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Wednesday, May 12, 2021

Human antibody that broadly neutralizes betacoronaviruses protects against SARS-CoV-2

 

Dora PintoMaximilian M. SauerNadine CzudnochowskiJun Siong LowM. Alejandra TortoriciMichael P. HousleyJulia NoackAlexandra C. WallsJohn E. BowenBarbara GuarinoLaura E. RosenJulia di IulioJosipa JerakHannah KaiserSaiful IslamStefano JaconiNicole SprugasciKatja CulapRana AbdelnabiCaroline FooLotte CoelmontIstvan BarthaSiro BianchiChiara Silacci-FregniJessica BassiRoberta MarziEneida VettiAntonino CassottaAlessandro CeschiPaolo FerrariPietro E. CippàOlivier GianniniSamuele CerutiChristian GarzoniAgostino RivaFabio BenigniElisabetta CameroniLuca PiccoliMatteo S. PizzutoMegan SmitheyDavid HongAmalio TelentiFlorian A. LemppJohan NeytsColin Havenar-DaughtonAntonio LanzavecchiaFederica SallustoGyorgy SnellHerbert W. VirginMartina BeltramelloDavide CortiDavid Veesler

This article is a preprint and has not been certified by peer review [what does this mean?].
PDF: https://www.biorxiv.org/content/10.1101/2021.05.09.442808v1.full.pdf

Abstract

The repeated spillovers of β-coronaviruses in humans along with the rapid emergence of SARS-CoV-2 escape variants highlight the need to develop broad coronavirus therapeutics and vaccines. Five monoclonal antibodies (mAbs) were isolated from COVID-19 convalescent individuals and found to cross-react with multiple β-coronavirus spike (S) glycoproteins by targeting the stem helix. One of these mAbs, S2P6, cross-reacts with more than twenty human and animal β-coronavirus S glycoproteins and broadly neutralizes SARS-CoV-2 and pseudotyped viruses from the sarbecovirus, merbecovirus and embecovirus subgenera. Structural and functional studies delineate the molecular basis of S2P6 cross-reactivity and broad neutralization and indicate that this mAb blocks viral entry by inhibiting membrane fusion. S2P6 protects hamsters challenged with SARS-CoV-2 (including the B.1.351 variant of concern) through direct viral neutralization and Fc-mediated effector functions. Serological and B cell repertoire analyses indicate that antibodies targeting the stem helix are found in some convalescent donors and vaccinees but are predominantly of narrow specificity. Germline reversion of the identified cross-reactive mAbs revealed that their unmutated ancestors are specific for the endemic OC43 or HKU1 viruses and acquired enhanced affinity and breadth through somatic mutations. These data demonstrate that conserved epitopes in the coronavirus fusion machinery can be targeted by protective antibodies and provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.

Competing Interest Statement

D.P., N.C., M.P.H., J.N., B.G., L.E.R., J.d.I., H.K., S.I., S.J., N.S., K.C., I.B., S.B., C.S.F, J.B., R.M., E.V., F.B., E.C., L.P., M.S.P., M.S., D.H., A.T., F.A.L., C.H.D., A.L., G.S., H.W.V., M.B. and D.C. are employees of Vir Biotechnology and may hold shares in Vir Biotechnology. D.C., J.S.L, F.S., A.C. and A.L. are currently listed as an inventor on multiple patent applications, which disclose the subject matter described in this manuscript. D.V. is a consultant for Vir Biotechnology Inc. The Veesler laboratory and the Sallusto laboratory have received sponsored research agreements from Vir Biotechnology Inc. The other authors declare no competing interests.

https://www.biorxiv.org/content/10.1101/2021.05.09.442808v1

COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction

 Eliyahu Kresch,1 Justin Achua,1 Russell Saltzman,2 Kajal Khodamoradi,1 Himanshu Arora,1 Emad Ibrahim,1 Oleksandr N. Kryvenko,1,3,6 Vania Wolff Almeida,4 Fakiha Firdaus,1 Joshua M. Hare,2,5 and Ranjith Ramasamy1


DOI:   https://doi.org/10.5534/wjmh.210055

PDF: https://wjmh.org/pdf/10.5534/wjmh.210055

Purpose

A pilot study to describe histopathological features of penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED).

Materials and Methods

Penile tissue was collected from patients undergoing surgery for penile prosthesis for severe ED. Specimens were obtained from two men with a history of COVID-19 infection and two men with no history of infection. Specimens were imaged with TEM and H&E staining. RT-PCR was performed from corpus cavernosum biopsies. The tissues collected were analyzed for endothelial Nitric Oxide Synthase (eNOS, a marker of endothelial function) and COVID-19 spike-protein expression. Endothelial progenitor cell (EPC) function was assessed from blood samples collected from COVID-19 (+) and COVID-19 (−) men.

Results

TEM showed extracellular viral particles ~100 nm in diameter with peplomers (spikes) near penile vascular endothelial cells of the COVID-19 (+) patients and absence of viral particles in controls. PCR showed presence of viral RNA in COVID-19 (+) specimens. eNOS expression in the corpus cavernosum of COVID-19 (+) men was decreased compared to COVID-19 (−) men. Mean EPC levels from the COVID-19 (+) patients were substantially lower compared to mean EPCs from men with severe ED and no history of COVID-19.

Conclusions

Our study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans. Our results also suggest that widespread endothelial cell dysfunction from COVID-19 infection can contribute to ED. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection leads to ED.


https://wjmh.org/DOIx.php?id=10.5534/wjmh.210055

SARS-CoV-2 infection induces autoimmune antibody secretion more in lean than in obese COVID patients

 Daniela Frasca, Lisa Reidy, Maria Romero, Alain Diaz, Carolyn Cray, Kristin Kahl, Bonnie Blomberg

Schools ditch student mask requirements in growing numbers

 As a lengthy, bitter fight over mask requirements for students neared its conclusion, the chairperson of a Florida school board announced that she would agree to lift a mandate that had been in place since September even though she preferred leaving it in place until the end of the academic year. Parents hurled insults in response.

“Communist! Democrat!,” opponents of making children wear masks in school shouted as board chair Wei Ueberschaer and the district superintendent explained at a May 3 meeting that they still considered masks advisable. “This is Santa Rosa County, America, not China!”

Moments later, the Santa Rosa school board voted unanimously to make masks optional for all grades effective immediately, joining dozens of other U.S, communities in declaring that masks were or would soon no longer be mandatory for students.

The debates have been emotional and highly divisive around the country, in some cases leading to the involvement of police. A few beleaguered school boards, caught between the demands of anti-mask parents and the appeals of employee unions, eliminated student mask rules only to reverse or revise the decisions. Where many see a continued need to protect children who aren’t vaccinated against COVID-19, opponents argue that masks make students uncomfortable and mandates impinge on freedom.

“The mask is a personal choice, and I wore it at the beginning, but I just decided that it wasn’t about the mask anymore,” said Cynthia Licharowicz, a Milton, Florida, parent who opposed Santa Rosa County’s rule. “So I decided to take it off, and I wanted my child to have the same choice.”

The dustups highlight competing risk narratives 14 months into the pandemic: Even as a number of U.S. schools remain closed to minimize infections, districts in states from Alabama to Wyoming decided to ditch student mask mandates. Many more are likely to do the same before the next school year starts, despite the Centers for Disease Control and Prevention’s guidance that schools “should prioritize universal and correct use of masks and physical distancing.”

Some public health experts are alarmed. While the Food and Drug Administration this week approved Pfizer’s COVID-19 vaccine for children as young as 12, it’s unlikely that many young adolescents will be vaccinated before the end of the academic year. Data from the CDC shows infection rates among U.S. residents ages 14-17 are now higher than for all Americans, while the rates among children 6-13 are getting closer to the national average.

“We know that masks work to reduce transmission,” Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security, said. “This is really not the time to remove one of the best tools we have to reduce transmission.”

In Arkansas, a law will make it illegal by the end of the summer for schools or any government entity to require masks. On Wednesday in South Carolina, schools Superintendent Molly Spearman dropped a statewide student mask mandate but said Gov. Henry McMaster had no legal basis for an order letting parents choose for their children whether or not to wear masks. Spearman said districts could continue to apply their own mask rules.

Many parents in school districts where masks have become voluntary are concerned.

“I am so frustrated....I don’t see any harm in wearing masks, and there is potential harm in not wearing a mask,” said Christie Black, the mother of a kindergartner and a third grader in Mesa, Arizona, who was puzzled by the decision of the state’s largest school district to make masks optional indoors starting earlier this month.

There’s little U.S. data about the spread of the coronavirus in schools where students didn’t wears masks since most reopened schools required them, said Adam Hersh, a professor of pediatric infectious diseases at the University of Utah. Mask supporters point to worrying examples, including high transmission at a maskless summer camp in Georgia.

Evidence from earlier in the pandemic found children less likely than adults to be infected with the coronavirus and less likely to become seriously ill from COVID-19. The CDC has said that while schools haven’t been associated with substantial spread, outbreaks in schools not following infection-prevention measures “tend to result in increased transmission among teachers and school staff rather than among students.”

Black continues to send her two children to school with masks but says “they flung their masks off” as soon as they saw classmates no longer covering their faces.

“I feel like because the governor and the school board caved to peer pressure, it’s now up to my children not to cave to peer pressure,” Black said. “It just feels like we’re more concerned with our own freedom and rights than doing what’s best for the most vulnerable.”

In Santa Rosa, east of Pensacola, mask opponents dominated public debate even though surveys of parents and teachers showed divided opinions in the 28,000-student district. A small majority of teachers wanted to require masks at least through the end of the school year, while a small majority of parents wanted the requirement lifted immediately.

The school board’s April 20 discussion about the issue nonetheless grew so heated that sheriff’s deputies escorted multiple attendees out of the meeting, including at least one who was shouting profanities at board members.

Jennifer Hensley, a Santa Rosa County parent and middle school teacher, was the only member of the public at the meeting who spoke in favor of keeping the mask mandate versus the 18 who spoke against the requirement. She said she was worried about the health of her fellow teachers and of her 15-year-old daughter, who has an autoimmune disorder.

“The atmosphere was so charged,” Hensley recalled later. “I don’t think they were expecting that level of emotion to be involved.”

Critics of the mask policy started organizing months earlier. Hailei Smead, a mother of three students, runs a Facebook group called Santa Rosa County Parents SPEAK UP that was created in September to oppose mask requirements and has nearly 900 members registered.

Smead said her fifth-grade daughter was repeatedly isolated in the school office for refusing to wear a mask and eventually obtained a medical exception allowing her to forego a face covering. Smead declined to state the medical reason.

“It’s not society’s job to protect every other individual,” Smead said. “It’s your own job to protect yourself and your own family.”

Santa Rosa County district leaders emphasized they were following public health guidance, but state officials undercut that position even as public pressure built locally. On April 29, Florida Surgeon General Scott Rivkees rolled back a series of health advisories that had been cited by the Santa Rosa district. So the school board called the May 3 meeting at which its five members voted to revoke the mask mandate.

“I still strongly recommend the use of face masks, especially for those who are not fully vaccinated,” board chair Ueberschaer said before the vote, raising her voice to be heard over shouting parents. “My hope is that the families will have a conversation with their children that face masks are now a personal choice, and that students should respect the choice of their peers.”

Some of the insults hurled at Ueberschaer, a longtime school volunteer who is of Asian descent, included references to China.

“It truly does make me sad that face masks have morphed from a virus-prevention strategy to a political statement,” she said.

https://apnews.com/article/coronavirus-pandemic-health-education-abb64bd20748bd95aea2a5e2017704fd

Ohio Gov. DeWine To Lift All COVID Health Orders On June 2

 Gov. Mike DeWinesaid in a statewide address Wednesday that the state will lift most of its health orders, including the mask mandate, in the next three weeks.

He also announced a series of $1 million drawings and other incentives for people to get the COVID-19 vaccine.

DeWine says the decision to lift all of the health restrictions related to the COVID-19 pandemic was made because of the effectiveness of the vaccine.

"Everyone can now control their own health. Everyone can now control their own destiny. So, it is time, it’s time to end the health orders. It’s been a year. You’ve followed the protocols. You’ve done what we’ve asked. You’ve bravely fought this virus. And now, our cases are down, and we have a tested and proven weapon in the vaccine that all Ohioans 12 and over can utilize," DeWine said.

According to DeWine the plan is for the Ohio Department of Health to remove all pandemic health orders on June 2. There is an exception: the health orders for nursing homes and assisted living facilities will remain in effect.

DeWine says he hopes people will use the next three weeks to get the vaccine if they have not done so already.

DeWine also announced that the state can start vaccinating people between the ages of 12-15.
"In preparation for the vaccination of 12- to 15-year-olds, Ohio’s children’s hospitals and pediatricians are already working with local groups to make the vaccine available to their patients and members of their community," DeWine said.

The announcement comes just hours after the Advisory Committee on Immunization Practices, an independent panel of advisers to the Centers for Disease Control and Prevention, voted to recommend the use of the Pfizer COVID-19 vaccine for ages 12 and up.

On Monday, the U.S. Food and Drug Administration approved an extension of its emergency use authorization for the Pfizer vaccine to include adolescents between the ages of 12-15. Pfizer is already the vaccine used for 16- and 17-year-olds.

DeWine said the key to lifting the health restrictions is the vaccine along with individuals and companies making their own responsible decisions when it comes to preventing the spread of the virus.

With that, DeWine announced a new incentive for adults to get the shot. The "Ohio Vax-a-Million" will be a drawing that occurs once a week for five weeks. Each winner will receive $1 million.

Here's how it will work, according to DeWine, those who have been vaccinated can have their name entered into the drawing. One person will be selected each week. That means there will be five people who will win $1 million.

A similar drawing will take place for people ages 12-17. The winner selected each week for five weeks will win a full-ride, four-year scholarship to any Ohio public university.

"I know that some of you now are shaking your head saying, 'That Mike DeWine, he's crazy! This million-dollar drawing idea of yours is a waste of money.' But truly, the real waste at this point in the pandemic, when the vaccine is readily available to anyone who want it, the real waste is a life that is lost to COVID-19," DeWine said.

DeWine says more information about the drawings will be announced on Thursday. In Ohio, 4.8 million people have received at least the first dose of the COVID-19 vaccine, that's more than 41% of the state population.

https://news.wosu.org/coronavirus/2021-05-12/gov-dewine-to-give-statewide-address-on-covid-19-vaccination-effort

Biogen Exercises Option to Acquire Investigational Drug TMS-007

 Biogen Inc Wednesday said it exercised its option from TMS Co. Ltd. to acquire TMS-007, an investigational drug for acute ischemic stroke.

Biogen said its decision to acquire TMS-007 was based on positive data from a Phase 2a study. The study met its primary safety objective with no incidence of symptomatic intracranial hemorrhage and demonstrated positive impacts on both blood vessel reopening in the brain as well as patient functional recovery.

Biogen will make a one-time $18 million payment as part of the acquisition of TMS-007. TMS is eligible to receive up to an additional $335 million in potential post-acquisition development and commercial payments should TMS-007 achieve certain developmental milestones and sales thresholds.

TMS is also eligible to receive tiered royalties in the high single digits to sub-teen percentages on annual worldwide net sales.

Biogen will be solely responsible for the costs and expenses related to the development, manufacturing and commercialization of TMS-007 after the acquisition.

Biogen said it is evaluating the next steps for the clinical development of TMS-007, including plans for global studies.

https://www.marketscreener.com/quote/stock/BIOGEN-INC-4853/news/Biogen-Exercises-Option-to-Acquire-Investigational-Drug-TMS-007-33237820/

Samsung BioLogics, Pfizer deny report on COVID-19 vaccine production in S.Korea

 

Samsung BioLogics Co Ltd and Pfizer Inc on Wednesday denied a report that they were working together to produce in South Korea a COVID-19 vaccine developed by the U.S. drugmaker.

The Korea Economic Daily reported earlier that the biotech arm of Samsung Group had been revamping production lines at its plant in Songdo to produce the Pfizer vaccine, which was jointly developed by the German BioNTech.

The report quoted an unnamed high-level government official as saying the plant had the capacity to make up to 1 billion doses per year and production could start as early as in August.

Samsung BioLogics said in a one-line filing to the stock exchange that the report was "not factual". The company did not respond to requests for a more detailed comment.

Pfizer said its current production strategy was centred on its two dedicated supply lines in the U.S. and Europe that which exclusively manufacture its vaccine for global use.

"At this time we are not in discussions for any additional manufacturing outside these established supply lines for this vaccine," Pfizer said in a statement.

"Once the pandemic supply phase is over and we enter a phase of regular supplies, Pfizer will certainly evaluate all additional opportunities available."

South Korean health authority in charge of COVID-19 vaccine procurement said it was not in a position to comment on the report.

The country has secured 192 million doses, enough to vaccinate all 52 million residents twice over.

But President Moon Jae-in is under pressure to secure more and faster deliveries of U.S.-made shots as he heads for his first summit with U.S. President Joe Biden next week.

South Korea has been relatively successful in its response to the pandemic, but questions over vaccine rollout amid global shortages and shipment delays drive public scepticism about Seoul's goal of reaching herd immunity by November.

Just over 7% of the population have received at least one dose, and the country reported 635 new COVID-19 cases on Tuesday, bringing the total number of confirmed cases to 128,918, with 1,884 deaths.

https://www.marketscreener.com/quote/stock/SAMSUNG-BIOLOGICS-CO-LTD-32042423/news/Samsung-BioLogics-Pfizer-deny-report-on-COVID-19-vaccine-production-in-S-Korea-33230636/