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QuickTake


WHAT’S THE BEST COVID VACCINE? WHY IT’S NOT SO SIMPLE

By
Jason Gale
and
Lisa Beyer
March 10, 2021, 9:27 AM GMT Updated on May 24, 2021, 7:50 AM GMT
Getting Covid After Being Vaccinated: How Does It Happen?


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As scientists raced to develop Covid-19 vaccines, public health specialists were
hoping that more than one group would succeed. Having multiple companies
producing vaccines would make it easier to inoculate a lot of people fast. Be
careful what you wish for. A range of vaccines with different efficacy results
now has given rise to worries that some people may refuse the shot on offer in
hopes of getting a “better” one later. In reality, comparing efficacy numbers
isn’t necessarily the best way to measure a vaccine’s value. And as suppliers
struggle to meet global demand, experts say the best vaccine for you is probably
whichever one you can get now.


1. WHAT DOES EFFICACY MEAN?

On a basic level, vaccine efficacy of 50%, for example, roughly means that an
immunized person has a 50% reduced risk of becoming ill compared with an
otherwise similar non-immunized person. However, the measurement can be applied
to different questions about a vaccine’s effect. For example, almost all
Covid-19 vaccines appear to successfully -- 100% -- avert hospitalization and
death. But since relatively few people infected with SARS-CoV-2 become
critically ill, it’s hard to measure such a rare outcome reliably in clinical
trials involving only tens of thousands of participants -- a comparatively small
pool. Instead, the primary aim of most late-stage trials has been to measure
broader efficacy against lab-confirmed Covid cases with any symptoms, including
mild ones.


2. WHAT EFFICACIES ARE BEING REPORTED?

Efficacy against Covid-linked disease averaged about 85% after a full course,
rising to almost 100% protection against severe disease, hospitalization or
death, Julia Shapiro, Natalie Dean, Ira Longini and colleagues said in a paper
released late-May before peer-review and publication. The University of Florida
researchers summarized the efficacy of vaccines to prevent any Covid-caused
disease after two doses below:


COMPARING SHOTS

How well vaccines prevent any Covid disease after a second dose



Source: Shapiro, Dean, Longini et al. Efficacy Estimates for Various COVID-19
Vaccines (Pre-print paper)




3. ARE THE NUMBERS RELIABLE?




It’s hard to say. Data from the clinical trials have been reported in various
ways and subject to varying degrees of scientific scrutiny. Although publication
in a peer-reviewed, scientific journal is considered the gold standard for
ensuring the accuracy, integrity and credibility of clinical data, only a
handful of Covid vaccine studies have undergone that rigorous vetting process so
far. Vaccine efficacy data from other studies have been reported in press
releases, articles in state-owned media and in papers released on so-called
pre-print servers and, therefore, weren’t reviewed by scientists not involved in
the research.




4. WHY ISN’T EFFICACY ALL THAT COUNTS?

For one thing, the figures aren’t directly comparable. That’s in part because
the vaccines weren’t tested using the same criteria or groups of people. Also:

 * The vaccines were tested at different times and in different places. The
   intensity of the epidemic and measures to mitigate it, such as mask-wearing,
   may contribute to differences in efficacy estimates between countries.
 * SARS-CoV-2 has mutated over time, generating variants that appear to be more
   dangerous. So, in general, the first vaccines to prove effective likely faced
   fewer of these viral strains than subsequent ones have.
 * Vaccines take time to work, and the periods during which efficacy was
   measured in clinical trials differ across studies.
 * Some trials may exclude participants with pre-existing conditions that could
   affect their response, while another trial might include such people. For
   example, Novavax reported a modest decline in efficacy in South Africa when
   HIV-infected individuals were included in the analysis.
 * While most of the trials were designed to evaluate how well vaccines
   prevented any symptomatic case of Covid, the J&J vaccine was tested for its
   ability to protect against moderate and severe Covid, which entails having at
   least two lesser symptoms or one or more serious one, such as an elevated
   respiratory rate.


5. NUMBERS MAY BE MISLEADING?

Yes, especially without understanding the clinical trial data on which they’re
based. Although efficacy is given as a single figure, it’s actually a point
estimate based on a range, or “confidence interval,” that scientists are 95%
certain contains the true number. The range is narrower for the Moderna and
Pfizer-BioNTech vaccines, and comparatively wider for the other shots. In any
case, research on all vaccines is incomplete because there hasn’t been
sufficient time or follow-up to understand their efficacy longer term. The best
way to determine with a high degree of certainty how one vaccine stacks up
against another is to compare the two under the same conditions. Such studies
are likely to be carried out eventually.




6. WHAT MATTERS BEYOND THE EFFICACY NUMBER?

Several things:

 * Match to local variants:
   * Mutations mean that some vaccines may work better or worse in certain
     regions than in others, depending on which viral strains are present.
   * University of Florida researchers found B.1.1.7 led to “somewhat reduced”
     efficacy compared with the “wild type” strain. In contrast, the P.1 and
     B.1.351 variants led to considerably lower vaccine efficacy, owing to
     mutations that affect immune function.
     * Estimates for vaccine efficacy for three variants of concern are
       summarized below:

B.1.1.7 variant (U.K.)Vaccine Efficacy %Pfizer89.5Novavax85.6AstraZeneca74.6

P.1 variant (Brazil)Vaccine Efficacy %Johnson & Johnson66.2Sinovac49.6

B.1.351 variant (South Africa)Vaccine Efficacy %Pfizer75.0Johnson &
Johnson52.0Novavax49.4AstraZeneca21.9

 * The B.1.617.2 variant that helped drive a dramatic second wave of Covid-19
   cases in India and smaller outbreaks in parts of the U.K., may result in a
   reduction in vaccine effectiveness after one dose, Public Health England said
   on May 22. However, any reduction after two doses is “likely to be small,” it
   said.
 * The finding supports “maximizing vaccine uptake with two doses among
   vulnerable groups,” researchers from the agency, along with scientists from
   the London School of Hygiene and Tropical Medicine and Imperial College, said
   in a paper released on May 22 ahead of peer review and publications. The
   group looked at the effectiveness of the Pfizer-BioNTech and AstraZeneca
   shots two weeks after administration, and their findings are summarized
   below:

Vaccine & Dose

Effectiveness against

B.1.1.7

Effectiveness against

B.1.617.2

Pfizer-BioNTech

- after 1st

49.2%33.2%- after 2nd93.4%87.9%

AstraZeneca

- after 1st

51.4%32.9%- after 2nd66.1%59.8%


 * Match to recipients:
   * The safety and efficacy of a vaccine can vary among individuals depending
     on characteristics such as age, gender, genetic background and pre-existing
     conditions, including allergies.
   * The Pfizer-BioNTech and Moderna vaccines, which use a novel technology
     called messenger RNA (mRNA), have been linked to a small number of cases of
     anaphylaxis, a serious allergic reaction that requires medical attention.
     It’s possible the trigger is an ingredient used just in these shots, in
     which case people prone to anaphylaxis might be better off with an
     alternative vaccine.
   * More worrisome, a life-threatening type of blood clot has been linked to
     the AstraZeneca shot, prompting Norway to remove the inoculation from its
     Covid vaccine program, and some other countries to limit its use in younger
     people. So-called vaccine-induced thrombotic thrombocytopenia, or VITT, may
     also occur with the Johnson & Johnson (Janssen) vaccine.
     * From Dec. 9 to May 5, more than 260 cases of VITT were reported out of
       30.8 million doses of the AstraZeneca vaccine administered in the U.K.
     * The overall risk of VITT following a dose of the vaccine is 10.9 per
       million doses. This varies according to age groups and it is estimated to
       be about one in 100,000 for people over 50 and one in 50,000 for people
       ages 18 to 49.
 * Dosing:
   * All the authorized Covid vaccines so far require two doses except for J&J’s
     and CanSino’s, which are single shot -- a big plus.
   * A one-dose vaccine reduces the burden on the health-care system, which is
     substantial in a mass-vaccination campaign. It eliminates the challenge of
     getting people to return on time for a second dose; a U.S. study found one
     in four senior citizens failed to do so after getting an initial injection
     of the shingles vaccine. And it means people get the vaccine’s full
     protection sooner, without having to wait for a booster shot to kick in.
 * Refrigeration needs:
   * Vaccines have to be kept cold while they’re transported and stored, but the
     complexity of the so-called cold chain varies. The Pfizer-BioNTech vaccine
     needs to be shipped and stored at temperatures so low that special pharmacy
     freezers are required; after thawing, undiluted doses may be stored in the
     refrigerator at 2°C to 8°C (35°F to 46°F) for up to 1 month. Moderna’s
     vials can be transported in regular freezers and stored for 30 days in a
     refrigerator.
   * AstraZeneca and J&J’s are even easier to handle: they can be transported
     and stored at normal refrigerator temperatures until their expiry, which is
     up to six months for AstraZeneca.
   * The Sinovac, Sinopharm and Covaxin vaccines can be stored in refrigerators
     for up to three years. That makes all those varieties better candidates for
     places that don’t have large freezer capacity.
 * Price:
   * The companies making Covid vaccines are getting different prices from
     different buyers and many of the figures aren’t public. Still, it’s clear
     that some are significantly more expensive than others.
   * Moderna’s is the priciest. Its chief executive officer has given a range of
     $25 to $37 per dose. Next comes Pfizer-BioNTech: the EU is paying about
     $14.70 a dose, the U.S. $19.50 and Israel $30.
   * The J&J and AstraZeneca vaccines are considerably more affordable. J&J’s
     formulation costs the EU $8.50 -- and only one dose is needed. The EU has
     paid $2.15 per AstraZeneca dose while South Africa shelled out $5.25.


7. WHAT’S THE BOTTOM LINE?

Public health officials say that, at least initially, the best vaccine is
whichever one is available at the time of eligibility. However, as supplies
become less of a limitation, it’s likely some vaccines will offer advantages for
different groups, such as a single shot for those for whom returning is
difficult. Also, the uptake of vaccines across the world and the resulting
effects on populations will inform the effectiveness of each vaccine at
preventing infections and symptoms and establishing herd immunity under
“real-world,” as opposed to clinical trial, conditions.



“The best vaccine is the one you can get into your arm,” says Emory University’s
Prof. Carlos del Rio.

More: https://bloom.bg/2OGokKl (Source: QuickTake)


THE REFERENCE SHELF

 * Related QuickTakes on the coronavirus variants, origins of the virus,
   delaying doses of Covid vaccines, vaccine-induced malaise, serious vaccine
   reactions, why the U.K. plans to infect volunteers with the coronavirus, and
   vaccines and transmission of the virus.

 * Bloomberg News explores the challenge of getting people to take the J&J
   vaccine given its relatively low efficacy; the vaccines that will help
   nations exit the pandemic faster; and “real-world” effectiveness of
   AstraZeneca and Pfizer’s vaccines.
 * Harvard University’s Marc Lipsitch and the University of Florida’s Natalie
   Dean explain Covid vaccine efficacy, and Dean discusses the spectrum of
   vaccine efficacy measures.
 * Emory University’s Carlos del Rio and Preeti Malani from the University of
   Michigan answer frequently asked questions about Covid vaccines.
 * A Yale Medicine brief outlines differences among efficacious Covid vaccines.
 * Scientists from the Coalition for Epidemic Preparedness Innovations present
   the evolution of the Covid-19 vaccine development landscape.

(Updates with chart in section 2.)


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