AstraZeneca: Positive meeting with EU over vaccine row

 AstraZeneca had a positive meeting with the European Commission last week, the Anglo-Swedish company said after an Italian newspaper said the group had not replied to an EU letter of complaint over COVID-19 vaccines within a 20-day deadline.

European Union member states and the pharmaceutical company are at odds over the delivery of shots after the group shipped less than indicated to the EU than in the initial agreement.

Italian daily Corriere della Sera said on Sunday AstraZeneca had yet to react to a letter sent by the Commission on March 19 to complain about low-contract supplies of COVID-19 vaccines.

“We can confirm we have responded to the Commission within the required time-frame of the dispute resolution mechanism, and that our team had a very collaborative meeting with the Commission last week,” AstraZeneca’s Director of Global Media Relations Matthew Kent said in an emailed message.

Earlier on Sunday a spokesman for the European Commission confirmed that Brussels on March 19 had written to AstraZeneca, calling it “a notice for dispute settlement”, adding this was a first step to engage in an dialogue to resolve the issue.

“At this stage we are still waiting for the necessary elements ... we remain in contact with AstraZeneca to ensure timely delivery of a sufficient number of doses,” the spokesman had told Reuters, without elaborating.

According to the contract signed between EU and the company, which is public, if a dispute arises, one of the parties shall first notify the problem with a letter. Then, after 20 days from the written notice, they “shall meet and attempt to resolve the dispute by good faith negotiations”.

Under the contract signed on COVID-19 vaccines, European Union states had expected to receive 120 million doses by the end of March from AstraZeneca, but the company had supplied only 30.12 million doses, Corriere said.

AstraZeneca’s spokesman did not comment on the supply data.

With contagion still rising in many European countries and vaccination campaigns hitting hurdles, some governments have shown increasing irritation with the pharmaceuticals group.

“Manifestly, they (AstraZeneca) did not honour their commitments and thus, in a certain way, they were mocking us Europeans,” France’s European Affairs Minister Clement Beaune said on Sunday, speaking to LCI television news channel.

Beaune said the EU letter to the Anglo-Swedish group could even lead to a battle in court.

“We sent a formal notice in recent days, it is the beginning of a possible judicial procedure if the company doesn’t fix things,” he said, adding that putting pressure on the company to accelerate production in Europe appeared to be a better option compared with starting a legal process, which would take time.

https://www.reuters.com/article/us-health-coronavirus-eu-astrazeneca/astrazeneca-says-it-had-positive-meeting-with-eu-over-vaccine-row-idUSKBN2BY0HI

Common COVID Vaccine Administration Errors

 In December 2020, the US Food and Drug Administration approved Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech and Moderna COVID-19 vaccines. As of March 20, 2021, more than 120 million COVID-19 vaccine doses have been administered to people in the United States. As we work toward expanding COVID-19 vaccination further, however, we must take care to minimize errors in vaccine administration.

Proper vaccine administration is necessary to ensure vaccine effectiveness, achieve optimal vaccine-induced protection, avoid safety implications, and assure confidence in the COVID-19 vaccination program. Since the launch of vaccination efforts on December 14, 2020, the Centers for Disease Control and Prevention (CDC) has received more than 300 inquiries through the CDC inquiry response services (eg, CDC-INFO, NIP-INFO) seeking guidance for managing an mRNA COVID-19 vaccine administration error that had occurred.

The most common error type described in inquiries (Table), representing more than one third of inquiries, was administration of a lower-than-authorized dose (eg, the needle disconnecting from the syringe, resulting in vaccine spillage). Other frequent error types queried included administration to someone younger than the authorized age (18.5% of inquiries) and administration by a route other than intramuscular (IM) (12.3% of inquiries).

These inquiries probably underestimate the actual number of COVID-19 vaccine administration errors and might not capture all inquiries CDC received.

Table. COVID-19 Vaccine Administration Error Inquiries Received by CDC, December 14, 2020, to February 28, 2021

Error type	Example	Number (%) of topics across inquires received (N = 324)a
Administration by the incorrect route	Subcutaneous administration	40 (12.3%)
Administration at an incorrect anatomic site	Administration into shoulder bursa; administration in the gluteal muscle of the buttock	33 (10.2%)
Higher-than-authorized dose volume administered	Administration of undiluted vaccine	11 (3.4%)
Lower-than-authorized dose volume administered	Dose leaked out of syringe; recipient pulled away and dose leaked out	114 (35.2%)
Administration to someone younger than the authorized age	Administration to person aged < 16 years (Pfizer-BioNTech) or < 18 years (Moderna)	60 (18.5%)
Administration of a mixed-product series	First and second doses from different manufacturer	16 (4.9%)
Administration of a second dose earlier than the 4-day grace period	Second dose administered < 17 days (Pfizer-BioNTech) or < 24 days (Moderna) after the first dose	21 (6.5%)
Dose administered after improper storage and handling	Temperature excursion; more than allowed time after first vial puncture; use after beyond use date	15 (4.6%)
Other	Incorrect diluent; incorrect needle length; expired syringe	14 (4.3%)
aSome inquiries represent errors affecting more than one vaccine recipient (eg, at a mass vaccination clinic).

The interim clinical considerations for the use of currently authorized COVID-19 vaccines contain guidance for managing vaccine administration errors. For most errors, CDC does not recommend repeating the dose. For dosage errors in which less than half the dose was administered, as well as errors in which only diluent was administered, CDC recommends repeating the dose as soon as possible in the opposite arm. CDC refers inquiries about errors related to improper storage and handling or use of an incorrect diluent to the vaccine manufacturer for guidance.

Errors Reducing Vaccine Effectiveness

Some vaccine administration errors might reduce vaccine effectiveness. Although data for mRNA COVID-19 vaccines are lacking, IM vaccine administration in general (compared with subcutaneous administration) optimizes immunogenicity and minimizes local adverse reactions. Subcutaneous fat has poor vascularity, leading to slow mobilization and antigen processing for some other vaccines administered subcutaneously.

When some vaccines (ie, hepatitis B, human papillomavirus, or influenza vaccines) are inadvertently administered subcutaneously, readministration by the IM route is recommended. However, it is not necessary to readminister vaccine doses intended for subcutaneous administration (eg, MMR or varicella vaccines) that were inadvertently administered by the IM route because immune response is unlikely to be affected.

Errors Affecting Safety

The safety implications of many COVID-19 vaccine administration errors remain unknown (eg, administration to someone younger than the authorized age or administration of a second dose earlier than the 4-day grace period). Shoulder injury related to vaccine administration (SIRVA) is a recognized consequence of unintentional injection of a vaccine into the tissues and structures lying underneath the deltoid muscle of the shoulder. It is an injury to the musculoskeletal structures of the shoulder, including ligaments, bursa, and tendons. SIRVA is thought to occur from unintended injection of vaccine or trauma from the needle into or around the underlying bursa of the shoulder.

Signs and symptoms of SIRVA include shoulder pain and decreased range of motion, hypothesized to be caused by an inflammatory reaction in the shoulder joint. SIRVA is preventable with correct recognition of anatomical landmarks and proper IM vaccine administration techniques.

As outlined in the EUA Fact Sheet for Healthcare Providers, vaccination providers are required to report vaccine administration errors — whether they are associated with an adverse event or not — to the Vaccine Adverse Event Reporting System. Vaccination providers should assess how the error occurred and take steps to prevent future errors.

Millions more doses of COVID-19 vaccines will be administered over the next few months. Although this report covers the time period when mRNA COVID-19 vaccines were administered, errors might occur with administration of other COVID-19 vaccine types, such as the newly authorized Janssen (Johnson & Johnson) viral vector vaccine.

Errors related to COVID-19 vaccine administration might result in reduced vaccine effectiveness and safety implications. A limited vaccine supply and strained vaccination provider workforce might preclude readministration of incorrectly administered doses. To prevent COVID-19 vaccine administration errors, providers should be aware of the EUA Fact Sheet for Healthcare Providers, Advisory Committee on Immunization Practices (ACIP) recommendations, and CDC's interim clinical considerations for COVID-19 vaccination (see the Resources section). Given the importance of vaccinating as many Americans as quickly and safely as possible, it is critical to prevent waste and make every dose count.

Resources

COVID-19 ACIP Vaccine Recommendations

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States

Vaccine Information for Healthcare Professionals

ACIP General Best Practice Guidelines for Immunization

List of Adverse Events Providers Are Required to Report to VAERS

Pfizer-BioNTech EUA Fact Sheet for Vaccination Providers

Moderna EUA Fact Sheet for Vaccination Providers

Janssen COVID-19 Vaccine (Johnson & Johnson) EUA Fact Sheet for Vaccination Providers

https://www.medscape.com/viewarticle/948294

New Side Effects With AstraZeneca and Janssen COVID-19 Vaccines?

 In addition to the unusual blood clots linked to the AstraZeneca COVID-19 vaccine, which have received extensive attention in the past couple of weeks, other safety signals are also being investigated with this vaccine, and now with Johnson & Johnson's Janssen vaccine as well, the European Medicines Agency (EMA) reports.

Highlights of the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) meeting April 6-9 include that the agency has started a review of a safety signal to assess reports of capillary leak syndrome in people who were vaccinated with Vaxzevria (formerly COVID-19 Vaccine AstraZeneca).

It also reports that PRAC has started a review of a safety signal to assess reports of thromboembolic events with low platelets in people who received the COVID-19 Vaccine Janssen.

Capillary Leak Syndrome with AZ Vaccine

An EMA press release issued today notes that five cases of capillary leak syndrome, characterized by leakage of fluid from blood vessels causing tissue swelling and a drop in blood pressure in individuals receiving the AstraZeneca vaccine, were reported in the EudraVigilance database.

"At this stage, it is not yet clear whether there is a causal association between vaccination and the reports of capillary leak syndrome. These reports point to a 'safety signal' — information on new or changed adverse events that may potentially be associated with a medicine and that warrants further investigation," the EMA states.

PRAC will evaluate all the available data to decide if a causal relationship is confirmed or not, it adds.

Thromboembolic Events with J&J/Janssen Vaccine

Four serious cases of unusual blood clots with low blood platelets have been reported postvaccination with COVID-19 Vaccine Janssen, EMA reports. One case occurred in a clinical trial and three cases occurred during the vaccine rollout in the US. One of them was fatal.

COVID-19 Vaccine Janssen is currently only used in the US, under an emergency use authorization. COVID-19 Vaccine Janssen was authorized in the EU on March 11. The vaccine rollout has not started yet in any EU member state but is expected in the next few weeks.

The Janssen vaccine uses an adenovirus vector, as does the AstraZeneca vaccine.

PRAC is investigating these cases and will decide whether regulatory action may be necessary, which usually consists of an update to the product information, it adds.

https://www.medscape.com/viewarticle/949048

Fauci Admits PPE Shortages Drove Up Covid Death Toll

 Dr. Anthony Fauci thanked America's health care workers, who "every single day put themselves at risk" during the pandemic, even as he acknowledged that PPE shortages had contributed to the deaths of more than 3,600 of them.

"We rightfully refer to these people without hyperbole — that they are true heroes and heroines," he said in an exclusive interview with The Guardian. The deaths of so many health workers from covid-19 are "a reflection of what health care workers have done historically, but putting themselves in harm's way by living up to the oath they take when they become physicians and nurses," said Fauci.

KHN and The Guardian have tracked health care workers' deaths throughout the pandemic in the "Lost on the Frontline" database. More than 3,600 health worker deaths have been tallied in the database, considered the most authoritative accounting in the country.

Personal protective equipment — including gloves, gowns and critical masks — have been in short supply since the pandemic began and heightened the toll. The U.S. is the world's largest importer of PPE, which made it especially vulnerable to the demand shock and export restrictions that hit the global market last spring.

"During the critical times when there were shortages was when people had to use whatever was available to them," said Fauci. "I'm sure that increased the risk of getting infected among health care providers."

Shortages were compounded by the federal government's failure to maintain a national stockpile of personal protective equipment, and the Trump administration's refusal to order more domestic manufacturing of PPE. That left health workers to use trash bags as gowns, reuse N95s for weeks and, at times, go totally without gloves.

The shortages led to protests by health workers, who said working amid the pandemic without equipment left them like "sheep going to slaughter." Nina Forbes, a nurse at an assisted living facility, was forced to wear a trash bag at times, according to her daughter, and later died. A year into the pandemic, gowns and gloves remain in short supply, according to the Food and Drug Administration.

Nearly 560,000 Americans have died in the covid pandemic, with many more experiencing long-term symptoms of covid.

Health workers have been especially vulnerable through the pandemic, as they have treated patients through early waves when the lack of personal protective equipment was especially acute, through summer surges and a disastrous peak in the winter.

A study of health workers in the U.S. and the United Kingdom in The Lancet found health workers are three times more likely than the general public to become infected with the covid virus, with disproportionate impacts on minority health workers.

"It's very clear when you just go to the media and see the images on television — the stress and the strain on the faces of health care providers, nurses, doctors, other people involved in the health care enterprise," said Fauci.

Nevertheless, the U.S. government has failed to systematically count health worker deaths. Members of Congress, the Health and Human Services Department and academic reports have cited The Guardian and KHN's reporting as the most comprehensive. A growing chorus of policy experts and unions have called for a comprehensive count of health worker deaths.

"We certainly want to find an accurate count of the people who die," said Fauci, without noting when the government should undertake such an effort. "Certainly, that's something I think would fall under the auspices of the federal government."

Even as the vaccine rollout picks up speed, health workers continue to be imperiled. More than 400 died between the time the rollout began and late February. Infections among vaccinated health workers have steeply declined, but because deaths are a lagging indicator of the spread of covid, some health workers will have been sickened before widespread vaccination.

At the same time, immunity to coronaviruses generally wanes over time and variants may blunt the efficacy of some vaccines. A global shortage of vaccines means dozens of poor nations have not inoculated a single person. Advocates argue this has led to a global "vaccine apartheid," which will contribute to the continued emergence of variants. Both scenarios could imperil health workers anew and necessitate a new round of adult mass vaccination.

Studies into the duration of immunity for vaccines, and variants' impact on vaccines, are ongoing. "If we're going to need to do boosting with a variant-specific boost, [we] will be prepared for it because we're already doing a study," Fauci said, with such research taking place at the National Institute of Allergy and Infectious Diseases, which he leads. Even so, "it looks like our ability to protect against variants with the standard vaccine might be better than we anticipated."

Regardless of how future vaccination campaigns play out, Fauci said, U.S. policymakers should learn from what has transpired over the past year.

"We better make sure the lesson we will learn is that we will never again be in a situation where people who are putting their health and their safety on the line don't have the appropriate equipment to protect themselves safely," he said.

https://www.medscape.com/viewarticle/949065

Alnylam: Positive Late-Breaking Data from Ongoing Hypertension Phase 1

 Single Doses of Investigational ALN-AGT Achieved Sustained Reductions in Serum Angiotensinogen (AGT) at 12 Weeks Resulting in Reduced Blood Pressure –

– Durability of AGT Knockdown Supports the Potential of Once Quarterly or Biannual Dosing –

– ALN-AGT was Generally Well Tolerated, with No Serious Treatment-Related Adverse Events or Study Withdrawals –

– Data Confirm Potential for AGT Silencing as a Novel Approach for Treatment of Hypertension and Support Initiation of Phase 2 KARDIA Studies Mid-Year –

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today positive interim results from the ongoing Phase 1 study of ALN-AGT, a subcutaneous investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) for the treatment of hypertension. Results were presented during a late-breaking oral presentation at the 2021 Joint Meeting of the European Society of Hypertension (ESH) and the International Society of Hypertension (ISH). ALN-AGT treatment was associated with dose-dependent knockdown of AGT and reductions in blood pressure (BP) with a durability that supports the potential for a once quarterly or biannual dosing regimen, and was found to be generally safe and well tolerated.

"We face an intractable challenge in controlling hypertension, which affects an estimated 1.13 billion people worldwide and is a major risk factor for cardiovascular disease morbidity and premature mortality.i Despite well-established treatments including lifestyle modifications and several classes of available anti-hypertensive medications, fewer than 20 percent of people with hypertension globally have it under control,"i said Reinhold Kreutz, M.D., Ph.D., Professor, Charité and Berlin Institute of Health, Institute of Clinical Pharmacology and Toxicology and President, ESH. "While several factors contribute to the high rate of uncontrolled hypertension, inconsistent blood pressure control and medication adherence in those patients receiving treatment may play critical roles, and the encouraging early-stage results for ALN-AGT suggest its potential as a novel therapeutic approach to address long-standing treatment gaps."

https://finance.yahoo.com/news/alnylam-presents-positive-breaking-data-142800584.html

Biden officials rebuff appeals to surge Covid-19 vaccine to Michigan

 Amid Michigan’s worst-in-the-nation coronavirus surge, scientists and public health officials are urging the Biden administration to flood the state with additional vaccine doses.

So far, though, their plea has fallen on deaf ears. Instead, the federal government is sticking to a vaccine-allocation strategy that largely awards doses to states and territories based on their population. As a result, most jurisdictions are still receiving similar per-capita vaccine supplies, regardless of how many people there are getting sick — or how many excess vaccine doses they have. 

Experts have cast a surge in Michigan’s vaccine supply as a critical tool in combating the state’s most recent Covid-19 crisis. The state is currently recording nearly 7,000 new cases per day, just shy of its all-time peak in December. Hospitalizations and deaths, which tend to lag a few weeks behind increasing case counts, are also on the rise. 

“I would be surging a lot of vaccines to Michigan right now,” said Ashish Jha, the dean of the Brown University School of Public Health. “To me, this is a no-brainer policy, and I would be curious to hear why the Biden team hasn’t done this.” 

During a media briefing on Wednesday, White House officials acknowledged that Michigan’s situation is dire. They gave no indication, though, that they would send additional vaccines there to help quell the surge, when STAT asked. They argued that it is too early in the national vaccine campaign to begin targeting supply based on case rates. 

Rochelle Walensky, the director of the Centers for Disease Control and Prevention, said the agency was working to expand testing capacity in the state, address outbreaks in Michigan’s jails and prisons, and scale up genomic sequencing. The one strategy she did not bring up was scaling up vaccine supply. 

“By and large, we are still allocating vaccines based upon population,” Andy Slavitt, one of President Biden’s top pandemic-response advisers, said during the briefing. “Clearly we will get to a place where more targeted strategies will work, but right now I would commit to you that we’re doing both.” 

The administration’s fixed position is at odds with public health experts like former Food and Drug Administration commissioner Scott Gottlieb; the physician-researcher Eric Topol; and the Flint, Mich.-based public health advocate Mona Hanna-Attisha. 

Some have attempted to quantify what’s at stake more precisely: One modeler, University of California, Berkeley, research programmer Joshua Schwab, projected recently that doubling Michigan’s vaccine allocation for two weeks could help prevent 10,000 hospitalizations and 1,200 deaths. 

The state’s Democratic governor, Gretchen Whitmer, first asked President Biden for additional vaccine supplies on March 30. But Jeff Zients, the White House’s Covid-19 response coordinator, rebuffed the request, the Washington Post reported.  

“I know that some national public health experts have suggested this as an effective mitigation tool, and I know we’d certainly welcome this approach in our state,” Whitmer reportedly said on a call between governors and Biden administration advisers. 

Instead, White House and CDC officials are working with Michigan to leverage its existing vaccine supply and potentially surge shipments within the state. 

Despite his resistance to increasing the number of doses Michigan received, Slavitt stressed that the federal vaccine effort is not a one-size-fits-all endeavor. 

As examples, he stressed that the Biden administration was now allowing community health centers to order vaccines directly; adding locations to the government’s retail pharmacy partnership “surgically”; and locating federal vaccination sites in the places determined to be most in need. 

“I wouldn’t want to give the impression that we are — someone is sitting back and managing this pandemic according to some formula,” Slavitt said. “It’s not true in the least.”

To date, the White House’s population-based system for determining vaccine supply has faced little pushback or criticism, even though states have experienced different rates of Covid-19 spread for months. 

Broadly, the federal vaccination effort is viewed as a major success. The U.S. is currently administering roughly 3 million vaccine doses per day. Nearly one-third of the country, and more than three-quarters of all older adults, have received at least one vaccine dose. 

Biden announced on Tuesday that he would direct states to open vaccine eligibility to all adults by April 19, almost two weeks earlier than his prior goal of May 1. Many states, including Michigan, had already done so. 

Even as the broader vaccination campaign continues to accelerate, however, momentum has built for surging vaccines to hot spots. The debate in Michigan mirrors one in New Jersey, which experts have argued should also receive additional vaccine supply. Federal officials have similarly ignored that request. 

Four months into the U.S. vaccination effort, though, vaccine supply is far less tight. 

“There are states like Alabama, Georgia, Mississippi, Louisiana, Utah, where throughout much of the day, the vaccine appointments are going unfilled,” Jha said. “What all of us are arguing for is, for the next couple weeks, surge a ton of vaccines to Michigan. And if certain states that have plenty of supply get a 25% lower allotment for two weeks, they probably won’t miss it. Then, get them back to their normal level, and catch them up if they need it.”

https://www.statnews.com/2021/04/08/michigan-covid-surge-biden-officials-no-additional-vaccine-doses/

Google exploring health record tool for patients

 After 13 years, Google is coming back for patient health records. The tech giant has launched an early user feedback program aimed at exploring how patients might want to see, organize, and share their own medical record data.

The work could inform the creation of a consumer-facing medical records tool along the lines of Apple’s Health Records app. It also follows an early attempt by Google — later panned by medical experts — at creating a new version of the electronic medical record in 2008. This time around, timing may be on the company’s side: Its new effort, which is still in the early stages, came on the heels of the introduction of the federal information blocking rule, which lets patients access their medical records through health apps.

Google is currently recruiting about 300 patients for its health records study from community health facilities and academic medical centers in Northern California, Atlanta, and Chicago who use Epic as their medical record vendor. The study is only open to patients who use Android devices.

In a statement, a Google spokesperson said the company was “running a user feedback program to test features that give users the ability to collect health information from their provider patient portals,” and added that any health data gathered as part of the feedback program will not be sold or used for Google ads. The information will be encrypted and stored in the cloud, the spokesperson said.

While the tech giant is not directly partnering with any organizations for the program, it has reached out to at least four health systems to alert them of the effort, including the University of California, Davis; UCSF; Alameda Health System in Oakland, Calif.; and Access Community Health Network in Chicago.

Bob Wachter, who chairs the department of medicine at the UCSF and has advised Google on its health records work on a noncompensatory basis, told STAT he was impressed but not blown away by the company’s latest health records initiative.

“It didn’t knock my socks off,” he said, but “I think they’re doing it in a thoughtful, measured, and mature way. And it seems like they’re making progress.”

The move follows Google’s other recent health records work in Care Studio, a search tool that assists clinicians with navigating patients’ medical records. Earlier this month, the tech giant named Beth Israel Deaconess Medical Center its second hospital partner, joining the hospital chain Ascension as part of the pilot program. The effort drew widespread criticism over the organizations’ patient data-sharing agreement, which Google and Ascension said was compliant with federal health data privacy rules.

In the coming months, Wachter said he hopes to see Google add more functionality to Care Studio, for example by smoothing its workflow integration and incorporating more features aimed at improving patient care.

Wachter, having advised technology companies on their health efforts since the early 2000s, said he has witnessed a number of tech giants including Google try and fail to create new versions of the electronic health record (EHR). Looking forward, he hopes to see more companies take a similar approach to Google’s most recent effort, which essentially builds assistive tools that layer on top of the existing EHR, rather than trying to reinvent the wheel.

“I think we’re entering an era where we have our EHR, but there are tools that help us use it in a better, faster, and safer way.”

https://www.statnews.com/2021/04/09/google-health-records-app-care-studio/