Antibody Titers Before, After 3rd Dose of SARS-CoV-2 BNT162b2 Vaccine in Adults ≥60

 Noa Eliakim-Raz, MD¹; Yaara Leibovici-Weisman, MD¹; Amos Stemmer, MD²; et al

doi:10.1001/jama.2021.19885

The durability of response to the SARS-CoV-2 BNT162b2 vaccine (Pfizer-BioNTech) in adults aged 60 years and older has yet to be determined. The immune response to 2 doses of BNT162b2 is lower in individuals aged 65 to 85 years vs 18 to 55 years.¹ Among 4868 health care workers receiving 2 BNT162b2 doses, a significant waning of the humoral response (IgG, neutralizing antibodies) within 6 months of the second dose was observed, especially among adults aged 65 years and older.² After a fourth SARS-CoV-2 wave in Israel, the Israeli Ministry of Health authorized, at the end of July 2021, a third BNT162b2 vaccine dose for individuals aged 60 years and older, which was subsequently expanded to younger age groups.

We assessed antispike (anti-S) IgG antibody titers before and after a third BNT162b2 dose in individuals aged 60 years and older because this population is at high risk of developing severe SARS-CoV-2 disease and was the first to receive authorization for a third dose.

Methods

After the initial authorization of a third dose in Israel, Rabin Medical Center (RMC) offered this dose to workers and their family members and recruited study participants aged 60 years and older at the vaccination center. Exclusion criteria included prior SARS-CoV-2 infection and active malignancy. Anti-S IgG titers were determined before (August 4-12, 2021) and 10 to 19 days after (August 16-24, 2021) the third vaccination. Serum from the blood samples was immediately transmitted to the microbiological laboratory, where titers of anti-S IgG antibodies were determined with the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). Seropositivity was defined as 50 arbitrary units (AU)/mL or higher. Additional information is available in the Supplement.

The study was approved by the ethics committee of RMC. All participants provided written informed consent.

The difference in IgG values before and 10 to 19 days after the third dose was evaluated with Wilcoxon signed rank test. Spearman correlation was used to assess the correlation between the IgG values and age of the participants. Multivariable analyses were performed by fitting a generalized linear model on the log of IgG values and included age and days from the first vaccination as continuous variables, and sex and comorbidities (dyslipidemia, hypertension, obesity, diabetes, and ischemic heart disease) as categorical variables. A 2-sided P < .05 was considered significant. Statistical analysis was performed with R version 4.0.2.

Results

Among the 97 study participants, the median age was 70 years (IQR, 67-74), and 61% were women (Table 1). Before the third dose (median, 221 days [IQR, 218-225] after the first vaccination), 94 participants (97%) were seropositive. The median titer level increased significantly after the third dose, from a median of 440 AU/mL (IQR, 294-923) to 25 468 AU/mL (IQR, 14 203-36 618) (P < .001), and all participants became seropositive (Table 1). No significant correlation was observed between age and IgG titers (R = −0.075; P = .47). No variable was significantly associated with higher IgG titers, including age, sex, days after first vaccination, and comorbidities (Table 2). No major adverse events were reported.

Discussion

This study found that a third BNT162b2 dose in adults aged 60 years and older was associated with significantly increased IgG titers after 10 to 19 days, with no major adverse events.

A third dose of the SARS-CoV-2 mRNA-1273 vaccine (Moderna) induced seropositivity in 49% of kidney transplant recipients who did not respond after 2 vaccine doses,³ although this observation cannot be generalized to older adults. In a study from Israel among 1 137 804 adults aged 60 years and older who had received 2 BNT162b2 doses 5 or more months earlier, a third dose was associated with lower rates of confirmed SARS-CoV-2 infections and severe illness.⁴ This study adds serologic data to the clinical data on response to a third dose in adults aged 60 years or older.

Study limitations include the small sample size, short follow-up, and lack of cellular immunity testing and neutralizing antibody testing. Although accumulating evidence suggests that IgG response is a correlate of disease protection,⁵ cellular immunity has also been suggested to play an important role in protecting against SARS-CoV-2.⁶

https://jamanetwork.com/journals/jama/fullarticle/2786096

U.S. Braces for Surge of Vaccinated International Travelers

 The United States is expecting a flood of international visitors crossing its borders by air and by land on Monday after lifting travel restrictions for much of the world's population first imposed in early 2020 to address the spread of COVID-19.

United Airlines is expecting about 50% more total international inbound passengers https://www.reuters.com/article/health-coronavirus-usa-travel-facts-idUSL1N2RM00E Monday compared to last Monday when it had about 20,000.

And Delta Air Lines Chief Executive Ed Bastian has warned travelers should be prepared for initial long lines.

"It's going to be a bit sloppy at first. I can assure you, there will be lines https://www.reuters.com/world/us/us-warning-international-travelers-long-lines-monday-official-2021-11-05 unfortunately," Bastian said, adding that "we'll get it sorted out".

Delta said in the six weeks since the U.S reopening was announced it has seen a 450% increase in international point-of-sale bookings versus the six weeks prior to the announcement.

White House spokesman Kevin Munoz said on Twitter "As we expect high demand when the US lifts its existing air and land travel restrictions Monday, we are taking critical steps to be prepared by providing additional resources."

The Biden administration has held multiple calls with U.S. airlines to prepare for the influx of additional travelers that will begin arriving at U.S. airports and has warned travelers crossing from Canada and Mexico by land or ferry to be prepared for longer waits starting Monday.

The rules have barred most non-U.S. citizens who within the prior 14 days have been in 33 countries -- the 26 Schengen countries in Europe without border controls, China, India, South Africa, Iran, Brazil, Britain and Ireland.

Trade group U.S. Travel said the countries accounted for 53% of all overseas visitors to the United States in 2019 and border communities were hit hard by the loss of tourists crossing from Mexico and Canada. The group estimates declines in international visitation "resulted in nearly $300 billion in lost export income" since March 2020.

U.S. airlines are boosting flights to Europe and other destinations that were impacted by the restrictions. Airlines are planning events on Monday with executives meeting some of the first flights.

Commerce Secretary Gina Raimondo and United Airlines President Brett Hart are holding an event at Chicago's O'Hare International Airport Monday to mark the reopening.

U.S. officials plan an Instagram live chat on Nov. 9 https://www.facebook.com/photo?fbid=253626883467036&set=a.227341039428954 to help answer questions.

Many international flights are expected to operate close to full or full on Monday, with high passenger volume throughout the following weeks.

Airlines will check vaccination documentation for international travelers as they currently do for COVID-19 test results. At land border crossings, U.S. Customs and Border Protection will ask if travelers have been vaccinated and spot check some documentation.

Children under 18 are exempt from the new vaccine requirements. Non-tourist travelers from nearly 50 countries with nationwide vaccination rates of less than 10% will also be eligible for exemption.

Also Monday, new contact tracing rules will take effect requiring airlines to collect information from international air passengers if needed "to follow up with travelers who have been exposed to COVID-19 variants or other pathogens."

https://www.usnews.com/news/top-news/articles/2021-11-07/us-braces-for-surge-of-vaccinated-international-travelers

SARS-CoV-2 variant detected in dogs and cats with suspected myocarditis

 A new study in the Veterinary Record reveals that pets can be infected with the alpha variant of SARS-CoV-2, which was first detected in southeast England and is commonly known as the UK variant or B.1.1.7. This variant rapidly outcompeted pre-existing variants in England due to its increased transmissibility and infectivity.

The study describes the first identification of the SARS-CoV-2 alpha variant in domestic pets; two cats and one dog were positive on PCR test, while two additional cats and one dog displayed antibodies two to six weeks after they developed signs of cardiac disease. Many owners of these pets had developed respiratory symptoms several weeks before their pets became ill and had also tested positive for COVID-19.

All of these pets had an acute onset of cardiac disease, including severe myocarditis (inflammation of the heart muscle).

"Our study reports the first cases of cats and dogs affected by the COVID-19 alpha variant and highlights, more than ever, the risk that companion animals can become infected with SARS-CoV-2," said lead author Luca Ferasin, DVM, PhD, of The Ralph Veterinary Referral Centre, in the UK. "We also reported the atypical clinical manifestations characterized by severe heart abnormalities, which is a well-recognised complication in people affected by COVID-19 but has never described in pets before. However, COVID-19 infection in pets remains a relatively rare condition and, based on our observations, it seems that the transmission occurs from humans to pets, rather than vice versa."

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Story Source:

Materials provided by Wiley. Note: Content may be edited for style and length.

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Journal Reference:

1. Luca Ferasin, Matthieu Fritz, Heidi Ferasin, Pierre Becquart, Sandrine Corbet, Meriadeg Ar Gouilh, Vincent Legros, Eric M. Leroy. Infection with SARS‐CoV‐2 variant B.1.1.7 detected in a group of dogs and cats with suspected myocarditis. Veterinary Record, 2021; 189 (9) DOI: 10.1002/vetr.944

https://www.sciencedaily.com/releases/2021/11/211105084113.htm

Analysts Raise Planet Fitness Price Target Post Q3 Beat

 

• Baird analyst Jonathan Komp raised Planet Fitness Inc's 
  PLNT+3.77%+ Free Alerts
   price target to $110 from $100 and kept an Outperform rating on the shares.
• The analyst said he sees a compelling lineup of additional drivers spanning marketing, digital, and pricing with the company's attractive growth outlook and increasing scale benefits supporting his confidence in positive estimate revisions and justifying its premium valuation.
• DA Davidson analyst Linda Bolton Weiser raised the price target to $105 from $85 (implying an upside of 9%) and kept a Buy rating on the shares. The analyst said the quarter marked the second period of a revenue beat since the start of the pandemic, with equipment sales serving as a "key area of upside."
• Jefferies analyst Randal Konik raised the price target to $115 from $100 (implying an upside of 19%) and kept a Buy rating on the shares.
• Randal opined that the company's results and guidance show a business that is "in full recovery post-pandemic" and one that is "stronger than pre-pandemic competitively" with "lots of unit growth and share gains ahead."
• Morgan Stanley maintained Planet Fitness with an Overweight rating and increased the price target from $93 to $101 (suggesting a 5% upside).

https://www.benzinga.com/analyst-ratings/analyst-color/21/11/23927718/analysts-give-fit-response-to-planet-fitness-q3-beat

Gottlieb not expecting travel from outside US to 'feed a lot of additional infections'

 Former Food and Drug Administration Commissioner Scott Gottlieb on Sunday said he is not expecting travel from outside the country to “feed a lot of additional infections,” one day before the U.S. is set to lift border restrictions for fully vaccinated international travelers.

Border restrictions for fully vaccinated international travelers coming into the U.S. will be lifted on Monday, after the White House announced last month that it was implementing a new travel policy.

The plan, which applies to both international air and land travel, is set to take effect on Monday.

Asked if the resumption of international travel will feed into the delta variant wave of COVID-19 infections the U.S. is experiencing, Gottlieb told host Margaret Brennan on CBS’s “Face the Nation” that he does not think the new policy will have a significant effect on cases in the U.S. because of the vaccine requirement and individuals not wanting to be trapped in a foreign country with the virus.

“I don't think the travel coming in from outside the U.S. is gonna feed additional infections or a lot of additional infections,” Gottlieb said.

“A lot of people who are coming into the U.S. first of all, they have to show that they've been vaccinated, a lot of them will make sure that they're not carrying the infection with them, they're not gonna want to get caught in a foreign country with the infection. So I suspect a lot of people are going to be cautious about coming into the U.S. with the infection,” he added.

He said there is not much the U.S. is able to do at this point to "interrupt" the delta wave, adding that it is "going to play out through the country."

"What's happening is that this delta infection is moving from less populated areas where it had engulfed those regions with infection, to more populated areas like Michigan like Minnesota like Wisconsin, so it's showing an overall stall in the decline nationally. This has to play out," Gottlieb said.

He added that the virus is now "gonna capture most people who remain unvaccinated at this point."

"We've done a phenomenal job vaccinating the adult population. Almost 81 percent of adults over the age of 18 have had at least one dose of vaccine. But for those who aren't getting vaccinated, they're going to get infected with this delta variant and that's going to ultimately be the end game," Gottlieb said.

While the U.S. is opening up travel to vaccinated international visitors on Monday, restrictions will remain in place for individuals traveling by land who have not yet been inoculated. Those travelers who have nonessential reasons for moving are barred from entering the U.S. until at least January.

https://thehill.com/homenews/sunday-talk-shows/580447-gottlieb-not-expecting-travel-from-outside-us-to-feed-a-lot-of

White House chief of staff 'confident' vaccine mandate will be upheld

 White House chief of staff Ron Klain said on Sunday that he was “quite confident” that a vaccine or COVID-19 test mandate for businesses would be upheld in the courts.

“I'm quite confident that when this finally gets fully adjudicated, not just a temporary order, the validity of this requirement will be upheld. It's common sense, Chuck, if OSHA can tell people to wear a hard hat on the job, to be careful around chemicals, it can put in place these simple measures to keep our workers safe,” Klain told “Meet the Press” moderator Chuck Todd on NBC News.

At least 26 states are filing legal challenges against a mandate developed by the Occupational Safety and Health Administration (OSHA) that requires businesses with at least 100 workers to either get vaccinated or adopt a policy that requires employees undergo weekly COVID-19 testing and wear face masks in lieu of the vaccination. 

States have either argued that the vaccine-or-test mandate is unconstitutional or that OSHA has not been authorized to put in place sweeping public health regulations. 

“OSHA’s vaccination mandate represents a real threat to individual liberty,” West Virginia Attorney General Patrick Morrisey said in a statement last week, whose state filed a lawsuit along with Kentucky, Idaho, Kansas, Ohio, Oklahoma and Tennessee.

“As we have seen throughout the country, it is also a public policy disaster that displaces vulnerable workers and exacerbates a nationwide shortage of front-line workers, with severe consequences for all Americans,” Morrisey added.

In a win for one coalition of states, the U.S. Court of Appeals for the Fifth Circuit issued a stay on the vaccine-or-test mandate on Saturday, temporarily stopping the federal requirement. The affected states include Texas, Louisiana, Mississippi, Utah and South Carolina. 

https://thehill.com/homenews/sunday-talk-shows/580443-white-house-chief-of-staff-confident-vaccine-or-test-mandate-will

White House faces onslaught of challenges to coronavirus vaccine rules

 The Biden administration is bracing for an onslaught of challenges to its coronavirus vaccine-or-test mandate for private sector businesses.

Administration officials insist they are on solid legal footing, but it’s not stopping business groups, religious organizations and GOP state attorneys general from filing a barrage of lawsuits or Republican lawmakers from threatening legislative actions.

The Labor Department on Thursday released the sweeping vaccine-or-test mandate, which President Biden had previously announced was coming. The requirement applies to businesses with at least 100 employees the agency set a Jan. 4 deadline for companies to comply. 

Biden has indicated he is running out of patience with Americans who refuse to get vaccinated against the coronavirus, and the rule is meant to force the issue in order to make workplaces safer.  

"Vaccination is the single best pathway out of this pandemic. And while I would have much preferred that requirements not become necessary, too many people remain unvaccinated for us to get out of this pandemic for good. So I instituted requirements – and they are working," Biden said in a statement.

Within hours of the rule's publication on Thursday, GOP governors and attorneys general promised lawsuits were forthcoming. By Friday, nearly all of them had either filed their own suit or joined an existing one. 

Republicans are framing the battle over vaccination mandates as a debate over civil liberties. 

A coalition of 11 states led by Missouri Attorney General Eric Schmitt (R), who is running for Senate, argued the Occupational Safety and Health Administration (OSHA) doesn't have the authority to put in place such sweeping federal public health regulations and that the rule unconstitutionally infringes on states' powers. 

Some businesses and organizations, including the Christian Employers Alliance and the Home School Legal Defense Association, joined Missouri's petition.

A separate group led by West Virginia Attorney General Patrick Morriesy (R) filed a similar lawsuit in the 6th Circuit, and asked for a stay of the requirement while the lawsuit is being argued. 

In the south, Alabama, Florida and Georgia joined together, as did Louisiana, Mississippi, South Carolina, Texas, and Utah. 

Despite the wave of litigation, White House officials have consistently expressed confidence that the requirements are legal.

White House deputy press secretary Karine Jean-Pierre on Friday said the administration is “very confident” the mandate can withstand legal challenges. 

“The Department of Labor has a responsibility to keep workers safe and the legal authority to do so,” she added. “We believe we have the authority to do this, the Department of Labor. And again, this is about saving people’s lives… and making sure their workplace is safe.” 

In an interview with McClatchy shortly after the rule was published, Labor Secretary Marty Walsh said state attorneys general have the right to sue, but he can't worry about the possibility that a judge could issue an injunction stopping enforcement.

"I’m not gonna really respond to hypotheticals. If that’s the route that the attorney general in Missouri or anyone takes, that’s the route they’re going to take, but the federal government has every right, every right, to put emergency temporary standards out to private businesses in the country," Walsh said. 

At the heart of the challenges is OSHA's authority to issue emergency temporary standards (ETS), which bypass the normal regulatory process and take effect immediately if the Labor secretary deems that employees are "exposed to grave danger from exposure to substances or agents determined to be toxic or physically harmful." 

Jeffrey Kopp, an employment lawyer and partner at Foley & Lardner, said the White House and OSHA has broad authority to enforce the requirements.

“OSHA did an exceptional job of validating its authority. I think in the ETS, they went to great lengths to detail the need for an emergency temporary standard,” he said. “It’s going to be a tough hill for challengers.”

But the lawsuits from conservatives argue there is no grave danger. For example, the Republican National Committee (RNC) on Friday said the administration's decision to impose a deadline two months away undermines the claim of an emergency. 

"Isn’t it interesting that this is such an emergency, this is so critical to our public health and safety, that we are going to delay it until after the holidays in January?" RNC Chairwoman Ronna McDaniel said Friday on Fox News. "It does seem politically motivated and takes away from the argument that Biden is making that it is a huge public health issue." 

West Virginia's coalition argued that OSHA's authority was limited to exposures from toxins in the workplace, and did not extend to a virus circulating widely in society. 

One potential advantage for the White House is that private businesses can give employees an option for regular testing instead of getting vaccinated.

“When you go in for an injunction, essentially you have to show that there’s irreparable harm that can’t be fixed with money. You could make the argument that if you have to be vaccinated, you’re suffering the irreparable harm. By offering the testing alternative, people still have the choice and the ability to choose to not be vaccinated,” King & Spalding employment lawyer Amanda Sonnebornshe said.

OSHA has used its ETS power nine times. Six of those were challenged, and only one withstood the scrutiny. Still, Sooneborn said the administration is in uncharted waters and there is no precedent, so it's hard to predict how different courts may rule.

“The workplace is certainly still not back to normal,” she said. “I can’t point to some other time or precedent that has been comparable. There has been challenges to OSHA ETS in the past but this one is so unique that it's almost not comparable in any way. Either way, I think both sides are going to argue that it’s an extreme situation.”

Outside of legal challenges, Republicans in Congress are also taking swipes at the new requirements. House GOP appropriators have introduced legislation that would block the administration from using federal money for enforcement.

In the Senate, Republicans led by Sen. Mike Braun (Ind.), the ranking member of a Senate committee on employment and workforce safety, are planning to use the Congressional Review Act (CRA) to force a vote on a resolution disapproving of the rule. 

It must be passed by the Senate and the House, both of which Democrats control, and be signed into law by the president. If Biden vetoes it, Republicans would need a two-thirds majority in each chamber to override it.

It's a tall task, but forcing a vote could put vulnerable incumbents in a tough spot.

While no congressional Democrats have spoken out against the rule, Democratic Kansas Gov. Laura Kelly on Friday said she doesn't think a mandate is the best solution for her Republican-leaning state.

Kelly, who is facing a difficult reelection next year, said she would seek an "alternative" plan.

https://thehill.com/homenews/administration/580340-white-house-facing-onslaught-of-challenges-to-coronavirus-vaccine