Anaphylaxis After 1st Dose of Pfizer-BioNTech COVID-19 Vaccine

 Tom Shimabukuro, MD, MPH, MBA¹; Narayan Nair, MD²

doi:10.1001/jama.2021.0600

n December 11, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine, administered as 2 doses separated by 21 days.¹ Shortly after, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use.² Following implementation of vaccination, reports of anaphylaxis after the first dose of the Pfizer-BioNTech COVID-19 vaccine emerged.³ Anaphylaxis is a life-threatening allergic reaction that occurs rarely after vaccination, with onset typically within minutes to hours.⁴

Notifications and reports of suspected severe allergic reactions and anaphylaxis following vaccination were captured in the Vaccine Adverse Event Reporting System (VAERS), the national passive surveillance (spontaneous reporting) system for adverse events after immunization.⁵ Physicians at the US Centers for Disease Control and Prevention (CDC) evaluated these reports and applied Brighton Collaboration case definition criteria⁶ to classify case reports as anaphylaxis or not anaphylaxis. Nonallergic adverse events, mostly vasovagal or anxiety-related, were excluded from the analysis. Anaphylaxis and nonanaphylaxis allergic reaction cases with symptom onset occurring later than the day after vaccination were also excluded because of the difficulty in clearly attributing allergic reactions with delayed onset after vaccination. Because the Moderna COVID-19 vaccine was only available beginning December 21, 2020, this article focuses on the Pfizer-BioNTech COVID-19 vaccine.

During December 14 to 23, 2020, after administration of a reported 1 893 360 first doses of Pfizer-BioNTech COVID-19 vaccine (1 177 527 in women, 648 327 in men, and 67 506 with sex of recipient not reported),³ CDC identified 21 case reports submitted to VAERS that met Brighton Collaboration case definition criteria for anaphylaxis (Table), corresponding to an estimated rate of 11.1 cases per million doses administered. Four patients (19%) were hospitalized (including 3 in intensive care), and 17 (81%) were treated in an emergency department; 20 (95%) are known to have been discharged home or had recovered at the time of the report to VAERS. No deaths from anaphylaxis were reported.

Table.  Characteristics of Cases of Anaphylaxis (N = 21) Following Receipt of Pfizer-BioNTech COVID-19 Vaccine Reported to the Vaccine Adverse Events Reporting System (VAERS), December 14-23, 2020^a

Median interval from vaccine receipt to symptom onset was 13 minutes (range, 2-150 minutes); 15 patients (71%) had onset within 15 minutes; 18 (86%) had onset within 30 minutes.³ The most common symptoms and signs were urticaria, angioedema, rash, and a sense of throat closure. Seventeen (81%) of 21 patients with anaphylaxis had a documented history of allergies or allergic reactions, including to drugs or medical products, foods, and insect stings; 7 (33%) had experienced an episode of anaphylaxis in the past, including one after receipt of rabies vaccine and another after receipt of influenza A(H1N1) vaccine (Table). During the same period, VAERS identified 83 cases of nonanaphylaxis allergic reactions after Pfizer-BioNTech COVID-19 vaccination.³ Commonly reported symptoms in nonanaphylaxis allergic reactions included pruritus, rash, itchy and scratchy sensations in the throat, and mild respiratory symptoms.

Mortality from COVID-19 in populations at high risk is substantial,⁷ and treatment options are limited. Widespread vaccination against COVID-19 with highly effective vaccines represents an important tool in efforts to control the pandemic. CDC guidance on use of mRNA COVID-19 vaccines⁸ and management of anaphylaxis is available.⁹ Specifically, vaccination locations should (1) ensure that necessary supplies are available to manage anaphylaxis, especially sufficient quantities of epinephrine in prefilled syringes or autoinjectors; (2) screen potential vaccine recipients to identify persons with contraindications and precautions; (3) implement recommended postvaccination observation periods, either 15 or 30 minutes depending on each patient’s previous history of allergic reactions; (4) ensure that physicians and other health care professionals can recognize signs and symptoms of anaphylaxis early; and (5) immediately treat suspected anaphylaxis with intramuscular epinephrine (because of the acute, life-threatening nature of anaphylaxis, there are no contraindications to epinephrine administration).

Patients experiencing anaphylaxis should be transported to facilities to receive appropriate medical care. All patients should be instructed to seek immediate medical care if they develop signs or symptoms of an allergic reaction after their observation period ends and they have left the vaccination location. Clinicians have an important role in vaccine safety monitoring by being vigilant in recognizing and reporting adverse events to VAERS.¹⁰

https://jamanetwork.com/journals/jama/fullarticle/2775646

NY vaccine debate focuses on seniors

 The Cuomo administration’s efforts to restrict county health departments from administering the COVID-19 vaccines to senior citizens is being questioned by some county leaders.

Gov. Andrew Cuomo and a top aide, Larry Schwartz, are telling county governments to make essential front-line workers their priority in using the dosages provided to them, while elderly people should be directed to pharmacies.

But Dutchess County Executive Marc Molinaro, who is the president of the New York State County Executives Association, said turning away seniors with no other health care options from county vaccination clinics “is just not logical.”

COULD BE JEOPARDIZED

Molinaro said the state Health Department advised county health departments this month that their future allocations of vaccine doses “could be jeopardized” if they bucked the state’s edict to reserve their supply for essential workers.

A Jan. 15 memo from Schwartz to local health administrators stopped short of threatening to limit doses to counties that buck the state government’s edicts. But Schwartz emphasized the counties should be focusing their efforts on “police officers, firefighters, teachers, college professors, and grocery workers, among others.”

“Local health departments are the best equipped providers to coordinate with the employers of these workers, such as police departments, fire departments, schools and universities, grocery stores, and unions,” Schwartz added.

Molinaro said the counties will try to direct their vaccination clinic notifications to the groups identified by Schwartz but are reluctant to reject requests from seniors who seek the inoculations from their local counties.

“Our public health departments can’t be forced into not helping the people they are constitutionally sworn to help,” Molinaro told CNHI. In 2018, Molinaro, a Republican, lost to Cuomo, a Democrat, in the governor’s race.

EXPRESSED CONCERN

Dave Bliss, the chairman of the Otsego County Board of Representatives, said he was on a conference call Friday with other members of the Mohawk Valley regional control room for pandemic matters, and some local county leaders voiced concerns about the state’s effort to curb counties from inoculating seniors. The Otsego Health Department opted to cancel scheduled vaccinations for seniors earlier this week in response to edicts from the Cuomo administration.

“The concern was expressed by several members of the control room that (Cuomo) is going to punish them by lowering the amount of vaccines allocated to our counties if they don’t follow his instructions to a T,” Bliss said.

At a press briefing Friday, Cuomo blamed the federal government for recommending the expansion of the pool of people in high priority groups by adding those who are 65 and older.

Some states opted not to add seniors to the early priority group for the shots. But Cuomo said he decided to accept the federal guidance, though it exacerbated the acute shortage of doses, with 7 million people eligible at a time when 300,000 dosages were being supplied to New York.

Had New York balked at adding people 65 and older to the vaccine priority groups, Cuomo said, “I think that would have increased the panic and the anxiety and the tension.”

He conceded the large eligibility pool now has led to problems.

“It should have been opened as you had allocation,” the governor said. “Anyway, that is not what we did. It’s not what they did. And now you have a period of confusion and anxiety because you’re trying to hit 7 million people with 250,000 a week.”

‘MADE SENSE’

Cuomo said “everyone agreed” to have the top priority for the vaccines be nurses, doctors, first responders and other front-line essential workers be in the first wave to get the shots because “they could all be potential super spreaders.”

‘Adding those 75 and older also “made sense,” he said, though he acknowledged it left the vaccine effort “way over capacity.”

The state, after using 1.3 million doses so far, was expecting to have exhausted its limited supply by this weekend, though another shipment is due to arrive soon, Cuomo said.

“I understand the stress level and the anxiety level,” Cuomo said. “At least we have to be able to say, ‘we are fair.’ If you give the police dosage to 65 plus, then the police don’t get it. If you give the 65 dosage to hospital workers, then the 65-year-olds don’t get it. So please follow the Department of Health prioritization. Otherwise, you’re robbing Peter to pay Paul.”

APPOINTMENT PROBLEMS

Meanwhile, the New York chapter of AARP, an advocacy group for seniors, said a survey of nearly 3,000 people found many have encountered problems lining up vaccination appointments. Some made appointments only to have them canceled by providers, while others complained vaccine sites were too far away from their homes, or had no appointments available.

Molinaro said he welcomes the state’s effort to pressure the federal government to increase New York’s vaccine supply. County officials, he noted, are eager to work with the state to improve the vaccine appointment process and create a fairer system so that “seniors don’t have to compete with people who are more savvy online” and thus beat them in the scramble for notching appointments.

https://www.pressrepublican.com/news/ny-vaccine-debate-focuses-on-seniors/article_c021db16-5d37-11eb-9203-73b4311ce6ce.html

No Europe deaths 'directly tied to Covid jabs'

 Despite dozens of deaths of people shortly after they were vaccinated against coronavirus, scientists say the evidence available so far does not incriminate the new anti-COVID vaccines.

Health agencies stress however that the vast majority of post-vaccination fatalities were elderly, already vulnerable and often sick.

Here's a review of the situation:

Elderly, vulnerable

Norway sparked alarm last week when it reported the deaths of 33 of some 20,000 retirement home residents who had received a first shot of the Pfizer/BioNTech vaccine.

At least 13 of the fatalities were not only very elderly but also considered frail with serious ailments, the Norwegian Institute of Public Health said.

While it noted that no analysis had yet been carried out on the causes of the deaths, it suggested that with the aged and vulnerable the normal side effects of vaccination such as fever or nausea could have contributed.

Outside Norway the news raised widespread concern and fed anti-vaccine scepticism, prompting the authorities to stress that no link had been established between the vaccine and post-jab deaths.

In France, of 800,000 people vaccinated, nine deaths of chronically ill residents of care and retirement homes were recorded by Friday.

The national medicines agency ANSM said that based on available evidence, "Nothing leads to the conclusion that the reported deaths were linked to vaccination."

Other examples include 13 deaths of elderly people recorded in Sweden and seven in Iceland, all with no link established.

In Portugal, a care worker died two days after being inoculated but the justice ministry said a post-mortem found no direct link.

France's interior ministry on January 18 listed 71 "observations of death" in Europe of people who had the inoculation, but offered no further details.

Continued monitoring

The European Medicines Agency said that despite the deaths, "to date no specific concerns have been identified with Comirnaty", the commercial name for the Pfizer shot.

The EMA noted that the authorities investigate fatalities to determine whether the vaccine was responsible.

National and European agencies check any problems with vaccinations reported by health professionals, pharmaceutical firms and patients themselves.

For the moment, the number and type of deaths among those vaccinated are not considered abnormal, with no cause-and-effect relationship identified.

In many countries—such as France, Norway, Britain and Spain—the frail and elderly are first in line for vaccinations.

"It is not unexpected that some of these people may naturally fall ill due to their age or underlying conditions shortly after being vaccinated, without the vaccine playing any role in that," the UK medicines regulator MHRA said.

Transparency, reassurance

The deaths are a highly sensitive issue, and approaches to informing the public vary.

France and some Nordic countries have reported post-vaccination deaths and detailed the potential side effects of the jabs even if no link has been established.

But Britain's MHRA said it would make a statement at a later date, possibly seeking to avoid spreading alarm.

"We will publish details of all suspected reactions reported in association with approved COVID-19 vaccines, along with our assessment of the data on a regular basis in the future," it said.

In any event, European health officials say the deaths do not call into question the safety of the vaccines.

Norway has not changed its vaccination rollout, even if it has recommended doctors consider the overall health of the most frail before giving them the jab, the policy of numerous other countries.

Globally, more than 60 million doses have been received in at least 64 countries or territories, according to an AFP tally on Saturday.

https://medicalxpress.com/news/2021-01-europe-deaths-tied-covid-jabs.html

Germany to use corona meds that helped Trump

 Germany will become the first European Union country to start using the same experimental antibodies treatment credited with helping Donald Trump recover from COVID-19, health minister Jens Spahn said Sunday.

"The government has bought 200,000 doses for 400 million euros ($486 million)," Spahn told the Bild am Sonntag newspaper, working out at 2,000 euros per dose.

The so-called monoclonal antibody cocktails will be deployed to university hospitals in the coming week, he said, adding that Germany was "the first country in the EU" to use them in the fight against the pandemic.

Spahn did not name the manufacturer that will be supplying the drugs but confirmed it was the same medicine given to then-US president Trump when he fell ill with COVID last October.

"They work like a passive vaccination. Administering these antibodies in the early stages can help high-risk patients avoid a more serious progression," Spahn said.

Trump, who was briefly hospitalised with the coronavirus, was given the antibody therapy developed by US firm Regeneron, known as REGN-COV2, even before the treatment had won regulatory approval.

He later said the medicine did "a fantastic job".

US company Eli Lilly has developed a similar therapy.

The novel treatment is a combination or "cocktail" of two lab-made antibodies: infection-fighting proteins that were developed to bind to the part of the new coronavirus that it uses to invade human cells.

The antibodies attach themselves to different parts of the virus's spike protein, distorting its structure—similar in a way to knocking a key out of shape so it no longer fits its lock.

Germany's order comes at a time of growing frustration in the EU over a slower-than-expected rollout of vaccines.

Vaccine makers Pfizer/BioNTech and AstraZeneca have both said they would be delivering fewer doses to Europe than anticipated in the short term because of production problems.

The German government has said it nonetheless expects to be able to offer all Germans a jab by the end of August.

https://medicalxpress.com/news/2021-01-germany-corona-meds-trump.html

In tracking virus mutations, most countries flying blind

 To monitor changes to the coronavirus that could supercharge the pandemic or render vaccines less effective, scientists must sequence its genetic code to catalogue potentially dangerous mutations as they emerge.

But so few countries are conducting and sharing surveillance that experts are as worried about the mutations they cannot see as those they can.

Publication of the first genomic sequence of SARS-CoV-2 in January last year, at the very outset of the pandemic, allowed scientists to identify it as a new coronavirus, and begin developing diagnostic testing and vaccines.

Since then, tens of thousands of sequences have been uploaded on public databases, enabling mutations to be tracked with a degree of detail and a speed never achieved before.

But the lion's share of this information has come from just one country: Britain.

As of mid-January, GISAID—a major data sharing platform originally created to monitor influenza—had received 379,000 sequences.

Of these, 166,000 were from Britain's COVID-19 Genomics UK (COG-UK), a partnership between health authorities and academic institutions.

"This is the first time we are ever seeing how a pathogen evolves at this scale," said Ewan Harrison, Director of Strategy and Transformation at COG-UK and a fellow at the Wellcome Sanger Institute where much of the sequencing is being done.

"We are learning that these mutations accrue way faster than we thought."

Factfile on the process of gene sequencing, and the mamoth task of applying the technology to the virus at the root of the Covid-19 pandemic.

Currently the programme is sequencing 10,000 genomes a week—roughly six percent of known cases in Britain although that fluctuates—and the plan is to double that.

"The UK blows everyone else out of the water," said Emma Hodcroft, an epidemiologist at the University of Bern and co-developer on the Nextstrain virus tracking project.

"To me, this has been the moonshot of the pandemic, alongside the vaccines."

Denmark, she noted, also routinely sequences and shares data, but the information coming from most other countries is sporadic at best.

Sequencing has identified distinct variants—strains that have acquired clusters of new mutations—in Britain, South Africa and Brazil in recent weeks.

The new, fast-spreading variant in the UK is "like a mini-pandemic within the pandemic", said Harrison.

But without systematic monitoring, he added, scientists might still not have figured out it was a "game changer".

Early warning did not stop the variant spreading—it has been detected in dozens of countries. But it has allowed other nations to prepare.

Without the warning from UK scientists, the world would probably be flying blind, said Hodcroft.

During the summer of 2020 new strains emerged, displacing the earlier incarnations of the virus 

"If this was expanding in another country, we would just be looking at whatever country it was and going: 'Oh, they're having a bad rise in cases, I guess people aren't following the guidelines'," she told AFP.

Other variants have become visible only when they spread internationally from their point of origin.

Earlier this month, for example, a new strain—carrying a mutation, known as E484K, that researchers fear could evade immunity—was identified in Japan in people arriving from Brazil.

'Eyes and ears'

The World Health Organization has said better sequencing capacity is a worldwide priority.

Maria Van Kerkhove, the WHO's COVID-19 technical lead, recently described the number of sequences shared so far as "astounding", but said they were coming from just handful of countries.

"Improving the geographic coverage of sequencing is critical for the world to have eyes and ears on changes to the virus," she told an online forum.

New WHO guidance said a "revolution" in virus genomic investigation has helped build a better understanding of everything from Ebola to influenza.

And now, it said: "For the first time, genomic sequencing can help to guide the public health response to a pandemic in near-real time."

Tens of thousands of sequences have been uploaded on public databases, enabling mutations to be tracked. But the lion's share of this information has come from just one country: Britain 

When another coronavirus, SARS, began spreading in 2002, only three genome variants were publicly shared in the first month, and 31 by month three.

This time, six genomes were available to researchers worldwide a few weeks after the virus emerged. Within six months there were 60,000 variants published.

Initially the new coronavirus did not show much genetic diversity, said Hodcroft, even as it "exploded across Europe" due mainly to widespread travel.

But that lack of mutation was an important clue in itself.

"We were able to see that it really did seem to originate in China, because all the other sequences that were detected around the world nested within the diversity of the Chinese sequences," she told AFP.

During the summer of 2020 new strains emerged, displacing the earlier incarnations of the virus.

Emerging mutations

Mutations are to be expected in viral evolution and occur when a pathogen infects someone and sets about replicating itself.

Most of these new strains confer no advantage to the virus, and some are even detrimental. But occasionally a mutation increases infectiousness or causes more severe illness.

Timeline on statements and discoveries relating to the origins of SARS-CoV-2, as China now says WHO experts will be allowed to conduct their research, despite denying them entry on their scheduled arrival on Jan 6.

SARS-CoV-2 picks up changes at a slower rate than some other viruses, like HIV or influenza. But the more people a virus infects, the greater the opportunity for mutation.

This becomes even more likely in someone with a chronic illness—an extended exposure to a weakened immune system gives the virus more time to rack up multiple mutations.

Harrison said this may be how the new variant emerged in the UK, and researchers are now sequencing tests from immunocompromised patients, as well as people whose vaccine failed.

'New vision'

Systematic, countrywide sequencing has given researchers new insights into viral transmission.

In one case, it helped identify a minibus as the culprit in a hospital outbreak.

On a wider scale, an analysis of tens of thousands of SARS-CoV-2 sequences, published in Science this month, found that abundant travel and virus imports to the UK at the beginning of the epidemic seeded more than a thousand transmission lineages.

The next step is testing how different mutations affect transmission, disease severity, and vaccine effectiveness, and predicting as quickly as possible how a new variant might behave.

The WHO has said global sequencing will help "better understand the world of emerging pathogens and their interactions with humans and animals in a variety of climates, ecosystems, cultures, lifestyles and biomes".

The WHO has said global sequencing will help "better understand the world of emerging pathogens and their interactions with humans and animals

"This knowledge will shape a new vision of the world and open new paradigms in epidemic and pandemic prevention and control."

But sequencing at scale is logistically complex.

"There were weeks when things didn't work properly, because you're building the systems from scratch at pace, mid-pandemic," Harrison said.

The Sanger Institute stores the tens of thousands of samples it receives every day in huge shipping container freezers and had to build robotics infrastructure to help sort through them.

Legal concerns meant COG-UK decided to share minimal information on the sequences in order to make them public, Harrison said. The issue was a hurdle for other countries, particularly those reliant on private healthcare providers retaining ownership of data.

Costs are also a challenge in many parts of the world, but Hodcroft said richer nations like the United States and those in Europe have no excuse.

"There is no reason we don't have coordinated sequencing responses, except... that we haven't decided to do it," she said.

https://medicalxpress.com/news/2021-01-tracking-virus-mutations-countries.html

Healthcare IPO filings last week

 

Filings During the Week of January 18th, 2021
Issuer Business	Deal Size	Sector	Lead Underwriter
Decibel Therapeutics (DBTX)	$75M	Health Care	Citi
Phase 1 biotech developing treatments for hearing and balance disorders.
Talis Biomedical (TLIS)	$150M	Health Care	JP Morgan
Developing diagnostic tests for COVID-19 and other infectious diseases.
Isleworth Healthcare Acq. (IHAU.RC)	$150M	SPAC	I-Bankers
Blank check company targeting healthcare innovation.
Priveterra Acquisition (PMGMU)	$200M	SPAC	Wells Fargo
Blank check company targeting the medical technology sector.
Bioventus (BVS)	$100M	Health Care	Morgan Stanley
Offers orthobiologics products for musculoskeletal conditions.
Compute Health Acq. (CPUH.U)	$750M	SPAC	Goldman
Blank check company targeting the intersection of computation and healthcare.
HH&L Acquisition (HHLA.U)	$300M	SPAC	Goldman (Asia)
Blank check company targeting the healthcare sector in Asia.
Adagene (ADAG)	$125M	Health Care	Goldman (Asia)
Phase 1 biotech developing antibody cancer immunotherapies in China.
Biophytis (BPTS)	$15M	Health Care	HC Wainwright
French Phase 2 biotech developing therapies for COVID-related complications and age-related diseases.
Decipher Biosciences (DECI)	$100M	Health Care	Evercore ISI
Provides genomic testing products for urologic oncology.
Longeveron (LGVN)	$30M	Health Care	Kingswood Cap. Mkts.
Phase 2 biotech developing cellular therapies for aging-related conditions.
NexImmune (NEXI)	$86M	Health Care	Barclays
Phase 1/2 biotech developing T cell immunotherapies for cancer.
Signify Health (SGFY)	$500M	Health Care	Goldman
Provides a value-based billing platform for in-home and bundled health services. https://www.renaissancecapital.com/IPO-Center/News/75527/US-IPO-Weekly-Recap-The-IPO-market-has-no-time-to-RLX-in-a-6-IPO-week

COVID-19 emergency measures and the impending authoritarian pandemic

 Stephen Thomson, Eric C Ip 

DOI:  https://doi.org/10.1093/jlb/lsaa064

PDF: https://academic.oup.com/jlb/advance-article-pdf/doi/10.1093/jlb/lsaa064/33801355/lsaa064.pdf

ABSTRACT

COVID-19 has brought the world grinding to a halt. As of early August 2020, the greatest public health emergency of the century thus far has registered almost 20 million infected people and claimed over 730,000 lives across all inhabited continents, bringing public health systems to their knees, and causing shutdowns of borders and lockdowns of cities, regions, and even nations unprecedented in the modern era. Yet, as this Article demonstrates—with diverse examples drawn from across the world—there are unmistakable regressions into authoritarianism in governmental efforts to contain the virus. Despite the unprecedented nature of this challenge, there is no sound justification for systemic erosion of rights-protective democratic ideals and institutions beyond that which is strictly demanded by the exigencies of the pandemic. A Wuhan-inspired all-or-nothing approach to viral containment sets a dangerous precedent for future pandemics and disasters, with the global copycat response indicating an impending ‘pandemic’ of a different sort, that of authoritarianization. With a gratuitous toll being inflicted on democracy, civil liberties, fundamental freedoms, healthcare ethics, and human dignity, this has the potential to unleash humanitarian crises no less devastating than COVID-19 in the long run.

https://academic.oup.com/jlb/advance-article/doi/10.1093/jlb/lsaa064/5912724