGO THEY WOULD HAVE SAID
IS ANYTHING WRONG WITH THE
PEOPLE AND NOW THE SKEPTICS ARE
SAYING HOW COULD ALL THESE
THINGS POSSIBLY BE WRONG WITH
THESE PEOPLE?
WELL, IT'S A FAIR QUESTION.
I THINK THERE'S SOME WAYS YOU
CAN IMAGINE THEY WOULD ALL BE
FOUND BECAUSE THEY MANY OF THEM
AS I'LL ARGUE EFFECT EACH OTHER.
THEY REINFORCE EACH OTHER.
AND IF ALL THESE ABNORMALITIES
ARE BY HAPPENSTANCE BUT
HAPPENING BECAUSE THEY ARE BEING
ORCHESTRATED BY A BIOLOGICAL
PROCESS, WHICH I WILL TRY TO
ARGUE MAY BE THE CASE, THEN THIS
IS EXACTLY WHAT WITH YOU WOULD
EXPECT.
YOU WOULD EXPECT AN ORCHESTRATED
RESPONSE TO PRODUCE A SERIES OF
BIOLOGIC CHANGES ALL OF WHICH
ARE DESIGN TO ACHIEVE PURPOSE
FOR THE ORGANISM.
SO, HOW DO THESE VARIOUS
ABNORMALITIES AFFECT EACH OTHER?
THE POINTER ISN'T WORKING.
A FEW OF THE ABNORMALITIES ARE
SHOWN HERE IN THE GRAPHIC.
MITOCHONDRIAL DYSFUNCTION,
OXIDATIVE STRESS, CHRONIC
INFLAMMATION THROUGH
INFLAMMASOME ACTIVATION AND THE
IMPORTANCE OF THE FIGURE IS
THESE -- YOU'LL SEE THE ARROWS
CONNECTING ALL THESE DIFFERENT
ABNORMALITIES ARE TWO-HEADED
ARROWS.
THESE ARE BI-DIRECTIONAL
CONNECTIONS.
IF MULTIPLE METABOLIC
IMMUNOLOGIC INFECTIOUS
CARDIOVASCULAR ABNORMALITIES
HAVE BI-DIRECTIONAL CONNECTIONS.
THAT, IF THEY CAN REINFORCE EACH
OTHER TWO THINGS ARE TRUE OR AT
LEAST POSSIBLE.
ONE, YOU HAVE THE POTENTIAL FOR
ONGOING VICIOUS CYCLES.
ONE THING IS BAD, IT MAKE
SOMETHING ELSE BAD WHICH IN TURN
MAKES SOMETHING ELSE BAD WHICH
MAKES THE THING WHICH MADE IT
BAD AND WORSE.
YOU WILL GET TO A STATE WHERE
THESE THINGS REINFORCE EACH
OTHER CHRONICALLY AND CAN'T TURN
EACH OTHER OFF.
SECONDLY, THE THING THAT'S
IMPLIED BY A SITUATION LIKE THIS
WHERE YOU HAVE A BUNCH OF
ABNORMALITIES THAT CAN EFFECT
EACH OTHER AND WITH ANY
INDIVIDUAL WITH THE ILLNESS, THE
INITIAL TRIGGERING EVENT THE
FIRST DOMINO TO FALL MAY HAVE
BEEN DIFFERENT FROM AN ANOTHER
PATIENT.
IT MAY HAVE BEEN SOMETHING THAT
UPSET REDOX BALANCE.
AND THAT INTERN TRIGGERED OTHER
ABNORMALITIES IN ONE PERSON AND
IN OTHER ANOTHER PERSON MAY HAVE
BEEN A VIRAL INFECTION THAT
CAUSED MITOCHONDRIAL INFECTION
AND SET THE CASCADE OF PATHOLOGY
INTO MOTION.
THE POINT IS IT CAN BE A
DIFFERENT TRIGGER IN EACH
INDIVIDUAL BUT THE STEW OF
REINFORCING ABNORMALITIES TURNS
OUT TO BE THE SAME.
SO WHAT TRIGGERS THESE
PATHOPHYSIOLOGIC ABNORMALITIES
AN WHAT TRIGGERS THE SYMPTOMS OF
THESE ILLNESSES?
I PUT FORWARD A HYPOTHESIS THE
SICKNESS BEHAVIOR HYPOTHESIS.
DR. KOROSHETZ ALLUDED TO THIS.
THIS HYPOTHESIS I LABEL IT THAT
IS VERY ATTRACTIVE TO ME BECAUSE
A LOT OF THE DATA WE'VE HEARD
AND NEW INFORMATION IN THE LAST
FOUR YEARS SINCE THERE WAS AN
NIH CONFERENCE ON ME/CFS IN
2019, IT MAY BE AN A TRIGGER OR
NON-INFECTIOUS INJURY.
THIS LEADS TO AN ORCHESTRATED
PROTECTIVE BIOLOGICAL RESPONSE
OR SET OF RESPONSES DESIGN TO BE
TEMPORARY TO HELP THE ORGANISM
INITIALLY HEAL THE INJURY,
ERADICATE THE INFECTION BUT FOR
WHATEVER REASON TEMPORARY
ORCHESTRATED RESPONSE BECOMES
PROLONGED.
WHY DOES IT BECOME PROLONGED?
IT COULD BECOME PROLONGED
BECAUSE LIKE EVERY HOMEOSTATIC
PROCESS IN THE BODY THERE'S ON
AND OFF SWITCHES AND IF AN OFF
SWITCH GETS STUCK YOU CAN GET
STUCK IN WHAT WAS MEANT TO BE A
TEMPORARY RESPONSE AND CAN
BECOME PERMANENT OR SECONDARILY
IF THERE IS IN FACT AN ONGOING
THREAT IN THE BODY LIKE AN
ONGOING RESERVOIR OF AN
INFECTIOUS AGENT EITHER LIVING
AGENT OR NUCLEIC ACID OR
ANTIGEN, THAT COULD TRIGGER AN
ONGOING RESPONSE BECAUSE THE
FIGHT HAS NOT YET BEEN WON.
SO WHAT ARE OTHER EXAMPLES IN
BIOLOGY OF SUCH ORCHESTRATED
PROTECTIVE RESPONSES.
YEAH, BESIDES SICKNESS BEHAVIOR
WHICH I'LL TALK ABOUT MORE IN
WHICH IS ITSELF A WHOLE MATURE
FIELD OF BIOLOGY, THERE IS THE
CELL DANGER RESPONSE TALKED
ABOUT IN THE 2019 MEETING.
THERE'S THE STATE OF DOWER IN
THE WORM C. ELEGANS AND
HIBERNATION AND TORPOR IN
ANIMALS AND THE INTEGRATED
STRESS RESPONSE TO A WHOLE
ORGANISM AND MAJOR VITAL THREAT.
IT'S A PLAUSIBLE HYPOTHESIS THE
SYMPTOMS OF THE ILLNESS MAY IN
FACT REFLECT SUCH A PROCESS.
AND HOW IN FACT DO WE GET THE
SYMPTOMS.
HOW ARE THEY PROTECTIVE AND WHAT
MECHANISTICALLY FINALLY CAUSES
THE SYMPTOMS THEMSELVES?
IS THERE A FIND FINAL COMMON
PATHWAY THAT LEADS TO THE
SYMPTOMS?
AND EVEN IF THAT FINAL COMMON
PATHWAY IS A SINGLE PATHWAY THAT
CAN BE TRIGGERED BY MANY OTHER
PHYSIO LOGIC ABNORMALITIES IF
THERE'S A FINAL COMMON PATHWAY
IT COULD BE THE TARGET FOR
THERAPIES.
SO LET'S DISCUSS THAT PLAUSIBLE
POSSIBILITY.
MAINLY PEOPLE WITH ME/CFS
DESCRIBE THE ILLNESS AS IT'S
LIKE A FLU OR VIRUS THAT NEVER
GOES AWAY.
WE'VE ALL HAD A FLU OR TEMPORARY
INFECTIOUS ILLNESS AND KNOW WHAT
WE FEEL LIKE.
WE HAVE A SET OF HARD WIRED
PROTECTIVE SYMPTOMS THAT LEAD TO
BEHAVIORAL CHANGE.
BECAUSE OF THE SYMPTOMS WE ARE
LESS PHYSICALLY ACTIVE AND LESS
MENTALLY ACTIVE AND SLEEPING
MORE AND NOT SPENDING A LOT OF
TIME THINKING.
WE DON'T EAT AND DIGEST AS MUCH.
WE HAVE LESS SEX, IN OTHER
WORDS, THERE'S A SET OF SYMPTOMS
GENERATED THAT CHANGES OUR
BEHAVIOR THAT REDUCES A WHOLE
GROUP OF ACTIVITIES THAT DO
WHAT?
THAT CONSUME ENERGY.
THAT CONSUME ATP.
THE PROTECTIVE RESPONSE IS DON'T
DO THOSE THINGS BECAUSE THEY'RE
GOING TO SPEND ATP ON THEM AND
WE NEED THE ATP TO FIGHT THE
INFECTION OR TO HEAL THE INJURY.
WHETHER THAT IS CORRECT THERE'S
NO DOUBT SICKNESS BEHAVIOR
FOLLOWING IN EXPERIMENTALLY
INDUCED INFECTION OR INJURY IS
SEEN AND DOCUMENTS ABUNDANTLY
ACROSS THE ANIMAL KINGDOM.
IT'S NOT HARD TO TELL WHEN OUR
PETS ARE ILL.
THEY ACT LIKE WE FEEL WHEN WE
GET ILL.
IT'S NOT HARD TO TELL WHEN
YOU'RE DOG'S UNDER THE WEATHER.
IT'S BEEN PRESERVED THROUGHOUT
THE ANIMAL KINGDOM.
THAT'S THE HYPOTHESIS.
THE SYMPTOMS HAVE A PURPOSE
WHICH IS IS BEHAVIOR CHANGE AND
THAT'S DESIGN TO PRESERVE ATP TO
DEAL WITH THE VITAL THREAT.
SO WHAT THEN MECHANISTICALLY
CAUSES SYMPTOMS?
IN THE 2019 ME/CFS CONFERENCE
THE FOLLOWING HYPOTHESIS WAS PUT
FORWARD THAT WE KNOW THE BRAIN
IS FILLED WITH A GROUP OF NUCLEI
OF NEURONS DEDICATED TO ONE
TASK.
THE THEORY WAS MAYBE THERE'S
NUCLEI FOR THE TASK OF
GENERATING SICKNESS SYMPTOMS.
THAT WAS PLAUSIBLE AND IN THE
LAST FOUR YEARS A WHOLE GROUP OF
NUCLEI IN THE BRAIN STEM AND
HYPOTHALAMUS HAVE BEEN
IDENTIFIED UP RODENTS IN PAPERS
ALL PUBLISHED IN NATURE THAT
MAKE MUCH MORE PLAUSIBLE THE
POSSIBILITY THAT INDEED THE
SYMPTOMS OF SICKNESS BEHAVIOR
THAT LOAD TO SICKNESS BEHAVIOR
ARE ORCHESTRATED BY A GROUP OF
NUCLEI IN THE BRAIN.
ANOTHER TARGET FOR THERAPY.
THE MODEL IS THAT NO
INFLAMMATION AUTONOMIC
ABNORMALITIES AND AUTO IMMUNITY
AND DEFECTIVE ENERGY AND IMMUNE
ABNORMALITIES CAN ALL CONVERGE
TO STIMULATE THESE FATIGUE
NUCLEI AND GENERATE THESE
SYMPTOMS THAT CHANGE BEHAVIOR TO
HELP THE ANIMAL, THE HUMAN IN
THIS CASE DEAL WITH THE VITAL
THREAT.
SO THAT'S THE HYPOTHESIS BUT
OBVIOUSLY FAR -- WE DON'T KNOW
THE NUCLEI EXIST IN HUMANS SO
THERE'S MORE TO BE DONE BUT TO
ME SCIENCE PROCEEDS BIG
REASONABLE HIYPOTHHYPOTHESES.
IN CONCLUSION, WHAT HAVE WE
LEARNED SO FAR IN THE NEARLY 40
YEARS OF RESEARCH ON ME/CFS AND
RECENTLY LONG COVID?
WHATEVER WE'VE LEARN IS BECAUSE
OF NIH AND CDC AND FOUNDATIONS
DEDICATED CURING THESE
ILLNESSES.
DESPITE THE FACT ONE HEARS
SOMETIMES PEOPLE REPORT THESE
ABNORMALITIES BUT NOTHING HOLDS
UP THERE'S MANY ABNORMALITIES
THAT HAVE HELD UP AND PLAUSIBLE
BUT FAR FROM PROVEN THEY
CO-EXIST AN REINFORCE EACH OTHER
AND GENERATE THE PERSISTENT
PATHOLOGY AND SYMPTOMS OF
CHRONIC DISEASE, ILLNESS.
AND ALSO PLAUSIBLE THEY CAUSE
THE SYMPTOMS BY ACTIVATING THE
FINAL COMMON PATHWAY THESE
NUCLEI IN THE BRAIN.
TO ME THE FACT THAT AND I WOULD
SAY ONLY IN THE LAST YEAR HAS IT
REALLY BECOME CLEAR SO MUCH OF
THE UNDERLYING PATHOLOGY IS
SHARED BETWEEN LONG COVID AND
ME/CFS DOESN'T MEAN THEY'RE
EXACTLY THE SAME ILLNESS.
WE KNOW THAT SARS COV2 PRODUCES
TWO SYMPTOMS THAT ARE REALLY NOT
SEEN IN ME/CFS, LOSS OF TASTE
AND SMELL, AND THERE ARE MANY
OTHER EXAMPLES TOO WHERE AN
ME/CFS-LIKE ILLNESS OR LONG
COVID-LIKE ILLNESS TRIGGERED BY
ONE AGENT MAY HAVE UNIQUE
ASPECTS AND MAY HAVE SHARED
SYMPTOMS AND PATHOPHYSIOLOGY.
MY BET IS WHAT IS LEARNED ABOUT
THE BIOLOGY OF LONG COVID FROM
THE RECOVER STUDIO AND OTHERS
WILL HAVE LESSONS APPLICABLE TO
ME/CFS.
WON'T KNOW FOR A COUPLE YEARS
BUT MY GUESS IS IT WILL APPLY TO
ME/CFS.
THE QUESTION IS WILL THERE BE AN
INVESTMENT TO SEE WHETHER THE
UNDERLYING ABNORMALITIES IN LONG
COVID ARE FOUND IN ME/CFS AS
WELL AND YOU HEARD A DETAILED
SET OF RESEARCH IN METABOLOMIC
AND IMMUNE SYSTEM AND NERVOUS
SYSTEM AND IMMUNE SYSTEM AND GUT
MICROBIOME AND GENOMICS AND THE
LITERATURE IS WELL SUPPORTED BY
PRIOR WORK THAT SAYS YES, THIS
IS GOING TO BE AN AREA TO LEARN
MORE ABOUT AND THE RESEARCH
AGENDA BE BROADENED WITH ENOUGH
FINANCIAL SUPPORT NOT JUST TO
FOCUS ON ME/CFS AND LONG COVID
AND OTHER POST-ACUTE SYNDROMES
LIKE LYME DISEASE AND
FIBROMYALGIA AND THE BEHAVIOR
CHANGES THAT FOLLOW CERTAIN.
IF YOU UNDERSTAND WHAT'S GOING
ON IN THE BODY HAVE YOU TARGETS
FOR EFFECTIVE TREATMENTS.
MUCH MORE LIKELY TARGETS TO GET
SPECIFIC WITH IF YOU DON'T HAVE
SPECIFICS TO MEASURE YOU ARE
SHOOT DARK.
I ASK THAT QUESTION BECAUSE I'M
ASKED BY PATIENTS WHY SO MUCH
INVESTMENT IN UNDERSTANDING THE
BIOLOGY OF THE ILLNESS AND IT'S
BECAUSE HOW WE GET TO TREATMENT
AND BETTER DIAGNOSTIC TESTS.
THE IMPORTANT RESEARCH TOPICS
BEYOND THOSE LISTED AND I WOULD
PLACE SPECIAL EMPHASIS ON SOME
YOU HEARD ON THE MEETING THE
ROLE OF THE PRO INFLAMMATORY GUT
AND MICROBIOME AND ENDTHELIAL
DYSFUNCTION AND VASCULAR
ABNORMALITIES THAT DIRECTLY LEAD
TO METABOLIC ABNORMALITIES,
COAGULATION ABNORMALITIES,
DIMINISHED BLOOD FLOW ENHANCED
HYPOXIA.
THE FORMATION OF MICRO CLOTS IS
A CONSEQUENCE OF ENDOTHELIAL
DYSFUNCTION.
THAT'S A FERTILE AREA WAITING
FOR US TO LEARN MORE ABOUT.
THE REACTIVATION OF HERPES
VIRUSES EPB AND VZV PERSISTING
RESERVOIRS OF SARS COV2.
YOU HEARD FROM OTHERS ABOUT THE
GROWING EVIDENCE IN LONG COVID
THERE'S PERSISTENT RESERVOIRS OF
NUCLEIC ACID AND ANTIGEN ELICIT
ELICITING AN IMMUNE RESPONSE
TIED TO THE ILLNESS.
PHENOTYPIC STUDIES AND YOU HEARD
ABOUT SPECIFIC DEFICITS IN
IMMUNE CELL SUBSETS THAT MAY BE
INVISIBLE IF YOU STUDY A GROUP
OF DIFFERENT IMMUNE CELLS AS A
GROUP AS TRADITIONAL IMMUNOLOGIC
STUDIES TENDED TO DO.
IMPAIRMENT OF SEVERAL NEURAL
ENDOCRINE AXIS.
SEROTONIN DEPLETION.
THERE'S MIXED EVIDENCE IN
ME/CFS.
THERE'S WORK IN LONG COVID AND
NEEDS TO BE PURSUED MORE
RIGOROUSLY AND SEROTONIN AND THE
PATHWAY BIOLOGY BECAUSE THAT HAS
IMPLICATIONS BOTH FOR NEUROLOGIC
FUNCTION AND ENERGY GENERATION.
DE FEFKT IN MOLECULAR ENERGY
SENSORS.
AND AMPK AND AND ANIMAL MODELS
OF SICKNESS BEHAVIOR.
THIS -- THE BIGGEST LIMITING
FACTOR IN STUDYING ME/CFS HAS
BEEN THE LACK OF AN ANIMAL MODEL
BECAUSE SO MANY OF THE
EXPERIMENTS WANT TO DO ONE CAN'T
DO IN HUMANS.
THERE ARE ANIMAL MODELS OF
SICKNESS BEHAVIOR.
THE QUESTION IS TO WHAT EXTENT
IS THE SICK APPEARING ANIMAL
REFLECTS WHAT'S HAPPENING IN A
SICK HUMAN BUT I THINK THOSE
SHOULD BE PURSUED.
SPECIFIC INVENTIONS IN
ESTABLISHED ANIMAL MODELS OF
BEHAVIOR THAT REFLECT THE
FINDING IN THE MEETING AND PRIOR
LITERATURE SHOULD BE CONDUCTED.
AND FINALLY TREATMENT TRIALS AND
I WOULD FOCUS ON
IMMUNOMODULATORS AND OXIDATIVE
STRESS.
THERE'S WAYS OF INTERSECTING
THOSE AND IMPROVING THOSE.
FINAL POINTS, THIS MEETING IF
YOU THINK OF THE QUALITY AND
EXTENSIVENESS OF THE WORK
PRESENTED AT THIS MEETING
COMPARED WITH THE MEETING FOUR
YEARS AGO IN MEETINGS IN THE
DECADE BEFORE THAT, SO MUCH MORE
WE KNOW ABOUT CERTAINLY ME/CFS
AND NOW LONG COVID BECAUSE OF
THE INVESTMENT IN RESEARCH.
IT'S PAID OFF MANY CORE
BIOLOGICAL ABNORMALITIES HAVE
BEEN IDENTIFIED.
HOW THEY'RE CAUSING THE
SYMPTOMS?
WE STILL DON'T FULLY UNDERSTAND
BUT THEY'RE PRETTY WELL
ESTABLISHED.
THAT'S WHERE YOU GO LOOKING AND
WHERE WE SHOULD GO LOOKING.
SO OBVIOUSLY I'D LIKE EVERYONE
ELSE AT THIS MEETING WOULD ARGUE
FOR CONTINUED AND EXPANDED
INVESTMENT IN STUDYING BOTH
ILLNESSES.
ALONG WITH THAT ADDED
INVESTMENT, I WOULD URGE THAT A
CONVENING BODY IN THE NIH IS THE
MOST OBVIOUS ONE I COULD THINK
OF AND IDENTIFY SCIENTISTS OUT
THERE WHO RECEIVE NIH SUPPORT
WHO HAVE EXPERTISE THAT BEARS
EXACTLY ON THE AREAS OF
ABNORMALITIES WE HEARD ABOUT AT
THIS MEETING BUT LABORATORIES
THAT DON'T KNOW THE FIRST THING
ABOUT ME/CFS OR LONG COVID
AREN'T WORKING ON IT NOW BUT
HAVE THE TOOLS TO LOOK AT THE
IMMUNOLOGIC ABNORMALITIES THAT
HAVE BEEN WELL ESTABLISHED IN
ME/CFS AND LONG COVID.
FIND THE FINANCIAL SUPPORT AND
AGGRESSIVELY GO OUT AND FIND THE
PEOPLE WHO HAVE THE SKILL SET WE
NEED TO SPEND SOME TIME STUDYING
THESE TWO IMPORTANT PROBLEMS.
I HOPE THAT'S WHAT HAPPENS AND
HOPE X YEARS FROM NOW WHEN WE
HAVE THE NEXT MEETING WE'RE
GOING TO SEE THE FRUITS OF THAT
ADDED EFFORT AND UNDERSTAND MORE
ABOUT BOTH OF THESE ILLNESSES.
THANKS VERY MUCH.
[INDISCERNIBLE]
>> I DID NOT.
THE QUESTION WAS IF I LOOKED AT
PARTICULAR EXPRESSED ENZYME
PATHWAY IN THESE ILLNESSES.
I'M NOT AWARE THERE'S BEEN MUCH
RESEARCH SPECIFICALLY IN
PATIENTS WITH THESE TWO
ILLNESSES.
I'M NOT CHALLENGING THE FACT
THAT THERE SHOULD BE BUT I'M NOT
FAMILIAR.
>> PAPER HAVE LOOKED AT THE
HEMOGENNASE LEVEL AND OTHERS
WERE AMONG THE PREDICTIVE
OUTCOMES IN COVID.
>> OKAY.
IF YOU COULD SEND ME A SUMMARY
OF THOSE I'D LIKE TO KNOW THAT.
>> THANK YOU.
I WANT TO THANK YOU ALL FOR
COMING AND EVEN MORE OR EQUALLY
IMPORTANTLY THE ENVIRONMENT
AUDIENCE FOR ATTENDING WHICH
INCLUDES A LOT OF FOLKS WHO
FRANKLY COULDN'T GET HERE TODAY.
WE HAD A SMALL SLICE WITH OUR
LIVED EXPERIENCE INDIVIDUALS AND
I KNOW AT TIMES IT'S BEEN HARD
TO WATCH FROM FRONT TO BACK AND
THE ENTIRE CONFERENCE WILL BE
ARCHIVED AND AVAILABLE ONLINE AT
NIH.
NIH.VIDEOCAST.gov AND WHILE TRY
TO ADDRESS QUESTIONS BY E-MAIL
FOLLOWING THE CONFERENCE.
THANK YOU FOR YOUR PATIENCE AND
ATTENDANCE ONLINE AND THE FOLKS
HERE.
THANK YOU TO THE SPEAKERS FOR
ATTENDING.
I WANT TO THANK NINDS AND THE
OTHER PARTNERS IN THE NIH
WORKING GROUP AS WELL AS THE
TREMENDOUS EFFORT I THINK WAS
ACKNOWLEDGED MULTIPLE TIMES AND
SHOULD BE FOR THE RESEARCH ROAD
MAP EFFORTS LED BY DOCTORS HANS
JON AND WHITTMORE AND BATEMAN.
FINALLY, I WANT TO THANK THE NIH
STAFF WHO HELPED WITH THIS
SOMETIMES CHALLENGING MEETING
WITH ZOOM AND VIDEO CONFERENCE
FOR PULLING THIS OFF AND
DELIVERING AND TRYING TO GET
INFORMATION BACK OUT TO THE
PUBLIC ABOUT THE GOALS OF THE
MEETING AND WHAT WE'RE TRYING TO
ACHIEVE AND OUR SUPPORT STAFF.
I HAVE TO CALL OUT GRACE TALINI
IN THE BACK WITH THOSE WHO
HELPED US PULL THIS OFF AND WITH
THAT I WILL END THE MEETING AND
THANK YOU AGAIN.