NYT issues correction after significantly overstating child COVID hospitalizations

 The New York Times (NYT) issued a correction to one of its stories this week, which significantly overstated the number of U.S. children who have been hospitalized for COVID-19.

The article discussed how countries were moving to “revisit the one-dose strategy” due to concerns over health data suggesting myocarditis was more common in children who receive the COVID-19 vaccine than previously thought. Conversely, the U.S. has not changed its guidance on the issue since June. The Centers for Disease Control and Prevention voted that month to recommend the vaccine for children older than 12 because “the benefits far outweighed the risk,” according to the NYT article.

The NYT used the misstated statistic as background information meant to describe the extent of COVID-19’s effect on U.S. children.

The Oct. 7 correction read:

The article also misstated the number of Covid hospitalizations in U.S. children. It is more than 63,000 from August 2020 to October 2021, not 900,000 since the beginning of the pandemic.

Other errors from the article were also discussed in the correction placed at the end of the article.

Those errors include incorrectly describing “actions taken by regulators in Sweden and Denmark,” who halted the use of pharmaceutical manufacturer Moderna’s vaccine for children. The NYT reported the two countries had only halted booster shots, not the vaccine entirely.

The article also misstated the timing of a Food and Drug Administration meeting on the authorization of the Pfizer-BioNTech vaccine for children. It will be held later this month.

https://abcnews4.com/news/nation-world/nyt-issues-correction-after-significantly-overstating-covid-hospitalizations-in-children

Variant A.30 spike heavily mutated, evades vaccine-induced antibodies with high efficiency

 

Prerna Arora, 

Cheila Rocha, 

Amy Kempf, 

Inga Nehlmeier, 

Luise Graichen, 

Martin S. Winkler, 

Martin Lier, 

Sebastian Schulz, 

Hans-Martin Jäck, 

Anne Cossmann, 

Metodi V. Stankov, 

Georg M. N. Behrens, 

Stefan Pöhlmann & 

Markus Hoffmann

DOI: https://doi.org/10.1038/s41423-021-00779-5

PDF: https://www.nature.com/articles/s41423-021-00779-5.pdf

The COVID-19 pandemic, caused by SARS-CoV-2, continues to rage in many countries, straining health systems and economies. Vaccines protect against severe disease and death and are considered central to ending the pandemic. COVID-19 vaccines (and SARS-CoV-2 infection) elicit antibodies that are directed against the viral spike (S) protein and neutralize the virus. However, the emergence of SARS-CoV-2 variants with S protein mutations that confer resistance to neutralization might compromise vaccine efficacy [1]. Furthermore, emerging viral variants with enhanced transmissibility, likely due to altered virus-host cell interactions, might rapidly spread globally. Therefore, it is important to investigate whether emerging SARS-CoV-2 variants exhibit altered host cell interactions and resistance against antibody-mediated neutralization.

We investigated host cell entry and antibody-mediated neutralization of the variant A.30 (also termed A.VOI.V2), which was detected in several patients in Angola and Sweden in spring 2021 and likely originated in Tanzania [2]. For comparison, we analyzed the Beta (B.1.351) and Eta (B.1.525) variants. These two variants were first detected in Africa, and the Beta variant, which is considered a variant of concern (VOC), shows the highest level of neutralization resistance among SARS-CoV-2 VOCs [3, 4]. Compared to the S protein of SARS-CoV-2 B.1, which circulated in the early phase of the pandemic, the S protein of the A.30 variant contains 10 amino acid substitutions and five deletions (Fig. 1a and Supplementary information, Fig. S1a). All deletions along with four substitutions are found in the N-terminal domain of the surface unit S1, which harbors an antigenic supersite that is targeted by most neutralizing antibodies not directed against the receptor-binding domain (RBD) [5]. In addition, three mutations are located inside the RBD, which binds to the cellular receptor ACE2 and constitutes the main target of neutralizing antibodies (Fig. 1a). Two of these mutations, T478R and E484K, are located close to the ACE2 binding site (Supplementary information, Fig. S1a), and E484K is known to reduce susceptibility to antibody-mediated neutralization. Finally, two mutations are located close to the S1/S2 cleavage site, and one mutation is found in the transmembrane unit S2, which facilitates fusion of the viral envelope with cellular membranes (Fig. 1a).

...In summary, A.30 exhibits a cell line preference not observed for other viral variants and efficiently evades neutralization by antibodies elicited by ChAdOx1 nCoV-19 or BNT162b2 vaccination. SARS-CoV-2 entry into cell lines depends on S protein activation by the cellular proteases cathepsin L or TMPRSS2 [8], and activation by the latter is thought to support viral spread in the lung. Therefore, it is noteworthy that enhanced A.30 entry was observed for cell lines with cathepsin L (Vero, 293 T, Huh-7, A549 cells)—but not TMPRSS2 (Calu-3, Caco-2)-dependent entry [8]. Thus, one could speculate that A.30 might use cathepsin L with increased efficiency and slight (but not statistically significant) resistance of A.30 against the cathepsin L inhibitor MDL 28170 supports this possibility (Supplemental information, Fig. S1c). Notably, robust entry into cell lines was combined with high resistance against antibodies induced upon ChAdOx1 nCoV-19 or BNT162b2 vaccination. Neutralization resistance exceeded that of the Beta (B.1.351) variant, which is markedly neutralization resistant in cell culture and, in comparison with the Alpha (B.1.1.7) variant, is less well inhibited by the ChAdOx1 nCoV-19 vaccine [9]. Nevertheless, heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination, which was previously shown to augment neutralizing antibody responses against VOCs compared to corresponding homologous vaccinations [7, 10], might offer robust protection against the A.30 variant. Collectively, our results suggest that the SARS-CoV-2 variant A.30 can evade control by vaccine-induced antibodies and might show an increased capacity to enter cells in a cathepsin L-dependent manner, which might particularly aid in the extrapulmonary spread. As a consequence, the potential spread of the A.30 variant warrants close monitoring and rapid installment of countermeasures.

https://www.nature.com/articles/s41423-021-00779-5

Louisiana to lift state mask mandate

 Louisiana Gov. John Bel Edwards (D) announced Tuesday he is lifting the state’s mask mandate Wednesday.

“After sustained improvement across the state in new cases, test positivity & hospitalizations, I will lift Louisiana’s statewide mask mandate in all settings except for K-12 schools, which may opt out as long as they continue implementing existing CDC quarantine guidance,” the governor said in a tweet.

Louisiana was one of the states hit hardest by the delta variant wave earlier in the fall and Edwards implemented the state-wide mask mandate toward the end of August.

COVID-19 cases in the state have been on the decline since then with Louisiana State University announcing earlier in the month it was rescinding its policy to require coronavirus vaccines to go to football games due to the drop in cases.

While Louisiana now has one of the lowest infection rates in the country, according to The Associated Press, the state still has one of the lowest vaccination rates as well.

The state only has 47 percent of its residents fully vaccinated against the virus, according to data from Johns Hopkins University. 

Edwards is keeping the mask mandate in K-12 schools, with schools without masks having to follow strict quarantine guidelines.

Universities and cities such as New Orleans have said they plan to keep their own indoor masking mandates in place despite the lifted statewide order, the AP noted.

https://thehill.com/policy/healthcare/578608-louisiana-to-lift-state-mask-mandate

DBV: FDA asks more changes to Viaskin Peanut development

 DBV Technologies S.A. (Euronext: DBV – ISIN: FR0010417345 – Nasdaq Stock Market: DBVT), a clinical-stage biopharmaceutical company, today reported financial results for the third quarter of 2021. The quarterly financial statements were approved by the Board of Directors on October 26, 2021. The Company also provided regulatory updates from the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for Viaskin™ Peanut.

US Regulatory Update:

On October 14, 2021, DBV received communication from the FDA concerning the STAMP protocol submission of May 6, 2021. The FDA has requested a stepwise approach to DBV’s modified Viaskin Peanut (mVP) development program. The FDA would like to review the data from DBV’s protein uptake release study prior to providing additional comments on the STAMP protocol design.

In its communication, FDA stated that guidance is forthcoming on how best to demonstrate the protein uptake comparability of the mVP to the reference or current patch (cVP).

The STAMP trial will not be initiated until DBV receives complete feedback from the FDA.

“DBV is working hard to find an efficient and timely path forward. On behalf of patients and providers urgently awaiting a therapeutic advancement in treating peanut allergy, DBV will continue to pursue our goal of bringing Viaskin Peanut to the food allergy community,” said Daniel Tasse, Chief Executive Officer, DBV Technologies.

https://finance.yahoo.com/news/dbv-technologies-reports-third-quarter-201500800.html

Exscientia started at Buy by 2 sell siders, at Neutral by 3rd

 

• BofA initiated coverage on Exscientia Plc 
  EXAI-8.43%+ Free Alerts
   with a Buy and $27 price target, implying a 25.5% upside.
• Analyst Michael Ryskin believes Exscientia stands out from other tech-enabled biotechs, as it uses AI to develop better drugs in a shorter period. 
• Ryskin adds that the company's lead compounds remain in the early Phase 1 trials as the platform validation continues.
• Goldman Sachs also initiated Exscientia with a Buy and $30 price target, suggesting a 39.5% upside. 
• Analyst Chris Shibutani believes the company is well-positioned to become a "pharmatech leader" in end-to-end artificial intelligence-enhanced drug discovery and development. 
• Exscientia's proprietary integration of advanced modeling and algorithmic learning could potentially result in better drug candidates & trials, more efficient development, and ultimately, higher probabilities of success, Shibutani tells investors.
• Morgan Stanley initiated coverage of Exscientia with an Equal Weight rating and a $25 price target, implying a 16% upside.
• Analyst Vikram Purohit says that Exscientia's platform "appears highly productive," and recent partnerships provide "significant validation of the company's AI-guided approach."
• But, Purohit prefers to remain on the sidelines as he awaits updates from the company's lead pipeline programs. 
• The company's most advanced programs: EXS21546 (Phase 1 study) and EXS617 (preclinical development), could have utility in indications such as lung & breast cancer. The analyst estimates about $1.5 billion in peak economic contribution to Exscientia.
• Earlier this month, Exscientia debuted on NASDAQ.

https://www.benzinga.com/analyst-ratings/analyst-color/21/10/23566243/three-analysts-initiate-coverage-on-this-ai-based-pharmatech

Half of unvaccinated California state workers not being tested: report

 Only about half of California's 59,000 unvaccinated state employees were tested in the first week of October, despite a mandate enacted this summer requiring state workers to be fully vaccinated against COVID-19 or submit to weekly testing. 

The finding from the The Los Angeles Times comes about three months after California Gov. Gavin Newsom (D) issued the first-of-its-kind mandate, and is based on data from the California Department of Human Resources. 

In its report, the Times specifically cited the California Department of Forestry and Fire Protection, in which 6,700 employees are either not vaccinated or did not provide their status to the department. However, Cal Fire said it is only testing 75 employees.

At the Department of Motor Vehicles, 59 percent of employees are fully vaccinated, but only 411 of the department's 3,600 unvaccinated employees are being tested, the Times added. 

"If we don’t have the warning system of testing, then we need to reconsider what we are doing,” Dorit Reiss, a law professor who specializes in vaccine policies at the UC Hastings College of the Law, said to the Times. “Testing is not a great substitute for vaccinating, but it’s a great backup and better than nothing.”

Newsom had set an Aug. 2 deadline for California workers to be vaccinated. But that deadline has been largely ignored with no repercussions for those who were non-compliant, according to the Times.

In total, California's Department of Human Resources said 66 percent of employees were vaccinated. Employees who were fully remote did not have to be tested or submit proof of vaccination, the Times noted.

"The entire point of Gov. Newsom being the first governor to say state employees should be vaccinated is because these employees are public interfacing, and the vaccine protects them and the public they serve. Then, if the testing component isn’t being universally applied, you are defeating the point," infectious-disease expert Dr. Monica Gandhi told the Times.

When Newsom announced the mandate for state employees, the governor also mandated vaccines for healthcare workers. Unlike other employees, people in healthcare were not given the option of testing instead of vaccination; however, they could request a medical or religious exemption.

The Times noted that the healthcare worker vaccination push was seemingly more successful than the one for state employees, with one hospital system reporting that its employee vaccination rate jumped from 60 percent to 90 percent following the mandate. 

https://thehill.com/homenews/state-watch/578553-half-of-unvaccinated-california-state-workers-not-being-tested-report

FDA panel recommends authorizing Pfizer COVID vaccine for younger kids

 A key Food and Drug Administration (FDA) expert advisory panel on Tuesday recommended the agency authorize Pfizer's COVID-19 vaccine for use in children between the ages of 5 and 11, bringing those children one step closer to getting a shot.

The Vaccines and Related Biological Products Advisory Committee (VRBPAC) found that the benefits of the vaccine outweighed its risks and voted nearly unanimously 17-0, with one abstention, to recommend the agency authorize the shot.

FDA is not bound to follow the panel's recommendation, though it often does. 

Extending vaccine eligibility to children younger than 12 has been a major goal of public health officials and eagerly awaited by many pediatricians and families. The FDA has been under pressure for months to move quickly to authorize vaccines for younger children, one of the final barriers to overcome in the country's historic vaccination campaign.  

Pfizer submitted data to the FDA in late September, and formally asked for emergency use authorization earlier this month. An agency review of the data published late Friday found that the benefits of the vaccine "clearly outweigh the risks," indicating that FDA scientists have a favorable view of the evidence.

Some members of the panel said they felt the recommendation was too broad. Not all children will need the vaccine, they argued, or some may only need a single dose because they've been previously infected with COVID-19.

There were also concerns about monitoring the safety profile of the vaccine, because of the potential for extremely rare but serious condition called myocarditis, or heart inflammation.

Cases of myocarditis are generally more common in teenagers between the ages of 16 and 19. It's less common in adolescents, and even more rare in young children. The problem did not turn up in the Pfizer-BioNTech pediatric clinical trial, though experts said it was too small to detect such a rare complication.

Patrick Moore, a professor at the University of Pittsburgh Cancer Institute, said the potential risks of myocarditis are important, but theoretical. The risks of COVID-19 to children are much more real, he said.

Moore noted that 94 children in the 5-11 year old age group have died of COVID. "All of them had names. All of them had mothers," he said. "It's very hard for me to believe the risk for a severe outcome is going to come close to the risk, known risk, that we've seen for this virus in this age group." 

A decision by agency regulators is expected in the coming days, and a Centers for Disease Control and Prevention (CDC) panel is scheduled to meet Nov. 2 and 3 to recommend how the vaccines should be used. 

If the panel gives favorable recommendations and CDC Director Rochelle Walensky accepts them, the vaccination campaign would begin.

A study from Pfizer released as part of its panel briefing document last week showed that smaller doses of its COVID-19 vaccine for children ages 5 to 11 appear safe, and are nearly 91 percent effective at preventing symptomatic disease.

Pfizer said vaccinating children in that age group "could prevent harms" including interruption of education, hospitalization, severe illness, long-term consequences, and death.

The Biden administration last week said it's purchased enough vaccine to inoculate all 28 million 5- to 11-year-olds in the U.S., and will distribute it through a network that will rely on more than 25,000 pediatrician's offices, as well as community health centers, schools and pharmacies.

Children ages 5 to 11 account for about 9 percent of all reported COVID cases in the U.S., according to FDA data presented to the panel on Tuesday. While it has been declining in recent week, the number of new COVID-19 cases in kids remains exceptionally high. This past week almost 118,000 child COVID cases were added, with more than one million over the past six weeks, according to the American Academy of Pediatrics.

https://thehill.com/policy/healthcare/578567-fda-panel-recommends-authorizing-pfizer-covid-vaccine-for-younger-kids