COVID-19, Vaccines, Prevention

by Editorial Board last updated 2021-11-22 10:16:13.287497-05:00
COVID-19 Post-exposure Prophylaxis, Primary Prevention, Vaccines

Post-exposure Prophylaxis

  • Primary prevention / post-exposure prophylaxis for previously uninfected household contacts:
    • Administer 1200 mg REGEN-COV (600 mg Casirivimab + 600 mg Imdevimab ) subcutaneously one time
    • Relative risk reduction 81.4% relative risk reduction in COVID-19 infection (N Engl J Med, Aug 4, 2021)

Vaccine Preferences (US)

  • Jump to Vaccine Table
  • Important Note August 2021:
    • Other than hypertransmissibility and high peak viral loads, current understanding of SARS-CoV-2 infection with the currently predominant Delta variant, is incomplete.
      • Most knowledge of clinical, epidemiologic, therapeutic, and diagnostic aspects of infection and COVID-19 are based on studies done in the pre-Delta era and most recommendations based on references that pre-date Delta should be interpreted in that context. 
      • We will continue to update COVID-19 information and recommendations based on new developments.
  • Vaccine Efficacy Against the Delta Variant
    • Studies from a number of countries and a number of settings as well as CDC data consistently show that vaccination with mRNA vaccines continues to provide more than 85% overall protection against hospitalization and death in the setting of delta variant predominance.  Observational data from Israel (subject to confounding) though detailed and robust remains an outlier.
    • VE of mRNA vaccines against any symptomatic infection with the delta variant has widely varying estimates (42%–88%) but shows a clear downward trend in protection from mild infection especially at 6 months.
      • Observational data from multiple countries are difficult to compare because of varying protocols on eligibility for COVID-19 testing post-vaccination and introduction of different vaccines in different order in the evolution of the pandemic in that country.
      • Data from South Africa, however, indicates a vaccine efficacy (VE) for the Janssen/J&J vaccine of only 71% against hospitalization due to the delta variant and 1 US cohort (CDC MMWR) indicates a VE of only 60% against hospitalization in the delta era.
  • Breakthrough infections in fully vaccinated persons 
    • Hospitalization and death in the delta variant era are extremely rare in fully vaccinated persons, and reliable population-based data in every country with suitable surveillance confirm this.
      •   In several different international populations, delta-variant breakthrough infections appear to occur in less than 0.5% of vaccinated persons (up to 1% in HCW) and less than 10% of hospitalized patients (> 65% immunocompromised) are fully vaccinated.
      • Deaths in breakthrough cases have almost all been in persons aged > 75 years. Most breakthrough infections are mostly mildly symptomatic though may not resolve fully for up to a week. 
    • Delta variant results in peak viral loads 1,000 times higher than the alpha variant and is equal between vaccinated and unvaccinated persons, but virus is cleared more rapidly in vaccinated persons.
      • The delta variant has been estimated by CDC to have an R0 of 5 to 7
    • Current incidence of breakthrough infections in the US is difficult to determine 
      • At present, US CDC is collecting data only on breakthrough infections severe enough to result in hospitalization and death and is only reporting relative proportions of cases in unvaccinated versus vacinnated cases.  
  • Bottom-line vaccination messaging for the three vaccines currently approved in the US (Pfizer, Moderna, Janssen/J&J) is that each:
    • Effectively eliminates the risk of COVID-19 death; rare breakthrough deaths median age >80
      • Nearly eliminates the risk of hospitalization.
      • However one recent US study indicates VE against hospitalization by vaccine (delta era): Moderna 95%, Pfizer 80%, J&J 60%.
    • Partially reduces the ability to infect somebody else but not to the extent to which transmission blocking occurred in the pre-delta variant era.
    • High rates of protection against delta requires completion of full 2-dose series with mRNA vaccines.
    • Vaccine induced levels of neutralizing antibodies appear to remain large enough that even significant drops with time to date remain protective against hospitalization and death.  The data in this regard is less robust with non mRNA vaccines.
      • A third vaccine dose in immunocompromised persons is not a booster but rather an additional primary dose to induce initial immunity in those unable to achieve it in the first place.
        • Dose 4 in this population is now recommended.
    • See table for complexities of timing and dose of booster regimens for each vaccine. 
      • Duration of protection induced by dose 3 boosters in indicated populations is not yet known.
    • In the delta variant era vaccination reduces transmission by 28-63% in household settings depending on scenario and study design.
      • On average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population (in the current case children younger than 16 years) decreased approximately twofold. www.nature.com/articles/s41591-021-01407-5.
  • Current vaccine preference considerations:
    • Direct in vitro comparison of vaccines. Functional antibody testing with a panel of 9 SARS-CoV-2 viral variant spike proteins (n = 196 subjects) revealed marked differences in vaccine responses 2 to 3 months after full vaccination in Mongolia. 

      • For example, low-blocking antibody levels were stimulated by the Sinopharm (15%), Gamaleya (26%), and AstraZeneca (38%) vaccines in comparison to the Pfizer (88%) vaccine.  Vaccine efficacy (VE) cannot be extrapolated from these data and vaccinees were enrolled retrospectively.

    • Substantial data indicate that the Moderna vaccine has both a VE and durability advantage over the Pfizer vaccine (likely due to the higher mRNA dose in the primary series), and that a single dose of Janssen/J&J vaccine is inadequate. Comparison data after the 3rd dose (6-month booster) of mRNA vaccines are not yet available
      • Two primary doses of an adenovirus vectored vaccine (Astra Zeneca or Janssen) are robust in preventing severe disease in the short run, but given an mRNA vaccine for dose 2 is a significantly superior strategy. 
      •  Adenovirus vaccines are progressively less favored by guideline making bodies in countries where vaccine supplies are ample. 
    • Sinovac Vaccine:
      • RCT from Hong Kong of a third dose of the Sinovac vaccine (n = 40) versus the Pfizer vaccine (n = 40) in nonresponders to 2 doses of the Sinovac vaccine (age range: 34-73 years).
        • The Pfizer vaccine elicited significantly higher neutralizing antibodies (nAbs; 95% against delta variant)  than the Sinovac vaccine (49% against delta variant).

Approved Vaccines

  Pfizer-BioNTech Moderna Janssen - J&J
Oxford-AstraZeneca SinoVac  Sinopharm Gamaleya
Vaccine

Pfizer-BioNTech COVID-19 Vaccine (Comirnaty, mRNA BNT162b2)

Moderna COVID-19 Vaccine (Spikevax or mRNA-1273) Janssen COVID-19 Vaccine
Janssen/Johnson & Johnson
(Ad26.COV2.S)
Vaxvevria or COVID-19 Vaccine AstraZeneca
(AZD1222 or
ChAdOx1, Covishield (India)).
CoronaVac SinoVac Biotech Co. BBIBP-CorV.
Sinopharm/Beijing
Institute of Biological Products
Sputnik V (Gam-COVID-Vac)
Gamaleya Research
Institute
Authorized for Use in US FDA (full approval), Health Canada, EU
EMA, UK, WHO EUL, Australia TGA
US FDA, Health Canada, EU EMA, UK, WHO EUL, Australia TGA

US FDA, Health Canada, EU EMA, UK, WHO EUL, Australia
TGA

 

 

Health Canada, EU EMA, UK, WHO EUL, Australia TGA, FDA
EUA application date now uncertain.
WHO EUL WHO EUL Russia. EMA application under review
Age

≥ 12 yrs in US/Canada/EU. ≥ 18yrs
elsewhere. 5-11 year old authorization in pediatric dose (10 μg). Age <5 yrs EUA unlikely until 2022.

≥ 18 yrs in USA. ≥ 12 yrs in Canada/EU.
Enrollment for age 12-17 trial complete with 100% efficacy (US EUA expected Q3 2021)

≥ 18 yrs. Trials for age 12-17 yrs
ongoing

≥ 18 yrs. Trial for age 12-17 yrs currently paused. Many countries not using in adults under 60 due
to thrombosis AE.
≥ 18 yrs ≥ 18 yrs ≥ 18 yrs
Type Lipid nanoparticle (LNP) encapsulated mRNA Lipid nanoparticle (LNP) encapsulated mRNA Non-replicating adenovirus vector Nonreplicating chimpanzee adenovirus vector Inactivated Inactivated Nonreplicating live
adenovirus
Overall Efficacy against symptomatic disease in Phase 3 trials pre-delta.
Specific VE data against beta, gamma no longer relevant.
95% 94.1% 76% (US trial); 66.9% (US, Brazil,
South Africa combined)
76% (US trial; n=33,000). 62%
based on UK approval using other
heterogeneous results from
multiple combined trials. 82.4% if
dose 2 given >12 weeks after
dose 1.
67% (WHO EUL
analysis)
78% (WHO EUL
approval analysis)
91.6% in 1 published but
highly criticised study. EMA review began March
4, 2021 with no approval to date; much standard
data parameters yet to be submitted. EMA WHO inspection found 1 plant
with quality issues. Seed strain uncharacterized.
Real-world overall efficacy against hospitalization,
observational data,
subject to confounding
VE by vaccine (delta era): against
hospitalization Moderna 95%, Pfizer 80%, J&J 60%. Several non-CDC US studies with VE against delta hospitalization >90% at 6 months. 94% in >1 million Israelis with
predominant alpha. 2-doses have 88% VE against delta and 93% VE against alpha. Variety of international trials vary from 40-88% against infection with delta variant when followed for 6 months or more clear downward trend over time since vaccination past 6 months. Waning immunity against
hospitalization for delta only definitive for >65 years of age.
VE by vaccine (delta era): against
hospitalization Moderna 95%, Pfizer 80%, J&J 60%.VE was 87.4% against infection, 95.8% against hospitalization, and 97.9% against death. VE was higher against symptomatic (88.3%) versus
asymptomatic infection (72.7%) but was
generally similar across age, sex, and racial/ethnic subgroups. Pre-delta: ~90%
against hospitalization, ICU admission, or
an ED visit. similar for both mRNA vaccines. VE from 81% to 95% among
adults aged ≥ 85 years, persons with chronic medical conditions, and black or Hispanic adults. Waning immunity against
hospitalization for delta only definitive for >65 years of age.
VE by vaccine (delta era): against
hospitalization Moderna 95%, Pfizer 80%, J&J 60%. Poor
efficacy of Janssen/J&J in South
Africa. Waning immunity against
hospitalization for delta very significant for >65 years of age.
60% VE against symptomatic
disease from delta, compared to 66% VE against alpha.
     
Efficacy Age >65
(Phase 3)
94.7% 86.4%. Real world: VE from 81% to 95%
among adults aged ≥ 85 years, persons
with chronic medical conditions
66.10% 85% Little data for age > 60 yrs Little data for age > 60 yrs 92% in age > 60 yrs
Pediatric Efficacy
(Phase 3)
100% in age 12-15 yrs, higher neutralizing titers than age 16-25 yrs. Two doses spaced by 21 days showed comparable nAb titers to 16-25 year old. 90.7% vaccine efficacy. No myocarditis but small N. 100% in age 12-17 yrs, higher neutralizing titers than age 16-25 yrs. In
children 5-11 years given two 50 μg doses 28 days gave nAb levels that were 1.5 times higher than those seen in young
adults; no VE data yet.
         
Efficacy vs. severe disease or death Pre-delta: ~100%; rare breakthroughs mostly in >80 yrs of age. Delta era: 91-94% against death. ~100%; rare breakthroughs mostly in >80 yrs of age. Delta era: 91-94% against
death.
85.4% vs severe / critical; 100% against death in Phase 3. 81% VE
against beta. Real world predelta:
68% against hospitalization
and 73% against an emergency department or urgent care visit.
approx 100% 80% in large
Chilean trial (non
peer-reviewed)
 No data 100% (preliminary)
Efficacy vs. asymptomatic infection or transmission 70-90% in asymptomatic infection with alpha variant. Delta variant results in peak viral loads 1,000 times higher than the alpha variant and is equal between vaccinated and unvaccinated persons, but virus is cleared more rapidly in vaccinated persons. Delta variant results in peak viral loads
1,000 times higher than the alpha variant
and is equal between vaccinated and
unvaccinated persons, but virus is cleared
more rapidly in vaccinated persons.
Delta variant results in peak viral
loads 1,000 times higher than the
alpha variant and is equal between vaccinated and
unvaccinated persons, but virus is
cleared more rapidly in vaccinated
persons.
67% (pre-Delta)  No data  No data  No data
Duration of efficacy after final dose All current data indicate that protection against severe disease remains >85% and may well last several years. VE against mild infection with mRNA vaccines may drop as low as 60% by 6 months according to observational studies. However, VE at least 8 months based on original mRNA trial
participants was 90% against any
symptomatic and 95% against severe disease. Duration against delta variant especially in immunocompromised and elderly is unknown and of concern.
All current data indicate that protection against severe disease remains >85% and may well last several years. VE against
mild infection with mRNA vaccines may drop as low as 60% by 6 months
according to observational studies.
However, VE at least 8 months based on
original mRNA trial participants was 90%
against any symptomatic and 95% against severe disease.
Durable humoral and cellular immune responses with minimal decreases for at least 8 months in pre-delta subjects. Few data with this vaccine. Duration against delta variant especially in
immunocompromised and elderly is unknown and of concern.
Duration against delta variant especially in
immunocompromised and elderly is unknown and of concern.
 No data  No data  No data
Primary Dosing 0.3 mL IM (30 ug); 2 doses 21 days apart (up to 42 days acceptable). Higher nAb titers with increased dosing interval to 12 weeks. 0.5 mL IM (100 ug); 2 doses 28 days apart
(up to 42 days acceptable).
0.5 mL IM (5 X 105 virions); 1 dose. If dose 2 given at 8 weeks (some consider a completion of
primary series) VE 94% against
severe disease US and 75% globally.
0.5 mL IM; 2 doses 4-12 wks apart (UK & EU) and 4 wks in US trial 2 doses 14 or 28 days apart 2 doses 14 or 21 days apart 2 doses 21 days apart.
Dose 1 is Ad26, Dose 2 Ad 5
Booster Dosing
(US guidelines presented; wide national variations
regarding boosters).
Clearcut evidence for use in >65 years of age.
0.3 ml IM 6 months (30 ug) same as primary dose after completion of primary series.
Should be given to persons aged ≥ 65 years, to long-term care facility residents aged ≥ 18 years, and persons aged 50-64 years with underlying medical conditions
May be given to persons aged 18-49 years with underlying medical conditions or persons aged 18-64 years at increased risk for COVID-19 exposure because of occupational or institutional (e.g., homeless
shelters and correctional facilities) settings, as assessed by a health care provider WHO EUL-may be considered for all over age 18. CDC encourages use for the booster dose of the same product that was used for the primary series but that any FDA authorized vaccine may be used if preferred;
most experts recommend that all booster doses be with an mRNA vaccine regardless of vaccine used for the primary dose or doses. VE of dose 3 95.6% against severe disease at 2.5 months after booster.
0.25 ml, (half-primary dose; 50 ug) IM 6
months after completion of primary series. Should be given to persons aged ≥ 65 years, to long-term care facility residents
aged ≥ 18 years, and persons aged 50-64
years with underlying medical conditions.
May be given to persons aged 18-49 years with underlying medical conditions or persons aged 18-64 years at increased risk for COVID-19 exposure because of occupational or institutional (e.g.,
homeless shelters and correctional facilities) settings, as assessed by a health care provider
WHO EUL-may be considered for all over
age 18 CDC encourages use for the booster dose of the same product that
was used for the primary series but that any FDA authorized vaccine may be used if preferred; most experts recommend
that all booster doses be with an mRNA vaccine regardless of vaccine used for the primary dose or doses.
O.5 ml IM (same as dose 1) given at least 2 months after the first Janssen/J&J dose—is recommended for all persons aged ≥ 18 years, including
immunocompromised persons. Many experts consider dose 2 as the second primary dose and not
as a booster dose. CDC encourages use for the booster dose of the same product that was used for the primary series but that any FDA authorized vaccine may be used if  referred;
most experts recommend that all
booster doses be with an mRNA
vaccine regardless of vaccine used for the primary dose or
doses.
No application in process. Booster recommendations may be to use and mRNA vaccine Booster at 6 months after Dose 2 implemented in
several countries.
WHO recommends
3rd dose for persons over 60 and 1-3 months after dose 2
in immune compromised but labels as 3rd dose in a primary
series. WHO allows
another kind of vaccine to be used
for Dose 3.
WHO EUL recommends
3rd dose for persons
over 60 and 1-3
months after dose 2 in
immunocompromised
but labels as 3rd dose in a primary series. WHO allows another
kind of vaccine to be
used for Dose 3.
No recommendation
Storage Store frozen at -90°C to -60°C (-130°F to -76°F) until expiration date or at 2-8°C (36-
46°F) for up to 1 month.
Store frozen at -50°C to -15°C (-58°F to 5°F) until expiration date. 2-8°C (36-46°F) for up to 30 days 2-8°C (36-46°F) for up to 3 mos
(for shipping and use); -20°C (-4°
F) for up to 2 yrs
2-8°C for 4-5 months. After
puncture store at 2-25oC for 6
hours
 2-8°C (36-46°F) 2-8°C (36-46°F) -18°C (0°F) for up to 6 mos; 2-8°C (36-46°F) for up to 30 days
Contraindications Anaphylaxis or immediate allergic reaction (within 4 hours of administration) to a
previous dose of an mRNA vaccine or separately to a vaccine constituent including polyethylene glycol (PEG) or polysorbate. Defer vaccination for 90 days after receipt of monoclonal or plasma
therapy.
Same as Pfizer mRNA Same as Pfizer and Moderna mRNA, except J&J has only polysorbate constituent Anaphylactic reaction to a vaccine constituent  No data  No data  No data
Precautions Immediate allergic reaction (within 4 hours of administration) to any other vaccine or injectable therapy not related to a component of mRNA-COVID-19 vaccines
or polysorbate. Persons with a reaction to a vaccine or injectable therapy that contains multiple components, one of which is PEG, another mRNA vaccine component or polysorbate, but in whom it is unknown which component elicited the immediate allergic reaction
Same as Pfizer mRNA Same as mRNA plus persons with a contraindication to mRNA COVID-19 vaccines (including
allergy to PEG) have a precaution to the Janssen/J&J vaccine (cross-reactive polysorbate 80) and vice-versa.
Women aged <50 years should be educated about the rare risk of
thrombosis with
thrombocytopenia syndrome (TTS) with the Astra Zeneca vaccine as well as the availability
of alternative COVID-19 vaccines to guide joint vaccine decisionmaking
with the provider.
Postpone vaccination in persons with acute severe febrile illness.
Rx with IVIG, N Engl J Med 385:720-8, 2021
No data  No data  No data
Not contraindications Food (including egg and gelatin), pet, insect, venom, environmental, latex, oral
medications (including the oral equivalents of injectable medications) allergies; any
other history of anaphylaxis not related to vaccine or injectables; or a family history of anaphylaxis. History of GBS in proximity to another vaccine.
Same as mRNA Same as Pfizer and Moderna mRNA    No data  No data  No data
Adverse effects Anaphylaxis 5.0 per million doses; 90%
within 30 minutes, 96% females. US vaccinees for the week following the first dose was: injection-site pain (67.8%), fatigue (30.9%), headache (25.9%), myalgia
(19.4%), fever (8.6%), and joint pain (8.7%).
For vaccinees with 2 doses rates were much
higher for dose 2: injection-site pain
(72.3%), fatigue (53.9%), headache (46.7%), myalgia (44%), fever (29.5%), and joint pain (25.6%). Rates same for Pfizer and Moderna. Mild myocarditis is rare but
associated with mRNA vaccination almost
exclusively in young males and mostly
within a week after the 2nd dose. The
highest incidence (12.6 cases per million) is
in those younger than 40 years, with a peak
incidence of 60 cases per million in males
aged 12-24 years. Baseline rates of
myocarditis in 15-18 males is 18 per million.
No deaths have been reported and only a
minority had abnormal echocardiograms;
long term sequelae cannot be ascertained at present. VSD: incidence of selected serious outcomes (including acute myocardial infarction, Bell's palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome,
myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome) was not
significantly higher 1 to 21 days post
vaccination compared with 22 to 42 days
post vaccination.
Essentially the same as Pfizer mRNA Very rare occurrence (7/1milliondoses) of TTS in women aged 18-50 yrs within 2 wks of vaccination. No data yet on
overall induction rate of PF4 antibodies or incidence of
thrombocytopenia. Treat with oral
anticoagulants and IVIG. No heparin for any thrombotic event
withing 2 weeks of vaccination without negative anti-PF4 result. N Engl J Med. 2021; 384:1964.
No data yet on anaphylaxis, none
in trials, contains polysorbate 80
related to PEG. Injection-site
reactions (pain), fatigue, headache, fever, and weakness.
Avoid if possible if previous GBS
especially males over 50. GBS approximately 8/million vaccinees
compared to 1.7 baseline rate.
Injection-site pain, fatigue, headache, fever, and weakness.
TTS in 1:25,000 to 1: 100,000 vaccinees in Europe. No data yet
on overall rate of PF4 antibodies or thrombocytopenia. N Engl J Med 2021, 384:2124
 No data  No data  No data
Pregnancy Use. VE after 56 days of was 96% for any documented infection, 97% symptomatic infection and 89% for hospitalization in 20,000 Israeli women. No reproductive or development concerns (preliminary); risk of disease effect > known vaccine risk; endorsed for use by CDC, ACOG, AAP. No reported issues in 70,000 pregnancies to date in the USA. US Vaccine Safety Datalink (VSD) analyzed 105,446 unique pregnancies and 13,160 spontaneous abortions with no increased risk in mRNA
vaccinees. No evidence of an increased risk for early pregnancy loss after vaccination in 14,000 Norwegian women.
Same as Pfizer mRNA Use. No reproductive or development concerns (preliminary); risk of disease effect > known vaccine risk;
endorsed for use by ACOG. VSD data with insufficient numbers
Unknown  No data  No data  No data
Immunocompromised or HIV Give dose 3, 28 days post primary series with same mRNA vaccine. Considered part of primary series in ths population and not a booster. Serology not indicated before or
after. Indicated for: Solid organ transplants, CAR-T-cell or hematopoietic stem cell transplant (within 2 years of transplantation
and on immunosuppression therapy), severe primary immunodeficiency, advanced or untreated HIV infection, active treatment with high-dose corticosteroids (i.e., ≥ 20 mg
prednisone or equivalent per day),
alkylating agents, antimetabolites, cancer chemotherapeutic agents classified as severely immunosuppressive, TNF
inhibitors, and other biologic agents that are immunosuppressive or immunomodulatory. When possible, mRNA vaccine doses (primary or additional) should be given at
least 2 weeks before initiation of
immunosuppressive therapies.
Same as Pfizer mRNA Give dose 2 (0.5 ml IM; same as dose 1) at least 2 months after the first Janssen/J&J dose—is
recommended for all persons aged ≥ 18 years, including
immunocompromised persons. Dose 2 with an mRNA vaccine
following vaccination with the Janssen/J&J vaccine is an option in the US but is preferable according
to most experts (30 ug if Pfizer; 50 ug if Moderna). Booster dose (dose 3) preferably with same
mRNA vaccine 6 months after dose 2. Serology not indicated
before or after. Janssen for doses
2 and 3 permitted but not
desirable.
Insufficient data WHO recommends
3 dose primary
series with dose 3 at
1-3 months
following dose 2.
WHO allows
another kind of vaccine to be used
for Dose 3.
WHO recommends 3
dose primary series
with dose 3 at 1-3
months following dose 2. WHO allows
another kind of vaccine to be used for Dose 3.
 No data
References

FDA Provider Fact Sheet / EUA Prescribing Information

N Engl J Med 2020; 383:2603

FDA Provider Fact Sheet / EUA Prescribing Information

N Engl J Med DOI: 10.1056/NEJMoa2035389

FDA Provider Fact Sheet (27 Feb 2021) here

EMA Authorization (29 Jan 2021) & Fact Sheet (18 Feb 2021) here     Phase III randomized trial data: Lancet 2 Feb 2020
Interchangeability with other COVID vaccines Use same vaccine for all doses if possible. Any mRNA vaccine may be administered for dose 2 after dose 1 of any mRNA, Janssen/J&J, AstraZeneca vaccine. Pfizer then Astra Zeneca is known to be effective. AstraZeneca then Pfizer produced 10X antibody levels compated to Pfizer-Pfizer or
Pfizer-Astra Zeneca (no efficacy study)https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3874014
See Pfizer Based on the lack of clinical data for efficacy of a single dose of Janssen/J&J against the delta
variant and the need for 2 doses of Astra Zeneca vaccine (both
adenovirus vectored) as well as the known prime-boost effect of
the Pfizer Astra Zeneca sequence,
many experts are now advocating
for recipients of the Janssen/J&J vaccine to receive a booster with an mRNA vaccine;
See Pfizer  No data  No data  No data

 

Development Scorecard

  • Current vaccine scorecard
    • 230 candidates, 90 in clinical trials, 27 in Phase III.  Table lists those in current use in at least >1 country.
      • All vaccines express similar antigenic components related to the original SARS CoV-2 strain isolated in China.  Two doses of mRNA vaccines clearly induce neutralizing antibody effective against all known variants. 
        • Trials of modified vaccines to include antigenic determinants derived from the delta variants have yet to reach Phase 2.
    • Efficacy data including for subgroups are not strictly comparable between vaccines as studies were carried out at different phases of the pandemic, with different population profiles and in different countries.

Advanced Pipeline

  • A 2-dose NVX-CoV2373 (Novavax; protein) vaccine candidate has efficacy of 89.3% against mild, moderate, or severe disease with onset at least 7 days after the second study vaccination (21 days later) in serologically negative (to SARS-CoV-2) adult participants at baseline. US trial trial data to be submitted in Q4 2021 to FDA. Major production difficulties at present.
  • In Phase 3 trials with 26,000 subjects in India COVAXIN (inactivated) vaccine efficacy overall VE of 77.8% against symptomatic disease, 63.4% against asymptomatic infection, 67.8% against symptomatic disease >60 yrs of age,  and 93.4% against severe infection; protection was 65.2% against the delta variant.

    • COVAXIN is not available outside of India.  WHO EUL granted November 2021 but not yet available in any developed country.

Comments

  • Definition of fully-vaccinated person for purposes of public health, mandates or US entry.  
    • US FDA-authorized/approved vaccine: ≥ 2 weeks following receipt of the second dose in a 2-dose series (Moderna [aged ≥ 18 years: 0.5 mL; 100 µg] or Pfizer [aged 5-11 years: 0.2 mL; 10 µg or aged ≥ 12 years: 0.3 mL; 30 µg]) or ≥ 2 weeks following receipt of 1 dose of a single-dose series (Janssen/J&J [aged ≥ 18 years: 0.5 mL; 5x1010 viral particles]).
  • Vaccine interchangeability (mix and match). 
    • Primary doses:
      • Any currently US FDA-authorized age-appropriate COVID-19 vaccine may be used when indicated and the same vaccine should be used for all doses (including additional primary or booster doses as indicated) if possible;
        • the second dose of an mRNA vaccine may be delayed for up to 6 weeks to allow for receipt of the same vaccine (preferred). However, if dose 1 brand is unknown, any available mRNA vaccine may be administered for dose 2 at a minimum interval of 28 days and constitutes a complete series.
        • In situations where a person received the first dose of an mRNA vaccine but is unable to complete the series, the Janssen/J&J vaccine may be considered at a minimum interval of 28 days from the mRNA vaccine dose and this constitutes a valid, complete single-dose Janssen/J&J vaccination and not a mixed vaccination series.
    • Booster doses:
      • US CDC encourages that the same product used for the primary series should be used for the booster dose, with leeway for personal choice and based on an assessment of their individual benefits and risks by a health care provider.
        • Most experts and Shoreland recommend that all booster doses be with an mRNA vaccine regardless of vaccine used for the primary dose or doses.
        • The eligible population and dosing interval for a heterologous booster dose are the same as those authorized for a booster dose of the vaccine used for the primary series.
        • When the Moderna vaccine is used as a heterologous booster, the dose is still half the primary dose (0.25 mL; 50 µg).
    • SARS-Cov-2 experienced persons: 
      •  Independent high-quality studies indicate that previously SARS-CoV-2–infected persons have an equal or better neutralizing antibody response including against viral variants after 1 dose of mRNA vaccine when compared to persons who received 2 doses but had not had SARS-CoV-2 infection.
      • A second vaccine dose in previously infected persons does not induce a further titer rise. Almost certainly 1 vaccine dose appears adequate for those with previous COVID-19
      • In vitro data indicates memory B cells persist for >1 year in these individuals.
      • Practicalities concerning the verification of previously documented infection during rapid vaccine rollout:
        • US authorities have yet to approve this approach in the absence of clinical efficacy data, and also argue that the correlates of protection by given levels of antibody are still unknown
        • Many experienced clinicians feel strongly that existing data already support this approach.
      • Previous infection with SARS-CoV-2 or COVID-19 vaccination both on their own provide immunity against subsequent SARS-CoV-2 infection and illness.
      • Whether vaccine-induced immunity alone is superior to natural immunity alone is not fully resolved, although hybrid immunity induced by vaccine in previously infected persons has been proven to provide the broadest and most durable immunity of all.
        • US CDC analysis (n= 7,348) has now shown that among COVID-19–like illness hospitalizations among adults aged ≥ 18 years whose previous infection or vaccination occurred 90 to 179 days earlier, the adjusted odds of laboratory-confirmed COVID-19 among unvaccinated adults with previous SARS-CoV-2 infection were 5.49-fold higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine who had no previous documented infection.
        • The data indicate that all persons should be vaccinated against COVID-19, including unvaccinated persons previously infected with SARS-CoV-2. See MMWR 70:1539 (11/5/2021).
  • Delayed second dose for 2-dose vaccines:  
    • US authorities remain strongly opposed to delaying the second primary dose of an mRNA vaccine.
    • Robust data from UK and Canada confirm the superiority of 12-week spacing between dose 1 and 2 in immunocompetent persons. 
  • Quarantine and vaccination: 
    • vaccinees do not need to quarantine after a SARS-CoV-2 exposure for the next 90 days after a complete 2 dose series but should be tested. 
    • Persons already in quarantine because of an exposure should not be vaccinated until quarantine is over.
  • Additional considerations
    • Antibody testing is not recommended to assess for immunity following COVID-19 vaccination or to assess the need for vaccination in an unvaccinated person;
      • no correlates of protection are available and the wide variety of antibody assays have variable targets (not all related to vaccine response) and performance. 
      • With no correlate of immunity; +ve IgG only minimally reassuring, -ve IgG unhelpful in patients whose ability to mount a B-cell response is uncertain such as transplant recipients and people on anti-B cell therapies.
    • Prevaccination prophylactic use of antipyretic or analgesic medications (e.g., acetaminophen [paracetamol] or NSAIDs) to prevent postvaccination symptoms is not recommended because the impact on mRNA COVID-19 vaccine-induced antibodies is unknown. However, these medications may be used to treat postvaccination local or systemic symptoms.
    • Persons with recent (time period now undefined) documented acute symptomatic or asymptomatic SARS-CoV-2 infection should be vaccinated but may choose to temporarily delay vaccination (conserves doses for others), if desired.
      • Risk of reinfection likely increases with time following initial infection. 
      • In acute illness, including for those who develop SARS-CoV-2 infection after the first vaccine dose but before receipt of the second dose, vaccination should be deferred until criteria for discontinuing isolation have been met
    • Currently available vaccines are not recommended for outbreak management or for post-exposure prophylaxis (vaccination to prevent the development of SARS-CoV-2 infection in a person with an exposure).
    • The majority of persons are protected by 12 days after the first dose but this single-dose immunity may well be very transient without a second dose; this could not be assessed one way or the other because all trial subjects eventually received a second dose.
    • If Dose 2 is administered no more than 4 days before the minimum (21 or 28 day) interval it is considered valid; however, a dose inadvertently administered > 4 days before the minimum interval does not need to be repeated.
    • Other non-COVID vaccines notably influenza vaccine may be administered simultaneously with or at any interval before or after any SARS-CoV-2 vaccine dose.
    • mRNA vaccines do not have a risk of modifying the vaccine recipient’s genetic makeup as mRNA does not enter cell nucleus where host DNA is located. 
      • Adenovirus vaccine DNA in the nucleus has deletions of critical genes therefore cannot replicate and cannot integrate into DNA. 
  • Further detail:  https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/

Management of COVID-19