Kevin Kunzmann

Because of 6 US cases of rare blood clot disorders that it may have caused, the Janssen Pharmaceuticals 

 will not be administered at federal sites, according to a ruling expected to be made by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). The agencies want to investigate exactly what’s going on.

The federal agencies will announce the decision for an immediate pause of the one-shot adenovirus Ad26.COV2.S while advising states distributing the product to consider doing the same, as 6 women aged 18-48 years old reported cerebral venous thrombosis, an extremely rare disorder associated with blood clotting, 6-16 days following their vaccination.

As of Tuesday morning, 1 woman afflicted with the condition has died, and a second woman in Nebraska is hospitalized and in critical condition.

FDA and CDC investigators intend to collaborate on assessment of possible links between the Janssen vaccine and cerebral venous thrombosis, in order to discern whether the company’s Emergency Use Authorization (EUA) should continue as-is or become limited.

The FDA reiterated the importance of an indefinite pause during this investigation in a statement shared on Twitter Tuesday morning.

"This is important to ensure that the health care provider community is aware of the potential for these adverse events and can plan due to the unique treatment required with this type of blood clot," 

The CDC’s Advisory Committee on Immunization Practices (ACIP) will hold an emergency meeting on the matter this Wednesday, according to 

Per the CDC, more than 6 million people in the US have received Janssen’s vaccine thus far, and another 9 million doses have been shipped to different states.

Comparatively, Pfizer-BioNTech and Moderna have delivered 23 million-plus doses weekly of their two-dose mRNA vaccines to the US, comprising a significant majority of the US’ vaccine distribution. No significant safety concerns have emerged from either product.

Just last month, the Biden administration announced 

the acquisition of another 100 million doses of Ad26.COV2.S from Janssen

, to be delivered in the latter half of 2021.

 in manufacturing at its Baltimore plant due to the inadvertent mixing of vaccine ingredients. The error resulted in the loss of up to 15 million doses.

Articles

The CDC and FDA are expected to announce an immediate pause for administering the one-shot adenovirus Ad26.COV2.S while advising states distributing the product to consider doing the same. 

Janssen COVID-19 Vaccine Expected to be Temporarily Discontinued 

The coronavirus disease 2019 (COVID-19) pandemic most likely began with a bat infecting another animal with the SARS-CoV-2 virus and that animal in turn transmitting it to a human host, according to a study by the World Health Organization (WHO) and China. The study is scheduled to be officially released tomorrow, but a draft was obtained by the Associated Press.

The findings, which contribute toward an interpretation of COVID-19’s origins, also state that it is “extremely unlikely” the pandemic virus occurred through a laboratory leak—a popular theory held among leadership outside of China at the beginning of the outbreak, and one 

 by some health experts in the United States, such as Robert Redfield, the former director of the Centers for Disease Control and Prevention (CDC). In talking to CNN, Redfield stressed that this was only his opinion, however.

Redfield said: “It's not unusual for respiratory pathogens that are being worked on in a laboratory to infect the laboratory worker. ... That’s not implying any intentionality. It’s my opinion, right? But I am a virologist. I have spent my life in virology.”

Redfield served under former President Trump. But President Biden’s Secretary of State Anthony J. Blinken indicated last week in an interview with CNN that he’s taking a wait-and-see attitude toward the report, questioning how the data were collected and interpreted.

“We’ve got real concerns about the methodology and the process that went into that report, including the fact that the government in Beijing apparently helped to write it,” Blinken said. “But let’s see what comes out in that report.”

Nevertheless, the WHO report discounts both Redfield’s opinion and Blinken’s misgivings. The report is largely based on a WHO investigator visit to Wuhan from mid-January to mid-February this year. The investigators detailed 4 scenarios by which SARS-CoV-2 could have emerged, listed in order of most likelihood to least:

Bats through another animal (very likely)

Direct spread from bats to humans (likely)

Cold-chain food products (possible but not likely)

As the report draft explains, the evolutionary distance between bat-based coronaviruses and SARS-CoV-2 is estimated to be several decades, “suggesting a missing link.”

The WHO-led expedition to the original outbreak epicenter, 

 and the American Lung Association (ALA), speaks to the gap of knowledge still missing in understanding how the pandemic began, and what means were capable of preventing it.

As Donald Alcendor, PhD, vaccinologist and immunologist from Meharry Medical College and Vanderbilt University School of Medicine, explained in the podcast, the zoological intermediary to human transmission is still just a prediction.

“We know this is a zoological transmission,” Alcendor explained. “We have to understand how this virus is being transmitted in the animals that service reservoirs. And once we do, we need to limit this zoological contact to humans.”

Alcendor’s suggestion that pangolins—better known as scaly anteaters—may be involved in the SARS-CoV-2 human origin was supported by the WHO report, which noted the mammals have been observed with highly similar viruses. The report also suggested that mink and cats could have served as the intermediary, as both species carry COVID-19.

That said, the report did not draw conclusion on the belief that the outbreak began at a Wuhan seafood market—which sold a range of animal products, from bamboo rats and deer, to even live crocodiles—that reported a case cluster in December 2019. Previous cases observed outside the area of the market suggest the outbreak began elsewhere.

“No firm conclusion therefore about the role of the Huanan market in the origin of the outbreak, or how the infection was introduced into the market, can currently be drawn,” investigators wrote.

Peter Ben Embarek, a food scientist and WHO expert leading the Wuhan assessment, told 

on Friday the report was finalized and awaiting public release.

The study states that it is “extremely unlikely” the pandemic virus occurred through a laboratory leak in Wuhan, China.

WHO, China Report Posits Origins of COVID-19 Pandemic

The first real societal change brought about by the vaccines for coronavirus disease 2019 (COVID-19) landed today, as the US Centers for Disease Control and Prevention (CDC) released new 

 about masking for people who have been vaccinated. This could be the first step to getting back to normal. The CDC guidance states that persons past 2 weeks of their final COVID-19 vaccine dose face little risk from unmasked, non-distancing indoor visiting of unvaccinated, low-risk members from a single household.

The guidance also states that fully vaccinated people should be able to freely gather indoors, without need for quarantine or post-exposure testing without COVID-19 symptoms present. In this update, viewed by many experts as the beginning of a return to societal normalcy via an increasingly vaccinated population, the CDC noted investigative evidence showing fully vaccinated people are indeed less likely to spread SARS-CoV-2 to others.

’s Editorial Advisory Board were cautiously optimistic about the ruling. Sharon Ward Fore, MS, MT(ASCP), CIC, noted that “common sense needs to apply—small means small, not 25 of your closest friends. And vaccinated people still need to remember a large portion of people are still not vaccinated, so when they are out in public, masking and social distancing still apply.”

Linda Spaulding, RN, BC, CIC, CHEC, CHOP, said that while the news from CDC is promising “everyone still needs to be cautious. What is still unknown is how long you may be protected after vaccination because few have had the vaccine onboard for 3 months. And there are variants we don’t know anything about yet. Personally, I would be comfortable hanging out with family who have been fully vaccinated. I’m still leary of hanging out with individuals who have not been vaccinated. It is a personal decision.”

Kevin Kavanagh, MD, said: “Relaxation of adivsements will come as a welcome relief. All are weary of living under public health restrictions. Obtaining both doses for the Pfizer/BioNTech and Moderna vaccines is essential, since this is what will give protection to the variants. The Johnson & Johnson vaccine is single dosage and even with this, its clinical trials demonstrate excellent protection against severe disease caused by the South African variant. The duration of vaccine induced immunity is a concern, especially for effectiveness against the South African and Brazilian variants. Thus, even if you become fully vaccinated, a booster may still be advised in the future.”

In its guidance, the CDC wrote that benefits to reducing social isolation “may outweigh the residual risk of fully vaccinated people becoming ill with COVID-19.”

The guidance additionally reiterated the risks of safe travel and mass gatherings, regardless of vaccination status—a federal advisory which bucks against recent decisions by state legislators to reopen businesses and attractions at full capacity during a recent decrease in new daily COVID-19 cases.

What the guidance essentially comes to provide is a pathway for the most at-risk COVID-19 patients, who were prioritized first for vaccination, to break isolation in a safe and evidenced fashion.

"We know that people want to get vaccinated so they can get back to doing the things they enjoy with the people they love,” director Rochelle Walensky, MD, said in releasing the guidance.

As of the end of last week, nearly 10% of the US population had been fully vaccinated against COVID-19.

Just how effective the vaccines are against the COVID-19 variants, including the highly infectious B.1.1.7, has not yet been nailed down. “Early data show the vaccines may work against some variants but could be less effective against others,” the CDC states. The CDC continues that “we’re still learning how well COVID-19 vaccines keep people from spreading the disease. Early data show that the vaccines may help keep people from spreading COVID-19, but we are learning more as more people get vaccinated.”

In addition, fully vaccinated people who “live in a group setting (like a correctional or detention facility or group home) and are around someone who has COVID-19, you should still stay away from others for 14 days and get tested, even if you don’t have symptoms.”

The CDC guidance states that persons past 2 weeks of their final COVID-19 vaccine dose face little risk from unmasked, non-distancing indoor visiting of unvaccinated, low-risk members from a single household.

People Vaccinated Against COVID-19 Can Mingle Maskless Again

The expert’s advising the US Food and Drug Administration (FDA) will have a lot to chew over this Friday when they meet to discuss the phase 3 trial data for Janssen Ad26.COV2.S, the drug company’s candidate for a 

. The FDA’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC) will review Janssen’s evidence that the one-shot adenovirus prophylaxis provided 66.1% efficacy (95% CI, 55.0 – 74.8) in preventing COVID-19 versus placebo ≥28 days after administration. The 

 are the most extensively reported outcomes of an adenovirus vaccine candidate for the pandemic, and the first to highlight efficacy with a single-dose product.

Janssen Ad26.COV2.S is an intramuscular injection vaccine consisting of a replication-incompetent recombinant adenovirus type 26 (Ad26) vector which expresses the SARS-CoV-2 spike (S) protein.

Per the FDA, the product additionally includes inactive ingredients citric acid monohydrate, trisodium citrate dihydrate, ethanol, 2-hydroxypropylβ-cyclodextrin (HBCD), polysorbate 80, sodium chloride, sodium hydroxide, and hydrochloric acid.

Stored at 2-8 degrees Celsius, the vaccine is provided in a five-dose vial and administered at 0.5 mL per person.

The Ad26 platform is prominent in use with Ebola vaccines, and is being used for investigative prevention of Zika virus, filovirus, HIV, HPV, malaria, and respiratory syncytial virus (RSV) in other vaccine forms.

Since December 2020, the Ad26 platform has been used in vaccines administered to nearly 200,000 real-world and clinical trial participants, and has been associated with an overall “acceptable clinical safety profile,” the FDA wrote.

Ad26.COV2.S is currently being investigated in 5 randomized, double-blind, placebo-controlled clinical trials. The data supporting Janssen’s EUA application comes from Study 30001, a phase 3 efficacy and safety study comparing the vaccine candidate to placebo in preventing COVID-19 among 40,000 adult participants.

Included in the EUA review will be blinded safety data from Study 3009, a phase 3 efficacy and safety trial observed a two-dose regimen of Ad26.COV2.S that began in November 2020 but is yet to provide usable outcomes.

In Study 3001, 40,000 adults were randomized 1:1 to either intramuscular vaccine injection or placebo. Investigators sought co-primary endpoints of single-dose vaccine efficacy in preventing centrally confirmed, moderate to severe COVID-19 occurring at 2 time periods:

≥28 days after vaccination, among participants without evidence of prior SARS-CoV-2 infection at baseline

The trial population was required to have at least 30% of all participants aged ≥60 years old at baseline, and a maximum of 20% participants aged 18-40 years old, to assure observations could be made on older, greater-risk populations.

Median follow-up duration for participants in both efficacy and safety assessments was 8 weeks post-vaccination, the FDA’s equivalent to the mandated two-month minimum for COVID-19 vaccine EUA consideration. Janssen’s full analysis set included 29,111 (63%) participants who reached the eight-week mark.

The international study population was comprised of 46.7% (n = 18,356) Americans, 40.6% (15,981) residents of Latin America, and 12.7% (4984) residents of South Africa.

Mean participant age was 51.1 years old, with participants aged ≥60 representing 34.6% of the population. A majority of patients were male (55.5%) and White (62.1%). Black or African American (17.2%) and American Indian or Alaska Native (8.3%) comprised the next most represented races. At least 1 comorbidity indicative of increased COVID-19 severity risk was present in 40.8% of all participants.

In the first primary endpoint of Ad.26.COV2.S prevention of COVID-19 ≥14 days after vaccination, investigators observed 116 cases among vaccinated participants versus 348 in the placebo arm, indicating a 66.9% vaccine efficacy across all participant age groups (95% CI, 59.0 – 73.4). Among participants ≥60 years old, the efficacy was 76.3% (95% CI, 61.6 – 86.0).

In the secondary endpoint of COVID-19 prevention ≥28 days after vaccination among those with no SARS-CoV-2 history, investigators observed just 66 cases among vaccinated participants versus 193 in the placebo arm, indicating a vaccine efficacy of 66.1%. There were no statistically significant differences among younger and older participants in this outcome.

“The majority of COVID-19 cases were among participants in the United States, South Africa, and Brazil,” investigators wrote. “Study participants with comorbidities were not over-represented among COVID-19 cases as compared to the overall study population.”

In subgroup analyses assessing the vaccine’s efficacy in differing regions, investigators observed an efficacy of 74.4% (95% CI, 65.0 – 81.6) at ≥14 days and 72.0% (95% CI, 58.2 – 81.7) at ≥28 days in American participants.

Results among South African residents were 52.0% (95% CI, 30.3 – 67.4) and 64% (95% CI, 41.2 – 78.7) at the respective endpoints. Among Latin America residents, results were 64.7% (95% CI, 54.1 – 73.0) and 61.0% (95% CI, 46.9 – 71.8), respectively.

In preventing severe or critical COVID-19, Ad.26.COV2.S was associated with 76.7% efficacy at ≥14 days, and 85.4% at ≥28 days.

“In a post hoc analysis of all COVID-19 related hospitalizations starting 14 days after vaccination, including non-centrally confirmed cases, there were 2 cases in the vaccine group (with no cases after 28 days) compared with 29 cases in the placebo group (with 16 cases after 28 days),” investigators wrote. “As of February 5, 2021, there were 7 COVID-19 related deaths in the study in the placebo group and no COVID-19 related deaths in the vaccine group.”

Among 43,783 participants eligible for safety analysis, investigators observed no specific safety concerns that would warrant assessment prior to an EUA.

Common solicited adverse reactions associated with the vaccine included injection site pain (48.6%), headache (38.9%), fatigue (38.2%), and myalgia (33.2%)—a majority of which were mild and moderate in severity.

Investigators observed a “numerical imbalance” in non-serious urticaria events among vaccinated participants (n = 5) versus placebo (n = 1) within 7 days post-vaccination, as well as imbalances in thromboembolic events (15 vs 10) and tinnitus (6 vs 0). However, data was not considered sufficient enough to determine a causal relationship between the vaccine and these outcomes.

“There was more frequent, generally mild to moderate reactogenicity in participants 18 to 59 years of age compared to older participants,” investigators wrote. “There were no specific safety concerns identified in subgroup analyses by age, race, ethnicity, medical comorbidities, or prior SARS-CoV-2 infection.”

On Friday morning, the FDA will convene for its third public expert panel hearing on the validity and benefit of a COVID-19 vaccine candidate up for EUA consideration.

The VRBPAC will provide recommendations, based on the above evidence and other submitted details on Ad.26.COV2.S, whether its benefits outweigh its risk in active immunization to prevent COVID-19 in persons aged ≥18 years old.

In December 2020, the VRBPAC gave supporting votes to Pfizer-BioNTech’s BNT162b2 and Moderna’s mRNA-1273 in separate meetings. The pair of two-dose mRNA-platform vaccines are currently the only authorized products in the US, having received emergency authorization shortly after their respective VRBPAC signoffs.

If VRBPAC support and emergency authorization comes at the end of this week, Janssen Pharmaceuticals anticipates to have approximately 4 million doses of Ad.26.COV2.S ready to ship in the US next week.

Kevin Kunzmann

Articles

Janssen COVID-19 Vaccine Expected to be Temporarily Discontinued

WHO, China Report Posits Origins of COVID-19 Pandemic

People Vaccinated Against COVID-19 Can Mingle Maskless Again

Janssen’s Single-Dose COVID-19 Vaccine Under FDA Review