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Thursday, March 4, 2021

Key Points

The RBD of SARS-CoV-2 shares sequence similarity with an ancient lectin family known to bind blood group antigens.
SARS-CoV-2 RBD binds the blood group A expressed on respiratory epithelial cells, directly linking blood group A and SARS-CoV-2.

Introduction

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the cause of COVID-19, has resulted in a global pandemic, overwhelming modern health care systems and reshaping the world economy. Despite the devastating consequences of SARS-CoV-2, not all individuals seem to be equally susceptible to contracting the virus. Recent genome-wide association studies identified the locus responsible for ABO(H) blood group expression, the first polymorphism described in the human population well over a century ago, as one of the most significant genetic predictors of SARS-CoV-2 infection risk.¹ Although previous and subsequent studies corroborate these results,^2-6 additional data have failed to observe a similar association between ABO(H) blood group status and SARS-CoV-2 infection.⁷ Although differences in study population numbers and other variables may influence these outcomes, these collective studies in general warrant a direct examination of a possible association between ABO(H) blood group antigens and SARS-CoV-2.

ABO(H) blood groups are not only the first polymorphisms described in the human population, they are also the most well-recognized. Naturally occurring antibodies against the blood group ABO(H) antigens in individuals who do not express these same polymorphic structures can cause potentially fatal hemolytic transfusion reactions after transfusion and severe acute graft rejection after transplantation.⁸ It is possible that anti–blood group antibodies may also influence SARS-CoV-2 infection through engagement of putative ABO(H) blood group antigens on the surface of the virus.⁹ However, these antibodies can be found in individuals of multiple blood types (eg, anti–blood group B antibodies are present in both blood group A and blood group O individuals) and thus may not fully account for the propensity of blood group A individuals, in particular, to exhibit an increased risk for SARS-CoV-2 infection. Furthermore, although ABO(H) antigens may influence disease progression,¹⁰ early studies suggested that increased risk was primarily associated with the likelihood of initial infection.^2-5,11 In this regard, the mechanism by which ABO(H) antigens, and particularly those of blood group A, influence the likelihood of infection is still unknown.

https://ashpublications.org/bloodadvances/article/5/5/1305/475250/The-SARS-CoV-2-receptor-binding-domain

Cal. to allocate 40% of COVID vax doses to vulnerable neighborhoods

California will begin setting aside 40% of all vaccine doses for the state's most vulnerable neighborhoods in an effort to inoculate people most at risk from the coronavirus and get the state's economy open more quickly.

Two officials in Gov. Gavin Newsom's administration shared details Wednesday on condition of anonymity.

The doses will be spread out among 400 ZIP codes with about 8 million people eligible for shots. Many of the neighborhoods are concentrated in Los Angeles County and the Central Valley. The areas are considered most vulnerable based on metrics such as household income, education level, housing status and access to transportation.

Once 2 million vaccine doses are given out in those neighborhoods, the state will make it easier for counties to move through reopening tiers that dictate business and school reopenings.

Right now, a county can move from the most restrictive purple tier to the lower red tier based on several metrics, including having 7 or fewer new COVID cases per 100,000 people per day over a period of several weeks. That metric will change to 10 new cases or fewer. In the red tier, businesses such as restaurants and gyms can open for indoor services at limited capacity.

Also in the red tier, schools that want to access new state funding must provide in-person learning for students in transitional kindergarten through grade 6 and at least one grade each in middle and high school.

About 1.6 million vaccine doses already have been given to people in those 400 ZIP codes, and the state will hit the 2 million mark in the next week or two, officials said.

Once the state gives out 4 million doses in those neighborhoods, it will revise the metrics for getting into the even less restrictive orange and yellow tiers.

Newsom has called equity the state's "North Star." Yet community health clinics focused on serving low-income and vulnerable Californians say they haven't been getting enough doses.

The changes mark a fresh round of twists in California's vaccination and reopening plans. People age 65 and over, farmworkers, educators and emergency service workers are also eligible for shots.

More counties have already been moving into the red tier as caseloads, hospitalizations and deaths drop. The state's average 2.2% test positivity rate over 7 days is a record low.

Officials are making it easier to move through reopening tiers, arguing the likelihood of widespread transmission that can overwhelm hospitals will decrease as more people are vaccinated. That's particularly true as the most vulnerable populations that are more likely to get seriously ill receive the shots.

While race and ethnicity are not explicit factors in designating vaccinations, the 400 vulnerable ZIP codes overlap heavily with neighborhoods with higher populations of Blacks, Latinos and Asian and Pacific Islanders, officials said.

Los Angeles County could move into the next phase of reopening with fewer restrictions as early as next week, though any actual lifting of coronavirus-related constraints would not happen immediately, county officials said earlier Wednesday.

Most San Francisco Bay Area counties have advanced to the next phase, which allows restaurants and movie theaters to open indoors at 25% capacity and gyms to operate at 10% capacity.

https://abc7.com/health/california-to-give-40%25-of-vaccine-doses-to-vulnerable-areas/10387415/

In Europe, a Vaccine Blame Game

The history of the AstraZeneca Covid-19 vaccine is a textbook example of political manipulation and its consequences that may one day fascinate political scientists.

When it became clear that Britain was immunizing its population much faster than the rest of Europe, the head of the European Commission, Ursula von der Leyen, accused the company that made one of the vaccines that Britain was using, Anglo-Swedish pharmaceutical giant AstraZeneca, of illegally favoring Britain and of not fulfilling its contract with the EU.

This turned out to be a doubtful excuse, to say the least, and few people believed it. Popular criticism was mounting of the very slow rate of immunization in the European Union compared not only with Britain but also with Israel and—worst of all, considering its reputation for poor public-health services—the United States. Another tactic to explain European tardiness had to be tried: anything to deflect blame.

Having first threatened to sue AstraZeneca for failure to supply its vaccine to Europe, various prominent figures, including von der Leyen herself and President Emmanuel Macron of France, cast doubts on the vaccine’s efficacy. If it didn’t work anyway, then the EU was not remiss in failing to secure supplies of it, and indeed had exercised foresight and wisdom in not doing so, especially compared with the British, who had frivolously put their population at risk by using an untried product.

Macron said that the vaccine was “quasi-ineffective” for those over 65. He is far too intelligent a man not to have known that he was not telling the truth. It was true that, at the time, the results for over-65s were unclear, but antibody studies and general principles suggested that the vaccine was very likely to be effective, as it has turned out to be. There never was any evidence to suggest that it was “quasi-ineffective.”

In Germany, Handelsblatt, the preeminent German economic newspaper, published an article quoting a senior civil servant to the effect that the vaccine was only 8 percent effective in older people. No evidence suggested that this was true. That it was printed suggests political manipulation of the press.

Though the European Medicines Agency licensed the vaccine for all adult age groups, many countries restricted its use to those under 65, or even under 55. Not surprisingly, the populations of those countries came to believe that the vaccine was “quasi-ineffective.” Moreover, false rumors began to spread about its side effects. Now it emerges that only a small proportion of the vaccines available has been used—as little as one-fifth or one-quarter.

Most countries are now changing their tune and accepting that the vaccine is effective and should be used in all adult age groups (though France, more anxious to save face than to be Cartesian, is sticking to those under 75). Whether public confidence can be restored is another question. The goal of the misinformation has been achieved; blame has been deflected.

The whole unedifying story demonstrates the lengths of dishonesty to which a political class is willing to go to save face (and possibly its own jobs)—but more interestingly, perhaps, the extent to which populations remain willing to look to that political class for guidance in making decisions. I confess to being surprised.

Theodore Dalrymple is a contributing editor of City Journal, a senior fellow at the Manhattan Institute, and the author of many books, including Out into the Beautiful World and Grief and Other Stories.

https://www.city-journal.org/eu-misinformation-about-astrazeneca-covid-19-vaccine

CDC Finalizing Guidance for Activities for Fully Vaccinated People

The CDC is expected to soon release guidelines on safe activities for fully vaccinated people, Politico and other news organizations reported.

The CDC will recommend that vaccinated people try to only socialize with other vaccinated people at home. They should still wear masks elsewhere while observing other safety measures, such as social distancing, reported Politico, citing two unnamed senior administration officials.

In describing the upcoming guidance during a news briefing Monday, Dr. Anthony Fauci, President Biden's chief medical officer, said:

"I use the example of a daughter coming in from out of town who is doubly vaccinated, and a husband and wife doubly vaccinated, and maybe a next-door neighbor who you know are doubly vaccinated," Fauci said. "Small gatherings in the home of people, I think you can clearly feel that the risk — the relative risk is so low that you would not have to wear a mask, that you could have a good social gathering within the home."

The new guidance was expected to be released today, but Politico reported later the rules have been delayed. A new date for publishing is not yet clear.

When published, the CDC guidance is expected to describe how vaccinated Americans should respond in certain scenarios, such as while traveling, Politico said.

The guidance comes as more people become vaccinated and coronavirus cases and deaths decline across the country, yet health experts warn that "normalcy" remains a long way off.

However, some state governments are already relaxing safety restrictions. Hard-hit Texas, for example, is lifting the statewide mask mandates and plans to lift other COVID restrictions soon.

The CDC says that 102.3 million doses of vaccine have been distributed and 78.6 doses administered. About 26.1 million people have received both doses of the two-dose Moderna or Pfizer vaccines. About 10.2% of the U.S. population over age 18 has received both doses, the CDC says.

Johnson & Johnson's one-shot vaccine received emergency use authorization last week, which means the amount of available vaccine should soon increase.

https://www.medscape.com/viewarticle/946891

Insurance Regulator to Warn on Virus-Test Billing

New Mexico's top insurance regulator is putting medical providers on notice that people cannot be charged for coronavirus testing after reports that residents have been required to pay for coronavirus rapid-result tests.

Insurance Superintendent Russell Toal said Wednesday that his office is preparing an administrative bulletin to ensure testing costs are not passed directly on to consumers, as state health officials push for robust testing to track infection rates and new strains of COVID-19.

Toal said the Office of the Superintendent of Insurance has received reports and complaints of people being charged in excess of $100 for testing services that should be free. The extent of the improper billing is unclear.

"We've got some providers out there that are charging individuals for so-called rapid tests," Toal said. "The new guidance from the federal government makes it really clear that those federal tests are to be covered without a charge to the patient."

The Biden administration in February issued guidance on 2020 emergency pandemic legislation that restricts cost-sharing with patients for coronavirus testing under a broad range of circumstances.

New Mexico officials this week described steep declines in new confirmed infections, hospitalizations and deaths because of the virus. Still, state Human Services Secretary David Scrase said they are monitoring variants and stressed the importance of testing as a way to keep tracking the virus.

The seven-day rolling average for tests administered is hovering around 11,800 — well above a benchmark of 5,000 per day set by the state for re-opening the economy.

New Mexico health officials say more vaccine doses are needed from suppliers if New Mexico wants to meet a new mandate for applying at least one shot to all teachers by the end of March.

Many New Mexico school districts have opted not to dramatically increase in-person learning despite approval from Gov. Michelle Lujan Grisham. Some have opened on a limited basis, allowing students to attend in-person based on the availability of teachers who volunteer.

Citing the limiting factor of vaccine supply, Lujan Grisham said in a statement that she was hopeful Biden's directive on schools reopening was an indication that the federal government would be sending more support to the states to get schools opened safely on a faster timeline.

New Mexico is leading the nation when it comes to the percentage of vaccine doses used, having administered more than 94% of its doses. It's the second-fastest state for administration with nearly one-quarter of residents partially vaccinated and nearly 13% fully vaccinated.

https://www.medscape.com/viewarticle/946887

March medtech merger madness

The medtech industry has really gone for it on the M&A front this year. 2021 started strongly, with more than $10bn-worth of deals announced in January alone; this week’s deals, notably Boston Scientific’s acquisition of Lumenis’s global surgical laser business for $1.1bn in cash, puts 2021’s total so far at $16.7bn.

In fact 2021 has had the strongest first quarter for device maker deal-making since 2016 – and the year is barely two months old. Should the rumoured takeover of Livanova by private equity for a price just shy of $4bn come off, 2021 could end up with the strongest opening period for a decade.

Boston has been particularly keen this year, already buying the remote cardiac monitoring company Preventice in January for $925m up front. Its second even bigger deal will net it a portfolio of laser systems for urology and otolaryngology procedures, chiefly Lumenis’s Moses laser, used to break up kidney stones. Lumenis’s current owner, Baring Private Equity Asia, will keep Lumenis’s aesthetics and ophthalmology businesses.

Boston’s motivation for opening its chequebook is clear. The Covid-19 pandemic and its consequent lockdowns were catastrophic for the group, whose devices tend to be used in non-urgent procedures from which hospitals shied away so they could focus on coronavirus patients. A recent Evaluate Vantage analysis found that, out of the top 10 largest medtechs, Boston’s revenues sank the most in the fourth quarter of 2020 (Medtech’s haves and have-nots, February 24, 2021).

Thus the company’s enthusiasm for buying high-growth businesses. Lumenis’s surgical unit expanded at double-digit rates in the five years before Covid-19 hit, and net sales are projected to hit $200m in 2021. Boston is likely to make more acquisitions throughout the year, though perhaps it might scale back to smaller tuck-ins.

More to come

A second, smaller deal announced yesterday also has growth as its focus. Bio-Techne, which makes instruments and reagents for clinical diagnostics, bought Asuragen for $215m via a combination of cash and an existing line of credit. Asuragen specialises in genetic carrier screening for conditions such as Fragile X as well as oncology testing.

According to Leerink analysts, Asuragen’s sales are currently growing in the mid-teens annually, but Bio-Techne’s management reckons this can be upped to around 20%. It also intends to increase Asuragen’s operating margins to 40% over time.

As impressive as the first quarter has been so far in terms of medtech M&A, another billion-dollar buyout could be on the cards. Yesterday shares in Livanova climbed 3% on rumours of an $80-per-share bid from the private equity group Permira that would value Livanova at around $3.7bn.

Livanova has also been hit by the pandemic, with demand for its neuromodulators and heart valves taking a temporary knock. Its 2020 sales were down 14% compared with 2019 – an even greater drop than that experienced by Boston Scientific. Livanova ended up selling its valve franchise in December.

The Permira deal is far from a sure thing. Livanova is often talked of as a takeover target – the last time rumours swirled, a year or so ago, the putative buyer was Medtronic. Analysts from Berenberg believe that Permira’s offer is too parsimonious to garner significant shareholder support, despite Livanova’s investor base being frustrated by its depressed near-term earnings, partly owing to its high R&D spend.

The analysts write that a strategic buyer makes more sense, since such a group could realise greater synergies than a PE shop, and believe a price of around $100 per share could get a deal done. Still, they add that there are few obvious signs of strategic interest.

If Livanova is claimed by Permira or anyone else, the first quarter of 2021 will set the year up to be a record-breaker.

Q1 M&amp: 11.4

https://www.evaluate.com/vantage/articles/news/deals/march-medtech-merger-madness

EU and Italy Block Export of AstraZeneca Covid-19 Vaccine Doses

Italy blocked the export of AstraZeneca PLC's Covid-19 vaccines to Australia, according to people familiar with the matter, in a move coordinated with European Union authorities, reflecting mounting frustration in Europe with slow deliveries of vaccines.

The move was prompted by the unsatisfactory compliance by the drug supplier with supply contracts, one of the people said.

Due to the current shortage of vaccine doses in the EU, it made sense to keep the shots in Italy, the person said. The 250,000 affected doses were bottled at a factory near Rome that is part of AstraZeneca's supply chain.

Representatives for AstraZeneca declined to comment.

The move is the first known use of a new EU policy that allows controls to be imposed on the export of Covid-19 vaccines.

In accordance with the EU policy, AstraZeneca had asked the Italian government for permission to export the doses. Rome refused and the European Commission supported the Italian government's decision, the people familiar with the matter said.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-EU-and-Italy-Block-Export-of-AstraZeneca-Covid-19-Vaccine-Doses-Update-32607369/