BioNTech: Can Make Mutation-Beating Vaccine In 6 Weeks if Needed

 The co-founder of BioNTech said Tuesday it was "highly likely" that its vaccine against the coronavirus works against the mutated strain detected in Britain, but it could also adapt the vaccine if necessary in six weeks.

"Scientifically, it is highly likely that the immune response by this vaccine also can deal with the new virus variant," said Ugur Sahin.

But if needed, "in principle the beauty of the messenger technology is that we can directly start to engineer a vaccine which completely mimics this new mutation -- we could be able to provide a new vaccine technically within six weeks."

Sahin said the variant detected in Britain has nine mutations, rather than just one as is usually common.

Nevertheless, he voiced confidence that the vaccine developed with Pfizer would be efficient because it "contains more than 1,000 amino acids, and only nine of them have changed, so that means 99 percent of the protein is still the same".

He said tests are being run on the variant, with results expected in two weeks.

"We have scientific confidence that the vaccine might protect but we will only know it if the experiment is done... we will publish the data as soon as possible," he added.

https://www.ndtv.com/world-news/biontech-says-can-make-mutation-beating-coronavirus-vaccine-in-six-weeks-news-agency-afp-2342027

How SARS-CoV-2 spike protein disrupts cooperative function of human cardiac pericytes - endothelial cells

 Elisa Avolio, Monica Gamez, Kapil Gupta, Rebecca Foster, Imre Berger, Massimo Caputo, Andrew D. Davidson, Darryl Hill, Paolo Madeddu

doi: https://doi.org/10.1101/2020.12.21.423721

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2020.12.21.423721v1.full.pdf

Abstract

Background: Severe coronavirus disease 2019 (COVID-19) manifests as a life-threatening microvascular syndrome. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses primarily the capsid spike (S) protein to engage with its receptors and infect host cells. To date, it is still not known if the S protein alone, without the other viral elements, is able to trigger vascular cell signalling and provoke cell dysfunction. Methods: We investigated the effects of the recombinant, stabilised S protein on primary human cardiac pericytes (PCs) signalling and function. Endpoints included cell viability, proliferation, migration, cooperation with endothelial cells (ECs) in angiogenesis assays, and release of pro-inflammatory cytokines. Adopting a blocking strategy against the S protein receptors ACE2 and CD147, we explored which receptor mediates the S protein signalling in PCs. Findings: We show, for the first time, that the recombinant S protein alone elicits functional alterations in cardiac PCs. This was documented as: (1) increased migration, (2) reduced ability to support EC network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm; and (4) production of pro-apoptotic factors responsible for EC death. Furthermore, the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in cardiac PCs. Accordingly, the neutralization of CD147, using a blocking antibody, prevented the activation of ERK1/2 and partially rescued the PC function in the presence of the S protein. Interpretation: Our findings suggest the new, intriguing hypothesis that the S protein may elicit vascular cell dysfunction, potentially amplifying, or perpetuating, the damage caused by the whole coronavirus. This mechanism may have clinical and therapeutic implication.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2020.12.21.423721v1

COVID-19 Anticoagulation Trials 'Paused' for Futility, Safety

 Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been "paused" because of futility and safety concerns, a statement from the US National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes. 

"Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question," the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

https://www.medscape.com/viewarticle/943085

Poll: More Want COVID-19 Vaccine Earlier

 Increasing numbers of people want the COVID-19 vaccine sooner, a new WebMD poll finds.

About 37% of people said they plan to get a vaccine in the next 3 months, compared to 27% in September and 26% in July.

A majority — 56% — said they would take one within the next year. That number is also up slightly from September, when 54.6% of people said they would get the vaccine in the first year. 

The findings mirror other recent polls that have tracked people's thoughts about the timing of the vaccine. About 40% of Americans say they plan to take a vaccine as soon as it's available to them, according to an ABC News/Ipsos poll released on Dec. 14.

Similarly, about 34% of people said they'd take a vaccine "as soon as possible," according to a Kaiser Family Foundation poll released Tuesday.

"People who may have been taking a 'wait and see' approach may be feeling more confident as we hear more about the vaccine's safety and how it works," says John Whyte, MD, chief medical officer of WebMD.  "After nearly a year, and we finally have some hope for an end to pandemic life."

The FDA has allowed the use of two COVID-19 vaccines as cases and hospitalizations continue to surge nationwide.

On Friday, the FDA granted an emergency use authorization for Moderna's COVID vaccine.

Hospitals and state health departments across the country are already receiving the first doses of the Pfizer-BioNTech vaccine. Some health care workers and residents of long-term care facilities received immunizations this week. The FDA granted emergency authorization to the Pfizer vaccine Dec. 11.

In the new WebMD poll of 1,785 readers, 12% said they won't get the vaccine at all, as compared with 12.5% in September and 28% in July. Another 23% of readers are still unsure or don't know when they'll get the vaccine. And 8% said they'd wait more than a year.

Public health officials and politicians have begun to encourage Americans to get the vaccine as soon as it's their turn on the priority list. Former presidents Barack Obama, George W. Bush, and Bill Clinton have said they'll take the vaccine when it's their turn, and they may get the immunization in public and on video to boost confidence among Americans.

The Trump administration is also rolling out a $250 million public education campaign to boost confidence in the vaccine. Vaccine hesitancy is one of the biggest concerns in the vaccine rollout process, Moncef Slaoui, PhD, chief medical adviser for Operation Warp Speed, told CBS This Morning .

"I really hope we are going to be able to change that," he said.

The average person with no underlying conditions should be able to get access to a vaccine by April or May, Slaoui said.

The WebMD poll also showed that people of all ages were more likely to say they'd take a vaccine in the next 3 months once it's available, though older adults were most likely to say they'd take it sooner. Readers ages 65 and older were the most likely to say they'd like a vaccine sooner, followed by those between ages 55 and 64.

The results varied by gender as well. Women were twice as likely as men to say they'd take a vaccine in the next 90 days, though both men and women were more likely to opt for the next 3 months than any other timeline.

The majority of people — about 70% — will need to take a vaccine for the U.S. to reach herd immunity and bring the pandemic to a halt. Most people in the country should be able to be vaccinated by late spring or early summer, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC this week.

"I believe we can get there by then, so that by the time we get into the fall, we can start approaching some degree of relief, where the level of infection will be so low in society, we can start essentially approaching some form of normality," he said.

Until then, people will need to follow public health measures to slow the spread of the virus by wearing masks, avoiding crowds, and social distancing, he said.

"A vaccine right now is not a substitute for the normal standard public health measures," Fauci said. "Only when you get the level of infection in society so low that it's no longer a public health threat can you then think about the possibility of pulling back on public health measures."

Sources:

WebMD poll of 1,785 readers, Dec. 7-9, 2020.

WebMD: "WebMD Poll: More Acceptance of COVID Vaccine," "WebMD Poll: Most Would Wait on COVID Vaccine," "WebMD Poll: Concerns Around COVID-19 Grow."

ABC News: "Americans willing to receive COVID-19 vaccine but divided on timing: POLL."

Kaiser Family Foundation: "KFF COVID-19 Vaccine Monitor: December 2020."

COVID Tracking Project: "Our Data."

https://www.medscape.com/viewarticle/942991

India likely to approve AstraZeneca vaccine by next week

 India is likely to approve Oxford/AstraZeneca’s coronavirus vaccine for emergency use by next week after its local manufacturer submitted additional data sought by authorities, two sources with knowledge of the matter told Reuters on Tuesday.

This could be the first country to give the regulatory green light for the British drugmaker’s vaccine as the British medicine regulator continues to examine data from the trials.

India, the world’s biggest vaccine-making country, wants to start inoculating its citizens next month and is also considering emergency use authorisation applications for vaccines made by Pfizer Inc and local company Bharat Biotech.

Getting vaccines to the world’s second-most populous country with one of the highest infection rates will also be a big step in the battle against the pandemic.

The AstraZeneca-Oxford shot is considered vital for lower-income countries and those in hot climates because it is cheaper, easier to transport and can be stored for long periods at normal fridge temperatures.

India's Central Drugs Standard Control Organization (CDSCO) first reviewed the three applications on Dec. 9 here and sought more information from all the companies, including from Serum Institute of India (SII), which is making the AstraZeneca shots.

SII, the world's biggest vaccine manufacturer, has now provided all the data, the two sources said. The authorities were still waiting for more details from Pfizer, a government health adviser told here a news briefing on Tuesday, while one of the sources said additional information was expected from Bharat Biotech.

Both sources said Indian health officials were in direct contact with their British counterparts over the AstraZeneca shot and that there were “strong indications” an approval would come by next week.

The expected approval comes after data from AstraZeneca’s late-stage trials in the UK and Brazil released earlier this month showed the vaccine had efficacy of 62% for trial participants given two full doses, but 90% for a smaller sub-group given a half, then a full dose.

The Indian regulator is only considering the two full-dose regimen of the shot despite it showing a lower success rate, the sources said.

“Serum is ready,” said one of the sources. “Initially, we may get around 50 million to 60 million doses.”

The sources declined to be named as deliberations were ongoing and the timeline could change.

CDSCO chief V.G. Somani did not immediately respond to a request for comment. Bharat Biotech and Pfizer declined to comment, while SII did not immediately respond to an email seeking comment.

India has not yet signed a vaccine supply deal with any company, but SII has already stockpiled more than 50 million doses of the AstraZeneca shot and plans to make a total of 400 million doses by July.

https://www.reuters.com/article/us-health-coronavirus-india-vaccine-excl/exclusive-india-likely-to-approve-astrazeneca-vaccine-by-next-week-sources-idUSKBN28W27B

U.S. will not impose COVID-19 screenings for flights from Britain

 The U.S. government does not intend to impose COVID-19 screenings for passengers traveling from Britain after the emergence of a highly infectious new coronavirus variant there, people briefed on the decision said.

White House coronavirus task force members backed requiring negative pre-flight tests after a meeting on Monday, but the Trump administration has decided not to take any action for the time being, the people said.

Much of the world shut their borders to Britain after the discovery of a mutated variant of the novel coronavirus, though the European Union recommended on Tuesday that members roll back sweeping closures to allow some travel.

Canada is implementing enhanced measures to screen travelers from Britain, including those arriving from other nations, its public safety minister said on Tuesday.

The three airlines that operate flights from London to John F. Kennedy International Airport - British Airways, Delta Air Lines and Virgin Atlantic - voluntarily agreed to a request from New York Governor Andrew Cuomo that they only allow passengers who test negative to fly.

The Trump administration has repeatedly refused to issue mandates for many federal COVID-19 safety policies for air travel, making only strong recommendations on issues such as mask wearing. President-elect Joe Biden has vowed to mandate masks in interstate air, bus and train travel after taking office on Jan. 20.

The White House in August scuttled an effort to require airlines to collect contact tracing information from U.S.-bound international passengers, Reuters reported.

The White House in July rejected a proposal to require facial coverings at U.S. airports, train and transit stations and onboard airplanes, trains and transit services and earlier dismissed proposals to require temperature checks of airline passengers.

Speaking on ABC’s “Good Morning America,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said it is possible the new COVID-19 variant is already in the United States.

“You really need to assume it’s here already,” Fauci said.

Michael Osterholm, a Biden COVID-19 adviser, on Tuesday said all options need to be considered to stem the spread of the new UK variant. He urged the Trump administration to come up with a plan.

“We really need to develop a national response,” he told CNN. “Everything needs to be on the table.”

https://www.reuters.com/article/us-health-coronavirus-usa-britain/u-s-will-not-impose-covid-19-screenings-for-flights-from-britain-sources-idUSKBN28W23B

AstraZeneca says its vaccine should be effective against new coronavirus variant

 British drugmaker AstraZeneca Plc told Reuters on Tuesday its COVID-19 vaccine should be effective against the new coronavirus variant, adding that studies were under way to fully probe the impact of the mutation.

“AZD1222 (AstraZeneca’s vaccine candidate) contains the genetic material of the SARS-CoV-2 virus spike protein, and the changes to the genetic code seen in this new viral strain do not appear to change the structure of the spike protein,” an AstraZeneca representative said in an email.

Drugmakers are scrambling to test their COVID-19 vaccines against the new fast-spreading variant of the virus that is raging in Britain, the latest challenge in the breakneck race to curb the pandemic.

“Through vaccination with AZD1222, the body’s immune system is trained to recognise many different parts of the spike protein, so that it can eliminate the virus if it is later exposed,” the AstraZeneca representative added.

The mutation known as the B.1.1.7 lineage may be up to 70% more infectious and more of a concern for children. It has sown chaos in Britain, prompting a wave of travel bans that are disrupting trade with Europe and threatening to further isolate the island country.

The AstraZeneca-Oxford shot is considered vital for lower-income countries and those in hot climates because it is cheaper, easier to transport and can be stored for long periods at normal refrigerator temperatures.

Data from AstraZeneca’s late-stage trials in the UK and Brazil released earlier this month showed the vaccine had efficacy of 62% for trial participants given two full doses, but 90% for a smaller sub-group given a half, then a full dose.

Reuters reported late on Tuesday that India is likely to approve AstraZeneca’s vaccine for emergency use by next week.

https://www.reuters.com/article/us-health-coronavirus-astrazeneca-vaccin/astrazeneca-says-its-vaccine-should-be-effective-against-new-coronavirus-variant-idUSKBN28W2GR