UPDATES*: COVID-19 Vaccines - Jennifer Mbuthia, MD FAAAI, FAAP, Diplomate in Clinical Informatics Queen's Health System Allergist/Clinical ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
UPDATES*: COVID-19 Vaccines
Jennifer Mbuthia, MD
FAAAI, FAAP, Diplomate in Clinical Informatics
Queen’s Health System
Allergist/Clinical Immunologist & Clinical Informaticist
(*As of 13 September 2021)
Disclosures • I have no conflicts of interest. • I am not an infectious disease doctor or a virologist. • I love vaccines and I have spent a decade doing adverse event evaluations, too. • Discussion of off-label or use beyond the EUAs is beyond the scope of this talk.
Comparison of Current COVID-19 Vaccines
Sinovac;
Pfizer-BNT Moderna JNJ/Janssen AstraZeneca Novavax
Sinopharm
• mRNA in LN • mRNA in LN • dsDNA in • dsDNA in • Protein sub-unit • Whole-
• 2 doses, 3 weeks • 2 doses, 4 weeks Adenovector Adenovector • 2 doses, 3 inactivated virus
apart apart (human Ad26) (chimpanzee) weeks apart • 2 doses
• 95% efficacy to • 94% efficacy to • One dose • 2 doses, 4-12 • Proprietary • 50-84% efficacy
COVID (original) COVID (original) • 66% efficacy to weeks apart adjuvant used but different
• 64-88% effective • Likely similar Delta COVID (original) • 70-80% efficacy (Matrix-M) trials showing
Delta variant protection to • USA: 72% to COVID • 90% efficacy higher rates
(unclear Pfizer • SA: 57% (Original) • Phase 3 started • Both w/WHO
• FDA Licensed, • EUA, 18 YO and • 85-100% against • 100% against in DEC, ?EUA emergency
16YO and older older severe disease severe disease thus summer? authorization
• EUA 12-15YO • Contains PEG • 60% to Delta For 18YO & up (June/May
• Good Delta
• Contains PEG infection, 90% • Prioritized 2021)
• 3rd dose approved protection
for immune hospitalization enrollment for
• 3rd dose approved • EUA, 18YO & older
compromised • Phase 3 in US diverse
for immune • Contains
18YO & up ethnicity &
compromised • 8-month booster polysorbate 80 medical
• 8-month booster recommended • Phase 3 2-dose • Widely used in
conditions
recommended trial currently Europe & Canada
• Sub-study on
• Contains
Flu coadmin.
Polysorbate 80
Available in US (Pfizer FDA licensed, Moderna/JNJ under EUA)
LN = lipid nanoparticle; PEG = Polyethylene Glycol; Sputnik V vaccine also uses 2-dose human Adenovector & reporting >90% efficacy
WHO-Approved Vaccines Under Emergency Use
• Pfizer-BioNTech COVID-19 vaccines (e.g., COMIRNATY, Tozinameran
• AstraZeneca-Oxford COVID-19 vaccines (e.g., Covishield, Vaxzevria
• Janssen (Johnson & Johnson) COVID-19 vaccin
• Moderna COVID-19 vaccin
• Sinopharm COVID-19 vaccin
• Sinovac-CoronaVac COVID-19 vaccin
• Anybody who has received the 2 doses (1 dose for J&J) of a similar vaccine can
be considered fully vaccinated
• Pfizer and Moderna are considered similar enough that if 1 dose of each already
received, consider fully vaccinated.
e
e
.
e
e
)
)
The Envelope and the Blueprint
i ke
Sp ein s
ro
P ct
t
i o n • Pfizer and Moderna vaccines use mRNA in a
ru
Ins
t lipid nanoparticle
• JNJ and Astra Zeneca use DNA in an inactivated
Adenovirus particle
How Current US COVID Vaccines Work
The Spike protein
and fragments are
then seen by the
immune system.
i ke
Sp ein s
r o t on
P cti Inflammation
t ru
I n s happens, causing
immune memory to
happen.
The mRNA and
adenovector
CELL MAKES S-PROTEIN vaccines have a final
AND FRAGMENTS
common pathway.
VACCINE: mRNA
or DNA + Envelope
PATIENT
Vaccine Mixing and Co-Administration with Other Vaccines
Co-Administration and TB Testing Considerations
• COVID-19 vaccines and other vaccines may be administered without regard to timing.
• Includes simultaneous administration of COVID-19 vaccine and other vaccines on the
same day, as well as co-administration within 14 days.
• It is unknown whether reactogenicity of COVID-19 vaccine is increased with co-
administration, including with other vaccines known to be more reactogenic, such as
adjuvanted vaccines or live vaccines.
• If multiple vaccines are administered at a single visit, administer each injection in a different
injection site (specifically, give COVID vaccine at a different site from other vaccines
• Testing with TB skin test or serum test can be done before, after, or at the same time as
COVID-19 vaccination. This recent change aligns with guidance about other inactive
vaccines and TB testing.
)
Interchangeability of Vaccines
• If 1st dose mRNA vaccine product given is unknown or unavailable, another mRNA
COVID-19 vaccine given 28 days later should be considered fully immunized.
• If vaccine series started overseas with a WHO-approved COVID-19 vaccine that is NOT
available in the US, current guidelines are to administer a complete vaccine series with
available US COVID-19 vaccine (minimum interval 28 days from last dose given overseas)
• Example: Patient got dose 1 of AstraZeneca in Canada and moved to Hawaii before
dose #2, would need to receive 2 doses of mRNA vaccine or 1 dose of J&J/Janssen
vaccine to be considered fully immunized
Interchangeability of Vaccines
• Intentional Mix-and-Match vaccination studies showing excellent immunogenicity but
higher reporting of local and systemic side effects.
• German Studies: vaccine interval of 10-12 weeks between doses of AZ and P izer compared to
P izer-P izer 3 weeks apart
• Excellent immunogenicity from heterologous series
• Heterologous vaccine series had slightly higher frequency of local reactions, but lower
report of systemic reactions (fever, chills, myalgia, etc) in one study and higher in another
• UK Study: Compared AZ-AZ, AZ-Pf, Pf-AZ, and Pf-Pf (dosed either 4 weeks or 12 weeks apart)
• Data so far showing slightly higher immunogenicity with heterologous schedule, but also
higher reactogenicity
• References at end of presentation
f
f
fCOVID Vaccine Safety Concerns
Anaphylaxis & COVID-19 Vaccines
• The only true contraindication to getting a COVID vaccine is history of anaphylaxis to
that vaccine or a vaccine component.
• Anaphylaxis after COVID-19 vaccines is rare (approx. 5 per 1 million doses), and easily
managed with epinephrine (same management as food or insect sting anaphylaxis)
• Emergency Mgt: If immediate objective symptoms are not quite itting anaphylaxis,
order serum tryptase
• Don’t need to prescribe home epinephrine autoinjector; these cases should all be
evaluated by an allergist
fAnaphylaxis & COVID-19 Vaccines
• Polyethylene glycol (PEG) is in both mRNA COVID-19 vaccines, and Polysorbate 80 is in
J&J/Janssen COVID-19 vaccine (and AstraZeneca vaccine).
• PEG & Polysorbate 80 are structurally related, and cross-reactive hypersensitivity
between these compounds may occur.
• Anaphylaxis to mRNA vaccine or PEG: precaution, but may receive J&J/Janssen COVID
vaccine
• Anaphylaxis to J&J or Polysorbate 80: precaution, but may receive mRNA COVID
vaccine
• Consider allergy consult for patients with history of anaphylaxis to medications
containing PEG or Polysorbate 80 (very rare)Vaccine-Induced Thrombosis with Thrombocytopenia (VITT) • Safety concern for J&J/Janssen vaccine, esp in females
Myocarditis/Pericarditis After mRNA Vaccination • Predominantly young males, age 12-29 YO, and more common after dose #2
Myocarditis/Pericarditis After mRNA Vaccination
• Important to rule out other potential causes of myo/pericarditis to include COVID infection and other
viral etiologies (enterovirus, comprehensive respiratory panel)
• Unclear if people who developed myocarditis or pericarditis after a irst dose of an mRNA COVID-19
vaccine may be at increased risk of further adverse cardiac effects following a second dose of the vaccine.
• Until additional safety data, experts recommend deferring second dose or additional COVID-19
vaccine doses
• History of myocarditis or pericarditis unrelated to mRNA COVID-19 vaccination:
• May receive any FDA-authorized COVID-19 vaccine after the episode of myocarditis or pericarditis
has completely resolved.
• This includes resolution of symptoms and no evidence of ongoing heart inflammation or sequelae
• Decision to vaccinate should be a shared decision with patient/parent and PCP or cardiologist
fGuillain-Barre Syndrome and J&J/Janssen COVID-19 Vaccine
• 13 July: FDA statement regarding investigation of 100 cases of GBS following
vaccination with J&J/Janssen COVID Vaccine (similar safety signal identi ied for AZ
vaccine)
• 95 initial US cases were serious and required hospitalization, 1 death
• Average onset was 14 days after receiving vaccine
• No similar signal from mRNA vaccines
• Onset appear to be within 2 weeks from receipt of vaccine
fOther COVID Vaccination Concerns
Third Dose mRNA Vaccine
• Two distinct categories fall under this topic
• Supplemental dosing for moderate to severely immune compromised
• Booster dose for otherwise immunologically intact people
• Currently, no of icial guidance has been provided for patient who received J&J
vaccine
fImmunode icient Patients and COVID-19 Vaccine Response
• Source: CDC Presentation at ACIP https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/06-COVID-Oliver-508.pdf
fQualifying Conditions Specifically Listed by CDC
• Active treatment for solid tumor and hematologic malignancies
• Receipt of solid-organ transplant & taking immunosuppressive therapy
• Receipt of CAR-T-Cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppressive therapy)
• Moderate or severe primary immunodeficiency (e.g., DiGeorge Syndrome, Wiskott-Aldrich syndrome)
• Advanced or untreated HIV
• Active treatment with:
• High dose systemic corticosteroids ( >/=20mg prednisone or equivalent per day) - or >2mg/kg per day)
• Alkylating agents (cyclophosphamide)
• Antimetabolites (azathioprine, 6-MP, MTX)
• Transplant-related immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil)
• Cancer chemotherapeutic agents classified as severely immunosuppressive
• TNF blockers (etanercept, adalimumab, certolizumab pegol, golimumab, infliximab)
• Other biologic agents that are immunosuppressive or immunomodulatory (thymoglobulin, alemtuzumab, rituxumab)Medical Conditions with Varied Immunodeficiency
& Not Specifically Mentioned
• Asplenic patients, including those with Sickle Cell Disease
• Chronic dialysis patients; End Stage Renal Disease
• Chronic Liver DiseaseConditions Without Significant Immunologic
Compromise
• Short term daily steroids, or daily therapy 1 month since stopping high-dose systemic steroids
• HIV patients without severe immunosuppression (usu based on CD4+ T-cell
counts)
• Autoimmune conditions that are stable and not being treated with
immunosuppressive or immunomodulatory medicationsTo Boost or Not to Boost?
• Vaccine effectiveness: does it wane over time, and what endpoint are
you looking at?
• VE against COVID infection vs VE against hospitalization/death
• Is a booster dose safe?
• Does booster dose improve VE against Delta variant?
• It is COMMON for inactive vaccines series to require multiple doses,
including a dose around 6 month point.
• Bump, set, spike (volleyball analogy): that last “hit” can give better
duration for protectionWaning Vaccine Protection
• Study in US shows vaccine ef icacy for mRNA vaccines started to wane
between 5-6 months (overlapping with rise of Delta variant in US).
• P izer ef icacy showed greater decline at 6 months against COVID
infection
• Both mRNA vaccines showed strong ef icacy against hospitalization
(~75%).
• BOTH vaccines showing decline. P izer and Moderna both requesting
approval for 6 month booster dose, but White House has said booster at 8
months for all (except J&J vaccines).
• https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v1.full.pdf
f
f
f
f
fWhat does this mean in terms of booster dosing?
• Risk-based boosting? ACIP currently looking at 3 high-risk groups
• Long-term Care facility residents
• Healthcare workers
• Elderly (>65 and >75 groups)
• Continued priority: vaccination of the unvaccinated
• Overall vaccine priority endpoint is still preventing severe disease, hospitalization,
and death.
• Literally, news about this likely to happen later this week.Additional Key Clinical Pearls
• Antibody testing post-vaccination is NOT recommended
• Vaccine response includes memory T cells, Memory B cells, and Plasma cells
(make antibodies)
• Antibody levels are only one component…and the speci ic correlates of
immunity are still not fully understood.
• The primary goal is to prevent hospitalization and death: CD8+ and CD4+ T
cells are MORE important in preventing this…and there is no commercial test
for T cell memory.
• VAERS reporting is important & V-Safe is available for parents to enroll their child.
• Vaccination is still CRITICAL for everybody who is eligible.
fQuestions?
• Submit cases to VCAC by using RL
reporting system or emailing clinical
information to VCAC@queens.org
• Clinical consults can be submitted to
Post-COVID Care Clinic (or faxed by
using form on Queen’s Post-COVID
Care Clinic webpage).
• Telehealth available to include NH
and MGHReferences for Heterologous Vaccine Schedules •Liu, X. et al. Preprint at SSRN https://doi.org/10.2139/ssrn.3874014 (2021). •Hillus, D. et al. Preprint at medRxiv https://doi.org/10.1101/2021.05.19.21257334 (2021). •Schmidt, T. et al. Preprint at medRxiv https://doi.org/10.1101/2021.06.13.21258859 (2021). •Shaw, R. H. et al. Lancet 397, 2043–2046 (2021).
You can also read
