Brazil's hospitals running out of sedatives as COVID-19 rages

RIO DE JANEIRO (Reuters) – Hospitals in Brazil were running out of drugs needed to sedate patients on Thursday, with reports of the seriously ill being tied down and intubated without effective sedatives.

FILE PHOTO: Medical workers take care of patients in the emergency room of the Nossa Senhora da Conceicao hospital that is overcrowding because of the coronavirus outbreak, in Porto Alegre, Brazil, March 11, 2021.  REUTERS/Diego Vara

The scenes playing out across Brazil, one of the countries hardest hit by the COVID-19 pandemic, are placing growing international pressure on President Jair Bolsonaro.

Aid group Médecins Sans Frontières (MSF) said Brazil’s “failed response” had led to thousands of avoidable deaths and created a humanitarian catastrophe that could still get worse.

Brazil has recorded a total of 361,884 coronavirus deaths – only the United States has more – and 13,673,507 confirmed cases.

More Brazilians are currently dying of the virus each day than anywhere else in the world. Bolsonaro has opposed lockdowns and held large events in which he often does not wear a mask. He has only recently embraced vaccines as a possible solution.

Brazil’s hospitals are struggling to cope.

Rio de Janeiro and Sao Paulo have both sounded the alarm over shortages of sedatives, with Sao Paulo’s Health Secretary saying the city’s ability to care for seriously ill COVID-19 patients is on the verge of collapse.

“I never thought that I would be living through something like this after 20 years working in intensive care,” Aureo do Carmo Filho, an ICU doctor in Rio, told Reuters.

“Using mechanical restraints without sedatives is bad practice…the patient is submitted to a form of torture,” he said.

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Seriously ill COVID-19 patients struggling for breath are sedated in order to put them on ventilators, an intrusive practice the body can naturally resist.

With ICU beds at or near capacity across the country, hospitals are being forced to create improvised intensive care beds which often lack equipment or professional expertise.

Globo television network on Wednesday reported cases from a Rio hospital in which patients were intubated with a lack of sedatives, tied to beds.

The Albert Schweitzer hospital, through the press office of the city of Rio which runs it, said there was a shortage of intubation drugs but that substitutes were being used to ensure medical assistance was not compromised. It said mechanical restraints were only used when prescribed by a doctor.

The city of Rio added that a batch of intubation drugs was set to arrive on Thursday.

“FAILED RESPONSE”

Médecins Sans Frontières said Bolsonaro’s government had not done enough to prevent the tragedy.

“More than one year into the COVID-19 pandemic, the failed response in Brazil has caused a humanitarian catastrophe,” said Christos Christou, a medical doctor and president of MSF, called Doctors Without Borders in English.

“Each week there is a grim new record of deaths and infections – the hospitals are overflowing and yet there is still no coordinated centralized response,” Christou said in a briefing with reporters, adding that the situation was expected to become even worse in the weeks ahead.

Bolsonaro has openly fought against state and local governments seeking to institute lockdowns, saying Brazilians need to get on with normal life and that job losses are more dangerous than the virus.

MSF Director-General Meinie Nicolai said the surge in cases cannot be blamed only on the contagious Brazilian COVID-19 variant, known as P.1.

“The P.1 variant is certainly a problem, but this doesn’t explain the situation in Brazil,” she said.

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Virus variants inciting India's second surge, epidemiologists say

NEW DELHI (Reuters) – The second surge of COVID-19 cases in India has swamped hospitals much faster than the first because mutations in the virus mean each patient is infecting many more people than before, epidemiologists and doctors say.

A patient lies in a bed as she is being shifted to a hospital for treatment, amidst the spread of the coronavirus disease (COVID-19) in Ahmedabad, India, April 15, 2021. REUTERS/Amit Dave

India’s daily infections skyrocketed more than 20-fold to more than 200,000 on Thursday since a multi-month-low in early February, though the government has played down the role of mutants in the latest rise, the worst anywhere this month.

The world’s hardest-hit country after the United States has reported about 950 cases of people contracting the variants first detected in the United Kingdom, South Africa and Brazil.

“The point is that these variants of concern are still not on top of the discourse,” said epidemiologist Rajib Dasgupta of New Delhi’s Jawaharlal Nehru University.

“Even if it is a new variant, you need to do the same things” to control it and treat patients “but it requires a different urgency to recognise that”, he said.

Doctors at New Delhi’s All India Institute of Medical Sciences have found that one patient is now infecting up to nine in 10 contacts, compared with up to four last year.

Scientists in Britain say the B.1.1.7 variant here, widely known as the British mutant, is 70% more transmissible than previous variants, and much deadlier.

The northern Indian state of Punjab, which has reported one of the highest recent fatality rates in the country, said late last month 81% of 401 COVID-19 samples it sent for genome sequencing were found to be the British variant.

“This virus is more infectious and virulent,” said Dhiren Gupta, a senior consultant at New Delhi’s Sir Ganga Ram Hospital.

“More children are reporting high-grade fever compared to last year. We have 35-year olds with pneumonia in intensive care, which was not happening last year.”

India has recorded 14.1 million infections and 173,123 deaths in total.

MASS GATHERINGS

The government has mainly attributed the big rise in cases to a reluctance to wear marks and crowding.

Still, it has refused to call off a mass gathering of Hindu devotees for a festival and its ministers are addressing tens of thousands of largely mask-less people in election rallies.

A scientist at the National Institute of Epidemiology said more evidence was needed to directly link the rise in cases to the variants, but that anecdotally that seemed to be the case.

“There are in-vitro experiments which can also tell us about the infectivity, the severity, how lethal it is, etc, but those are not completed yet, they are ongoing,” said Tarun Bhatnagar.

“We haven’t had a virus that has spread so rapidly, and we haven’t had the time to study it. Everything is on the go. We are dealing with it, being affected by it and studying it. The pace of every thing is too fast.”

But with crowding still common in many regions of India, “we are about to find out just how dangerous this strain is”, said Om Srivastava, head of infectious diseases at Mumbai’s Jaslok Hospital who also advises India’s worst-hit Maharashtra state.

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Updated Moderna vaccines neutralize South African SARS-CoV-2 variant in mice

Researchers in the United States have conducted a pre-clinical study demonstrating the efficacy of two updated versions of the Moderna mRNA-1273 vaccine against variants of severe acute respiratory syndrome coronavirus 2 – the agent that causes coronavirus disease 2019 (COVID-19).

Study: Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

The updated vaccine candidates include the monovalent mRNA-1273.351, which is designed to target the B.1.351 variant that emerged in South Africa, and the multivalent mRNA1273.211, which comprises a mixture of the original mRNA-1273 vaccine and mRNA-1273.351.

The vaccines were evaluated in mice as both a primary vaccination series and as a booster dose among animals that had previously been immunized with two doses of mRNA-1273.

The team reports that while the mRNA-1273.351 vaccine elicited high levels of neutralizing antibody titers against B.1.351, the multivalent mRNA-1273.211 was most effective at providing broad cross-variant neutralization.

In addition, a booster dose of mRNA-1273.351 dramatically increased neutralization titers against both wild-type SARS-CoV-2 and the B.1.351 variant.

“Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies,” says the team from Moderna Inc and the National Institute of Allergy and Infectious Diseases.

Global surveillance for the emergence of further variants of concern (VOCs) is also ongoing, as are efforts to test the ability of mRNA-1273 to neutralize VOCs.

“If additional variants emerge that reduce the neutralization capacity of mRNA-1273 further, additional mRNA vaccine designs may be developed and evaluated,” writes Kai Wu and colleagues.

A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.

Model of S protein. mRNA-1273.351 encodes the B.1.351 lineage S variant. Surface representation of the trimeric S protein in the vertical view with the locations of surface-exposed mutated residues highlighted in red spheres and labeled on the grey monomer. The inset shows superimposition of ACE-2 receptor domain and the RBD. S protein structure, 6VSB. ACE2-RBD structure, 6M0J. ACE2, angiotensin converting enzyme 2; NTD, N-terminal domain; RBD, receptor-binding domain.

Variants increasingly pose a threat to vaccination

The emergence of SARS-CoV-2 variants has raised concerns that the virus may have evolved the ability to escape vaccine-induced immunity. Several variants have demonstrated resistance to neutralization by vaccinated sera, particularly the South African B.1.351 lineage that was first identified in December 2020.

The initial stage of the SARS-CoV-2 infection process is mediated by the viral spike protein, which attaches to the host cell receptor via its receptor-binding domain (RBD). This spike RBD is the primary target of the neutralizing antibodies that are generated following infection or vaccination. A neutralization “supersite” has also been identified in the N-terminal domain (NTD) of the spike protein.

Studies have shown that several recently emerged SARS-CoV-2 variants harbor mutations in the RBD and NTD of spike that may confer resistance to vaccine-induced neutralization activity.

“Importantly, mutations in the NTD domain, and specifically the neutralization supersite, are extensive in the B.1.351 lineage virus,” says Wu and colleagues.

Furthermore, “studies have demonstrated reduced neutralization titers against the full B.1.351 variant following mRNA-1273 vaccination,” they add.

What did the researchers do?

Now, Wu and colleagues have evaluated the efficacy of two updated vaccines.

The monovalent mRNA-1273.351 vaccine encodes the spike protein found in the B.1.351 lineage, while the multivalent mRNA-1273.211 comprises a 1:1 mix of mRNA-1273.351 and mRNA-1273.

The original mRNA-1273 vaccine targets the ancestral wild-type virus (Wuhan-Hu-1 variant) that contains a mutation called D614G.

The vaccines were administered in mice as a two-dose primary series and their immunogenicity against D614G and B.1.351 pseudoviruses was evaluated 2 weeks following the first and second immunizations.

The mRNA-1273.351 vaccine was also evaluated as a booster dose in animals that had previously received two doses of mRNA-1273.

What did the study find?

Vaccine mRNA-1273.351 elicited approximately 4-fold higher neutralization titers against B.1.351 than against D614G.

Vaccine mRNA-1273.211, on the other hand, elicited robust neutralization responses against both D614G and B.1.351, with no significant difference observed in neutralization titers.

“Thus, as a primary vaccination series, a multivalent approach appears most effective in broadening immune responses,” says the team.

Next, the researchers tested the ability of mRNA-1273.351 to serve as a booster shot for neutralization against both D614G and B.1.351.

Mice were injected with mRNA-1273 on days 1 and 22 and then evaluated for antibody responses over the course of 7 months before being vaccinated a third time with mRNA-1273.351.

Following this booster injection, neutralization titers against D614G increased 4.5-fold, while titers against B.1.351 increased 15-fold.

The mRNA-1273.351 vaccine is an “effective booster”

“mRNA-1273.351 is an effective third (booster) dose in animals previously vaccinated with a primary vaccination series of mRNA-1273,” says Wu and the team.

“Ongoing studies will evaluate the ability of mRNA-1273, mRNA-1273.351, and mRNA-1273.211 to effectively boost immunity driven by a primary vaccination series of mRNA-1273,” they add.

The team says the mRNA platform approach against SARS-CoV-2 VOCs has now been demonstrated in mice to effectively broaden neutralization across variants and boost antibody levels when applied as a third dose.

“The mRNA platform allows for rapid design of vaccine antigens that incorporate key mutations, allowing for rapid future development of alternative variant-matched vaccines should they be needed,” writes Wu and colleagues.

“Additional VOC designs can be rapidly developed and deployed in the future if needed to address the evolving SARS-CoV-2 virus,” they conclude.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Wu K, et al. Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.04.13.439482, https://www.biorxiv.org/content/10.1101/2021.04.13.439482v1

Posted in: Medical Research News | Disease/Infection News

Tags: ACE2, Allergy, Angiotensin, Antibodies, Antibody, Cell, Coronavirus, Coronavirus Disease COVID-19, Efficacy, Enzyme, Infectious Diseases, Mutation, Protein, Receptor, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine, Virus

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Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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U.S. pauses J&J COVID-19 vaccine over rare blood clots

(Reuters) -U.S. federal health agencies on Tuesday recommended pausing the use of Johnson & Johnson’s COVID-19 vaccine after six women under 50 given the shot developed rare blood clots, dealing a fresh setback to efforts to tackle the pandemic.

FILE PHOTO: A woman receives a dose of the Johnson & Johnson coronavirus disease (COVID-19) vaccine during a visit of U.S. Vice President Kamala Harris to a vaccination center in Chinatown, in Chicago, Illinois, U.S., April 6, 2021. REUTERS/Carlos Barria

Following the news, Johnson & Johnson (J&J) said it was delaying the rollout of the vaccine to Europe, a week after regulators there said they were reviewing rare blood clots in four recipients of the shot in the United States.

The moves come after European regulators said earlier this month they had found a possible link between AstraZeneca’s COVID-19 vaccine and a similar rare blood clotting problem that led to a small number of deaths.

J&J’s single dose vaccine – most COVID-19 shots are delivered over two doses – and AstraZeneca’s low-cost vaccine are seen as vital tools in the fight against a pandemic that has claimed more than three million lives.

The White House said the pause would not have a “significant” impact on its plan to administer about three million shots per day and a total of 200 million shots before President Joe Biden’s 100th day in office.

The U.S. Food and Drug Administration (FDA) said one person had died from the rare blood clotting condition after taking the J&J vaccine and another was in a critical condition.

Immunology experts stressed the risk posed by the J&J vaccine appeared extremely low, and that the shot remained a valuable tool against the risks of COVID-19. However they acknowledged the need for health officials to proceed with caution to understand the best ways to mitigate any risk.

“Even if causally linked to the vaccine: 6 cases with about 7 million doses (lower than the risk of clots with oral contraceptives) is not something to panic about,” Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security in Baltimore, said in an email.

“People are asking me if they should cancel their J&J vaccine appointments and I have told them not to but I know many will and this will stall progress in controlling the pandemic.”

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FDA acting commissioner Janet Woodcock said it expected the pause to be a matter of days, and it was aimed at providing information to healthcare providers so that they can diagnose, treat and report such blood clots.

FDA official Peter Marks said that part of the reason for the pause was to warn doctors that administering the standard treatments for clots can cause tremendous harm, or be fatal.

‘LESS THAN ONE IN A MILLION’

Most of the available J&J vaccine has been used in the United States due to production issues that have limited the company’s supply. As of April 12, more than 6.8 million doses of the J&J vaccine had been administered in the United States, compared with more than 180 million shots combined of the Moderna and Pfizer/BioNTech shots.

U.S. health officials said during a press briefing there had been no similar blood clot cases reported among recipients of the Pfizer/BioNTech of Moderna vaccines.

An advisory committee to the U.S. Centers for Disease Control and Prevention (CDC) will meet on Wednesday to review the cases, and the FDA will review the analysis, the agencies said in a joint statement.

All six cases involved women between the ages of 18 and 48, and the symptoms occurred six to 13 days after vaccination.

In the cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets (thrombocytopenia).

J&J said it was working closely with regulators and noted no clear causal relationship had been established between the cases and the COVID-19 vaccine made by its Janssen unit.

“Even if all of the cases were caused by the vaccine, the risk of less than one in a million would have to be set against the benefits of protection from COVID-19 disease; a disease which, in itself, causes clotting in many cases,” said Peter English, a retired consultant in communicable disease control and a vaccine expert.

‘ABUNDANCE OF CAUTION’

“The FDA recommendation to pause the administration of the Johnson and Johnson vaccine out of an abundance of caution makes sense in terms of the nature of the unusual and serious side effect not seen with the other vaccines,” said Dr. Robert Klugman at the UMass Memorial Medical Center in Massachusetts in an email.

J&J’s shares were down 2.6% in early New York trade.

The J&J and AstraZeneca vaccines both use an adenovirus vector – a harmless cold virus that instructs human cells to produce a protein found on the surface of the coronavirus, thereby spurring the immune system to prepare an arsenal against the COVID-19-causing virus.

Among leading global COVID-19 vaccine developers, China’s CanSino Biological and Russia’s Gamaleya Institute with its Sputnik V vaccine are also relying on this approach. The Pfizer/BioNtech and Moderna vaccines use mRNA technology.

The rollout of J&J’s vaccine has been slowed by issues at production plants.

The company has supplied the United States with at least 20 million doses but is behind schedule on its deliveries. Problems at a Baltimore, Maryland plant run by outside contractor Emergent BioSolutions forced the companies to trash a batch of vaccine substance.

J&J only began delivering its COVID-19 vaccine to European Union countries this week. It has committed to delivering 55 million doses to the bloc by the end of June and another 120 million in the third quarter.

J&J has been doing vaccinations in South Africa to study the effects on health workers, and had vaccinated just under 300,000 people there as of Monday, according to data from the country’s health department. J&J recently struck a deal with the African Union for up to 400 million doses.

Europe’s drugs regulator continues to recommend the use of AstraZeneca’s COVID-19 vaccine, saying the benefits outweigh the risks. Several EU countries, however, have limited its use to certain age groups.

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German government seeks more powers to set pandemic rules

BERLIN — Chancellor Angela Merkel said Tuesday her government wants clear rules that include nighttime curfews imposed in all regions with high numbers of COVID-19 infections, ending the patchwork of measures that have characterized the pandemic response across Germany’s 16 states.

“The uniform, nationwide emergency brake is overdue because even though it’s difficult to hear this again, the situation is serious,” Merkel told reporters in Berlin after her Cabinet approved the plan.

Many Germans have expressed frustration and confusion in recent months as governors interpreted rules agreed with the federal government in different ways, despite having similar infection rates.

Merkel warned that Germany remains “firmly in the grip of the third wave” of infections, citing figures from the country’s disease control agency that showed 10,810 newly confirmed cases in the past 24 hours, and 294 deaths.

Since the start of the pandemic, Germany has registered more than 3 million infections and 78,746 deaths from COVID-19.

“If we were to wait until all the intensive care beds were occupied, then it would be too late,” Merkel said, adding that governments and citizens need to help doctors and nurses tackle the surge in cases.

The emergency brake, proposed in a bill that will be submitted to Parliament, will apply in regions with more than 100 new weekly cases per 100,000 inhabitants. It entails the closure of stores, cultural and sports facilities, limits on personal contacts and nighttime curfews.

States would be free to set more flexible rules in regions with fewer than 100 new cases each week per 100,000 inhabitants.

Merkel said she hoped Parliament would swiftly debate and pass the bill.

She again asked for Germans to show patience and noted that the country’s sluggish vaccine program had picked up with the recent start of vaccinations in GP practices. Last week, some 3.2 million shots were administered in Germany, compared with 1.9 million the previous week.

The Cabinet also agreed that companies will need to offer all employees who aren’t working from home at least one coronavirus test each week, and that parents will get more paid leave to care for children who cannot go to school due to the pandemic.

Separately, Germany’s top security official ordered an end to temporary border controls along with frontier with the Czech Republic. The checks, which caused lengthy tailbacks along the border and were a headache for commuters, had been in place for two months due to the high rate of infection in Germany’s eastern neighbor.

Interior Minister Horst Seehofer said the spot checks would continue to take place to ensure that people have a negative coronavirus test when entering Germany from the Czech Republic.

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Follow all of AP’s pandemic coverage at https://apnews.com/hub/coronavirus-pandemic, https://apnews.com/hub/coronavirus-vaccine and https://apnews.com/UnderstandingtheOutbreak

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AstraZeneca has not reacted yet to EU letter on vaccines – Corriere

MILAN (Reuters) – AstraZeneca has yet to react to a letter sent by the European Commission to complain over below-contract supplies of COVID-19 vaccines, Italian daily Corriere della Sera said, adding the Anglo-Swedish group missed a deadline indicated by Brussels.

FILE PHOTO: Empty vials of Oxford/AstraZeneca’s COVID-19 vaccine are seen at a vaccination centre in Antwerp, Belgium March 18, 2021. REUTERS/Yves Herman/File Photo

The European Union member states and the pharmaceutical company are at odds over the delivery of the shots after the group shipped to the block less than indicated in the initial agreement.

“AstraZeneca has breached and continues to breach its contractual obligations on the production and supply of the initial 300 million doses for Europe,” EU Head of Health and Food Safety DG Sandra Gallina said in a letter sent to the company on March 19, according to Corriere.

The Italian daily said that Brussels had asked AstraZeneca to “remedy the material breaches of contract within 20 days of the letter”, but added that the deadline expired two days ago without any reaction from the company.

AstraZeneca has not replied to a request for comment from Reuters.

A spokesman for the European Commission confirmed that Brussels on March 19 sent a written message to AstraZeneca, calling it “a notice for dispute settlement”, adding this was a first step to engage in an dialogue to resolve the issue.

“At this stage we are still waiting for the necessary elements … we remain in contact with AstraZeneca to ensure timely delivery of a sufficient number of doses,” the spokesman told Reuters, without elaborating.

According the contract signed between EU and the company, which is public, if a dispute arises one of the parties shall first notify the problem with a letter. Then, after 20 days from the written notice, they “shall meet and attempt to resolve the dispute by good faith negotiations”.

Under the contract signed on COVID-19 vaccines, the European Union states had expected to receive 120 million doses by the end of March from AstraZeneca, but the company had supplied only 30.12 million doses, Corriere said.

With contagion still rising in many European countries and vaccination campaigns hitting hurdles, some governments are shown increasing irritation against the pharma group.

“Manifestly, they (AstraZeneca) did not honour their commitments and thus, in a certain way, they were mocking us Europeans,” France’s European Affairs Minister Clement Beaune said on Sunday, speaking to LCI television news channel.

Beaune said that the EU letter to the Anglo-Swedish group could even lead to a battle in court.

“We sent a formal notice in recent days, it is the beginning of a possible judicial procedure if the company doesn’t fix things,” he said, adding that putting pressure on the company to accelerate production in Europe appeared to be a better option compared with starting a legal process, which would take time.

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The Latest: S Korea to resume AstraZeneca jab for ages 30-60

SEOUL, South Korea — South Korea says it will resume administrating AstraZeneca’s coronavirus vaccine to all eligible people between the ages of 30 and 60.

Last week, South Korea suspended the use of AstraZeneca vaccines for those 60 years old or younger while awaiting the outcome of the European Medicine Agency’s review.

The Korea Disease Control and Prevention Agency said Sunday it will restart the use of AstraZeneca vaccine beginning Monday, citing studies showing that the vaccine’s benefits outweighs the risk of side effects.

An agency statement said those aged 30 or younger will be excluded, as U.K. authorities have recommended they take alternative vaccines.

It says it’s found three cases of blood clots from vaccinated people in South Korea — but none belong to the type of side effects determined by European authorities.

Those who would get AstraZeneca vaccines from Monday include medical workers and people in long-term care facilities, those at special schools and welfare centers for disabled people and homeless people.

In recent days, South Korea has been experiencing a steady increase in new coronavirus infections. Earlier Sunday, South Korea reported 677 new confirmed cases, raising the total to 109,559 with 1,768 deaths.

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THE VIRUS OUTBREAK:

— More Black Americans say they are open to taking vaccine

— Delayed vaccine shipments could stall progress against COVID-19 in some of world’s poorest countries

— Iran enforces 10-day lockdown amid fourth wave of pandemic

— Nearly one-third of Texans have received virus vaccine

— Ecuador, Peru head to polls under strict virus measures

— Follow AP’s pandemic coverage at https://apnews.com/hub/coronavirus-pandemic and https://apnews.com/hub/coronavirus-vaccine

———

HERE’S WHAT ELSE IS HAPPENING:

BEIJING — China has reported 10 new confirmed coronavirus cases and no deaths.

All the new infections were believed have been acquired abroad, the National Health Commission announced Sunday.

China’s death toll stood at 4,636 out of 90,410 confirmed cases.

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ISLAMABAD— Pakistan has reported it’s highest single-day death toll from COVID-19.

The National Command and Control Center announced Sunday that 114 deaths from coronavirus had been confirmed, as well as more than 5,000 new cases.

A weekend ban on inter-city transport has been extended until mid-April, as part of measures to control a surge in virus infections and deaths. The ban will not apply on freight, ambulance services and supplies of medical equipment.

Pakistan, with a population of 220 million people, has vaccinated more than a million people using the Chinese Sinopharm vaccine since February.

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COLOMBO, Sri Lanka — Sri Lankan health authorities have imposed tough restrictions ahead of this week’s New Year festival in a bid to contain the spread of COVID-19.

Health officials on Sunday banned musical shows and many other traditional games, including the tug-of-war, for the April 14 holiday.

They’ve also ordered other gatherings not to exceed 100 people, and asked that gatherings for rituals be limited to immediate family members and close relatives.

The country’s New Year festival typically involves large-scale events, games, competitions and musical shows.

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BUCHAREST — Marchers have taken to the streets of the Romanian capital of Bucharest to protest restrictive measures to fight the spread of COVID-19 even as new daily infections and deaths rise in the European Union nation.

About 1,000 people converged Saturday on Victory Square and University Square, expressing frustration with an earlier curfew and shop closures that took effect at the end of March. Many demonstrators waved tri-color Romanian flags and chanted “Freedom!” and “Down with the government!”

“We came to fight against this state of alert that buries all our rights and freedoms,” Dumitru Balan, leader of the civic movement Action for the Nation, told The Associated Press.

The protest was held on the same day that Romania passed 1 million confirmed COVID-19 cases. Hospital intensive care units are struggling to cope with the record demand of just under 1,500 COVID-19 patients; 12,000 others are in other wards.

“There are now very severe patients admitted in our clinical ward that normally would require intensive care … we don’t have enough ICU beds available and patients are waiting with sub-optimal care,” Dragos Zaharia, a pneumologist at Marius Nasta Institute, told the AP. “We are at risk of being accused of malpractice.”

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NEW YORK — State lawmakers across the U.S. are taking actions to limit the emergency powers of governors — not just in the current coronavirus pandemic, but for any future emergencies.

The pushback is coming primarily from Republican lawmakers but is not entirely partisan. GOP lawmakers are targeting both Democratic and Republican governors.

When the pandemic hit a year ago, many governors and their top health officials temporarily ordered residents to remain home, limited public gatherings, prohibited in-person schooling and shut down dine-in restaurants, gyms and other businesses. Many governors have been repealing or relaxing restrictions after cases declined from a winter peak and as more people get vaccinated.

The potential remains in many states for governors to again tighten restrictions if new variants of the coronavirus lead to another surge in cases.

The U.S. has recorded 31 million coronavirus cases and more than 561,000 confirmed deaths, the most in the world.

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LONDON — As many as 60 countries might be stalled at the first shots of their coronavirus vaccinations because nearly all deliveries through the global program are blocked until as late as June.

The COVAX initiative is designed to provide vaccines to countries lacking the clout to negotiate on their own for scarce supplies. In the past two weeks, only 2 million doses were cleared for shipment to 92 countries through the program, the same amount injected in Britain alone.

Internal World Health Organization documents obtained by The Associated Press say uncertain deliveries are causing some countries to lose faith in COVAX.

The vaccine shortage stems mostly from India’s decision to stop exporting vaccines from its Serum Institute factory because of a surge of coronavirus cases in that country. The factory produces the majority of the AstraZeneca doses that COVAX counted on to supply about a third of the global population.

WHO Director General Tedros Adhanom Ghebreysus says while one in four people in rich countries had received a vaccine, only one in 500 people in poorer countries had received a dose.

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Researchers discover a new monoclonal antibody that is effective against SARS-CoV-2 variants

A new monoclonal antibody targets a particular region of the receptor-binding domain (RBD) on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This region is usually not accessible to immune cells,  which may be why it has broad neutralizing capabilities.

With the coronavirus disease 2019 (COVID-19) pandemic continuing around the globe, new mutants of SARS-CoV-2 are emerging. These new variants are likely more infectious and can better evade our immune response.

The SARS-CoV-2 spike protein, in particular the RBD, is key in binding to host receptors, mainly the angiotensin-converting enzyme 2 (ACE2) in humans. One highly conserved region of the RBD, called antigenic site II, can elicit neutralizing antibodies. However, this region is generally inaccessible because of the RBD conformation, and there is a low fraction of antibodies targeting this site in infected individuals.

Study: Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody. Image Credit: Design_Cells / Shutterstock

In a new study published in the bioRxiv* preprint server, researchers report a new monoclonal antibody that is targeted toward site II and has a broad neutralizing capability.

Testing potency of monoclonal antibody

The authors sorted spike protein-specific memory B cells from a convalescent individual 75 days after symptom onset. They found one monoclonal antibody, called S2X259, which reacted with 29 of 30 spike proteins of sarbecoviruses, including SARS-CoV-2 and its new variants. The antibody also reacted with bat sarbecoviruses, suggesting its broad neutralizing capability.

The antibody also bound strongly to 10 RBDs from different sarbecoviruses. The binding of this antibody was not affected by the different single-point RBD mutations seen in the new variants of SARS-CoV-2, including the United Kingdom, South African, Brazilian, and the B.1.427/B.1.429 variants.

Using pseudotyped virus systems, the team found that the antibody neutralized SARS-CoV-2 and did not lose its potency against the different variants or the N439K or Y453F mutation. The antibody not only neutralized a variety of sarbecoviruses that use the ACE2 receptor but also cross-reacts with sarbecoviruses that do not use ACE2 for infection.

To understand how this antibody has high neutralizing potency, the team imaged the complex formed between the spike protein and the antibody using cryo-electron microscopy. They found that the antibody recognizes a glycan-free site, which requires two RBDs to be in the open conformation. It forms contacts with residues 369-386, 404-411, and 499-508 in the RBD.

The epitope the antibody binds to is conserved in all the circulating SARS-CoV-2 variants. In addition, it does not target the 417 or 484 residues (mutations here are found in B.1.351 and P.1), and this could be why it is potent against the different variants.

The action of this antibody does not affect the neutralization effect of class 1 and class 3 antibodies. The majority of approved antibodies for clinical use belong to these classes. Hence, the new antibody can be used in combination with other antibodies to increase neutralization breadth.

The S2X259 broadly neutralizing sarbecovirus mAb recognizes RBD antigenic site II. a-b, CryoEM structure of the prefusion SARS-CoV-2 S ectodomain trimer with three S2X259 Fab fragments bound to three open RBDs viewed along two orthogonal orientations. c. The S2X259 binding pose involving contacts with multiple RBD regions. Residues corresponding to prevalent RBD mutations are shown as red spheres. d-e, Close-up views showing selected interactions formed between S2X259 and the SARS-CoV-2 RBD. In panels a-e, each SARS-CoV-2 S protomer is coloured distinctly (cyan, pink and gold) whereas the S2X259 light and heavy chain variable domains are coloured magenta and purple, respectively. N-linked glycans are rendered as blue spheres in panels a-c.

Potential use against a broad range of sarbecoviruses

Using computational analysis, the team determined what RBD mutations could escape the antibody from binding. They found only a few RBD mutations disrupt the binding of this antibody. The substitution of the residue at position 504 gave the most significant disruption in binding.

When they replicated a pseudotyped SARS-CoV-2 virus in the presence of the S2X259 antibody, the only mutation they found caused by selective pressure was G504D. This mutation has rarely been seen in human isolates so far.

The selection of a single escape mutation suggests the region targeted by the antibody might not tolerate amino acid substitutions without changing viral fitness. Hence it is conserved across different sarbecoviruses. Thus, there is a high barrier for the emergence of mutations against this antibody, suggesting it could become key in combating the pandemic.

When Syrian hamsters were challenged with SARS-CoV-2, with the antibody administered 48 hours before virus infection, the authors found more than two orders of magnitude decrease in virus in the lungs compared to hamsters that did not receive any treatment. In addition, the antibody also protected hamsters infected with the B.1.351 strain.

The detection of a large variety of sarbecoviruses in bats and other mammals, along with the increased human-animal interactions, makes it likely that more cross-species transmission of viruses can occur. With increasing evidence that antibodies targeting the RBD form a major proportion of neutralizing activity, RBD-based vaccines could elicit high levels of antibodies like S2X259 with high potency. Such strategies can help overcome the current COVID-19 pandemic and help prepare for future sarbecovirus infections.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Tortorici, M. A. et al. (2021) Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody. bioRxiv. https://doi.org/10.1101/2021.04.07.438818, https://www.biorxiv.org/content/10.1101/2021.04.07.438818v1

Posted in: Medical Science News | Medical Research News | Miscellaneous News | Disease/Infection News | Healthcare News

Tags: ACE2, Amino Acid, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Coronavirus, Coronavirus Disease COVID-19, Electron, Electron Microscopy, Enzyme, Glycan, Glycans, Immune Response, Lungs, Microscopy, Monoclonal Antibody, Mutation, Pandemic, Protein, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Virus

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Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).

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Famed Animal Expert Jack Hanna Diagnosed With Dementia

Jack Hanna, the director emeritus of Ohio’s Columbus Zoo and Aquarium known for his many TV appearances, has been diagnosed with dementia, his family announced Wednesday in a post on Twitter.

His condition is now believed to be Alzheimer’s disease, the family wrote. Hanna, 74, announced his retirement last year.

“His condition has progressed much faster in the last few months than any of us could have anticipated,” his daughters Kathaleen, Suzanne and Julie Hanna wrote in the letter.

“Sadly, Dad is no longer able to participate in public life as he used to, where people all over the world watched, learned and laughed alongside him,” they wrote.

Jack Hanna

Hanna often appeared on “Good Morning America,” “The Tonight Show,” “Late Show,” “Late Late Show,” “Larry King Live,” “The Ellen DeGeneres Show” and “Maury.” He also hosted his own weekly TV programs, including “Jack Hanna’s Animal Adventures,” “Jack Hanna’s Into the Wild,” and “Jack Hanna’s Wild Countdown.”

Hanna joined the Columbus Zoo in 1978. He is credited with transforming the zoo from an “aging collection of pens and buildings” into what it is today — often listed as one of the best zoos in the U.S., according to NBC News.

“While Jack retired from his official role at the end of 2020, his legacy will be ever-present in our work as we continue to fulfill our organization’s mission to lead and inspire by connecting people and wildlife,” the Columbus Zoo and Aquarium told CBS News.

The family said that Hanna spent his life connecting with wildlife and people because he believed that seeing and experiencing animals was the “key to engaging them in more impactful conservation efforts.” The media appearances allowed him to bring awareness to global conservation and the natural environment, they wrote.

Hanna is no longer able to travel and work in the same way as before, the family added, but they hope his enthusiasm will continue a legacy. At the Columbus Zoo, Hanna advocated for improved wildlife habitats and connection between animals and humans. After he left the role of executive director in 1992, he continued to be a spokesman for the zoo until retirement.

His wife, Suzi, has been by his side for 53 years and continues to be the family’s “rock,” his daughters wrote in the letter. They asked for privacy during this time, especially due to safety concerns during the COVID-19 pandemic, and thanked readers and viewers for their ongoing support.

“While Dad’s health has deteriorated quickly, we can assure you that his great sense of humor continues to shine through,” they wrote. “And yes — he still wears his khakis at home.”

Sources:

Jack Hanna, “Twitter post at 12:59 p.m. on April 7, 2021: A Letter from the Hanna Family.”

NBC News, “Beloved animal expert Jack Hanna has dementia, steps away from public life.”

CBS News, “Celebrity zookeeper Jack Hanna diagnosed with dementia, family says.”

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New Zealand could open border with Australia from end of week: 1NEWS

SYDNEY (Reuters) – New Zealand could open its borders to Australian travellers as soon as the end of the week, New Zealand broadcaster 1NEWS reported on Tuesday without saying where it obtained the information.

FILE PHOTO: People jog past a social distancing sign on the first day of New Zealand’s new coronavirus disease (COVID-19) safety measure that mandates wearing of a mask on public transport, in Auckland, New Zealand, August 31, 2020. REUTERS/Fiona Goodall

The report comes as New Zealand Prime Minister Jacinda Ardern is scheduled to announce the date for quarantine-free travel with Australia later on Tuesday, after facing mounting pressure from businesses to open the border.

The so-called ‘travel bubble’ would restrict travellers from certain areas in the event of an outbreak in Australia and is expected to run on a state-by-state basis, the broadcaster said.

Australian tourists visiting the country during the ski season and school holidays would “really matter” to struggling industries in New Zealand, Deputy Prime Minister Grant Robertson said during a breakfast show also on 1News.

Robertson, however, did not give any indication of when the border will open.

Both Australia and New Zealand have managed the COVID-19 crisis more successfully than most other developed nations after closing their international borders to non-citizens and permanent residents very early during the pandemic.

Most Australian states have opened their borders to New Zealanders since last October but New Zealand has delayed returning the favour due to sporadic outbreaks in some Australian cities.

Meanwhile, The Australian newspaper reported on Tuesday citing government and industry sources that quarantine-free travel between the countries could begin on April 12 or 19.

Airlines have started bookings with “the 19th pretty much definite”, the Australian Chamber of Commerce and Industry tourism chief John Hart was quoted as saying in the report.

Australia’s foreign ministry did not immediately respond to requests seeking comment.

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