SARS-CoV-2 Vaccination in Immunocompromised Patients: What We Know & What We Don't Know | May 27, 2021

Transcript

• 00:07Good evening everybody.
• 00:09I'm doctor Stuart Seropian and
• 00:11I'm happy to welcome you to this
• 00:14forum on SARS Co V2 vaccination
• 00:18in immunocompromised patients.
• 00:20Town Hall for healthcare
• 00:22providers being sponsored by
• 00:24Smilow and Yellow Haven Hospital.
• 00:29So we're going to talk tonight about
• 00:31what we know and what we don't know
• 00:34about vaccination for SARS, Co V2.
• 00:38And we'll start with a overview of COVID
• 00:42infection in immunocompromised patients
• 00:44that I will give briefly to set the stage
• 00:49for review of the available vaccines,
• 00:52which will be given by Doctor Jeffrey to
• 00:55Paul and our section of infectious disease.
• 00:58Doctor Malinas and Doctor Azar from
• 01:01our infectious disease program
• 01:04are going to discuss vaccine data
• 01:07in immunocompromised patients.
• 01:09And doctors are will also talk
• 01:11about the role of antibody testing.
• 01:14I doctor Yildirim from Pediatrics
• 01:17will talk about COVID vaccination
• 01:19considerations in pediatric patients
• 01:22and then at the end we'll have time
• 01:26for some discussions both via the
• 01:28chat function and the Q&A function
• 01:31for a live discussion.
• 01:35So we have a lot to cover,
• 01:36so will will begin with an overview
• 01:40of outcomes of COVID infection
• 01:43in immunocompromised patients
• 01:45and as of Tuesday of this week.
• 01:47This is where things stand in
• 01:49the United States to date,
• 01:51as reported by the CDC,
• 01:55almost 33 million cases of COVID with 500
• 02:01and 87,000 deaths since the pandemic began.
• 02:06Last seven days have been 100
• 02:08and 62,000 new cases reported.
• 02:10I and it is estimated that 3% of
• 02:15the US population are in some
• 02:17way considered immunocompromised,
• 02:19so it's roughly 9 million people.
• 02:21So this is obviously a large
• 02:23patient group to consider.
• 02:30In the early days of the pandemic,
• 02:33or many studies published regarding
• 02:35the risk of mortality related to COVID,
• 02:38I chose to show results from the UK
• 02:41Health system Open safely study this is
• 02:44published in the literature in nature.
• 02:47Alright, which looked at risk factors for
• 02:50poor outcomes in 40% of the UK population,
• 02:53so 17 million adults, 11,000 COVID deaths,
• 02:57and you can you can see on the
• 03:01left some medical conditions
• 03:03associated with higher risk.
• 03:04These are age adjusted hazard ratios for
• 03:08mortality adjusted for age and gender,
• 03:11so older age and male gender
• 03:13are known risk factors.
• 03:15You can see neurologic disease,
• 03:17stroke or dementia diabetes.
• 03:20Respiratory disease these carriers.
• 03:24Hazard ratios of 1 1/2 to 2 1/2 on the right
• 03:29are some common immunocompromised states.
• 03:33An hazard ratios to mortality.
• 03:34There you can see high risk of death
• 03:37in solid organ transplant recipients.
• 03:40Cancer, active hematologic malignancy.
• 03:43Other immunosuppressive states,
• 03:46including things like HIV,
• 03:48aplastic anemia,
• 03:49congenital diseases, lupus,
• 03:51or rheumatoid arthritis so.
• 03:54I the general view here would
• 03:57be fairly high mortality in
• 04:00immunocompromised populations.
• 04:05So holding down in some patient
• 04:08specific patient populations,
• 04:10this is from a review of cancer patients
• 04:14and I'll just draw your attention to the
• 04:18relatively high mortality and mostly
• 04:21hospitalized patients with COVID from
• 04:24multiple large registry type reports.
• 04:27Patients with solid tumors showing mortality,
• 04:30usually within a month of diagnosis,
• 04:32ranging anywhere from 9 to 30%.
• 04:36Risk factors, of course,
• 04:38standard ones of comorbidities, older age.
• 04:42Human logic malignancy.
• 04:43Here you can go onto the next slide.
• 04:47Hematologic malignancy appears to
• 04:49be a significant state with a higher
• 04:53mortality than other cancers in two
• 04:55large registry type studies of over 1000
• 04:58patients with hematologic malignancies
• 05:00showed adjusted mortality's of 3037%,
• 05:05including in younger
• 05:07patients and risk factors.
• 05:10Here included acute leukemia.
• 05:12And particularly monoclonal antibody therapy.
• 05:16Next line.
• 05:22So transplant recipients also
• 05:25appear to be a significant risk
• 05:27of morbidity and mortality.
• 05:30One of the larger solid
• 05:33organ transplant studies.
• 05:35Showed age and underlying comorbidity
• 05:38were very important and more important
• 05:42than measures of immunosuppression.
• 05:45And this is predominantly kidney allograft.
• 05:47Recipients, who often have comorbidities
• 05:4920% mortality for hospitalized patients.
• 05:53The Center for International
• 05:56Bone Marrow Transplant Research
• 05:58Registry collected COVID patients
• 05:59last year and reported a 30 day
• 06:02mortality of 32% for all comers,
• 06:04age and gender were important time
• 06:07from transplantation and lymphoid
• 06:09malignancies were quite important.
• 06:12Next slide.
• 06:16Other email compromised populations.
• 06:18The risk of COVID infection
• 06:20or somewhat less clear.
• 06:21There have been a number of
• 06:23large scale studies reported.
• 06:25An initial study from a single Hospital
• 06:28in London following 1000 sequential
• 06:30patients separated in outpatients on highly
• 06:34immunosuppressive treatment steroids.
• 06:35Methotrexate biologics this is where
• 06:38the where their definition and the
• 06:40hazard ratio for mortality was.
• 06:42Two the Johns Hopkins registry
• 06:45had a very well controlled.
• 06:47Study with propensity matching
• 06:49for over 2000 patients.
• 06:52Hundred of eight were
• 06:54considered immunocompromise,
• 06:55mostly solid organ transplant or HIV,
• 06:58mostly on Prednisone and
• 07:00calcineurin inhibitors,
• 07:01and they found no difference
• 07:03in hospital mortality rates
• 07:05of mechanical ventilation.
• 07:07The VA today very large study of boot
• 07:11arthritis with over 30,000 patients
• 07:14and showed a somewhat higher ratio
• 07:17of mortality in patients on disease
• 07:21modifying agents or Prednisone
• 07:24and then for other populations.
• 07:26Reports are smaller scale and in general
• 07:30seem to suggest that patients with GI.
• 07:37Inflammatory disorders or neurologic
• 07:39disorders are not clearly at higher
• 07:42risk of mortality from COVID infection,
• 07:44and there may be issues
• 07:46with their treatments.
• 07:46Biologics, for instance,
• 07:48do seem to blunt antibody responses,
• 07:52go on to the next.
• 07:56B cell depleting antibodies are are
• 07:59among the agents that appear to lend
• 08:02significant risk to morbidity with COVID.
• 08:05There are multiple case reports
• 08:07of patients treated with the
• 08:10anti B cell antibody rituximab.
• 08:12Leading to persistent or recurring infection,
• 08:16the French rheumatology registry,
• 08:19compared with TUXMATH treated patients to
• 08:23other patients with rheumatologic disease.
• 08:26And, though they did not see
• 08:28an increase in mortality,
• 08:29they saw an increase in the
• 08:31severity of COVID infection.
• 08:32Prolonged hospital stay and this was
• 08:35particularly pronounced in patients who
• 08:37are more recently treated with rituximab.
• 08:42So some other concerning observations
• 08:45in mental compromised patients with
• 08:48COVID and I'll start with this case
• 08:50report in the New England Journal
• 08:52last year that described a five month
• 08:54history of recurring or persisting
• 08:56COVID infection in a very email
• 08:59compromised individual where viral
• 09:02evolution and mutation was documented
• 09:04in serial samples in a patient was
• 09:08unable to clear the virus in December
• 09:11for Memorial Sloan Kettering.
• 09:13It was demonstrated that patients
• 09:16receiving stem cell transplant or
• 09:18CAR T therapy had viable viable
• 09:20virus shedding for up to two months,
• 09:23which certainly throws some monkey wrench
• 09:26in the works with regard to clearing
• 09:29people to return to normal exposures.
• 09:32So many reports in the literature of
• 09:35this phenomenon and in limited reports.
• 09:38I anybody response to infection or
• 09:42vaccination email compromise patients
• 09:44appears to be diminished or sometimes absent.
• 09:49So to conclude.
• 09:55Most studies of COVID-19 infection
• 09:58email compromised patients report
• 10:01higher morbidity and mortality.
• 10:04Patients with human logic, malignancies,
• 10:06solid cancers that are advanced solid
• 10:09organ transplant appear very vulnerable.
• 10:12Although their Cornwall morbidities
• 10:15clearly contribute to mortality.
• 10:18Delayed clearance of virus
• 10:20occurs and immunocompromised
• 10:22hosts says implications for.
• 10:25Their infectivity and isolation and
• 10:29treatment an anti B cell antibodies
• 10:32in particular appear to blunt
• 10:34antibody production and Millie to
• 10:38prolonged infection in a metabolites
• 10:40and solid organ transplant.
• 10:42Infliximab may also play similar roles,
• 10:46so we're going to move on to doctor Topol,
• 10:49hoteles about our available vaccines.
• 10:59Thank you Sir, for that overview
• 11:02of COVID in email compromise.
• 11:05Population, I hope these next few slides
• 11:08will be hopefully review for everybody.
• 11:12As you all know, we have currently 3
• 11:16COVID-19 vaccines available in the US.
• 11:19Two of them are messenger RNA
• 11:22vaccines and they are still under EU.
• 11:25A status by the FDA.
• 11:28Obviously, the two that we have
• 11:31the experience with today to
• 11:33Pfizer violin to COVID-19 vaccine
• 11:35at the Moderna COVID-19 vaccine.
• 11:38Both are M RNA vaccines which
• 11:40require two doses.
• 11:42The Pfizer product requires the
• 11:44second dose be given at 21 days after
• 11:47the first dose and adorable product
• 11:49requires that the second dose is
• 11:52given 28 days after the first dose.
• 11:55Next line.
• 11:58In terms of the M RNA vaccines,
• 12:00this technology has been around
• 12:02for quite some time and has
• 12:05been used in other vaccines.
• 12:07It's very ingenious.
• 12:08You take the M RNA,
• 12:10which codes for the spike protein
• 12:12of the SARS Co V2 virus an you
• 12:16rap it in ripping nanospheres.
• 12:18There's no live virus after
• 12:20injection the vaccine.
• 12:22Stick it up by antigen presenting cells.
• 12:24The M RNA from the vaccine is then
• 12:26translated by the cell to produce.
• 12:28Spike protein and then the spike
• 12:30protein then stimulates both
• 12:32antibody and so immediate immunity.
• 12:35The M RNA rapidly degrades
• 12:37similar mechanisms.
• 12:38The M RNA does not enter the
• 12:40nucleus of the binary human DNA,
• 12:42making it a very safe vaccine.
• 12:45As we have seen today.
• 12:47Next line,
• 12:48the two vaccines are quite similar.
• 12:51Pfizer vaccine contains 30 micrograms
• 12:54of the M RNA for journal takes contains.
• 12:59The excipients on listed below as you
• 13:04can see there are multiple different
• 13:06types of lipids present in the vaccines.
• 13:11Next line they do not contain preservatives,
• 13:14antibiotics, food, animal protein,
• 13:16and they don't contain latex.
• 13:19These are very,
• 13:20very clean vaccines as vaccines go.
• 13:23In terms of vaccine efficacy,
• 13:25as one can see,
• 13:26this is from the data that
• 13:28was submitted to the FDA.
• 13:30These studies were done both
• 13:32in immunocompetent patients.
• 13:34There were some well controlled
• 13:36HIV patients in the study,
• 13:39but there were no immuno
• 13:41compromised patients in this study.
• 13:43So you know competent responses
• 13:46were extremely high in terms
• 13:49of vaccine efficacy 9495%.
• 13:52Next line.
• 13:54And this was seen across all age groups,
• 13:57race, ethnicity and comorbidities,
• 13:59excluding women suppressed status.
• 14:02They are associated with severe
• 14:05COVID-19 disease next line.
• 14:07Cancel carbon 19 vaccine.
• 14:13Mechanism it uses an adenoviral vector
• 14:16which is immuno competent and not capable
• 14:19of our replication unlike the other
• 14:22two vaccines them are may vaccines.
• 14:24It was designed as a single
• 14:28dose vaccine next line.
• 14:30Again, it is very clean vaccine.
• 14:33Overall, it does contain the non replicating
• 14:38Anna viral particles which contain the.
• 14:44M RNA contains the gene for spike protein
• 14:49and again similar to the Alano vaccines.
• 14:54That is a purely clean vaccine
• 14:56in terms of what's in it,
• 14:59and again, no preserve and biotics,
• 15:01animal protein or latex.
• 15:04The vaccine efficacy for the Janssen
• 15:08anavar vector vaccine was lower.
• 15:11A lot was made of this compared
• 15:14to the M RNA vaccines,
• 15:16but one must remember that this
• 15:20is a time difference that this
• 15:25vaccine was studied much later in
• 15:29the evolution of the covert pandemic
• 15:32and obviously variants started to.
• 15:36Become apparent,
• 15:37which may have impacted the vaccine efficacy.
• 15:42Next slide.
• 15:44But when you look at against its efficacy
• 15:48against severe critical COVID-19 at 20 days,
• 15:53you see very high overall efficacy's 84%.
• 15:57And again,
• 16:00even in the 1859 year group,
• 16:0592% and greyling, 60 years of age,
• 16:0972% vaccine efficacy next line.
• 16:14One thing that the Jensen Changer vaccine
• 16:18had available just because of time
• 16:20when it was studied that it was studied
• 16:23against different variants in the various
• 16:26countries where it was being studied.
• 16:29And again that last column where shows
• 16:33the vaccine efficacy remain very high.
• 16:36In all these different variants
• 16:39with severe critical disease being
• 16:42prevented as you can see next slide.
• 16:45Now there's a lot of concern about variance,
• 16:48and there are many variants circulating.
• 16:53Interestingly, most variants don't
• 16:55have significant impacts of vaccine
• 16:57efficacy from the data thus far.
• 17:00We have the UK variant.
• 17:03B117 has increased transmission but actually
• 17:06as member impact of vaccine efficacy.
• 17:09The South African California variants
• 17:13also again increased rates of
• 17:16transmission and SMAD reduction.
• 17:19Neutralization titers impose vaccinees.
• 17:22Next line.
• 17:26And again, this trend continues
• 17:28and the most recent variants
• 17:30that have been seen in India.
• 17:32They've only seen slight reduction
• 17:35neutralization in postvaccination serum.
• 17:39Next line, now often the questions
• 17:42we get infectious diseases red
• 17:45is circulating in Connecticut.
• 17:47We don't exactly have real time data,
• 17:50but our data is much better than
• 17:53historically we've had and this particular
• 17:56website actually is updated every
• 17:59Thursday with all the recent varying
• 18:02data that is from the circulating
• 18:04COVID cases in the recent past,
• 18:08and you can see here that the UK variant.
• 18:11Accounts for over 3/4 of the variants
• 18:15that are circulating in Connecticut
• 18:18at this time we have very low
• 18:21numbers of the Brazilian variant
• 18:24as well as the California variants,
• 18:27and we I think this has actually improved
• 18:33with time in terms of what we're seeing.
• 18:37The last that I want to talk.
• 18:40About all the side effects and it's
• 18:43important to realize when you're
• 18:45looking at these side effects.
• 18:47These are actually not much different
• 18:50than other vaccines we give individuals.
• 18:53I think what's different in terms of
• 18:58patients looking at their side effect
• 19:01profiles were vaccinating literally millions.
• 19:04Hundreds of millions of individuals
• 19:06all at the same time.
• 19:08And they may not have had any recent
• 19:12vaccinations to compare side effects too,
• 19:15but you can see pain,
• 19:16redness and swelling.
• 19:18It's really injection site pain
• 19:20which is seen across the board,
• 19:23and it's really no different than to see
• 19:26with tenderness or the shingles vaccine.
• 19:28When one looks at fatigue,
• 19:30headache and myalgia again,
• 19:32very similar rates to what we see
• 19:36with the shingles vaccine and the
• 19:39last bullet dinner is for fever.
• 19:41Again,
• 19:42actually not much fever in comparison
• 19:44to what we normally see with shingles,
• 19:48vaccination and one thing I think
• 19:51it's important is just to have a
• 19:54visual sense and these are just
• 19:56pictograms to try to.
• 19:58Really show that there's not much
• 20:00difference in injection site pain,
• 20:03next slide.
• 20:05And again,
• 20:06feet redness at the injection site is
• 20:09much less than shingles vaccine next line.
• 20:13Swelling is much less next line
• 20:16and fever is much less common.
• 20:19These are well tolerated vaccines.
• 20:21We've had a robust surveillance
• 20:23system in place looking for any
• 20:26types of side effects,
• 20:27and I'm going to hand it off to Doctor Yoder.
• 20:31Mean when we talk about COVID
• 20:33vaccines in children.
• 20:37It is really hard to add anything meaningful
• 20:41about vaccines after Doctor Topol's period.
• 20:44Comprehensive talk as usual,
• 20:47but I will just touch base on the
• 20:49most common question I I receive.
• 20:52I have been receiving since the
• 20:54beginning of the pandemic and that is do
• 20:58children really need COVID-19 vaccine,
• 21:00independent from whether they have
• 21:02in a compromising status or not?
• 21:04So this slide.
• 21:06Shows us the case distribution in
• 21:09the United States and if we define
• 21:14pediatric population as those under 18,
• 21:17you could see that air on one in every
• 21:20five citizen in the United States is a
• 21:23pediatric case or pediatric individual.
• 21:26But we have roughly 10% around 12% of
• 21:30the old cases in the pediatric age group.
• 21:36Which is likely much lower than what
• 21:39we have been seeing with adults,
• 21:42but if you look at the mortality numbers,
• 21:46we have around 400 pediatric deaths and
• 21:49again this is likely much more lower
• 21:51than what we have with the adults,
• 21:54but it is quite significant and This is why.
• 21:58Next slide please.
• 21:59These are the different vaccine,
• 22:01preventable and hoping that it will stay
• 22:06vaccine preventable diseases over years.
• 22:09The year that we have licensed
• 22:12vaccine for the infection,
• 22:13the you know burden with the
• 22:16hospitalization per year,
• 22:17the mortality per year for pediatric
• 22:19age group and the vaccine efficacy.
• 22:22So so far the.
• 22:23You know we don't have a licensed
• 22:26vaccine for pediatric age group.
• 22:29Are rates in terms of hospitalization
• 22:31per year in pediatric age,
• 22:33group is between 56 to 94 per 100,000
• 22:37depending on the age group and we have
• 22:40400 kids who died because of the source code.
• 22:43So infection 300 of these were
• 22:47lost during a 12 month period.
• 22:49And if we compare these numbers
• 22:51basically to influenza for example,
• 22:53that we had been influenza vaccine as
• 22:55well that we have been using since.
• 22:572000 it is much much higher
• 23:01burden than influenza,
• 23:03and the vaccine efficacy as doctor
• 23:06triple has revieved is much,
• 23:08much better compared to influenza,
• 23:11and I want to finish with one more slide.
• 23:15If you could go to next slide, please.
• 23:17Obviously you know we don't want
• 23:19the pediatric patients to be in the
• 23:21hospital or die because of SARS Co V2,
• 23:23but there's a big discussion
• 23:24about whether they heard.
• 23:26I mean, they will be achieved if we.
• 23:28Vaccinate Pediatric age group.
• 23:30This is one of the earlier
• 23:33studies that came from China.
• 23:35They did follow around 1200
• 23:39household contacts of 400 stars,
• 23:42quit reinfection cases and
• 23:44what they have seen is.
• 23:47The blue bars are the attack rates
• 23:50in different age groups and if you
• 23:52look at the younger age group younger
• 23:55than 19 they were getting infected
• 23:58as much as those who are older.
• 24:02Except 60, an older age group.
• 24:05But if you look at the disease severity
• 24:08in those who are the secondary cases
• 24:11which are depicted in the red squares,
• 24:14they did have milder diseases compared
• 24:17to older individuals who got infected.
• 24:20And most importantly,
• 24:21the green bars are here showing
• 24:24that proportion of those who did
• 24:26not have any fever.
• 24:27So the message from this slide
• 24:29is children do get infected as
• 24:32much as the older individuals.
• 24:34They have milder disease.
• 24:35Which may be an obstacle because they do
• 24:38carry the virus without showing a big,
• 24:41you know clinical syndrome so.
• 24:46Unfortunately or fortunately again,
• 24:49the immunocompromised population specific
• 24:51data in the pediatric age group is much,
• 24:55much,
• 24:55much limited,
• 24:56much more limited compared to
• 24:58what we have heard so far.
• 25:00We have registries in the US and globally,
• 25:03and we can talk about what is the
• 25:05impact of COVID-19 specifically in
• 25:07pediatric transport transplant or
• 25:09email compromise patients as we go,
• 25:12but this is my last slide
• 25:14and I will pass it to.
• 25:17My eye Doctor Magnus marikar madness.
• 25:26Thank you and see.
• 25:28So come next slide yes, so the clinical
• 25:32trials of the source code B2 vaccines
• 25:35have demonstrated clinical efficacy
• 25:37in the prevention of severe COVID-19,
• 25:40but mostly focus on the general population.
• 25:43An have definitely excluded those
• 25:46with immuno compromising condition.
• 25:48So doctor, Azar and I will be
• 25:53discussing specific subpopulations
• 25:55of immunocompromised patients.
• 25:56And what's available data to
• 25:59kind of discuss about safety and
• 26:02immunogenicity of the vaccines next.
• 26:08Alright, so let's start with the
• 26:11solid organ transplant population.
• 26:12So this data was actually published
• 26:15early this year from the Hopkins Group.
• 26:19By Brian boyarski.
• 26:20So in this study they did a nationwide
• 26:24campaign requesting volunteers
• 26:26for this study on vaccine safety,
• 26:29an emergency city of SARS Co V2
• 26:32vaccine in transplant recipients,
• 26:35and they have reported the
• 26:37experience in the 187 transplant
• 26:39patients that they enrolled.
• 26:40And as you can see more than half
• 26:42were health care workers due to
• 26:44the timing of the rollout of the
• 26:46vaccine and the start of the study.
• 26:48An mostly were female.
• 26:50And young patients,
• 26:51relatively with a median age of 48.
• 26:53An majority were white,
• 26:55so patients were far out from their
• 26:58transplant and mostly work kidney
• 27:00transplant recipients as expected.
• 27:02Given that you know we mostly do
• 27:05kidney transplants in comparison
• 27:06to the other types of organs,
• 27:09an significant number of these
• 27:11patients are also an anti metabolite.
• 27:13Half and half received Pfizer
• 27:16and Moderna vaccine,
• 27:17and I think one major observation
• 27:19is that there is no observed
• 27:21acute rejection because this has
• 27:23always been controversial with
• 27:24vaccines in transplant patients,
• 27:26but that has always been debunked
• 27:28even with prior vaccine.
• 27:29As you can see on the right side on this.
• 27:34So that showed that there are
• 27:37acting minimal side effects and
• 27:39there's barely any patient who
• 27:41really develop any severe local site
• 27:44reaction or systemic adverse effect,
• 27:46in contrast to what the data
• 27:48presented by Doctor Dobel.
• 27:50So next slide.
• 27:55So the same study also evaluated
• 27:58immunogenicity of the vaccine,
• 27:59and this was published recently.
• 28:01I think less than a month ago,
• 28:04wherein they reported 658 transplant
• 28:06patients who received two doses of
• 28:09M RNA vaccine and they have followed
• 28:11these patients up to April 13 of 21,
• 28:14and they basically measured humoral immune
• 28:17response through two different platforms.
• 28:20So in this patient population,
• 28:24most of the patients had measured antibody.
• 28:27With the median dates of 29 days
• 28:30after the second dose of the vaccine,
• 28:32and only 54% of patients
• 28:35had detectable antibody.
• 28:37So this measured antibody levels were below.
• 28:40That has been historically reported in
• 28:43normal host focusing on the right table.
• 28:47The side of the decide.
• 28:49Not sure if actually it shows well,
• 28:52but patients who are age greater
• 28:54than 60 underwent long and pancreas
• 28:56transplant and had transportation
• 28:58within the last two years and maintain
• 29:01an anti metabolite were shown to
• 29:03have actually poor humoral response.
• 29:07And notably,
• 29:08there's a higher proportion of
• 29:10non immune response among those
• 29:11who received the Pfizer vaccine,
• 29:13in contrast to the Moderna vaccine.
• 29:15So the authors acknowledge that
• 29:17the limitations of the study was
• 29:19the lack of a of a control of
• 29:22immunocompetent control group,
• 29:23and lack of post vaccination.
• 29:24SARS, Kobe 2 assessment,
• 29:26which means actually,
• 29:27like really identified,
• 29:29those who develop infection and lack
• 29:32of evaluation of any memory B cell or
• 29:36T cell immune response next slide.
• 29:39So this actually just came out this
• 29:41week evaluating immunogenicity of the
• 29:44vaccine in lung transplant recipients.
• 29:47I think this is in Australia were
• 29:50in the evaluated 48 long transplant
• 29:52recipients who completed two doses
• 29:54of vaccine and no prior source
• 29:56code V2 infection.
• 29:57So they initially measured humoral
• 30:00response and they also assessed
• 30:03for SARS Co V2 specific T cells
• 30:05limited to 12 patients.
• 30:07This they explained that these
• 30:08are the patients who are in close
• 30:11proximity to the center because
• 30:12they require frequent blood draws.
• 30:14As you can see that patients had no
• 30:18detectable antibody post vaccine even
• 30:20up to six weeks after the second dose.
• 30:23An amongst the 12 patients who had
• 30:26the measure T cell response only a
• 30:30third of this patient had detectable
• 30:33T cell response after nine weeks.
• 30:36Next next day there.
• 30:38So just to mention that three out
• 30:40of 48 of these patients had mild
• 30:43COVID-19 and that is defined as
• 30:45after breakthrough infection more
• 30:47than 14 days post second dose.
• 30:51So what is our local experience in
• 30:53our solid organ transplant recipients?
• 30:55So we acted quickly,
• 30:56gathered our data so we have data
• 30:59to after the report to our patients
• 31:01who are especially very hesitant in
• 31:03accepting that, you know, vaccines.
• 31:05So we have a total of 459 patients
• 31:09who are fully vaccinated.
• 31:10That means 14 days after their
• 31:12last dose of the vaccine series.
• 31:14So this is a mix of the M RNA
• 31:17vaccine and the JMG vaccine.
• 31:19Only three patients developed.
• 31:22Breakthrough infections,
• 31:24two kidneys and one liver,
• 31:25and there mostly mild.
• 31:27One was hospitalized for non COVID
• 31:29related reasons.
• 31:30Three received monoclonal antibody.
• 31:34And they all did well with good.
• 31:36Follow up up to three
• 31:38minimum of three weeks now,
• 31:40in contrast to the general population,
• 31:43and this is based on the CDC data.
• 31:45Next, click only.
• 31:49And breakthrough infection is .001%,
• 31:52so this is a 6 on the immunocompromised
• 31:55patient has a 650 fold increase
• 31:57risk of breakthrough infection.
• 31:59Next soum there's not a
• 32:04lot of data on the stem.
• 32:07Cell transplant patients,
• 32:09and hematologic malignancy.
• 32:11But to start off,
• 32:12you know the discussion.
• 32:14I'll kind of just give a background on some
• 32:16of these patients who had acquired SARS, Co.
• 32:20V2 infection naturally,
• 32:21and there's like small case series.
• 32:24As you can see,
• 32:26there's a range of between 67%
• 32:28to 88% of patients developing
• 32:31detectable antibody postinfection.
• 32:34Next slide.
• 32:37So this is a small study
• 32:40that was after the publish.
• 32:42It's basically an abstract,
• 32:43so finer details of the study are
• 32:46not really available in this study.
• 32:49They evaluated the humoral immune
• 32:51response to M RNA vaccine in patients
• 32:53with chronic lymphocytic leukemia,
• 32:55and then the second stage of
• 32:57the study was comparing to an
• 33:00age match healthy individuals.
• 33:01So almost 167 CLL patients,
• 33:04only 39% had detectable immune response.
• 33:08And when they further sub
• 33:11analyzed the patients,
• 33:12they found that response rate
• 33:14is better amongst those who had
• 33:16achieved clinical remission after
• 33:17treatment followed by those who
• 33:19are treatment naive and those who
• 33:21are currently under treatment.
• 33:23And that's for obvious reasons that
• 33:25the under treatment obviously are receiving.
• 33:27You know email suppression.
• 33:29Next patients with BT BTK inhibitor
• 33:33and then I took clocks had acted
• 33:36poor response rate to the vaccine.
• 33:39And those who had received anti CD 20
• 33:42even up to 12 months prior to the vaccine,
• 33:45had no detectable antibody when they checked.
• 33:48Now, in contrast to the healthy controls,
• 33:50the CLL has 52% with detectable antibody,
• 33:54in contrast to the healthy controls,
• 33:56which, as with all,
• 33:58have detectable antibody
• 33:59in response to the vaccine.
• 34:04Next, slide so this is a preprint
• 34:08coming from Pittsburgh or in the
• 34:11evaluated their hematologic malignancy.
• 34:13Patients who had received two
• 34:15doses of the M RNA vaccine,
• 34:17and they excluded those who had prior
• 34:20COVID-19 vaccine and they actually very did.
• 34:24After we checked the antibodies by using
• 34:27two platforms as stated in this slide,
• 34:29they have 67 patients only 46 percent,
• 34:3446% had negative antibody.
• 34:37Result post vaccine.
• 34:43And this one day after he did further
• 34:45so kind of sub analysis of patients
• 34:48who are responders and nonresponders.
• 34:51And you can see the reach of the antibody
• 34:55response and clearly low CLL patients
• 34:58are after we have barely detectable
• 35:02antibody response in contrast to patients.
• 35:05Of who had lymphoma and multiple myeloma?
• 35:08Next one. So amongst the bone
• 35:12marrow transplant patients in
• 35:13bone marrow transplant patients,
• 35:15there's not very limited data and I
• 35:17just want to highlight what is the
• 35:19recommendation of the American Society,
• 35:21Hematology, Hematology and American Society.
• 35:25Now this is something that I always
• 35:27forget and probably still work in sign in.
• 35:30The American Society of Transport
• 35:32and Cellular Transport.
• 35:33Am I correct about that transplant,
• 35:35cellular therapy, real therapy?
• 35:38I know it's like a tongue twister,
• 35:40so the current recommendation of ash and
• 35:43asto CT is to still encourage their patients.
• 35:47It offering vaccines as early as three
• 35:49months to transplant in car T cell
• 35:52despite awareness of less efficacy
• 35:54in this patient population based
• 35:56on their experience with influenza
• 35:58vaccine and they recommend.
• 36:00If possible to delay any cytotoxic
• 36:02or B cell depleting therapies for
• 36:05two weeks after the second dose
• 36:07to allow memory T cell formation,
• 36:09an routine serologic testing post
• 36:11vaccine is unclear and they recommend
• 36:14only under a research protocol.
• 36:17I will pass on to doctor Easter.
• 36:21Thanks very much, so I'll be talking
• 36:24about the vaccine responses and several
• 36:27other immunocompromised patients.
• 36:29I'll start off with patients who have
• 36:32solid malignancies, so in one study,
• 36:34the antibody response measured by stars kovi,
• 36:37two anti spike protein,
• 36:39IgG to one dose of Pfizer developed
• 36:43and only 39% of patients with
• 36:46solid cancer as compared to 97% of
• 36:49healthy controls of note around.
• 36:5240% of patients with cancer in this
• 36:54study were actively receiving an
• 36:56anti cancer treatment within 15 days
• 36:58prior to the first dose of vaccine,
• 37:01but they went on to look at the humoral
• 37:04response to two doses of Pfizer,
• 37:06and they found that that was
• 37:07significantly improved.
• 37:08At 95% seroconversion rates,
• 37:1018 out of 19 patients with solid
• 37:13malignancies developed antibodies.
• 37:16After two doses,
• 37:17they found that the booster
• 37:19substantially increased.
• 37:20The anti spike IgG titers.
• 37:23Even in patients who had developed an
• 37:25antibody response to the first dose and
• 37:28became compareable to healthy controls,
• 37:30and in this study and others vaccine,
• 37:33the vaccine was better tolerated in
• 37:35cancer patients than in controls.
• 37:37Next slide.
• 37:39There's also been some data out of
• 37:41Israel about the safety of vaccination
• 37:44in patients on checkpoint inhibitors,
• 37:47which is a theoretical concern
• 37:48given the revving up of the immune
• 37:50system as part of the mechanism,
• 37:52and so in this study,
• 37:54135 patients on checkpoint inhibitors with
• 37:57or without chemotherapy were evaluated.
• 37:59Post two doses of Pfizer vaccination.
• 38:02The incidence of side effects was found
• 38:05to be similar in the control group as.
• 38:09For the checkpoint inhibitor group,
• 38:11as you can see here for fatigue,
• 38:12headache, muscle pain and other things,
• 38:14and a very important Lee,
• 38:16there were no new immune related side
• 38:19effects or exacerbations of existing
• 38:21immune related side side effects
• 38:24like cytokine storm for example,
• 38:26in this cohort and this included
• 38:29patients who already had a history
• 38:31of these side effects. Next slide.
• 38:33I'll talk a little bit about
• 38:35multiple sclerosis now,
• 38:36so the in one study the
• 38:39antibody response again.
• 38:41Measured by SARS,
• 38:42Kobe 2 IgG to one to two doses
• 38:45of Pfizer vaccination was 100%
• 38:48in multiple stroke sclerosis.
• 38:50Patients on disease modifying therapy,
• 38:52not on disease.
• 38:53Modifying therapy compared
• 38:55to healthy controls.
• 38:56Again,
• 38:56that sort of makes sense because
• 38:58these patients immune system
• 39:00approximates that of healthy people.
• 39:02Patients on cladribine therapy.
• 39:04It did not have decreases in vaccine humoral
• 39:07response which was which was encouraging.
• 39:10However,
• 39:10the median last dose of cladribine was
• 39:13four to five months prior importantly,
• 39:16and this is a theme that has
• 39:18already been mentioned and will
• 39:20be evident in my future slides.
• 39:22Is that antilymphocyte therapy is
• 39:24like fingolimod Enoch Oralism AB
• 39:26which are used in this population,
• 39:28were associated with significant
• 39:30decreases in humoral response to
• 39:33vaccination only 3.8 and 22%.
• 39:35Of patients,
• 39:37respectively developed
• 39:38antibodies while on these.
• 39:41Therapies M RNA and ginger vaccines
• 39:43were safe and there have been no clear
• 39:47reports of increased risk of Ms relapse
• 39:50and per consensus recommendations.
• 39:53There are no preferred vaccines
• 39:55for this population.
• 39:56Next slide. For patients with
• 40:00rheumatologic and musculoskeletal
• 40:02disorders like rheumatoid arthritis
• 40:04and other rheumatologic disorders,
• 40:07the humoral response to one dose of Pfizer
• 40:10or Moderna developed in 75% of patients
• 40:13with a variety of these disorders.
• 40:15Importantly again rituximab which
• 40:17is an anti CD 20 antibody led
• 40:21to much lower antibody response.
• 40:23There were only six patients in this
• 40:26study and only two out of 6 developed
• 40:29measurable antibody responses.
• 40:32In contrast, 94% of patients on TNF alpha
• 40:36inhibitors developed an antibody response,
• 40:38and so this sort of starts to show you
• 40:40that you know not all immunosuppressive
• 40:42agents are created equal.
• 40:43They really have very disparate
• 40:46impacts on antibody response.
• 40:49M RNA vaccine was safe in this population.
• 40:52There was one case report that was shared
• 40:54with me of an acute flare up of rheumatoid
• 40:57arthritis in a patient with known RA,
• 41:00and this happened 12 hours after
• 41:02their second vaccine, Pfizer dose.
• 41:04And a patient who had been in remission
• 41:07or without a flare for two years.
• 41:09So it is it is something that has
• 41:12been anecdotally and occasionally
• 41:15mentioned next slide.
• 41:17In patients with IBD,
• 41:18the humoral response to two doses of
• 41:21Pfizer or Moderna developed in 100% of
• 41:24IBD patients compared to healthy controls.
• 41:26In one study of 26 patients who
• 41:29were on either TNF alpha inhibitors,
• 41:31vandalism app and others.
• 41:33Notably,
• 41:33the titers were lower than their
• 41:36matched controls and another important
• 41:38thing is that code treatment with an
• 41:40immunomodulator like methotrexate,
• 41:42in addition to TNF alpha or vandalism AB,
• 41:45reduced response.
• 41:45As you can see in this chart.
• 41:47When when patients were in
• 41:49combined treatment,
• 41:50they had lower response rates.
• 41:52However,
• 41:52after the second vaccine dose 85
• 41:55and 86% of infliximab,
• 41:58individualism app treated
• 42:00patients seroconverted.
• 42:04After the second dose, thank you.
• 42:07Next slide, so in patients with mixed
• 42:10chronic inflammatory diseases and these
• 42:12are studies that have essentially included
• 42:15a mixture of the aforementioned patient
• 42:18populations and so less more heterogeneous,
• 42:21but basically in one study of 133
• 42:24adults with 53 immuno competent controls
• 42:27and these included IBD patients,
• 42:30Ms patients and rheumatology,
• 42:32and MSK patients.
• 42:34B cell depletion with things like rituximab.
• 42:37Exerted the strongest effect with a 36
• 42:40fold reduction in humoral responses.
• 42:43Glucocorticoids also had an impact
• 42:45around 10 fold reduction and then
• 42:48other things like methotrexate blunted
• 42:50antibody titers to a lesser extent.
• 42:53Therapy is like TNF alpha inhibitors,
• 42:55aisle 12 and 23 inhibitors and others had
• 42:58only a modest impact on antibody formation.
• 43:03Next in another study with in
• 43:05patients with mixed inflammatory
• 43:08disorders and healthy controls,
• 43:10these included patients with psoriasis,
• 43:12psoriatic arthritis, RA IBD and others,
• 43:15and they were variably on biologic or
• 43:18targeted synthetic demars conventional
• 43:20synthetic demarks or no treatments.
• 43:23None of these patients were
• 43:26on antilymphocyte agents.
• 43:27100% of controls versus in 94%
• 43:30of patients with CID0 converted,
• 43:32and so it was a good response rate,
• 43:35but.
• 43:35None of these patients were an
• 43:37anti lymphocyte agents.
• 43:38There were no differences in vaccine
• 43:40response per type of therapy in
• 43:42this study and there was a greater
• 43:44seroconversion rate to two doses of M
• 43:46RNA vaccine than a single JNJ dose.
• 43:49Next slide.
• 43:51So the take home points for the
• 43:54immunocompromised vaccine response
• 43:55sections are that M RNA Angie Angie
• 43:58vaccines are safe and immunocompromised
• 44:00populations based on available data both
• 44:04in immunocompromised and general populations.
• 44:06Reductions in vaccine immunogenicity is
• 44:09happen especially with antilymphocyte
• 44:11therapies like rituximab,
• 44:13oralism,
• 44:13AB and or went on multiple agents
• 44:16and you can see that the impact
• 44:18of anti lymphocyte agents is
• 44:20significantly greater than.
• 44:22Uh,
• 44:23other immunomodulating therapies
• 44:24like mycophenolate and it?
• 44:27Seems like TNF alpha inhibitors
• 44:29and I'll 1223 and Jack inhibitors
• 44:32seem to exert an lesser effect.
• 44:34There's no clear preferred vaccine,
• 44:36and in fact most guidelines clearly
• 44:38state that there is no preferred vaccine,
• 44:40and patients should get the one
• 44:42that they are offered.
• 44:44However,
• 44:44there are data that two doses of
• 44:46vaccine may be associated with
• 44:48greater immunogenicity,
• 44:49answer conversion rates,
• 44:50vaccines should be administered
• 44:52as soon as possible.
• 44:53In most cases,
• 44:55there are some stipulations based
• 44:57on specific guidelines like the
• 44:59American College of Rheumatology
• 45:01and then multiple sclerosis
• 45:03guidelines about timing of vaccine.
• 45:05With regards to specific immunotherapy's
• 45:07and you know you guys can look
• 45:11at specific recommendations,
• 45:13but in general as soon as possible is
• 45:16the overarching message and then it's
• 45:19still unclear if vaccines increased.
• 45:21The risk of autoimmune disease flares.
• 45:23There are some rare reports,
• 45:24so that's something to look out for.
• 45:27Next slide.
• 45:29So I'll move on to talk about
• 45:31the role of antibody testing.
• 45:32Unfortunately, this is,
• 45:33you know,
• 45:34we we were in need of much more
• 45:36data and starting standardization,
• 45:38but the general points are that
• 45:41serology for us.
• 45:42Our Scovie 2 is not currently
• 45:45recommended by multiple oversight
• 45:47sort of committees and agencies,
• 45:49including CDC, FDA,
• 45:51and the Infectious Disease Society of
• 45:54America for assessing for prior infection
• 45:57before vaccination or for assessing.
• 45:59For humoral response,
• 46:00post vaccination and the reasons
• 46:03for this are that the currently
• 46:05FDA approved their logic tests are
• 46:08qualitative or semiquantitative.
• 46:10They're not validated as quantitative tests,
• 46:13meaning that the numerical values
• 46:15generated do not necessarily
• 46:17indicate the degree of immunity,
• 46:19and so they must be interpreted with caution.
• 46:22The titers of antibody that correlate
• 46:25with protection are not currently known.
• 46:27We don't know what thresh be.
• 46:29Above what threshold we can say you're
• 46:31immune and be below that threshold,
• 46:33we can say you're not immune.
• 46:34We don't have that threshold.
• 46:36Commercial tests do not measure
• 46:39neutralizing antibodies,
• 46:40which are the strongest correlate
• 46:42of immunity.
• 46:43An in vitro studies,
• 46:44and the role of cellular immunity is unclear.
• 46:47There are data to suggest that some
• 46:49patients who do not form antibodies
• 46:51may produce a cellular immune
• 46:53response that may be productive,
• 46:54but the data is still very preliminary.
• 46:57Next slide.
• 47:00Alright, so I think. We're done
• 47:03with the actual presentations.
• 47:06Yes, thank you everyone.
• 47:08I think you did a great job outlining.
• 47:12Presentation and before we take questions.
• 47:16I would like to thank the members of the.
• 47:21The yelled, covered,
• 47:22immuno compromised working group for
• 47:25their participation in helping too.
• 47:30Organize an review.
• 47:31Our policies with regard to
• 47:33the care of these patients.
• 47:36So there are a number of questions
• 47:38that have come through on the chat,
• 47:40some of which I think have been answered.
• 47:44Maybe I can ask the rest of the panelists
• 47:46if they have anything else to add about.
• 47:48Antibody testing beyond
• 47:50Doctor Azar's comments.
• 47:51Just 'cause everyone has this
• 47:53question and I don't think anyone
• 47:55likes the answer to that question.
• 47:57No, I don't, but
• 47:58does anyone else have anything to add?
• 48:01I, I think to me the biggest
• 48:03difficulty is what does the result
• 48:06actually mean for a patient,
• 48:08and does it change what they need
• 48:10to do to protect themselves.
• 48:13And I think that's where we're kind of stuck.
• 48:17The patient has had a fair
• 48:19response or no response.
• 48:21We have no data giving them an additional
• 48:24dose of vaccine will improve that
• 48:26response beyond what they have received,
• 48:29so I think that's for that
• 48:31particular patient population.
• 48:33Obviously, additional doses.
• 48:35We don't have evidence
• 48:38that they're beneficial.
• 48:40And the other issue,
• 48:42even when patients do respond,
• 48:45you know,
• 48:46one needs to think about what is the
• 48:49relative risk of in the Community as
• 48:52well in terms of how much virus is
• 48:56present in the Community in terms of
• 48:59their risk for Community transmission.
• 49:01So I think the long and short of it
• 49:03is that immunosuppressive patients
• 49:05still need to mask social distancing limit.
• 49:10Their exposure to large groups as
• 49:15the vaccination process continues.
• 49:19In Connecticut and other states,
• 49:21we are lucky we are in a state
• 49:24that does have high rates of
• 49:26vaccination at this point,
• 49:27but until Community transmission is nil,
• 49:31there's always going to be that
• 49:33potential risk and we just don't
• 49:35have a good laboratory correlate to
• 49:37say what your risk is going to be.
• 49:41I think Jeff are wanting
• 49:43to add due to what you have said is
• 49:45one thing that we advise patients is
• 49:47that their household members should
• 49:49all be vaccinated because if there is,
• 49:51you know the risk of getting infection.
• 49:54It's always a household member
• 49:56most likely because they don't do
• 49:58the social distancing obviously,
• 50:00nor wear mask in the house and
• 50:02that's almost like impossible.
• 50:04Ask you know for
• 50:05any of the household member
• 50:06so that you know if they are,
• 50:08you know I would say some would say it's
• 50:10a cocoon. Or above protection.
• 50:13It's like, you know,
• 50:13it's the people around you,
• 50:15so I think that should be
• 50:17strongly advised to our patients
• 50:18to that they should be a
• 50:20strong advocate for themselves
• 50:21that we do know that works for influenza,
• 50:24for example. In terms of the same
• 50:28population may not respond well
• 50:30to email influencing innovation,
• 50:32but vaccinating their house sold and
• 50:35closed contents actually prevents
• 50:37them from being exposed to influenza.
• 50:41I see two questions that relate to
• 50:44the role of non Schumer or immunity.
• 50:49In COVID man, wondering if someone
• 50:52wants to try and tackle that.
• 50:54I know there's not a lot
• 50:56of not a lot of data.
• 50:58There was a recent I think it's a
• 51:01preprint and solid organ transplant
• 51:03patients that looked at both humoral
• 51:06and cellular response post vaccination.
• 51:09It was a small study.
• 51:10I don't remember exactly the number,
• 51:12but there was a proportion of patients who
• 51:17developed a measurable T cell response
• 51:21who did not develop an antibody response.
• 51:24So it was something around I think 30%
• 51:27developed an antibody response and.
• 51:30Maybe 15 or something like that
• 51:32percent of up cellular response
• 51:34and they weren't 100% overlapping.
• 51:35There were some patients who developed an
• 51:38antibody response without a set of response,
• 51:39and vice versa.
• 51:40So I think we need way more way more
• 51:42data and the role of cellular immunity is
• 51:45going to become more and more important.
• 51:47But I I don't think it's not
• 51:49measurable clinically outside of
• 51:50research a research setting right now,
• 51:53I think Marwan you're referring
• 51:54to a study that Anthony was accepted in
• 51:57American Journal Transplantation were in.
• 52:00Happy, it's mostly kidney transplant
• 52:02recipients and they said 65% of
• 52:04patients either or had humoral
• 52:06or cellular immune response.
• 52:10But I I think one take home point
• 52:12is what we have seen in terms of
• 52:15the risk of persistent and severe
• 52:18COVID infections in the MENA.
• 52:20Suppressed population really has been
• 52:23the patients who received the cell
• 52:26depleting therapy and the profound impact
• 52:29that has had on the illness itself.
• 52:34So in this particular viral disease
• 52:37does seem to appear that the humerus.
• 52:40Bonds is a critical part of
• 52:43controlling the virus.
• 52:48OK, there's also a question
• 52:50regarding the timing of vaccination
• 52:53relative to therapies such as
• 52:55infliximab and other agents.
• 52:58I and I know we do have some
• 53:00policy's or recommendations.
• 53:04I can touch upon that and then maybe
• 53:06I don't Jeff who was looking at our
• 53:09internal policies can comment more.
• 53:11But at least in looking at the American
• 53:14College of Rheumatology guidelines,
• 53:16they do come up with predominantly expert
• 53:20opinion based recommendations on timing.
• 53:23But what they recommend for TNF alpha
• 53:25inhibitors is to proceed with vaccination
• 53:28without altering the time of infusion.
• 53:31And I think that is reflected
• 53:32in the data that I shared,
• 53:34which is the TNF alpha inhibitors.
• 53:36Have only a modest impact at
• 53:38seemingly at least at the hospital.
• 53:40Now on vaccine seroconversion.
• 53:42So at least for that class,
• 53:45it seems like you can move forward.
• 53:47They do have recommendations for you know,
• 53:50every every group of different agents.
• 53:52And, for example, with the toxin AB,
• 53:54which is the one that is has been shown to
• 53:56most predominantly impacts their conversion.
• 53:59They do recommend vaccinating at four
• 54:01weeks before the rituximab infusion,
• 54:04for example,
• 54:04and so they have they have
• 54:06specific recommendations,
• 54:07but Jeff,
• 54:07maybe you can talk about.
• 54:09So very difficult topic because some
• 54:13disease stage you can delay exposure to.
• 54:19Shouldn't such as rheumatoid arthritis
• 54:21and methotrexate given weekly,
• 54:23so you should try to hold a
• 54:27methotrexate for one to two weeks.
• 54:31After vaccination to really
• 54:33allow the usual immune response
• 54:37mechanisms developed through an,
• 54:40it's probably not unreasonable.
• 54:42Other immunosuppressive agents where you can
• 54:45do that that they're given intermittently.
• 54:49The more difficult issue,
• 54:51or really the patients who are on
• 54:55Riverside depleting medications.
• 54:58And, for example,
• 54:59we talk some AB has a profound of.
• 55:02In fact, for many many months,
• 55:05six months in most patients
• 55:07number and some others,
• 55:10and many patients cannot
• 55:12delay therapy that long.
• 55:13I eat too informal population so it does
• 55:18become really based on each an agent.
• 55:21What can be done in terms of is
• 55:24there a window that may allow the
• 55:27normal immune response to occur?
• 55:30The VSL depleting agents though
• 55:32you may make an immune response.
• 55:34Once I give you a piece of
• 55:36depleting agent again.
• 55:37I'm gonna lower your antibiotic
• 55:40production significantly.
• 55:41So what I think is different in this
• 55:45particular vaccine issue is that remember,
• 55:48this is a novel antigen that most
• 55:52individuals have not seen before.
• 55:54So unlike many other vaccines where
• 55:57we've been exposed previously during
• 56:00childhood and during adulthood,
• 56:02in terms of routine vaccination and
• 56:04then becoming little suppressed,
• 56:06this is kind of a different paradigm.
• 56:12OK, there is. There is a
• 56:14question about any data on
• 56:16response to vaccination
• 56:17in the HIV population.
• 56:22In terms of pure data,
• 56:24we have if the patient is
• 56:26well controlled on a RT,
• 56:29we do see significant
• 56:31responses to vaccination.
• 56:33Again, it really would be the
• 56:35level of the mirror suppressions.
• 56:38Those who have low CD,
• 56:394 count and uncontrolled disease
• 56:42would be higher risk of non response.
• 56:48OK, and then there's a another question
• 56:51that I thought interpreting this correctly.
• 56:54In patients with the MALIGNANCY'S who
• 56:57developed COVID infection but need to
• 56:59continue in their suppressive agents,
• 57:01is there a role for the this?
• 57:04Is antivirals, I think maybe
• 57:07it's the the antibodies.
• 57:09Is in this is this is a tough
• 57:12good question I think.
• 57:14How should those patients be treated?
• 57:15Doctor told was not in 'cause he knows.
• 57:17I asked him about this morning.
• 57:19Very common question.
• 57:21It does make sense that the monoclonal
• 57:24antibodies that we have to treat
• 57:27actual COVID mild to moderate
• 57:29COVID disease in outpatients.
• 57:32It would be kind of akin to what we
• 57:35do normally with Ivy IG populations
• 57:37try to prevent bacterial infections.
• 57:40The problem is our hands are really tight
• 57:43because these monoclonal antibodies.
• 57:45Or under the FDA.
• 57:47E Ray, which limits which patients
• 57:50we actually could prescribe them to,
• 57:53we actually have to keep track of every
• 57:55patient we administer the medication to,
• 57:58because these medications are
• 58:00provided by the federal government
• 58:03and subject to audit of their use.
• 58:05So if the drugs were FDA approved and
• 58:09then we'll talk about off label use,
• 58:11that would be a very different story,
• 58:13but unfortunately they don't have an FDA.
• 58:16Label yet, so we can't even do off label use.
• 58:27So there's a question about. Strategy
• 58:31if someone has a a bad
• 58:34reaction to the first vaccines.
• 58:37And can't take the second dose.
• 58:41It's not really defined
• 58:42what a bad reaction means.
• 58:43Obviously anaphylactic reaction
• 58:46would necessitate avoiding
• 58:49further administration.
• 58:52I would would anyone recommend
• 58:55switching to the J&J if someone
• 58:58only got one of the Madonna or
• 59:01Pfizer's or just there was paper
• 59:03that came out in The Lancet recently
• 59:05about sort of crossing over with
• 59:08different types of vaccines and they
• 59:10actually showed that the incidence
• 59:12of side effects was higher in
• 59:14patients who got a second booster
• 59:16dose of a different type of vaccine.
• 59:19So based on that study which I
• 59:21think just came out last week.
• 59:22I would not advise necessarily
• 59:24going to a different vaccine unless
• 59:27there's a very particular component
• 59:29of a vaccine that can be clearly
• 59:32identified and isolated as the cause.
• 59:35But you know in terms of general
• 59:37reactions that that was one sort of
• 59:40take home point from that paper that
• 59:42you know people who got AstraZeneca,
• 59:44and I think it was Pfizer.
• 59:47Did sort of had worse side effects.
• 59:50The other thing that was clear or
• 59:53that seemed to be a take home point
• 59:56from the review of like non assaultive
• 59:59patients with who got the vaccine is
• 01:00:03that immunocompromised patients tend to
• 01:00:05have lower incidences of adverse events.
• 01:00:08So that is one sort of positive
• 01:00:10of of being immuno compromised.
• 01:00:12So hopefully it's a less of a
• 01:00:14problem in your populations.
• 01:00:17OK, I think we have time for
• 01:00:19one or maybe two more questions.
• 01:00:21There is a question about the
• 01:00:24myocarditis cases in young men.
• 01:00:26Any comments on this? A towel.
• 01:00:31Make one comment, I'll let.
• 01:00:33I'll let probably I think in see your doctor,
• 01:00:36doctor Topel comment and that is just
• 01:00:40to ask that people take was reported in
• 01:00:43the media with the understanding that
• 01:00:45millions and millions of people are
• 01:00:48getting vaccinated an idiosyncratic or
• 01:00:50rare side effects are always going to occur.
• 01:00:53We're just hearing about
• 01:00:54from more than we used to.
• 01:00:55But with that said,
• 01:00:56this seems to be a real thing.
• 01:00:58It can see.
• 01:00:59Do you want you want to comment there?
• 01:01:01Really nice that you left.
• 01:01:03Easiest question at the end and I
• 01:01:05will go first so that Jeff at doctor
• 01:01:08to Palkin complete what I miss.
• 01:01:10So we have been talking about
• 01:01:11it more than a month now.
• 01:01:13We do see cases specifically with the
• 01:01:15younger adults and now vaccinating
• 01:01:1712 and older with Pfizer vaccine.
• 01:01:20But this was already report has been
• 01:01:23reported by Israel where they vaccinated
• 01:01:25millions of people around like 5,000,000.
• 01:01:28They do not vaccinate.
• 01:01:3112 to, you know they don't
• 01:01:33use the pediatric vaccine.
• 01:01:34But they did have a round six the cases
• 01:01:36out of five million that they gave.
• 01:01:38Also U.S.
• 01:01:39Army had air and like high teens in
• 01:01:43like hundreds and hundreds of billions.
• 01:01:46I think they get.
• 01:01:48They get like 130 million doses and
• 01:01:51then they serve that much myocarditis.
• 01:01:53What we have been observing over
• 01:01:56the last two weeks is these
• 01:01:59myocardial carditis cases do happen.
• 01:02:02They both M RNA vaccines.
• 01:02:05They do happen after the first
• 01:02:07dose or the second dose.
• 01:02:10They do tend to happen within first week,
• 01:02:14mostly within four days of the vaccination,
• 01:02:17and so far almost all of the
• 01:02:19cases had been mild and they're
• 01:02:22back to their normal lives.
• 01:02:24We do not know if it is an autoantibody
• 01:02:27antibody induced reaction so far,
• 01:02:30but if you look at what the Late
• 01:02:32Show put out two days ago about the
• 01:02:34vaccine safety and what CDC put out.
• 01:02:36Today it is we will observe
• 01:02:39and see how it goes,
• 01:02:41but currently the recommendation
• 01:02:42is vaccination for 12 and older as
• 01:02:45it has been for the last two weeks.
• 01:02:50Thank you, thank you. That's really,
• 01:02:52I think important perspective to have
• 01:02:55about the incidence of potentially
• 01:02:57significant side effects from vaccination.
• 01:03:01I think what we need to keep in mind
• 01:03:04is we're looking at for extremely
• 01:03:07rare events in vaccinating 10s to
• 01:03:11hundreds of millions of individuals.
• 01:03:14And I think our surveillance systems
• 01:03:16that are in place at multiple levels.
• 01:03:19Or really. Working well to pick
• 01:03:22these things up and to allow
• 01:03:24further investigation an I think
• 01:03:26you just have to recall back in,
• 01:03:29you know, 1976,
• 01:03:31when the federal government came up
• 01:03:34with the swine flu vaccine and we first
• 01:03:37saw a link between swine flu vaccine
• 01:03:41and Guillain Barre syndrome that really
• 01:03:45kind of print these type of vaccine
• 01:03:49side effects on people's radars.
• 01:03:51And again, there is even,
• 01:03:54you know,
• 01:03:55today risk of gambare post vaccination
• 01:03:59of different vaccines at different
• 01:04:01rates or be extremely low.
• 01:04:03So I think the message is we should
• 01:04:07vaccinate and watch patients
• 01:04:09look for these signals.
• 01:04:12And again the good news is the
• 01:04:14majority of these individuals
• 01:04:15these rare individuals have done
• 01:04:18quite well after vaccination.
• 01:04:23OK, I well, so lots of great questions
• 01:04:27that obviously illustrates what we
• 01:04:29will be knowing what we we don't know.
• 01:04:33So I thanks everyone for joining us.
• 01:04:36Thanks to the panelists and the
• 01:04:40link from the Flyer still has
• 01:04:41an address of people have other
• 01:04:43questions that they would like to
• 01:04:44send in that we can try and answer.
• 01:04:49And with that will say goodnight.