The Yale LISTEN Study Town Hall: September 2022
February 27, 2024Information
Drs. Harlan Krumholz and Akiko Iwasaki discuss preliminary findings and answer questions from LISTEN participants.
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- 00:04Maybe I'll just start just to stay
- 00:06for a minute or two and then I'll,
- 00:08I'm going to hand it to Akiko and
- 00:11maybe just five us can introduce
- 00:15ourselves just to say hello.
- 00:17Leslie, you want to? Sure.
- 00:19No, I just I'm, I'm here on
- 00:20behalf of Hugo Health and Kindred.
- 00:21I just want you to welcome
- 00:23everybody and appreciate
- 00:25everybody's engagement here.
- 00:27For those of you that came to our
- 00:30cafe last week that it was just an
- 00:32incredible exchange of ideas and
- 00:34and conversation and and really
- 00:36appreciate people that were there.
- 00:38You know, we, we're here to serve you guys.
- 00:40We want to have your, we want to be
- 00:42sure that your voices are heard,
- 00:43whether it's by participating,
- 00:45listen or joining some of the
- 00:46other activities that we're doing
- 00:48on the Kindred side.
- 00:49Talia is also here who's
- 00:51our community manager.
- 00:52She's been capturing people's
- 00:54stories and putting, you know,
- 00:56posting those stories on on the Kindred site.
- 00:59There's lots of great content
- 01:00that's showing up there.
- 01:01There'll be more coming.
- 01:03So please, please, you know,
- 01:05reach out to us if you need anything.
- 01:06And you know,
- 01:07as Harlan said,
- 01:08this is the first listen town hall meeting.
- 01:10I know they have plenty more that
- 01:11they'd like to do with those of you
- 01:13that have signed up for the study.
- 01:15So I'm going to pass it over to them.
- 01:17And again,
- 01:17thank you so much and we're really
- 01:19excited about what's coming forth.
- 01:21So I'll pass it on tomorrow.
- 01:22I'll just say just I should
- 01:24have introduced myself.
- 01:25So I'm Harlan Krumholz,
- 01:27I'm a professor of medicine at Yale.
- 01:29I'm a cardiologist and also Co
- 01:32founder of Hugo and and Leslie's
- 01:34husband which is probably one of
- 01:37the nicest things about me the
- 01:41and and we're here with Born Alley
- 01:43and Cesar who are key members of
- 01:45the Liston team and were part of
- 01:47the cafe last week and of course
- 01:49Akiko Iwasaki who is going to be
- 01:52presenting some information about
- 01:53a study that we recently completed.
- 01:55But I I just want to sit there for
- 01:57a moment that so we're this is all
- 01:59about trying to think differently
- 02:00about how the research is done.
- 02:02And like we said this is all
- 02:05iterative and maybe and I think
- 02:06next time it would be better for
- 02:07everyone to see everyone's face is
- 02:09to feel better since the community.
- 02:10But it's unusual for research
- 02:12study to say like, hey,
- 02:14let's run some town halls,
- 02:15let's have some back and forth,
- 02:16let's have Ask Us Anything sessions
- 02:18and also share ideas about the study.
- 02:20And to be able to listen,
- 02:22the states called listen,
- 02:23listen to all of our teammates,
- 02:26all of the people who are participating
- 02:27so that we can think about how we can
- 02:30do this better and how we can race
- 02:32faster towards progress that will
- 02:34impact positively people's lives.
- 02:36And so far,
- 02:37I mean we've enrolled largely
- 02:40by word of mouth.
- 02:41I mean, you know,
- 02:42we've promoted some stuff on social media.
- 02:44People will join Kindred.
- 02:45Kindred,
- 02:45a community where people can
- 02:46interact and get information,
- 02:47have the opportunity to link
- 02:48to their data and join studies.
- 02:50The promise of Hugo is that people
- 02:52can gain agency over their data and
- 02:55that the data won't move without
- 02:56anyone's permission or be kept safe.
- 02:57And it's up to people,
- 02:59as their data assets grow,
- 03:00whether they want to join studies and
- 03:02be able to help move things forward.
- 03:04The profiles within Kindred are
- 03:06meant to help match with studies
- 03:08and accelerate that.
- 03:09When we ask for stories,
- 03:10it's because we want to know like real life,
- 03:13like,
- 03:13how's it affecting you in ways that
- 03:15questionnaires may not be able to capture?
- 03:16And then if people connect
- 03:18to their data sources,
- 03:19their electronic health record and
- 03:21wearables and payers and others,
- 03:23it creates a rich source of data
- 03:25about them that they have agency over.
- 03:27And then if they consent to be in
- 03:29a study and they think that the
- 03:30study's worthy of them and then
- 03:32they can agree to have that data
- 03:34be used in the study.
- 03:35And it's up to us to try to make sure
- 03:36data doesn't move without permission.
- 03:38And in the studies that are offered are
- 03:40ones that will treat people as partners.
- 03:43And of course we're starting this first day,
- 03:44but but we hope that there may be
- 03:47many opportunities that come down
- 03:48the Pike that will be part of this.
- 03:50And again,
- 03:50part of it is trying to foster a
- 03:54sense and when I say sense it,
- 03:56I mean authentically convey
- 03:57that we're interested in.
- 03:59In and working directly with people
- 04:02and again other studies tend to
- 04:04go through sites and depend on a
- 04:06physician offering a study to someone
- 04:08or there there's lots of of people in
- 04:10the middle between the researchers
- 04:12and the people participating.
- 04:14We're trying to say what if
- 04:15it's a direct to consumer idea,
- 04:17what if it's decentralized
- 04:18and anybody can join.
- 04:20And what if we can talk directly
- 04:22with the group and and again
- 04:24listen to to questions,
- 04:25be able to interact and and then think
- 04:27about how we can make progress together.
- 04:31For me, one of the great
- 04:33privileges of this study.
- 04:34Now we'll just talk about the listen
- 04:35study and we're glad to answer a lot of
- 04:37questions about listen study as we go.
- 04:38But one of the great privileges
- 04:40of LISTEN study has been my my
- 04:43opportunity to work with Akiko,
- 04:45who is just the most remarkable
- 04:47scientist and also individual person
- 04:49who cares deeply about the people that
- 04:52she's trying to generate knowledge
- 04:54about to help them do better.
- 04:56And is also conducting science in
- 04:58a way with utmost integrity and
- 05:00leadership and trying to think in
- 05:02an innovative ways about how we can,
- 05:04how we can all work together.
- 05:05So and and the central idea here
- 05:09is that if we can be able to
- 05:12collect information about people,
- 05:13their lives, their journey,
- 05:14their experience and understand
- 05:16the diversity of ways in which
- 05:18they're affected and also include
- 05:20people who are control populations.
- 05:22And by the way we're talking about
- 05:24lists and we're talking about
- 05:25people who are in with long COVID.
- 05:26We're also have heard a lot from
- 05:28people who are reporting vaccine
- 05:30injury and have symptoms that
- 05:32often can sound very similar.
- 05:34And we're very interested in working
- 05:36with them respecting honoring the
- 05:37kind of experience that they're
- 05:39having and seeing whether or not we
- 05:41can reflect through the through,
- 05:42you know,
- 05:43what we're collecting about them
- 05:44and the biology try to breakthrough
- 05:46information on that side too.
- 05:48What we're working with Akiko for me
- 05:50is the opportunity to both profile
- 05:52people from their experience and then
- 05:54combine it with this deep immuno
- 05:56phenotyping that she's going to talk about.
- 05:58Really the very best science that
- 06:00we can imagine.
- 06:01And being able to generate lots
- 06:03of data about people,
- 06:04their experience and how their bodies
- 06:06are working in order to try to come
- 06:09up with some insights about what's
- 06:10causing this and where we can go
- 06:12for diagnostics and therapeutics.
- 06:14And most importantly to reflect
- 06:16back to people that that you know we
- 06:18believe you like we hear you we we
- 06:20know that there's there's something
- 06:22real going on and it's important for
- 06:24us to work together to demonstrate
- 06:26what that is and to be able to
- 06:28provide evidence based guidance
- 06:29about what people can do to help themselves.
- 06:31And and anyway So what we'll we're
- 06:34going by the when people are like
- 06:35even I know a lot of people have had
- 06:38very difficult experiences where
- 06:39either they're being dismissed or or
- 06:41people doubt them or or wonder if
- 06:43it's really people doubt themselves even.
- 06:45And just to say that we're here to
- 06:47say that let's learn together and
- 06:49and again you know we're we're we
- 06:51hope people will consider us allies
- 06:52in this as we try to make progress
- 06:54together and help us be better better
- 06:57partners because we know that that
- 06:58you know there'll be places where
- 07:00we could do better maybe we we
- 07:01haven't been as sensitive as we
- 07:03could could be or should be
- 07:04and we're eager to learn about
- 07:06how we can be better partners.
- 07:07So with this, I want to turn it over
- 07:10to Kiko who's who's got a presentation
- 07:12planned and and I know people are
- 07:14putting in questions and we can try to,
- 07:16we got Bernali and Cesar who can either
- 07:18answer on their own or they can tee
- 07:20them up for us in the second part of
- 07:22the presentation where we can answer
- 07:24them and we're lucky to have them
- 07:26engaged and also part of the project.
- 07:28And let me hand this over to my dear friend,
- 07:31my colleague and partner in this project,
- 07:35Akiko to welcome you all and
- 07:36then talk a little bit about a,
- 07:39a study that we've recently done.
- 07:40So thank you so much.
- 07:42All right. Thank you so much Leslie
- 07:45and Harlan for the introductions.
- 07:47And you know, I, I feel equally
- 07:50honored and fortunate to be working
- 07:53with Harlan and Born Alley and
- 07:56Cesar and Leslie as a partner.
- 07:58So just a little bit of background about
- 08:01myself, I'm an immunologist at Yale.
- 08:04I've been studying infection with
- 08:06variety of viruses and immune responses
- 08:10and seeing how we can use that
- 08:13knowledge to improve people's health.
- 08:16And mostly I'm basic immunologist so
- 08:19I study basic mechanism of diseases
- 08:22as well as vaccine developments.
- 08:26We're currently working with the nasal
- 08:29vaccine booster strategy that will
- 08:31hopefully prevent any diseases like long
- 08:33COVID from happening in the future.
- 08:36So what I'd like to do today is
- 08:38to first of all welcome everyone.
- 08:40I see the names of attendees and you
- 08:43know many of you have reached out
- 08:45to me and I I I feel like I know
- 08:47you and it's it's wonderful to see
- 08:49your names at least on the list.
- 08:51And some of you are superstars.
- 08:53You're advocates and I really
- 08:56appreciate everything you do.
- 08:58So I'm.
- 08:58I'm playing a small part in this
- 09:01whole equation of your lesson study,
- 09:03but essentially what I want to
- 09:05do today is to kind of give you
- 09:07an overview of a prototype study
- 09:10that we did in collaboration with
- 09:12Mount Sinai School of Medicine with
- 09:15David Petrino's group and give you
- 09:17a sense of what what we can do.
- 09:19By the way, this is the tip of the iceberg.
- 09:21We can do a lot more and we
- 09:23are doing a lot more.
- 09:24But we wanted to get this information
- 09:26out to people as soon as possible so that
- 09:29you can read about it and in fact it this,
- 09:31the study has already been posted in
- 09:33mid archive and has been picked up by,
- 09:36you know I think 80 media outlets already.
- 09:39So you've probably heard about it.
- 09:40But I want to tell you what how
- 09:42we interpret the results.
- 09:44So I'm going to share the screen.
- 09:49OK. All right. You can see this. Yes.
- 09:55OK. So yeah, today I want to talk
- 09:58about the immunology of long COVID.
- 10:01The reason we're studying the immune
- 10:04system in people with long COVID is
- 10:07because the immune system is it's
- 10:10it's like an amazing orchestration of
- 10:14molecules and cells and biological
- 10:18process that can tell us a lot about
- 10:20what's happening in in a person's body
- 10:23even just by collecting blood and
- 10:25looking at what's in inside of that.
- 10:27And so today I'm going to focus
- 10:29mostly on the blood analysis,
- 10:31but we can do a lot more by collecting
- 10:34tissues and mucosal surf secretions.
- 10:36So today's focus will be in the blood.
- 10:41Before I get into long COVID,
- 10:43I want to highlight the fact that
- 10:46there are many other infectious agents,
- 10:48many viruses as well as non viral
- 10:52pathogens that can induce long term
- 10:55symptoms of post acute infection
- 10:57syndrome of place that that we have
- 11:00summarized in a recent review with Jan
- 11:04Chotka that we we published together.
- 11:08And so Jan himself,
- 11:10he's suffers from MECFS and he has read
- 11:14every paper under the sun on this topic.
- 11:17And he I I kind of helped him with
- 11:20the strategy for this, this review.
- 11:22And essentially what you see are a
- 11:24lot of different viral pathogens,
- 11:27some of which has really no
- 11:29name for those diseases.
- 11:30But it's well known to have a sequela
- 11:34way after the initial infection process.
- 11:37Some of these post infection sequela
- 11:41can take decades to manifest,
- 11:44whereas others become apparent
- 11:46within days or weeks.
- 11:48So stars COVID to the long COVID.
- 11:50Obviously the CDC definition is
- 11:54symptoms that last for over 4 weeks
- 11:57and and that that is certainly
- 11:59true for stars COVID too.
- 12:01But other viruses have different
- 12:03onset of these types of post
- 12:07infection syndromes and there are
- 12:09other non viral pathogens,
- 12:11bacteria and parasites that can also
- 12:14cause post infectious syndrome at
- 12:15the the famous ones at the Q fever,
- 12:18fatigue syndrome and the post Lyme disease.
- 12:21But there are probably many others
- 12:23that are under recognized that
- 12:25many people are suffering from
- 12:27without really knowing what the
- 12:29causative agents might be.
- 12:32Just taking some of the examples of
- 12:35literature on say Epstein BA virus,
- 12:38this is a from the same review
- 12:40what we see it is studies.
- 12:43So different colors
- 12:44indicate different studies.
- 12:46We compile them into one graph and
- 12:48looking at time since mononucleosis
- 12:50which is caused by Epstein by virus
- 12:53infection and then the unrecovered
- 12:56participants on the Y axis.
- 12:58You see that there are large
- 13:00number of unrecovered participants
- 13:02within about two months post mono.
- 13:04But this percentage declines over time
- 13:07and the studies are pretty consistent.
- 13:11But even after 24 months this
- 13:13number does not go to zero.
- 13:15There are about 4% of the individuals
- 13:18who had mono are two years still
- 13:21suffering from various symptoms
- 13:23and many of these have turned
- 13:25into Chronic fatigue syndrome.
- 13:29Diagnosis service COVID 2 also
- 13:33has a similar type of curve.
- 13:35When you look at people who are
- 13:39having at least one of 12 common
- 13:42symptoms or self reported long
- 13:44COVID in days since COVID-19,
- 13:46you see that there is there is
- 13:48definitely decline in these numbers,
- 13:51but some of these are unfortunately
- 13:54quite persistent.
- 13:58And So what might be causing these
- 14:01long symptom after an acute infection
- 14:04we we think that there may be many
- 14:08different causes and it's not that
- 14:10one of these mechanisms are right,
- 14:12it's probably many of these
- 14:14things that are going on.
- 14:15In some people there might be multiple
- 14:17of these things going on at once.
- 14:19But some of the top hypothesis are
- 14:22viral reservoir or viral pathogen
- 14:25associated molecular patterns.
- 14:27These are sort of the RNA or
- 14:29the DNA of the viral genome that
- 14:32triggers innate immune responses.
- 14:34And also this persistent antigen can
- 14:37drive T cells and B cells to act
- 14:40for chronic in a chronic manner,
- 14:43stimulating chronic inflammation.
- 14:46Second hypothesis is autoimmunity.
- 14:49It's possible that you generate
- 14:51autoreactive antibody after
- 14:53an acute infection.
- 14:54This is a a well known thing
- 14:56that happens after an infection.
- 14:58You generate these bystander
- 15:00activation of T cells and B cells,
- 15:02but if they persist that could
- 15:05also trigger long term symptoms.
- 15:07Now C is this dysbiosis of the microbiome,
- 15:11the commensal bacteria that live in the gut.
- 15:15Their composition changes over time
- 15:17and it's possible that the the bad type
- 15:19of bacteria may be replicating in in
- 15:22the gut to cause some of the symptoms.
- 15:24It's also possible that there is
- 15:27reactivation of latent viruses like
- 15:30the Epstein virus or other herpes
- 15:32virus family members that could become
- 15:35reactivated and cause some symptoms.
- 15:38And then it's also possible that there's
- 15:40tissue damage in various different
- 15:42organs that might contribute to inflammation.
- 15:46There are many, many studies that
- 15:48have been done and these are
- 15:50just handful of the examples that
- 15:52indicate possible viral reservoir.
- 15:55There is antigen, there is RNA,
- 15:57there's combination of these, sorry
- 16:03of these viral features that are found in
- 16:08people with COVID months after an infection.
- 16:13There's also EBV reactivation,
- 16:15the Epstein biovirus that I talked about just
- 16:18now that that was identified to be one of
- 16:21the four predictive factors for long COVID.
- 16:24There are also papers showing autoreactive
- 16:27antibodies against G protein couple receptors
- 16:30as well as Lupus related auto antibodies.
- 16:35And then we also published the mouse
- 16:38model in which central nervous system
- 16:41damage can be caused by an acute
- 16:44respiratory infection with SARS COV two.
- 16:47So there's evidence of all these
- 16:49things and and like I said long COVID,
- 16:52it it is definitely heterogeneous
- 16:55disease that encompasses probably many of
- 16:59these in combination of these features.
- 17:04Well this is one of my favorite studies
- 17:07where people have found that dogs that
- 17:10are trained to detect SARS COV to infected
- 17:14supernatant identified about half of the
- 17:17people with long COVID where 0% of the
- 17:21controls were identified by these dogs.
- 17:24This is a very unbiased way of
- 17:27detecting viral persistence I think in
- 17:30in people and it's it's a interesting
- 17:33indication of possible viral reservoir.
- 17:38So the study that came out earlier this
- 17:41year by Jim Heath's group demonstrated by
- 17:45studying people who had acquired COVID and
- 17:49following them for two to three months.
- 17:51They identify 4 anticipating risk
- 17:53factors at the time of initial diagnosis
- 17:57that predisposed people to long COVID.
- 18:00One is type 2 diabetes,
- 18:03second is SARS Co V2 RNA aemia,
- 18:06this is viral RNA found in the blood,
- 18:09Epstein biovirus,
- 18:10Viremia again ABBDNA found in the
- 18:14blood and then auto antibodies
- 18:17against lupus related antigens.
- 18:19These four factors could explain
- 18:21a lot of the risk associated
- 18:23with development of long COVID.
- 18:28So then talking, this is the background,
- 18:32just kind of give a sense of what's known,
- 18:34what's not known and what we've done.
- 18:37So we have carried out our first human
- 18:41long COVID studies and as I said,
- 18:44this is a prototype.
- 18:46We plan to do this hopefully with the
- 18:50real lesson cohort and asking distinct
- 18:52questions about the immune phenotypes and
- 18:55what's driving some of these symptoms.
- 18:58And I just wanted to introduce
- 19:01the team that we worked with,
- 19:03which is, as I mentioned earlier,
- 19:05David Petrino at Mount Sinai
- 19:08School of Medicine.
- 19:09He sees thousands of long haulers.
- 19:13He's an amazing human being as well and
- 19:17I have the fortune of collaborating
- 19:19with him and his team Jamie Wood,
- 19:22Laura Tabakov and Dana McCarthy and
- 19:25and others from his team who have been
- 19:29working for over 2 years together.
- 19:32I actually reached out to David when I
- 19:35first heard about long COVID during an
- 19:39interview with Ed Young from the Atlantic.
- 19:42He was asking me about what are what
- 19:44are your hypothesis about these long
- 19:46COVID And that was like really the
- 19:48first time I heard about these post
- 19:50acute sequela of COVID because it was
- 19:54summer of 2020, so pretty early on.
- 19:57But then in the same articles David
- 20:00Petrino was quoted and I realized that
- 20:03he he really cares about patients and
- 20:06he's very knowledgeable about the
- 20:08clinical features associated with long COVID.
- 20:10So I'm very happy that he responded to
- 20:13my e-mail and we started a collaboration.
- 20:15And so that's the,
- 20:16the work that I'm going to tell
- 20:19you about today.
- 20:20And of course I'm just a conduit of what?
- 20:23My team and others have done together,
- 20:26so these are really the heroes who carried
- 20:30out the studies and students and postdocs.
- 20:33And so John Klein is the first
- 20:36of the Co first authors.
- 20:39He's an MD PhD student in the lab.
- 20:43Jill J Cox is a MDPHD student in Aaron
- 20:46Rings Laboratory who is also a key
- 20:49collaborator in this home endeavor.
- 20:52Rahul is a postdoctoral fellow in David
- 20:57van Dyke's lab who is does the machine
- 21:01learning algorithm for the study.
- 21:03Jeff Sasha pay When are three other
- 21:06members of the laboratory who really
- 21:09work tirelessly to analyze the samples?
- 21:12And so this is I'm just presenting
- 21:15their work.
- 21:17So the Mount Sinai Yale my long COVID
- 21:22study was to really try to collect
- 21:25as many information as possible from
- 21:28people who have had long COVID it.
- 21:31So this is from Mount Sinai.
- 21:33So New York got its first wave
- 21:35pretty early during the pandemic.
- 21:37When we collected the sample samples,
- 21:40they were about at least a year out
- 21:43from their original infection and we
- 21:46we included people who are older than
- 21:4818 years of age and who fit The Who
- 21:52guideline criteria for COVID infection.
- 21:55And we excluded certain types
- 21:57of individuals because we didn't
- 22:00have a large number.
- 22:01As you can see,
- 22:03we have 99 long COVID in purple
- 22:06at the convalescent control.
- 22:08These are the people who got infected
- 22:10around the same time but completely
- 22:13recovered 39 people and healthy Control,
- 22:16these are 39 people who never had COVID.
- 22:19And then we also had a healthcare
- 22:21workers who provided samples for the
- 22:24antibody analysis and we conducted
- 22:26multiple immune phenotyping.
- 22:28One is a flow cytometry to look
- 22:31at cell cellular factors and
- 22:33composition and activation phenotype.
- 22:36We also did human exoprotium
- 22:39antibody analysis.
- 22:40This is also known as a rapid
- 22:44extracellular antigen profiling or
- 22:46REAP technology developed by Doctor
- 22:49Ring and SARS COV 2 antibody profiling.
- 22:53This is looking at virus specific antibodies.
- 22:57We also did a peptide display library.
- 23:00This is really looking at antibodies
- 23:03against virtually any epitope that we we
- 23:06were interested in plasma proteomics,
- 23:08so we'll get cytokines and hormones and
- 23:10then of course EMR and symptoms survey,
- 23:13we wanted to correlate people's symptoms
- 23:16to different immune features and
- 23:19that's how we did the study and this
- 23:22is in met archive, not by archive, OK.
- 23:27So the demographic of the population
- 23:30were similar between the long COVID
- 23:33and the convalescent controls.
- 23:35Median age was 45.8 versus 41.4
- 23:40female dominant.
- 23:42This is typical of long COVID,
- 23:44there are a lot more female
- 23:46patients than male patients.
- 23:48And then we have also most of the
- 23:51people were not hospitalized and then
- 23:53there were some that were hospitalized.
- 23:55But there was no significant difference
- 23:58between these groups and days from
- 24:00acute COVID as I mentioned the
- 24:04they're about at least a year out
- 24:07from their infection around the year
- 24:10to 18 months or so mean both the
- 24:13convalescent and long COVID groups,
- 24:17so long COVID patients.
- 24:19So we did all these different analysis.
- 24:21I'm just going to highlight some
- 24:23of the key things that we found.
- 24:25So again, just to Orient you,
- 24:27the healthy controls are
- 24:29already always in orange,
- 24:31the convalescent controls are in yellow and
- 24:34long long COVID participants are in purple.
- 24:38So of all the features that we
- 24:40looked at by flow cytometry,
- 24:42what we see is an elevated level
- 24:45of non conventional monocytes.
- 24:48These are.
- 24:49So I don't want to get into the
- 24:51details about these cell types,
- 24:53but essentially these are the cells that you,
- 24:55you know often find during a chronic viral
- 24:58infection and they seem to be activated.
- 25:01We also see reduction in these
- 25:04conventional dendritic cell type one,
- 25:06these are the cells that are known
- 25:08to stimulate antiviral T cells and
- 25:11they're kind of reducing the blood.
- 25:14We also see activated B cells,
- 25:17B cells are the cells that make
- 25:20antibodies and they they have this
- 25:23interesting activation phenotype
- 25:24in the long COVID patients and we
- 25:28also see double negative B cells.
- 25:30These are B cells that are thought to be
- 25:33involved in extra follicular activation.
- 25:35It's just too technical to
- 25:37get into what what they are.
- 25:39But essentially this was what we saw,
- 25:42what was these cells were also elevated
- 25:45and then when we looked at the T cells,
- 25:48so T cells are the ones that's that
- 25:51can detect virus infected cells and
- 25:53kill them and some of the other
- 25:55T cells are known as helper cells
- 25:57of CD4T cells or the helper cells
- 26:00that kind of remember different
- 26:02viruses and and stimulate it.
- 26:04They're like the the central control
- 26:06commander of the immune system and
- 26:09they play very important role in
- 26:11every aspect of the immune system.
- 26:13What we saw was that in a long
- 26:16COVID patients,
- 26:16what we call the the central memory
- 26:19cell population of T cells were
- 26:22reduced in circulation whereas the
- 26:25exhausted T cells were elevated both
- 26:27the CD four and the CD eight types.
- 26:30So exhausted T cells are interesting
- 26:33because they are only present when T
- 26:37cells detect the antigen over and over.
- 26:40So for instance,
- 26:41you find these cells during a
- 26:43chronic viral infection.
- 26:44You find these cells in a,
- 26:46in a tumor setting,
- 26:48people who have tumors that can't be removed.
- 26:51So the T cells that are specific to
- 26:53that specific antigen become exhausted
- 26:55because they've been stimulated too long.
- 26:58So that's elevated.
- 27:00That's interesting.
- 27:01We don't know what these T
- 27:03cells are actually detecting,
- 27:04but it means there's some kind of chronic
- 27:07antigen that's stimulating this response.
- 27:10We also found that cytokines
- 27:13that are secreted by these
- 27:15helper T cells are elevated.
- 27:18So cytokines are like the languages
- 27:20that the T cells speak to communicate,
- 27:23you know,
- 27:24different signals to other other leukocytes
- 27:27or other cell types in the body.
- 27:30They're very important.
- 27:31But what we're seeing here is that
- 27:33these types of cytokines Interleukin 2,
- 27:36four and six are elevated in the
- 27:40CD 4T cells of people,
- 27:42long COVID patients but not the others.
- 27:45So the convalescent controls,
- 27:46they were infected but recover,
- 27:48they don't have these features.
- 27:51And if you look at there are
- 27:53some T cells that secrete both
- 27:54Illinois four and Illinois 6.
- 27:56These double positive cells are pretty
- 27:59much only found in people with long COVID.
- 28:03So that's very interesting.
- 28:04We don't know what they're doing but
- 28:06they do correlate with something.
- 28:08I'm going to tell you what that is soon.
- 28:13The other features we looked at are
- 28:16antibodies against the virus and what we saw
- 28:19was that the long COVID patients have so,
- 28:22so we controlled for the number of
- 28:25vaccinations because of course the the more
- 28:27vaccines you receive the more antibody
- 28:29you generate against the spike protein.
- 28:32So we only took people who had two doses
- 28:34of vaccines and then asked what is
- 28:37their antibody level against the spike
- 28:39or the S1 region of the spike or the
- 28:41receptor binding domain of the spike.
- 28:43So the purple again the long COVID
- 28:47patients with two doses of vaccines,
- 28:49they had higher levels of antibodies and
- 28:52that that was really consistent among
- 28:55these participants against SS1 and RBD.
- 29:00And so this is interesting again it
- 29:04suggests that these B cells may be
- 29:07undergoing maturation process because
- 29:09they're seeing the antigen over and over.
- 29:12That's just a speculation.
- 29:14We don't know why they have higher
- 29:16levels but that could be one reason.
- 29:20The other thing that we looked at,
- 29:22I mean we we looked at actually
- 29:24thousands of factors from the
- 29:26blood of these participants and we
- 29:29asked what are the features that
- 29:31are most significantly different
- 29:33between people with long COVID
- 29:35and people without long COVID.
- 29:37And the number one factor,
- 29:39the most significant was the cortisol,
- 29:42plasma cortisol level.
- 29:44Now we didn't do a cortisol
- 29:46measurement throughout the day,
- 29:48which is what we're planning to
- 29:50do to find out if their pattern of
- 29:53cortisol secretion is different.
- 29:55But at the time when we collected the
- 29:58data most participants were collected,
- 30:01their blood was collected a
- 30:03similar time during the day.
- 30:05So let me go to that So the
- 30:07collection time for healthy Control,
- 30:09the Calm Blessing control or the long
- 30:12haulers were about similar time from the.
- 30:15So Kiko,
- 30:17let me let me ask you this just because
- 30:19you've got a lot of good amazing stuff here.
- 30:22So just because I'm thinking you
- 30:25know you've got it's such good detail
- 30:28but a lot of people will like I I
- 30:31think what we want them to take home
- 30:33from this is that you've got it what
- 30:35you your approach is let's measure
- 30:37thousands of different things,
- 30:39multiple different domains.
- 30:41I mean it's just for people listening.
- 30:43I mean look Akiko as you can tell
- 30:44is like at the top of the field and
- 30:47and you know and there are others of
- 30:49course who are thinking hard about
- 30:51this stuff but one of the central
- 30:53messages from the study was that
- 30:55that there was something there.
- 30:57So all these people generally had
- 30:59you know lots of other tests and I'm
- 31:01seeing in the and I I'm just going
- 31:03saying this because we're also getting
- 31:05questions that I want to be able to
- 31:07to get to but people are getting
- 31:08lots of tests we're all come back
- 31:10to normal And then with this vast
- 31:13array of testing many of it and very
- 31:16different you know kinds of things.
- 31:18Some looking for substances produced
- 31:19by the immune system.
- 31:20Some persons by antibody proteins
- 31:23something looking at evidence
- 31:25reactivation all this kind of stuff
- 31:27that that people who and this is just
- 31:29a long COVID we didn't have a vaccine
- 31:32injured that we're going to we're
- 31:33hopefully develop cohorts like that
- 31:35but people are different we're different.
- 31:37I mean and and I think that one of
- 31:39the central things I've been telling
- 31:41people is you know this is evidence
- 31:43that what people are saying I don't
- 31:45feel right and then people are doing
- 31:46a bunch of tests and they're saying I
- 31:49can't find anything wrong with you.
- 31:51Well, maybe that's not me,
- 31:53the person who's telling you
- 31:55something's wrong.
- 31:55Maybe it's the tests that you know,
- 31:57and we don't yet have the right tests that
- 32:00are detecting what it is in your body.
- 32:03That's not going right.
- 32:04At least it's different than it was before.
- 32:08That's causing you to feel a whole
- 32:09bunch of symptoms.
- 32:09And one of the things that you
- 32:11think about listen is, you know,
- 32:12with more than 600 people in listen
- 32:14and people haven't filled out,
- 32:16a lot of these profiles is that
- 32:18people are are severely affected.
- 32:20So you know,
- 32:21that remember that scale that
- 32:22was like was zero to 100.
- 32:23Like if you go out to the, you know,
- 32:25the United States general population
- 32:27for the age group that we've got,
- 32:29you know,
- 32:29people aren't perfect health or their,
- 32:31their numbers are something like 84 or 85.
- 32:33Something like that is a that's the
- 32:35average score that people will say
- 32:36when you say how's your health.
- 32:37And in this group it's 5050 and
- 32:41and many people were down.
- 32:43And I'm just telling you what you
- 32:44already know, 'cause you filled it out.
- 32:46Some people are down 30 and and
- 32:48and even lower
- 32:49and showing that,
- 32:50you know people are severely affected
- 32:52and lots of people are representing
- 32:54their previous lives as very healthy.
- 32:57I mean, and many people,
- 32:58marathon runners doing all sorts of things.
- 33:00So what the most important thing
- 33:02I think what what what Akiko is
- 33:04showing is that we actually she in
- 33:07her lab and all the people working
- 33:08with her I'll say I like to say we
- 33:11but really it's it's her and her
- 33:12lab you know are detecting very
- 33:15important changes that have occurred.
- 33:18We believe changes is cross-sectional
- 33:19but that you know that that that
- 33:22differentiate people who are reporting
- 33:23all these symptoms from people who
- 33:25aren't reporting all these symptoms.
- 33:27And it again, we think it's the
- 33:28first half of the first inning,
- 33:29it's just the beginning of
- 33:31unpacking all of this.
- 33:32But but like when you're seeing all this,
- 33:35these you know,
- 33:36numbers I know can be overwhelming
- 33:38amount of information.
- 33:39But I think we wanted to give you a sense of
- 33:42the substance of the work that's going on.
- 33:44But maybe I'm just thinking,
- 33:47Kiko, it's, you know,
- 33:48we got 20 minutes,
- 33:49maybe we can just start taking
- 33:50some questions.
- 33:51And a lot of these questions by the way,
- 33:53I I I think I'm interested in hearing
- 33:54what you have to say about them
- 33:56because a lot of them are really
- 33:57tuned towards people having already
- 33:59had other tests and stuff like that.
- 34:01And and I'm just thinking you know
- 34:04for some people this might be it's
- 34:06it's great to get the high level but
- 34:07but let's maybe just get into some of
- 34:10the questions that'd be all right.
- 34:12Of course, it's fine.
- 34:13I'm sorry if I went on and on but I
- 34:16can listen to you forever.
- 34:17But also I got a lot to learn
- 34:18even when I'm listening to you.
- 34:20I'm thinking you know I need there's
- 34:21more I would need to learn to get up
- 34:24to because it's so deep and broad.
- 34:27But. But it should give everyone
- 34:29a sense of of the depth here.
- 34:31You know that this isn't just like
- 34:32one test or another test but it's
- 34:34like it's a depth of information
- 34:35which she was sort of showing you
- 34:37that we're looking in this way.
- 34:38That way.
- 34:38I mean, the immune system is amazing.
- 34:40I mean it's and the body's amazing
- 34:42and there's so many different
- 34:43ways that we can look at this
- 34:44that are far beyond what our
- 34:45traditional tests people have done.
- 34:47So maybe we can just go on one does
- 34:52vascular endothelial inflammation fit
- 34:53with hypothesis be of autoimmunity?
- 34:55I don't know.
- 34:56If you want to Give your opinion about that,
- 34:59yeah. It could be autoimmunity.
- 35:01You can imagine antibodies that are
- 35:04binding to the vascular endothelial
- 35:06cells causing some inflammation.
- 35:09It could be complement deposition.
- 35:11It could be inflammation itself
- 35:14that's causing vascular damage. Yeah.
- 35:17So there are a lot of possibilities
- 35:18of how vascular damage could happen,
- 35:21but autoimmunity is one of them.
- 35:23And I'm going to just pepper you with
- 35:24these like, I'm just going to go fast.
- 35:25So if you don't mind put you on the hot seat.
- 35:29OK If you think I'm missing anything or
- 35:31you think there's something else but this
- 35:33regarding the theory viral reservoir.
- 35:34I'm vaccine injured and have had my COVID
- 35:37antibodies checked eight weeks from injury
- 35:38and had never had had the infection.
- 35:40The nucleic capsid antibodies were found
- 35:42so it's the an autoimmunity for us.
- 35:44I had immediate reaction dizziness
- 35:46within minutes of the shot and then
- 35:49someone else that you know they were
- 35:51sorry to hear that and that they had
- 35:52both post booster and post infection.
- 35:54long COVID after Pfizer booster.
- 35:56I could barely stay in the next
- 35:575 days and barely walk straight
- 35:58for the following two weeks.
- 36:00Even now almost a year later I can't
- 36:02stand with eyes closed might bounce off.
- 36:03Let me just say what I'm saying
- 36:05these when we're talking about these
- 36:06things that people are suffering,
- 36:07I mean, my heart hurts to hear them,
- 36:09but let's we'll try to go through
- 36:11these quickly.
- 36:11But I want to say to each and
- 36:13everyone of you that I'm sorry
- 36:14for what you're experiencing.
- 36:15We're trying to move forward.
- 36:16But I think this was just a question
- 36:18of whether or not your thoughts about
- 36:20vaccine injury and are we going to
- 36:22take the same approach to look at it
- 36:23or are there special features to it?
- 36:26Yeah, great question.
- 36:27So I'm sorry I didn't get into the
- 36:31vaccine injured injury hypothesis,
- 36:33but other than the viral reservoir,
- 36:36which obviously isn't part of the vaccine,
- 36:40I think all of these hypothesis
- 36:42can still hold true.
- 36:44And that's why we're very excited to
- 36:47compare vaccine injury versus long COVID.
- 36:49We now have really a lot of insights
- 36:53which I was sharing with you about
- 36:55long COVID and immune phenotype.
- 36:57But for post vaccine and it it's
- 37:01possible that these four hypothesis
- 37:03except for the viral reservoir,
- 37:05I would replace that by
- 37:07potentially the antigen reservoir.
- 37:09But we don't know,
- 37:11we don't know whether the spike itself
- 37:14can be triggering the chronic sort
- 37:16of activation of T cells and B cells.
- 37:19And that we can tell by looking
- 37:21at the flow cytometry data.
- 37:23You know,
- 37:24I was showing you the activated
- 37:25B cells and T cells.
- 37:27This is a feature that we can
- 37:29immediately sort of decipher by doing
- 37:32a similar study on vaccine injury.
- 37:34So if the injury happens within
- 37:37minutes of the first vaccine,
- 37:39though it's unlikely to be driven
- 37:43by adaptive immune response
- 37:45because adaptive immunity takes
- 37:48couple weeks to develop.
- 37:50So if it's within minutes,
- 37:52you know you may be reacting
- 37:55to components of the vaccine in
- 37:58either sort of an allergic manner
- 38:00or it's possible that you may be
- 38:03reacting to the 3D native immune
- 38:06response to the to the vaccine that
- 38:09somehow cannot be repressed later.
- 38:12So but if it's happening after
- 38:15the booster dose,
- 38:16it may be driven by adaptive immune
- 38:19responses that you generate with the
- 38:22first primary series of the the vaccine.
- 38:25So I I think we have to be open minded
- 38:27about what might be causing those and
- 38:30and that's what we're trying to give
- 38:32as many people we're we're going
- 38:34to start implementing this part
- 38:35of selecting certain people to see
- 38:37whether they'd be willing to provide
- 38:38blood and and saliva so that we
- 38:40can run some of these same tests.
- 38:41So here's another one.
- 38:42Do you think it's possible for dogs
- 38:44to recognize injured vaccine vaccine
- 38:45injury and are they recognizing virus
- 38:47or the combination of the immune
- 38:49response present with the virus?
- 38:52Yeah. First of all,
- 38:53we don't know what the dogs are detecting,
- 38:56the volatile organic compounds
- 38:57that the the dogs are sensing.
- 39:00We we no one has identified what that is.
- 39:03So we don't know.
- 39:04It would be pretty amazing if the
- 39:07dogs can recognize the vaccine
- 39:09injury because that would very
- 39:13much suggest the spike, you know,
- 39:16because that's sort of the common
- 39:18thing that they've been trained with
- 39:21the viral infected supernatant.
- 39:22Unless it's something that's induced by the
- 39:25infection that's also induced by the vaccine,
- 39:27that has nothing to do with the spike.
- 39:29It's possible, right?
- 39:30But like logically spike would
- 39:32be the common feature there.
- 39:34So yeah,
- 39:35it would be great to see if the
- 39:37dogs can recognize vaccine injury.
- 39:41I thought there was another one that
- 39:43just disappeared, but I'll go this one.
- 39:45I was told by the Long Hawk COVID
- 39:46clinic at Johns Hopkins that
- 39:48Professor Pretorius is currently
- 39:49affiliating her research with Yale.
- 39:51Is this correct? And if so,
- 39:52we'd be following up with a micro
- 39:55clotting studies in potential testing.
- 39:58Yeah, definitely we.
- 39:59We've been in touch with Doctor Pretorius
- 40:03Group and we are learning how to do
- 40:07the micro clot analysis in the lab.
- 40:10You know we we have very limited
- 40:12number of people in the lab so
- 40:14we can't do everything but micro
- 40:16clot is certainly on the radar.
- 40:19It's not like the central focus right now,
- 40:21but it's something we'd like
- 40:23to do in the future.
- 40:25Great. I I think maybe that's just
- 40:27about the theories about vaccine,
- 40:29but I think that you you covered
- 40:31your thoughts about the the
- 40:33vaccine injured hypothesis there.
- 40:35There would be maybe even more
- 40:37that you thought but let me go.
- 40:39Will you be testing or looking
- 40:40at immune mediated small fiber
- 40:42neuropathy related antibodies,
- 40:46TSHDSFG, FR3, MAG, many of us with
- 40:48chronic neurologic vaccine reactions
- 40:50test positive for small fiber neuropathy
- 40:52via skin biopsies are sometimes
- 40:53positive for these antibodies,
- 40:57absolutely. So there are two technologies
- 41:00that that would cover those the REAP
- 41:04that I was telling you about which is
- 41:07an human exoprotium antibody analysis
- 41:09that Doctor Ringslam has developed
- 41:12it it covers over 6000 proteins.
- 41:15So many of these are in that at
- 41:18least fragments are in there.
- 41:20So if you are developing auto antibodies,
- 41:22we would be picking them up.
- 41:25The other strategy that I mentioned is
- 41:28the phase display library that one can
- 41:30also pick up antibody against any episode.
- 41:33So we should be able to pick those up.
- 41:36So yeah, I mean whatever it is,
- 41:38we are going to find it.
- 41:42Someone asked why was it that injured
- 41:44folks like me who clearly have SFN
- 41:46are showing negative test results.
- 41:48I think that's that's a question, Yeah.
- 41:52So you know if we only did 10 tests,
- 41:55we would also not find much in long COVID.
- 41:58We did thousands of,
- 42:00we we tested thousands of parameters and
- 42:03and that's why we were able to identify
- 42:06distinguishing features for long COVID.
- 42:09I I think this wide net sort of approach
- 42:13that we're doing will reveal something
- 42:16common in a post vaccine injury.
- 42:19So I'm hopeful that we're going to
- 42:22find something but you know standard
- 42:25lab testing and will maybe not
- 42:27pick up the the the key features
- 42:28that we are able to pick
- 42:31up and Michelle Ash is there
- 42:33specific anti star COV 2 IgG test
- 42:35that we can take that will allow
- 42:37you to capture the same kinds of
- 42:38readings many of us have had antibody
- 42:40tests but different types Quest,
- 42:41LabCorp, Academic Centers, Radiance.
- 42:45So it's harder to compare,
- 42:49yeah. So in in our preprint we also
- 42:54found that people with long COVID
- 42:57make antibodies to specific epitope
- 43:00within the spike that that is not
- 43:03found in the convalescent controls.
- 43:05So it's something that's induced
- 43:08by the features, viral features
- 43:11associated with long COVID and it's
- 43:14not related to vaccine status because
- 43:17we compared people who are vaccinated.
- 43:20And so it's, it's possible that the
- 43:22molecular kind of analysis that
- 43:25we're doing will pick up unique
- 43:27features of your antibodies.
- 43:29Yeah. It's not a standard sort
- 43:31of quest type of testing.
- 43:33So, yeah, I'm not sure whether they're
- 43:35going to pick up any difference.
- 43:38Yeah. And I think you really
- 43:39have to have the laboratory
- 43:40research test to get the kind of
- 43:42things that you're you're doing,
- 43:43which again the reason for the study,
- 43:45the those antibody tests may
- 43:47give you some information,
- 43:48but not exactly what you're been looking at.
- 43:50Someone's asking based on your test,
- 43:51So the people should be going
- 43:53out and getting cortisol tests.
- 43:55Yeah. So that's the other thing.
- 43:57I don't want to, you know,
- 44:00first we need to do more research.
- 44:03You know, it's a limited number of
- 44:04people and it's, it's one site.
- 44:05And that's why this,
- 44:06listen study is great,
- 44:07'cause we can this, you know,
- 44:09in a decentralized manner,
- 44:10we can collect samples from many of
- 44:13you and test it, the standard sort of,
- 44:17you know, clinical cortisol test.
- 44:19We don't know whether they're going
- 44:21to pick up the difference if you're
- 44:24doing it for some reason anyway,
- 44:25yeah, why not?
- 44:26But I I cannot promise you that
- 44:28that's going to be a sensitive
- 44:30way of detecting the differences.
- 44:32So again,
- 44:32we do have to do some head
- 44:33to head comparison.
- 44:35Yeah
- 44:35Karen. So if you consider running the
- 44:37same tests as a group of vaccine injured
- 44:39that have long COVID type of symptoms,
- 44:41I'd just say I can just pick that up
- 44:42say like that's on that's in the plan.
- 44:44Actually we're starting that now.
- 44:46We're already contacting a few
- 44:47people to get started on that.
- 44:48But that's exactly what we want to do.
- 44:50We want to demonstrate you know what
- 44:52what does what do People's Kiko Star
- 44:55calling these immune signatures you
- 44:56know what is it that looks like that's
- 44:58going on in their bodies and and can
- 45:00we learn from that so that that's
- 45:02that's definitely in the plan soon to
- 45:05be launched will there be translation
- 45:08these findings into clinical trials.
- 45:10So what's timeline been I I'll just
- 45:12say quickly that you know Kiko and I
- 45:14recognize that people are suffering and
- 45:16we can't wait for a full understanding of
- 45:18this condition in order to move forward.
- 45:20And and I'll give you,
- 45:21you know there are lots of situations
- 45:23in medicine where you may not
- 45:24fully understand some,
- 45:25but you have some hints that things that
- 45:27are worth trying and they actually can
- 45:29give insight into the underlying cause too.
- 45:31At the same time.
- 45:32So we we are eagerly moving forward to
- 45:35try to figure out how we can use this
- 45:37platform to to to run trials and to get
- 45:40candidates based on what we know already.
- 45:43We're in discussions actually
- 45:45there's a potential trial that could
- 45:47run as as soon as in a few months.
- 45:49And we're hoping that we'll have a bunch
- 45:51of people from this community ready,
- 45:53eager to go and we can enroll it
- 45:56within weeks, run it, you know,
- 45:58within a month and figure out
- 45:59the answer and then keep going.
- 46:01And then we're trying to,
- 46:02we're all the time talking to people
- 46:04who may have therapies that we can try.
- 46:06And if this group is up for it,
- 46:08then, you know,
- 46:09we'll be able to learn stuff rapidly.
- 46:10But I think it's essential that
- 46:12we do this in rigorous ways with
- 46:15trials just to bring in a few other
- 46:18people who haven't asked.
- 46:19Some of us not all,
- 46:21seem to get significantly worse
- 46:22immediately after steroids like Prednisone.
- 46:24Maybe it's because Prednisone also lowers
- 46:26cortisol for an already low cortisol subject.
- 46:29I I'll just say I think it's
- 46:31important for this group to share
- 46:32experience about what triggers them,
- 46:34what makes things better,
- 46:34what makes things worse.
- 46:35We can continue to ask those kind
- 46:37of questions and collect that,
- 46:38share that information and figure
- 46:40out other clusters and people
- 46:41have the same kind of triggers.
- 46:42I don't think we know yet.
- 46:45You know have a strong enough
- 46:47evidence base to be able to say
- 46:49that reproducibly you know because
- 46:51some people are you know have even
- 46:53reported steroids helped them.
- 46:54Some people reported it's made them worse.
- 46:57It's it's hard to know but we need
- 46:58to like if we can get a bunch
- 47:00of people who are
- 47:00having different reactions then be
- 47:02able to compare them with many of
- 47:04the tests that that Kiko's running
- 47:06maybe that'll provide some insight.
- 47:08Can you talk about TNF?
- 47:09Mine was very high.
- 47:11Also there's overlap with
- 47:12reactivated viruses.
- 47:13Chronic Lyme.
- 47:14What's the spike protein and
- 47:16what have you attributed to
- 47:17other diseases and have you seen
- 47:19anemia in the long haul vaccine
- 47:21injured and positive Lyme IGN
- 47:23is has not converted to IG G
- 47:26you have any comments on that?
- 47:29Yeah. So we did measure TNF,
- 47:31it's one of our cytokine
- 47:34that we measured the and just
- 47:37to say to people just some people may
- 47:38not know a cytokine is a substance
- 47:40that's released in the course of
- 47:41a response for the immune system.
- 47:43I mean you can do better job definition,
- 47:45but it's just, I'm just assuming
- 47:46people like even that word might
- 47:48not be familiar to many people.
- 47:50Sorry. Yeah. Cytokines are,
- 47:51yeah, like I said, like you know
- 47:54language that does immune cells
- 47:55use to communicate with each other.
- 47:57TNF is one of the like loudest
- 47:59alarms you can imagine.
- 48:01TNF, Illinois 6, Illinois one,
- 48:03these are cytokines that is
- 48:05released during an acute infection,
- 48:07bacterial or viral.
- 48:09And if you have high levels of TNF,
- 48:12you're not going to feel well
- 48:14because it has many pleotropic
- 48:16impact throughout the body anyway.
- 48:19We did measure TNF and it's elevated
- 48:21in some people but not others.
- 48:22It wasn't one of the significantly
- 48:25different factors,
- 48:25but I wouldn't discount that
- 48:27as a part of the, you know,
- 48:29pathological process.
- 48:30And you know we did also
- 48:33look at antibody to many,
- 48:36many pathogens including Lyme
- 48:39antigens and we did not see any
- 48:42significant difference between the
- 48:44long haulers and non long haulers.
- 48:47But what I didn't get to my
- 48:50presentation is that we did see
- 48:52the Epstein biovirus reactivate
- 48:55reactivation feature in our antibody.
- 48:57So that that's one of the the highest
- 48:59feature after cortisol that is
- 49:02different in the long COVID patients.
- 49:08And and that's that was a great question
- 49:10a great answer just to confirm study
- 49:12found higher levels of cortisol long
- 49:14COVID actually it's a lower levels of
- 49:18cortisol in in the long COVID patients.
- 49:23This was nice professor sake even
- 49:24though I don't understand all the
- 49:25cell biology I find the president
- 49:26very engaging hope to hear from you
- 49:28more in the future that was just a
- 49:29a lovely and we recognized we need
- 49:31to work you know this is our first
- 49:33one and and we've got to figure out
- 49:34how to calibrate the communication.
- 49:36Just, you know,
- 49:37forgive us if we're still learning.
- 49:39This is about trying to figure out
- 49:41how we share information and we
- 49:42need to again continue to do better
- 49:44about how we how we communicate.
- 49:46Recognizing the people with very
- 49:48different levels of backgrounds and also
- 49:50many people still suffering brain fog
- 49:52and heart difficulty concentrating and
- 49:54it may be an hour presentation like this.
- 49:56You know we should just only be
- 49:58doing questions if people have can
- 49:59even put them up in in advance.
- 50:01We we want to be as helpful as possible.
- 50:03Realize that every time I get vaccinated
- 50:05I suffer many side effects for months.
- 50:06It's still ongoing.
- 50:07Nervous about getting the latest by Valent.
- 50:09I was told it's safer than
- 50:11actually getting COVID.
- 50:12What do you think?
- 50:16I'll take that as a clinician.
- 50:17I don't know if you have an idea,
- 50:17but I'm just saying like,
- 50:18I I don't know what to say in this case.
- 50:21I mean, I hear from a lot of people,
- 50:23they're, they're concerned about
- 50:24getting the vaccine because they've not
- 50:26had a great experience with the past.
- 50:28They're even more concerned
- 50:29about getting COVID.
- 50:30The vaccine, by the way,
- 50:31doesn't fully prevent COVID,
- 50:32as many of you know.
- 50:34It does mitigate the consequences
- 50:36of the COVID infection and it may
- 50:38decrease the infection rate by some
- 50:40percentage in in the same way,
- 50:41flu vaccine, you know,
- 50:42it doesn't keep everyone from getting flu,
- 50:44but it reduces the risk and
- 50:47reduces the consequence.
- 50:48This is just a really hard one.
- 50:50I don't think we want to be
- 50:51giving medical advice here,
- 50:53but just to acknowledge that that's a tough,
- 50:56tough one.
- 50:57There are a few questions
- 51:00regarding medical records.
- 51:01People are asking how like what is
- 51:03the timeline for them to connect
- 51:05medical records and what records do
- 51:07we like are we expecting from them.
- 51:09So the I think I'll just take this one.
- 51:11So the idea about for example the
- 51:121st I'll just take the survey.
- 51:14So you've been asked to fill
- 51:16out surveys in Kindred and then
- 51:17come into into this.
- 51:19And though all those service help
- 51:21provide profiling information and
- 51:24we're likely to then augment that
- 51:25information with more information
- 51:27as we learn more about people in
- 51:29the study and figure out what we
- 51:31need to dig into more detail on.
- 51:32And one of the innovations of
- 51:34the study is that rather than
- 51:36having you give us permission and
- 51:38then going to every healthcare
- 51:40system and then believe it or not,
- 51:42faxing them consents and then get
- 51:44then you know waiting weeks before
- 51:46they give us like paper copies of
- 51:48the records and then having to go
- 51:50through them and abstract them.
- 51:51You know we're using this digital way
- 51:53and the way the digital way was work,
- 51:54you connect to your records
- 51:56or wearables or everywhere.
- 51:57You've got your data assets,
- 51:59your personal data assets grow comes
- 52:01into your own cloud based account.
- 52:04One day sometime in the future we'll
- 52:05be able to actually show a viewer
- 52:07where you can see what you've got.
- 52:08You don't have that yet and Hugo but
- 52:10it comes to your cloud based account.
- 52:11Then you with your permission,
- 52:12it's going into the study and
- 52:14the way it works is once you've
- 52:16connected to your records that way,
- 52:18it's being refreshed all the time
- 52:19in your secure cloud based account.
- 52:21And if you've given permission
- 52:22for it to go into the study,
- 52:24it moves into the study and and kind
- 52:26of keeps the study all updated.
- 52:28If you ever decide you want to stop,
- 52:30you can just stop it. It just stops.
- 52:32If you ever decide you want to delete
- 52:34your records, you can delete records.
- 52:35But meanwhile your data assets
- 52:37are growing and all we're
- 52:38encouraging is the more places you connect
- 52:40to do you connect to your health systems,
- 52:42the health systems where you've gotten
- 52:44who have who have electronic records
- 52:46where we can make this connection
- 52:48pharmacies like like you know Walmart,
- 52:51Walgreens, Kroger's,
- 52:52anywhere you've got large major
- 52:55pharmacies or labs or wearables.
- 52:57The more data assets are growing that can
- 53:00help the study to have more insight into
- 53:02your journey in what's going on with you.
- 53:05So we're just you know and part of
- 53:06this we're trying to learn together.
- 53:08You could come and tell us it's
- 53:09too burdensome, it's hard,
- 53:10or what you're encountering is challenges.
- 53:12And we want to be able to hear
- 53:14that and figure out how we
- 53:15can make it better and easier.
- 53:16But the alternative is a
- 53:18really labor intensive,
- 53:20difficult and delayed process where
- 53:21everybody goes out and tries to get records.
- 53:24Then I can go out and get your records,
- 53:25but then more things happen
- 53:26and we got to go out again.
- 53:28But with this digital process,
- 53:30we protect your privacy.
- 53:32We protect your records only.
- 53:33Everything moves with your permission
- 53:35and then but stuff is constantly
- 53:37being refreshed and the study can
- 53:39continue to follow people over time.
- 53:41Once you are connected,
- 53:43it's automated.
- 53:44But that's the way we're trying to
- 53:46to to do this as a new approach.
- 53:48You look like and I just want to add too,
- 53:49because
- 53:50I think people are concerned
- 53:51about the Kindred side of it and
- 53:52that is how Kindred is built.
- 53:53So there's nothing that will
- 53:54happen to your records in Kindred.
- 53:56We we assure you that nothing
- 53:58moves without your permission.
- 53:59The only place we're sharing it
- 54:00is with listen if that's what
- 54:02you've given us permission to do.
- 54:03But that that is,
- 54:05you know foundational
- 54:07to what we are doing on Kindred. You it's
- 54:09they're your records and
- 54:12and that's the other things like
- 54:13Kinder doesn't own your data.
- 54:14Hugo doesn't own your data you own your
- 54:16data and and everything is permission
- 54:18based there's no back end selling nothing.
- 54:20It's it's it's a matter of trying to put
- 54:23people in a position where they gain
- 54:25agency over the data and then can be
- 54:27parts of studies where they're allowing
- 54:28that data to come into the study.
- 54:30But but that's the the way we're doing this.
- 54:33I I know we're we're we're at time and
- 54:34I know we could have probably done a
- 54:36lot of things better than what we did
- 54:38and there's lots of questions here.
- 54:40So I I think that we can be looking
- 54:41at these questions and kind of bring
- 54:43some of them together and then share
- 54:45them back through you know an e-mail or
- 54:49something to all the listen participants
- 54:51and they'll learn from these important
- 54:54questions that people have raised.
- 54:57I see lots of people here as I look down
- 54:59here that we have just so appreciative
- 55:01of all of you and that you're being
- 55:03part of this and helping us do better.
- 55:06And we can definitely answer these questions
- 55:09and and when we don't have answers,
- 55:10we can just be honest with you
- 55:11and say we don't know,
- 55:12you know and that we hope we will know soon.
- 55:14But I don't know, Kiko,
- 55:16if you I'm trying to just be respectful
- 55:18of your time and everyone's time.
- 55:20We have a lot more questions.
- 55:21Let me just say we're committed to getting
- 55:23information back to you with these questions.
- 55:25So don't think that we're
- 55:26going to ignore them.
- 55:28But Kiko,
- 55:28do you have anything you want
- 55:30to say at the end?
- 55:31Oh, yeah, absolutely.
- 55:32So I yeah, maybe I can do another
- 55:35one just to complete my presentation.
- 55:37If anyone's interested,
- 55:38I'm happy to come back and do it.
- 55:41The other thing is that, you know,
- 55:43we really don't know much about
- 55:45the vaccine injury and we're very
- 55:46eager to find out what's going on.
- 55:48So it's just a matter of starting
- 55:51the study and with your help
- 55:53understanding what's going on.
- 55:55And the idea generally is like we
- 55:57should have regular town halls.
- 55:59We should continue to you know interact with
- 56:03people who are you know you all of you.
- 56:05And and by the way you can reach out to
- 56:07us other times too like it's not just
- 56:09constrained by this what does it say?
- 56:10So listen study at yale.edu.
- 56:12Anybody can send us an e-mail at
- 56:14any time and you know the notion
- 56:16should be that we're we want to
- 56:18it's not like we're the researchers
- 56:19we don't want to hear from you.
- 56:21It's just exactly the opposite and
- 56:23we but we need to learn like how do
- 56:25we do this how do we make it better.
- 56:26How do we interact appropriately.
- 56:28How do we communicate clearly?
- 56:30And yeah, and Kiko,
- 56:31it's not like we've just regularly
- 56:33come back to this group.
- 56:34And if it's a ton of questions,
- 56:36then we can just spend the
- 56:38time answering questions.
- 56:39And I think also if we can figure
- 56:41this out where it looks more like a
- 56:42meeting where everyone's together,
- 56:43I think that'll make us all feel good too.
- 56:45That there's a a large group of people
- 56:47who are all part of this together.
- 56:50But just again, you know,
- 56:52I've said this to everyone and
- 56:53listened before, deep gratitude less.
- 56:55He's telling me there's 656 people.
- 56:57And listen now that's pretty good as a
- 57:00number of people growing by word of mouth,
- 57:04we've had you know I think
- 57:0680 some people on this call.
- 57:08That's pretty good percentage
- 57:09of people who are listening and
- 57:10we're we we're just open to ideas.
- 57:13What we really want to do is
- 57:14grow this community.
- 57:14We want to make it as big as possible
- 57:16bring in and more people get,
- 57:17the more we can learn from each other
- 57:20and also start really revving up this
- 57:22immuno phenotyping part for listen
- 57:24so that we can start to to have very
- 57:27detailed information that we can
- 57:29leverage to to bring some answers.
- 57:33So with that I I just like this isn't like,
- 57:36OK, we're over this is
- 57:38just like this hour's over.
- 57:39But we're going to continue to be
- 57:42involved in and and communicate
- 57:44and yeah thanks. Thanks Akiko.
- 57:46Great job and say something
- 57:48Bernali and and for everyone who's
- 57:50got questions and I'm looking
- 57:51at these questions is terrific.
- 57:52So this would be great for us
- 57:54to to get back to Bob.
- 57:55Thank you.
- 57:57Thank you everyone.