What’s the Best Covid Vaccine? Why It’s Not So Simple

By Jason Gale and Lisa Beyer | Bloomberg,

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:

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:

• 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:

• 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.

(Updates with additional efficacy data for vaccines against variants in the U.K. in section 6.)

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