United will require new employees to show proof of Covid vaccine, following Delta

 United Airlines this month will start requiring new hires to show proof that they have been vaccinated against Covid-19, following a similar move by Delta Air Lines.

The new rule requires external candidates with job offers made after June 15 to confirm they have been fully vaccinated by their start date, the Chicago-based airline said.

The move comes as companies are grappling with whether to require staff to get vaccinated or find a way to incentivize them get inoculated. United, Delta and American have offered extra time off or pay to employees who are vaccinated. Big employers like Walmart have taken similar measures.

“As we welcome new employees to the company, it’s important we instill in them United’s strong commitment to safety,” the airline said in a note to staff, which was tweeted earlier by Brian Sumers, editor-at-large at travel-industry site Skift.

The new employees “will be required to upload their COVID vaccine card in My Info no later than 7 days post hire date,” the airline said. The company added it will evaluate any religious or medical circumstances of candidates who can’t be vaccinated.

United CEO Scott Kirby said in January that he wanted to make Covid vaccines mandatory for employees but the airline hasn’t taken that step.

Airlines spent much of the last year shedding workers but carriers like United have announced they will resume hiring of pilots and other positions as travel demand picks back up.

https://www.cnbc.com/2021/06/05/united-will-require-new-employees-to-show-proof-of-covid-vaccine-following-delta.html

'Lab Leak' Debate Matters -- But Not for the Reasons You Think

 First, an admission: this is not really a column about the origin of SARS-CoV-2. Others have written great ones, and I am not terribly interested in the question. Why? Right now, the two most widely discussed possibilities are the virus underwent zoonotic transmission (from some animal to a person), possibly at a wet market, and the other is that it escaped from the Wuhan Institute of Virology due to poor safety protocols in a biosafety level (BSL) 3 or 4 laboratory.

If it escaped due to a wet market, I would strongly suggest we clean up wet markets and improve safety in BSL laboratories because a future virus could come from either. And, if it was a lab leak, I would strongly suggest we clean up wet markets and improve safety in BSL 3 and 4 ... you get the idea. Both vulnerabilities must be fixed, no matter which was the culprit in this case, because either could be the culprit next time.

I want to talk about the real lesson of "lab leak," which in my mind is the way in which the idea moved from a taboo subject -- a conspiracy theory -- to a perfectly acceptable topic of discussion. In fact, last week, Facebook removed its ban on posts discussing the laboratory escape of the virus as a possibility. How could this happen? What was misinformation yesterday is something that needs investigating today? Other writers have discussed how prominent social media accounts took extreme positions that dissuaded the media from fairly considering the possibility of a lab leak, and on the heels of an election, turned the lab-leak idea into a political issue.

"Lab leak" isn't the only topic that has undergone massive swings in opinion. In early March 2020, for example, experts advised against mask wearing. A few weeks later the pendulum swung the other way, and the U.S. and CDC went beyond World Health Organization (WHO) guidance and recommended cloth masks to kids as young as 2 years old (WHO said 5 and up). With time, we may still see more shifts on this topic, as at least two cluster randomized trials are ongoing. In January of this year, I wrote two columns arguing that 14 days after the second dose of vaccination, people can ditch the mask or hug a loved one. There was fierce pushback on Twitter. A few months later, CDC guidance fell in line with my perspective.

Recently, a Tweet from an anonymous cardiologist was flagged as misleading for arguing that mRNA vaccines may have a stronger link to myocarditis than asymptomatic SARS-CoV-2. The jury is still out, but since that warning, based on early Israeli data, the CDC has announced an investigation into the link between mRNA vaccines and myocarditis. Finally, I continue to believe the pendulum on school closures is going to swing so far the other way it will make your head spin -- prolonged closure will someday be seen as a crime against kids with negligible impact on viral spread.

I chose these examples not because I want to rehash whether one side is right (though for several I have my pick), but to make the broader point that stifling debate, shrinking the acceptable bounds of dialogue, and banning discussion has got to be wrong when we see over and over again how quickly debates can move. Yesterday's misinformation is today's popular view.

Times Have Changed

When I was in college, 20 years ago, life was different. We did not have phones capable of audio or video recording and social media did not exist. I remember staying up till dawn with kids in my dorm and having vigorous discussions about politics, science, and the good life. I went to college at Michigan State University. We had Republican kids, Democrat kids, and kids who weren't interested in politics (most of us); we had kids whose parents were executives at General Motors, and kids whose parents worked on the plant floor. The debates were on hot topics -- topics that these days would lead to Twitter pile-ons and folks calling someone's employer. Yet, that never happened back then.

People who disagreed politically still met on Saturday to tailgate together and sing the fight song. We argued, but didn't believe anyone was morally superior -- in fact, we all recognized how small and insignificant we were in the world. When we spoke, we never felt like we would offend. You could make a crass joke, and folks might groan, but they wouldn't disavow you. You could hold views that others would disagree with, but they only hated you if you drank the last beer. For me, the child of immigrants, that is what America meant -- a place where people from different backgrounds could talk about different things. Debates could be serious, but they were seldom personal.

In 2021, we are swirling in a craze. Entire swaths of the human condition are taboo topics that you dare not talk about. Jokes can enter your mind, and you have to pinch yourself lest you say it. You have to study people silently for days to see if they might be the type of person who likes to hear jokes. With some people, you never take a chance. You go to a dinner party, and never know if someone will capture a 15-second video of you to post online, claiming that you are a bad person for your views on a technical and complex regulatory issue, such as whether the emergency use authorization was warranted for 12- to 15-year-olds. The America I knew seems to be on life support.

Limiting Debate Is Dangerous

If we learn anything from the shift on the lab-leak theory, it is that curtailing free expression and limiting reasonable debate is a mistake. That's especially true when information is dynamic, and you are making unprecedented decisions. In human history, we have never asked so many people to deprive themselves of social interaction for so long. We have never closed schools for so many kids and for so long. Naturally, these policies will spark disagreements, even fierce ones. Restricting the bounds of what's appropriate -- particularly with the brute force of platforms like Facebook -- is a fool's errand. Pseudo-consensus is cheap and easy in a world of social media.

Fostering Liberalism in Science

One persistent mistake we make is confusing democracy and liberty. Liberty is the right to govern your own life, your own mind, to make a future as you see fit, with whomever you wish to. Democracy is the will of the majority. Although we live in a place where we have both, the two are not linked. Some autocracies have been astonishingly liberal, and democracies can succumb to tyranny of the majority, and become profoundly illiberal. The idea that we could not discuss the lab-leak hypothesis for over a year represents a failure of scientific liberalism, and possibly the tension between the majority and liberalism. Many scientists on social media may have viewed the lab leak as a hypothesis that would help their political opponent, and pushed to curtail its consideration. Such a gambit was dangerously shortsighted.

Liberalism in science -- the ability to hold and discuss a broad range of views -- is a newborn bird. We hold it in our hands. It matters even more than the right answer. Lab leak is just a salient reminder of how vulnerable that bird is -- and that's the real lesson we need to learn.

Vinay Prasad, MD, MPH, is a hematologist-oncologist and associate professor of medicine at the University of California San Francisco, and author of Malignant: How Bad Policy and Bad Evidence Harm People With Cancer.

https://www.medpagetoday.com/opinion/vinay-prasad/92868

Blackwater founder Prince takes role in COVID vaccine venture

 Erik Prince, the founder of controversial private military firm Blackwater and a supporter of former President Donald Trump, jumped into the COVID-19 business late last year with a deal to distribute an experimental vaccine should it be approved, according to three people familiar with the arrangement and business records seen by Reuters.

The COVID-19 vaccine, known as UB-612, is being developed by a privately-held U.S. firm called COVAXX.

The company has said the vaccine shows promise in protecting people against coronavirus, based on a small study of 60 patients in Taiwan. It hasn't provided data on safety and efficacy from large clinical trials, information that is usually required before a vaccine is authorized for public use.

COVAXX is unrelated to the similar-sounding but better-known "COVAX," a global vaccine distribution program backed by the World Health Organization.

Since the start of the pandemic in 2020, the COVAXX vaccine has attracted some big-name backers, including endorsements from entrepreneur Peter Diamandis, who co-founded the company, and motivational speaker Tony Robbins. In March, the company raised $1.35 billion in a private placement, according to U.S. securities filings.

Prince's involvement in vaccine distribution, which has not been previously reported, sheds new light on the race to profit from the uncertainties of the pandemic. Vaccine supply deals have often been forged through direct government ties to drugmakers, global health organizations or diplomatic channels.

Reuters couldn't determine how Prince first became associated with COVAXX, or whether he has brokered any vaccine supply deals.

Prince did not respond to questions for this story. A source close to Prince said that "Erik has been helping a vaccine manufacturer set up distribution," but declined to give details.

Diane Murphy, a public relations consultant for Vaxxinity Inc, which owns COVAXX, declined to answer questions related to Prince. In a statement to Reuters, she said that the company has "accepted introductions from a variety of private, public and non-profit intermediaries, both formally and informally."

'DOLLARS PER DOSE'

Prince has made headlines for years, first as chief executive of Blackwater, whose security guards fatally shot more than a dozen Iraqi civilians in Baghdad in 2007. After he left Blackwater, Prince pushed to privatize the war in Afghanistan by having contractors fight instead of the U.S. military and became embroiled in an investigation into possible collusion between the Trump election campaign and the Russian government.

Prince sought to recruit a close associate, the late Paul Behrends, a former Republican congressional staffer and lobbyist who represented Blackwater for over two years, to help in the COVAXX project.

In a series of text messages to Behrends, Prince described the potential for profit from selling the vaccines.

"There's room for a couple dollars per dose in commissions," Prince said in a Nov. 9 text to Behrends. He shared with Behrends a "Letter of Authorization" on COVAXX letterhead signed by senior vice president Brandon Schurter as proof of his distribution deal. Schurter did not respond to requests for comment.

The October 2020 letter said that an entity called Windward Capital, with an address in Abu Dhabi, was authorized to "assist in the process of creating distribution networks." Reuters could not find a Windward Capital registered in Abu Dhabi. But a company called Windward Holdings that handles "professional, scientific and technical activities" is listed there, with Erik Prince the sole named shareholder.

Prince is also the managing member of a corporate entity called Windward Wyoming LLC, which says it has a "global distribution" deal with COVAXX, according to records of non-public business agreements seen by Reuters. The company was formed in October 2020, public incorporation records in Wyoming show.

Lawyers and other officials affiliated with the various Windward entities did not respond to requests for comment.

Prince and Behrends were negotiating how to carve up prospective sales territories by country, said Barry Angeline, a friend of Behrends. But their possible collaboration was cut short in December, when Behrends died.

Vaxxinity consultant Murphy told Reuters the company has a "focus on the developing market" – including the many countries that have been unable to acquire the shots made by global drugmakers and stockpiled by wealthier nations.

HIGH-PROFILE BACKERS

COVAXX was formed in early 2020 as a subsidiary of United Biomedical Inc (UBI), a maker of diagnostic tests and veterinary vaccines, to address the coronavirus pandemic. In April, the company announced it was being consolidated into a new holding corporation called Vaxxinity.

COVAXX's backers were quick to publicize the vaccine's potential beginning in July, based on early tests in animals, and before the first clinical trials in people began in Taiwan.

Diamandis, who is listed as a co-founder of Vaxxinity, wrote in a July 30 post on his personal blog that the vaccine was safe for patients and likely effective in the elderly. He told Reuters he made it clear in those posts that his assertions were based on previous trial results of other vaccines developed by the company.

A few weeks later, Robbins, the self-help coach, held a webinar promoting COVAXX titled "The most powerful vaccine you've never heard of." Robbins said in the video that he was one of the company owners. "I've invested in the company, so everyone knows. Because I've been blown away by seeing these results," he said.

Robbins "remains an investor," his spokeswoman Jennifer Connelly said in a statement to Reuters. She added, "Mr. Robbins is not involved in the management or daily operations."

In October, COVAXX and shipping giant Maersk announced a partnership to provide global transport of the vaccine as soon as it becomes available. The Maersk official quoted in the release, Rob Townley, said the company recognized the urgent need to safely deliver COVID-19 vaccines worldwide.

Townley was briefly an aide to former U.S. Army general Michael Flynn during Flynn's short tenure as Trump's National Security Adviser. In an interview, Townley said he knows Prince but couldn't discuss Prince's involvement.

Data on how well the vaccine works is still pending. In an email to Reuters, Vaxxinity’s Murphy said the company had completed the Phase 1 trial of 60 volunteers aged 20 to 55 in Taiwan, and is conducting a new study of 3,800 people there, including teens and elderly participants. The company plans larger trials in Brazil and India later this year.

https://www.reuters.com/business/healthcare-pharmaceuticals/exclusive-blackwater-founder-prince-takes-role-covid-vaccine-venture-2021-06-04/

Many COVID-19 patients produce immune responses against their body's tissues or organs

 A University of Birmingham-led study funded by the UK Coronavirus Immunology Consortium has found that many patients with COVID-19 produce immune responses against their body's own tissues or organs.

COVID-19 has been associated with a variety of unexpected symptoms, both at the time of infection and for many months afterwards. It is not fully understand what causes these symptoms, but one of the possibilities is that COVID-19 is triggering an autoimmune process where the immune system is misdirected to attack itself.

The study, published today (June 4) in the journal Clinical & Experimental Immunology, investigated the frequency and types of common autoantibodies produced in 84 individuals who either had severe COVID-19 at the time of testing or in the recovery period following both severe COVID-19 and those with milder disease that did not need to attend hospital. These results were compared to a control group of 32 patients who were in intensive care for another reason other than COVID-19.

An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins and can cause autoimmune diseases. Infection can, in some circumstances, lead to autoimmune disease. Early data suggest that SARS-CoV-2 infection can trigger long-term autoimmune complications and there are reports of SARS-CoV-2 infection being associated with a number of autoimmune disorders including Guillain-Barre Syndrome.

Supported by UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR), the study found higher numbers of autoantibodies in the COVID-19 patients than the control group and that these antibodies lasted up to six months.

Non-COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID-19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies.

The authors also find that those with more severe COVID-19 were more likely to have an autoantibody in their blood.

First author Professor Alex Richter, of the University of Birmingham, explained: "The antibodies we identified are similar to those that cause a number of skin, muscle and heart autoimmune diseases.

"We don't yet know whether these autoantibodies are definitely causing symptoms in patients and whether this is a common phenomenon after lots of infections or just following COVID-19. These questions will be addressed in the next part of our study."

Senior Author Professor David Wraith, of the University of Birmingham, adds: "In this detailed study of a range of different tissues, we showed for the first time that COVID-19 infection is linked to production of selective autoantibodies. More work is needed to define whether these antibodies contribute to the long-term consequences of SARS-CoV-2 infection and hence could be targeted for treatment."

Professor Paul Moss, Principal Investigator of the UK Coronavirus Immunology Consortium and Professor of Haematology at the University of Birmingham added: "This is an interesting study that reveals new insights into a potential autoimmune component to the effects of COVID-19. Research like this has been made possible by the huge collaborative efforts made by those that are a part of the UK Coronavirus Immunology Consortium. This study is another important step towards delivering real improvements in prevention, diagnosis, and treatment of COVID-19 to patients."

The study participants were separated into four cohorts:

Group one: 32 individuals sampled during their stay in intensive care for reasons other than COVID-19. 41% of individuals had autoantibodies. In this group, there were many different causes of their illness (over half was pneumonia) and autoantibodies were found against nearly all of the different autoantigens examined, indicating a more random distribution.

Group two: 25 individuals who were sampled during their stay in intensive care following a diagnosis of severe COVID-19. 60% had autoantibodies. Of those who tested positive for autoantibodies, 41% had epidermal (skin) antibodies, while 17% had skeletal antibodies.

Group three: 35 individuals who had been admitted to intensive care with COVID-19, survived and were sampled three to six months later during routine outpatient follow up. 77% of individuals had autoantibodies. Of those who tested positive for autoantibodies, 19% had epidermal (skin) antibodies, 19% had skeletal antibodies, 28% had cardiac muscle antibodies; and 31% had smooth muscle antibodies.

Group four: 24 healthcare workers sampled one to three months after mild to moderate COVID-19 that did not require hospitalisation. 54% of individuals had autoantibodies. In those who tested positive for autoantibodies, it was against only four autoantigens: 25% had epidermal (skin) antibodies; 17% had smooth muscle antibodies; 8% had anti-neutrophil cytoplasm (ANCA) antibodies that target a type of human white blood cells; and 4% had gastric parietal antibodies which are associated with autoimmune gastritis and anaemia.

https://www.eurekalert.org/pub_releases/2021-06/uob-mcp060321.php

'Mexican variant' and monitoring actions of SARS-CoV-2 genome

 A research group of the Department of Pharmacy and Biotechnology of the University of Bologna analyzed more than one million SARS-CoV-2 genome sequences. This analysis led to the identification of a new variant that, over the past weeks, has been spreading mostly in Mexico but has also been found in Europe. Their paper published in the Journal of Medical Virology presented the so-called "Mexican variant", whose scientific name is T478K. Like other strains, this presents a mutation in the Spike protein, which allows coronaviruses to attach to and penetrate their targeted cells.

"This variant has been increasingly spreading among people in North America, particularly in Mexico. To date, this variant covers more than 50% of the existing viruses in this area. The rate and speed of the spread recall those of the 'British variant'", explains Federico Giorgi, who is the study coordinator and a professor at the Department of Pharmacy and Biotechnology of the University of Bologna. "The mutation of the Spike protein is structurally located in the region of interaction with human receptor ACE2. Coronaviruses attach to this receptor to infect cells, thus spreading the infection with more efficacy".

The researchers started from the analysis of almost 1.2 million sequenced samples of the SARS-CoV-2 genome found in international databases until April 27, 2021. The new T478K variant was detected in 11435 samples. This is double the number of samples that presented the same variant just a month earlier. Such an increase since the beginning of 2021 alarmed the researchers.

The "Mexican variant" spreads evenly across males and females and age ranges. This variant represents 52.8% of all sequenced coronaviruses in Mexico, whereas in the United States it shows up only in 2.7% of the sequenced samples. As concerns Europe, the "Mexican variant" has spread feebly in Germany, Sweden, and Switzerland. In Italy is virtually non-existent with only 4 reported cases.

The mutation characterizing this variant is located in a region of the Spike protein that is responsible for the interaction with the human receptor ACE2: this is the mechanism allowing coronaviruses to access the cells. Similar mutations are common to all variants that have been at the center of attention in the past months. Indeed, recent coronavirus variants stand out for their high infection rates, which made them pervasive in many areas of the world.

Researchers tested the action of T478K Spike protein with in silico simulations and found out that this mutated protein can alter the superficial electrostatic charge. Consequently, it can change not only the interaction with the ACE2 human protein but also with the antibodies of the immune system and thus hinder drug efficacy.

"Thanks to the great amount of data available in international databases, we can hold an almost real-time control over the situation by monitoring the spread of coronavirus variants across different geographical areas", concludes Giorgi. "Keeping up this effort in the next months will be crucial to act promptly and with efficient means".

###

"Preliminary report on SARS-CoV-2 Spike mutation T478K" is the title of the study published in the Journal of Medical Virology. The authors are Simone di Giacomo, Daniele Mercatelli, Amir Rakhimov, and Federico Giorgi, all from the Department of Pharmacy and Biotechnology of the University of Bologna.

https://www.eurekalert.org/pub_releases/2021-06/udb-va060421.php

Gene protection for COVID-19 identified

 The first evidence of a genetic link explaining why some people who catch Covid-19 don't become sick has been discovered

A scientific and medical team led by Newcastle University, UK, has demonstrated that the gene, HLA-DRB1*04:01, is found three times as often in people who are asymptomatic. This suggests that people with this gene have some level of protection from severe Covid.

The study, funded by Innovate UK, the UK's innovation agency, compared asymptomatic people to patients from the same community who developed severe Covid but had no underlying illnesses, and is published in the HLA journal.

The study team believe this is the first clear evidence of genetic resistance because this study compared severely affected people with an asymptomatic COVID group and used next generation sequencing to focus in detail and at scale on the HLA genes which are packed together on chromosome 6. Other studies have scanned the whole genome but that approach is less effective in the tissue typing complex.

Genome wide studies can be likened to a satellite image. The high density and complexity of the histocompatibility complex and variation in different populations means significant variation can be overlooked. For example, different alleles or versions of the same gene could have opposite effects on the immune response. This study was much more focused and compared symptomatic to asymptomatic in the same population revealing the "protective" qualities of the allele.

It is known that the human leukocyte antigen gene identified, HLA-DRB1*04:01, is directly correlated to latitude and longitude. This means more people in the North and West of Europe are likely to have this gene.

This suggests that populations of European descent will be more likely to remain asymptomatic but still transmit the disease to susceptible populations.

Dr Carlos Echevarria from the Translational and Clinical Research Institute, Newcastle University who also works as a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust and is a co-author of the paper says: "This is an important finding as it may explain why some people catch Covid but don't get sick.

"It could lead us to a genetic test which may indicate who we need to prioritise for future vaccinations."

"At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch Covid but don't show symptoms, then they risk spreading the virus while asymptomatic."

The effect of genes being linked to geolocation is an accepted scientific concept and it is well known that HLA genes develop over generations in reaction to disease-causing pathogens.

Study author, David Langton, whose company ExplantLab helped fund the study through an Innovate UK research award, added: "Some of the most interesting findings were the relationships between longitude and latitude and HLA gene frequency. It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been put down in part to reduced UV exposure and therefore lower vitamin D levels. We weren't aware, however, that one of the main risk genes for MS, that is DRB1*15:01, directly correlates to latitude.

"This highlights the complex interaction between environment, genetics and disease. We know some HLA genes are vitamin D responsive, and that low vitamin D levels are a risk factor for severe COVID and we are doing further work in this area."

The study used samples from 49 patients with severe Covid who had been hospitalised with respiratory failure, samples from an asymptomatic group of 69 hospital workers who had tested positive through routine blood antibody testing and a control group from a study into the relationship between HLA genotypes and the outcomes of joint replacement surgery.

The research used next generation sequencing machines to study the different versions, or alleles, of the HLA genes in depth which was combined with a variety of expertise and modelling. The work was limited to samples from North East England during the first lockdown, this reduced variation in the study groups but more studies will be needed in the UK and other populations as there may be different copies of the HLA genes providing resistance in other populations.

###

The work was a collaboration between Newcastle University, Newcastle Hospitals NHS Foundation Trust, Northumbria Healthcare NHS Foundation Trust as well as the James Cook University Hospital and North Tees and Hartlepool Hospitals NHS Foundation Trust.

Co-author, Professor Sir John Burn, Professor of Clinical Genetics at Newcastle University said: "SARS Cov-2 is one of the greatest threats Mankind has faced. The more we understand why some people become sick, the better we can defend ourselves against this virus and others like it in future."

REFERENCE: The influence of HLA genotype on the severity of covid-19 infection, Carlos Echevarria et al, HLA. https://onlinelibrary.wiley.com/doi/abs/10.1111/tan.14284

https://www.eurekalert.org/pub_releases/2021-06/nu-gpf060421.php

NRx hopes 'guided missile' COVID-19 antiviral will get FDA clearance on 2nd attempt

 The FDA told NRx Pharmaceuticals to try again in September when they attempted to obtain authorization for a COVID-19 therapy. Now, the biotech thinks they have the data they need to finally get the nod. 

Radnor, Pennsylvania-based NRx filed for emergency use authorization yesterday with the FDA for aviptadil-acetate, or Zyesami, to be used in COVID-19 patients with respiratory failure. 

Zyesami is already being used in the Caucasus region, including the Republic of Georgia, Ukraine, Uzbekistan and Tajikistan, where “the pandemic is absolutely raging,” said Chairman and CEO Jonathan Javitt, M.D., in an interview. The therapy was found to increase the likelihood of patients being free of respiratory failure at 60 days compared to those with placebo in a phase 2b/3 clinical trial. The study of 196 people at 10 U.S. hospitals also showed patients who took Zyesami experienced a significantly shorter hospital stay. 

Javitt said the U.S. regulator already “knew a lot about our drug,” and he's expecting a prompt reply. The agency typically responds to emergency use authorization requests within 60 days.

The CEO is no stranger to the FDA process, having previously worked on drug development for Big Pharmas like Novartis, Pfizer, Merck and Allergan as well as serving in healthcare roles under four presidents.

NRx had sought permission from the FDA in September to allow the “most desperately ill patients who had the least chance of survival” to take the treatment without randomized data, but the FDA declined.

“They requested prospective data, but they did say in the letter that they were very interested in this drug and that they would review randomized data promptly, so this is the first time we're giving them randomized data on this drug,” Javitt said.

NRx hit another bend in the road last month when Relief Therapeutics issued comments on the COVID-19 drug in which the Swiss company claimed collaboration agreement disputes, such as refusing to share clinical trial data.

“We originally went into this with the expectation that Relief would fund all of the development, and they decided not to do that," Javitt said. "They decided to fund part of the development, but of course we’re not going to let that slow us down in any way, shape or form with regard to the drug getting to patients."

Zyesami is a synthetic version of vasoactive intestinal polypeptide (VIP), which is primarily in the lungs but first purified in the intestinal tract. VIP binds to alveolar type II cells (ATII) in the alveolus, stimulating the cells to make surfactant, which Javitt analogized as a “soap bubble that coats the inside of the lung.” COVID-19 binds to ATII and shuts down surfactant production, which causes respiratory failure.

“If nature were to design a guided missile against the effects of the coronavirus, this would probably be pretty close to that,” Javitt said of the therapy.

Few treatments have been approved for treating COVID-19, and the ones that have can only be used for very narrow indications for specific patients. Gilead Sciences' Veklury, also know as remdesivir, is one. That therapy is approved for treating COVID-19 in hospitalized adult and pediatric patients ages 12 years and up. It's also authorized for younger hospitalized pediatric patients.

Veklury is a “systemic antiviral,” whereas Zyesami has antiviral effects concentrated within ATII, according to Javitt.

NRx also plans to see whether Zyesami can be used earlier in the treatment process for COVID-19 patients and if the current intravenous formulation can be turned into an inhaled formulation. The company is also working on a phase 3 multicenter, multi-country clinical trial sponsored by the National Institutes of Health and funded by the US Government COVID-19 Therapeutics Response.

“We’re hoping that if you treat people earlier, you can keep them out of the ICU in the first place,” Javitt said.

All of this is happening amid the backdrop of NRx commencing trading last week on the Nasdaq through a merger with Big Rock Partners Acquisition, a special purpose acquisition company (SPAC).

Javitt said the SPAC process came together before the company could think about a traditional IPO. The deal happened “just in the nick of time” as the Securities and Exchange Commission has heightened oversight of SPAC accounting rules.

“The traditional IPO players have not necessarily rushed to do transactions around COVID,” Javitt said. "There's been some sentiment that COVID is a temporary phenomenon."

NRx’s stance, though, is that “COVID will be with the human race as long as the flu.”

“It'll hopefully stop being a pandemic, but it's always going to be out there lurking and therapeutics that treat COVID will be needed for the foreseeable future,” the CEO added.

The pandemic did put a roadblock in the company’s original mission: NRX-101, an investigational drug for suicidal bipolar depression. NRx was “well established” in a phase 3 program when the pandemic shut down most of the psychiatry beds being used, Javitt said. The company is now “re-establishing that drug in the clinic."

https://www.fiercebiotech.com/biotech/nrx-files-eua-for-covid-19-intravenous-drug-as-it-predicts-covid-therapeutics-will-be