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

May 28, 2021

Information

Hosted by Dr. Stuart Seropian

Presentation by: Drs. Jeffrey Topal, Maricar Malinis, Marwan Azar, Inci Yildirim, and Lisa Barbarotta, RN

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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.