Kevin Kunzmann

Just who should get a COVID-19 booster shot and when continues to be 

 as the delta variant rages on, deaths climb (

, according to Johns Hopkins University), and while the Centers for Disease Control and Infection say that breakthrough infections are very rare, the agency only counts breakthrough infections that lead to hospitalizations and/or death. So, who knows?

Well, Johnson & Johnson thinks that it may have the answer.

The company announced to-be-published phase 3 data from a real-world evidence trial showing that their single-dose adenovirus-based 

 Ad26.COV2.S was associated with 79% overall efficacy for the prevention of COVID-19 and 81% effective for the prevention of hospitalizations associated with the virus.

The new data from the company’s pivotal ENSEMBLE trial program also included data from ENSEMBLE 2, an assessment of a two-dose regimen of Ad26.COV2.S. A booster dose provided 56 days after the first dose was associated with a 94% efficacy in preventing symptomatic COVID-19 in the US, and 75% efficacy worldwide.

The company is now seeking US Food and Drug Administration (FDA) authorization of their booster dose regimen on the basis of this data, which has yet to be peer-reviewed.

In the preprint data from Johnson & Johnson’s cohort assessment of nearly 400,000 participants vaccinated with Ad26.COV2.S, investigators sought to observe the single-dose vaccine’s effectiveness in preventing COVID-19 and related hospitalizations in US clinical practice. They additionally wanted to observe its duration of protection over a longer, real-world observation, as well as its efficacy in preventing infection via more transmissible delta variants.

Trial participants were newly vaccinated adults aged ≥18 years old, matched with up to 10 unvaccinated persons with similar demographics and COVID-19 risk factors. Vaccine effectiveness was estimated for observed COVID-19 infections and related hospitalizations, and was stratified by age, immunocompromised status, calendar time, and regions/states with greater incidence of the circulating delta variant.

The trial population included 390,517 vaccinated and 1,524,153 unvaccinated individuals.

Estimated vaccine effectiveness was 79% (95% CI, 77 – 80) for COVID-19 and 81% (95% CI, 79 – 84) for COVID-19 hospitalizations. An assessment of calendar months from March – July 2021 showed overall vaccine effectiveness did not “meaningfully” vary over time:

Investigators additionally observed a greater vaccine effectiveness in persons aged <50 years (83%; 95% CI, 81 – 85), and a lower effectiveness in immunocompromised patients (64%; 95% CI, 57 – 70).

Among participants in states with high incidence of delta variant infection, COVID-19 prevalence was greater among both vaccinated and unvaccinated cohorts. Investigators observed, however, an overall vaccine effectiveness of 79% (95% CI, 75 – 83) and 78% effectiveness versus hospitalization (95% CI, 73 – 82) in these states during June and July—the observed months when delta variant incidence was at its greatest.

That said, this estimated data does not entail sequence-specific information, meaning there is no specific certainty of the vaccine effectiveness of Ad.COV2.S in preventing delta variant-driven infection.

Nonetheless, investigators concluded the population-based US data demonstrate the “high and stable effectiveness” of the single-dose COVID-19 vaccine across both high-risk patient subpopulations, as well as residents in areas more adversely affected by the delta variant.

“As the COVID-19 pandemic continues and variants evolve the observed effectiveness may change in the future as new variants emerge,” they concluded. “Our data and data to be generated over the coming months using this system of claims data contribute important and otherwise unattainable evidence to policymakers, physicians, and patients.”

The phase 3 ENSEMBLE 2 trial is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of 2-dose Ad26.COV2.S regimen administered at a 56-day interval, versus placebo among an international population of adults with varying risk for severe COVID-19.

Median follow-up in the trial, according to Johnson & Johnson, was 36 days since the second dose administration; just 29% of trial participants had ≥2 months of follow-up data after receiving the investigative booster dose.

Investigators observed 100% vaccine effectiveness (95% CI, 33 – 100) against severe or critical COVID-19 in ≥14 days post-booster dose. They additionally observed 75% overall effectiveness (95% CI, 55 – 87) versus symptomatic COVID-19 in patients globally, and 94% overall effectiveness (95% CI, 58 – 100) in US patients.

The company stated that a booster dose of Ad26.COV2.S was associated with a 4- to 6-fold increase in antibody titers versus a lone single-dose administration at 2 months. At 6 months, the booster dose was associated with a 12-fold increase in antibodies.

Johnson & Johnson intends to submit the full ENSEMBLE 2 study data for publication in the coming months.

In a statement accompanying the reported data, Paul Stoffels, MD, Johnson & Johnson Vice Chairman of the Executive Committee and Chief Scientific Officer, called it “critical” to prioritize prevention of hospitalization and death during the continued COVID-19 pandemic.

“A single-shot COVID-19 vaccine that is easy to use, distribute and administer, and that provides strong and long-lasting protection is crucial to vaccinating the global population,” Stoffels said. “At the same time, we now have generated evidence that a booster shot further increases protection against COVID-19 and is expected to extend the duration of protection significantly.”

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Investigators concluded that their data demonstrate the “high and stable effectiveness” of the single-dose COVID-19 vaccine across both high-risk patient subpopulations, as well as residents in areas more adversely affected by the delta variant.

Johnson & Johnson Touts COVID-19 Vaccine Booster Shot 

Eight months after the Food and Drug Administration (FDA) granted emergency use authorization (EAU) to the Pfizer/BioNTech COVID-19 vaccine, the agency today gave the vaccine full approval. As 

, the FDA’s move might go a long way to mitigate vaccine hesitancy, not only 

 as well. Infection preventionists are often tasked with the job of 

 their hesitant fellow heath care workers into getting vaccinated.

The Pfizer/BioNTech vaccine becomes the first COVID-19 vaccine given Biologics License Application (BLA)—or full approval. The BLA was given for the companies’ 

 BNT162b2 (Comirnaty). The fully approved vaccine is for people 16 and older; the EUA version is available for children aged 12–15 years and as a third “booster” dose in immunocomrpomised patients.

Health care experts have been pushing the FDA to grant full approval to the COVID-19 vaccines as soon as possible as a way of inducing the vaccine hesitant to get inoculated in the hope that that will stem the rising tide of the delta variant, which has become the 

The FDA’s granting full approval of the Pfizer/BioNTech vaccine comes at a time of a renewed push for 

This newest decision by the FDA comes while new cases of the pandemic virus have reached their highest in the US this year and COVID-19 vaccination rates nearly plateaued last month, although the Centers for Disease Control and Prevention (CDC) has seen a 

 in vaccination rates the last few weeks. The CDC states that as “of August 19, the 7-day average number of administered vaccine doses reported (by date of CDC report) to CDC per day was 823,355, a 17.78% increase from the previous week.” Yesterday, the White House reported that more than 800,000 vaccine doses were administered; marking the fifth consecutive days that about 700,000 COVID-19 vaccine doses have been administered. That’s an increase of 25% in the last 2 weeks

BNT162b2 is a nucleoside-modified messenger RNA (mRNA) vaccine encoded with the SARS-CoV-2 full-length Spike protein glycoprotein. It was selected for continued assessment against 3 other candidates by Pfizer and BioNTech investigators in July 2020, and was granted Fast Track Designation by the FDA around the same time.

FDA granted the vaccine EUA in December 2020

, based on supporting data showing a 95% overall vaccine efficacy in preventing symptomatic COVID-19 among Phase 3 trial participants without previous SARS-CoV-2 infection prior to 7 days after their second vaccine dose.

The EUA was also backed by a 17-4-1 vote 

in favor of the vaccine’s benefit-risk profile

 from the Vaccines and Related Biological Products Advisory Committee (VRBPAC) at the time. Pfizer and BioNTech’s BLA submission was 

granted Priority Review by the FDA last month

, streamlining the regulatory review and decision-making timeline for the vaccine.

Peter Hotez, MD, PhD, Professor in the Departments of Pediatrics, Molecular Virology & Microbiology at Baylor College of Medicine, told 

’s sister publication, that one of the benefits of the FDA’s approval is that it will come with new prescribing capabilities granted through the BLA, noting physicians will now have “more wiggle room” in strategically reducing COVID-19 risk among their patients.

Carlos del Rio, MD, Executive Associate Dean of Emory School of Medicine & Grady Health System, expressed concern that vaccine-hesitant groups will continue to reject the validity of COVID-19 vaccines regardless of FDA designations. He told 

 that the BLA, in regard to public response, may land somewhere between a small win and a non-factor; he estimated that 1 or 2 of every 10 unvaccinated US adults may be now persuaded to seek immunization because of the BLA.

Del Rio believes the full approvals will rather change the scope of employer-level 

 and public work industries—including transportation—have already begun to establishing COVID-19 vaccination mandates for workers.

“Full approvals are going to make mandates a lot easier, and that will make people get vaccinated,” del Rio explained. “You’re going to see an explosion of mandates happening when the full approval occurs.”

The delta variant has been largely to blame for this newest spike in COVID-19 cases, hospitalizations, and deaths. Per the CDC, the now-prominent strain is estimated to be more than 2-fold more contagious than previous SARS-CoV-2 variants, has been linked to more severe illness among unvaccinated persons and more breakthrough infections in vaccinated persons.

However, the CDC reiterates the benefit of authorized COVID-19 vaccines in reducing risk of infection, serious illness, and death from the delta variant, as well as in reducing risk of virus spread from a vaccinated person to others.

Other vaccine regulation strategies are currently at play in the US. Earlier this month, 

 to Pfizer/BioNTech and Moderna for third “booster” doses of their respective mRNA vaccines in severely immunocompromised patients. Days later, a report revealed the Biden administration’s plan to advocate for

 COVID-19 vaccine booster dose availability for all Americans at 8 months

 following their final dose. Their timeline, dependent on FDA allowance, would authorize booster doses for the adults by mid-September.

The national push for booster dose-improved immunity against a surging virus, as well as expanded vaccine indications to include children, will likely to play out in the coming months. Today’s designation by the FDA marks a new precedent for the scientific response against COVID-19—a mark which Hotez anticipates Moderna and Johnson & Johnson developers will also reach soon.

“I welcome the development and think it will happen for all 3 vaccines we have, hopefully before the end of the year,” he said.

Health care experts hope that the move will induce the vaccine hesitant—in the public, and among health care professionals—to get inoculated in the hope that that will stem the rising tide of the delta variant.

FDA Grants Full Approval to Pfizer/BioNTech Vaccine

Medical experts, including those with the 

Centers for Disease Control and Prevention

, have been urging Americans to get vaccinated if for no other reason than that the COVID-19 vaccines have proven somewhat effective in beating back the delta variant. New research out of the UK seems to back this up. It finds that two-dose 

 effectiveness rates remain high against symptomatic disease brought on by the delta variant.

Investigators at Public Health England showed 2-dose administration of Pfizer-BioNTech mRNA vaccine BNT162b2 and AstraZeneca-University of Oxford adenovirus vaccine ChAdOx1 nCoV-19 were associated with 88% and 67% effectiveness against symptomatic delta variant-derived COVID-19, respectively. The findings, published today in 

, provide support for 2-dose vaccine uptake in the wake of surging cases driven by the highly transmissible delta variant.

The vaccines’ highly efficacious benefit in symptomatic COVID-19 prevention has been observed largely in clinical trials and real-world research involving the first prominent B.1.1.7 (alpha) variant, the study notes.

“Data on the effectiveness of COVID-19 vaccines against clinical outcomes with (delta) variant have been limited,” they write. In their conclusion they write that “the findings are observational and should be interpreted with caution. Low sensitivity or specificity of PCR testing could result in cases and controls being misclassified, which would attenuate the estimates of vaccine effectiveness.”

’s Editorial Advisory Board, notes that “the data from the United Kingdom which reports that the Pfizer mRNA vaccine is 88% effective against symptomatic infections appears to be in stark contrast to the 41% effectiveness reported by the Ministry of Health in Israel. The difference can be explained by waning of immunity over time and the vaccine dosage schedule in the two countries.”

Israel was one of the first countries to administer vaccines to their population and has a dosage schedule similar to the US. The UK, on the other hand, spaced the 2 doses apart by up to 3 months, says Kavanagh.

“Thus, most in Israel completed their vaccination schedule far ahead of those in the United Kingdom,” says Kavanagh. “Israel is currently administering boosters to those above the age of 60 and more than 5 months since vaccination. The United Kingdom is planning to start booster shots in September.”

In the UK study, a team led by Jamie Lopez Bernal, PhD, sought to interpret the effectiveness of currently available 2-dose vaccines in the UK against the B.1.617.2 (delta) variant of SARS-CoV-2—at a time when cases borne from the variant were spreading from India to dozens other countries, while investigators had little indication of the COVID-19 vaccines’ effectiveness in curbing it.

Investigators conducted a test-negative case-control assessment to estimate vaccine effectiveness against symptomatic disease caused by the delta or alpha variant. They identified variants based on sequencing and spike (S) gene status observation, using data from all symptomatic cases of COVID-19 sequenced in England to determine proportion of cases with either variant according to vaccination status.

The team included 19,109 sequenced cases which included persons ≥16 years old, appropriately vaccinated with either BNT162b2 or ChAdOx1 nCoV-19 regimens, with symptomatic COVID-19 caused by either alpha or delta variant. They observed the alpha variant in 14,837 (77.6%) cases, and delta in 4272 (22.4%).

More than one-third of observed patients in each variant population were aged 16-29 at the time of sequencing; approximately 99% of both populations did not have a history of travel that would implicate international SARS-CoV-2 infection risk. A total of 307 (2.1%) sequenced COVID-19 cases from either variant group were linked to health or social care workers.

In observing a single dose of either regimen, Lopez Bernal and colleagues observed significantly lower vaccine effectiveness versus the delta variant: 30.7% (95% CI, 25.2 – 35.7). Single-dose vaccine effectiveness versus the alpha variant was 48.7% (95% CI, 45.5 – 51.7).

Two-dose BNT162b2 was associated with a 93.7% vaccine effectiveness versus the alpha variant (95% CI, 91.6 – 95.3), compared to an 88.0% effectiveness versus the delta variant (95% CI, 85.3 – 90.1).

Two-dose ChAdOx1 nCoV-19 was associated with a 74.5% vaccine effectiveness versus the alpha variant (95% CI, 68.4 – 79.4) and a 67.0% effectiveness versus the alpha variant (95% CI, 61.3 – 71.8).

“A clear effect was noted with both vaccines, with high levels of effectiveness after 2 doses,” investigators noted. “Vaccine effectiveness against either variant was smaller after the receipt of 2 doses of the ChAdOx1 nCoV-19 vaccine than after the receipt of 2 doses of the BNT162b2 vaccine, a finding that is consistent with reported clinical trial findings.”

Investigators concluded that their findings show “high levels of vaccine effectiveness” with 2-dose vaccination against symptomatic COVID-19 brought on by the delta variant.

“These estimates were only modestly lower than the estimate of vaccine effectiveness against the alpha variant,” they wrote. “Our finding of reduced effectiveness after the first dose would support efforts to maximize vaccine uptake with two doses among vulnerable groups in the context of circulation of the delta variant.”

The original version of this article appeared in

The findings provide support for 2-dose vaccine uptake in the wake of surging cases driven by the highly transmissible delta variant.

2-Dose COVID-19 Vaccines Work Against Delta Variant, Says Study

The coming flu season may be like no other. True, as Lynnette Brammer, who heads the domestic influenza surveillance team at the Centers for Disease Control and Prevention, 

Flu can cause lots of problems every fall. We say all the time—and I know people get tired of hearing it, but I think right now it’s truer than ever—flu is incredibly unpredictable.”

Still, there’s the little matter of us reemerging from the COVID-19 pandemic. Last year, infection preventionists 

 that hospital emergency rooms would be filled with patients suffering from respiratory diseases and providers would have to difficulty determining whether to treat for COVID-19 or some other problem, like the flu. That didn’t happen. The mitigation efforts used to combat COVID-19—hand hygiene, social distancing, masking—stopped the flu in its tracks and the U.S. had the lowest flu rates on record.

This year, COVID-19 mitigation efforts won’t be in general use and that could cause problems. Brammer told 

 that last year “the diagnosis was a lot easier, because almost all the respiratory illness was due to one thing…. We expect flu will come back.” However, she added that COVID-19 greatly enhanced flu surveillance in the United States and the rest of the world.

Also, testing for respiratory illnesses have improved dramatically, and innovation continues.

For instance, findings presented this week at the 

American Society of Microbiology (ASM) 2021 World Microbe Forum

 demonstrated that a multiplex PCR assay may be capable of simultaneously detecting and differentiating influenza viruses, respiratory syncytial virus (RSV), and 

The real-time assay was still able to detect low abundances of SARS-CoV-2 in human clinical samples with high concentrations of influenza and/or RSV—meaning patients with previous SARS-CoV-2 infection and current respiratory viral infection can be defined.

Led by Benjamin M. Liu, of the Department of Pathology at the University of Utah School of Medicine in Salt Lake City, investigators sought to contribute to the “urgent need” for differential and definitive diagnoses of viral infections and co-infections after the COVID-19 pandemic—and especially during major respiratory infection seasons.

The ChromaCode HDPCR Respiratory Virus 6 (RV6) qPCR assay used probe-limited chemistry and calibrators that allow for multiplexing and end-point fluorescence detection and differentiation of SARS-CoV-2, influenza A and B viruses (IAV; IBV), and RSV.

“Common respiratory viruses, e.g. RSV, IAV, and IBV mimic SARS-CoV-2 in clinical presentations but have different clinical courses, therapies and outcomes,” Liu and colleagues wrote. “Some commercially available single-well multiplex assays…allow for large scale screening in the context of the pandemic, but lack the ability to distinguish IAV and IBV.”

The team sought to evaluate the analytical and clinical performance of the RV6 assay through a limit of detection (LOD) study through all 4 viruses, with LOD defined as the lowest dilutions with a detection rate of 100%.

They evaluated the assay through 77 nasophrayngeal specimens previously assessed via the multiplex assay from TaqPath, as well as discrepant samples being tested by the orthogonal Panther Fusion Flu/A/B/RSV assay.

Through the 77 samples, the RV6 assay detected 2 more single positives for IBV or RSV than the TaqPath assay; both samples tested negative by the Panther assay as well. All but 1 of 29 “flu” positive samples identified by the TaqPath assay were differentiated by the RV6 assay as either IAV (n = 15) or IBV (n = 14). The remainder sample returned as IAV+IBV.

“The RV6 assay demonstrated high analytical sensitivity and specificity in simultaneous detection/differentiation of IAV, IBV, RSV and SARS-CoV-2 in human clinical specimens and warrants further clinical validation,” investigators concluded.

A multiplex PCR assay may be capable of simultaneously detecting and differentiating influenza viruses, respiratory syncytial virus (RSV), and SARS-CoV-2.

Kevin Kunzmann

Articles

Johnson & Johnson Touts COVID-19 Vaccine Booster Shot

FDA Grants Full Approval to Pfizer/BioNTech Vaccine

2-Dose COVID-19 Vaccines Work Against Delta Variant, Says Study

Test Might Determine What Ails You: COVID-19 or Influenza