CanSinoBIO's mRNA COVID vaccine candidate cleared for trials in China

 

Chinese vaccine developer CanSino Biologics Inc (CanSinoBIO) said on Monday its potential COVID-19 vaccine using the messenger RNA (mRNA) technology has been approved by China's medical products regulator to enter clinical trials.

Unlike other major countries, China is yet to approve any foreign-made mRNA vaccines such as that produced by U.S.-German duo Pfizer Inc and BioNTech SE.

With around 88% of its 1.4 billion population already vaccinated, China is trailing several domestically developed mRNA vaccine candidates, including one candidate that is being tested in a large, Phase 3 clinical trial.

CanSinoBIO said in a press release that studies before clinical trials had showed the candidate can elicit high-level neutralising antibodies against multiple variants, including Omicron.

CSPC Pharmaceutical Group Limited said on Sunday that its potential mRNA COVID vaccine SYS6006 was cleared by China's National Medical Products Administration to conduct clinical trials.

https://www.marketscreener.com/quote/stock/CSPC-PHARMACEUTICAL-GROUP-6170821/news/CanSinoBIO-s-mRNA-COVID-vaccine-candidate-cleared-for-trials-in-China-39953756/

Burst of accumulated zinc shows how mineral boosts immune function, suggest ways to improve health

 Zinc's immune-boosting properties are well-established, but scientists haven't known exactly how it works. In a new study published online March 25 in the journal Blood, Fred Hutchinson Cancer Research Center scientists reveal two ways the mineral supports immunity and suggest how it could be used to improve health.

Using mice, the team discovered that zinc is needed for the development of disease-fighting immune cells called T cells and prompts regeneration of the thymus, the immune organ that produces T cells.

"This study adds to our knowledge of what zinc is actually doing in the immune system and suggests a new therapeutic strategy for improving recovery of the immune system," said senior author Dr. Jarrod Dudakov, an immunologist at Fred Hutch.

The study also revealed that an experimental compound that mimics zinc's action in this organ works even better than the natural mineral to promote immune recovery.

"We are now looking into how zinc may fit in with our other discoveries of how the immune system repairs itself and could eventually lead to therapies to improve immune function for people who receive a blood stem cell transplant for a blood cancer or people with chronic immune decline that accompanies aging," Dudakov said.

Thymic regeneration and immune function, and zinc

Previously, Dudakov and his team have outlined the molecular pathways and cell types that govern how the immune system's thymus repairs itself after injury. Such treatments could improve vaccine efficacy and hasten thymic regeneration after stressors like chemotherapy, blood stem cell transplant and radiation exposure.

Dudakov began studying zinc a few years ago when Dr. Lorenzo Iovino, the study's first author and a research associate at Fred Hutch, joined Dudakov's lab. Since the scientists knew that low levels of zinc are linked to fewer infection fighting T cells and a shrunken thymus, where T cells develop, Dudakov and Iovino explored how to supplement with zinc in mouse models where the immune system is damaged.

Iovino, who's also a blood stem cell transplant physician, had shown in a previous study that zinc could boost immune recovery in patients undergoing stem-cell transplants for the blood cancer multiple myeloma.

But the study didn't explain why zinc was helping.

Zinc is critical for T-cell development and thymic regeneration

As in humans, Iovino and Dudakov found that the thymuses of mice deprived of dietary zinc shrink and produce notably fewer mature T cells, even after as little as three weeks of a no-zinc diet. Iovino was able to show that without zinc, T cells cannot fully mature.

He also found that zinc deficiency slows recovery of T-cell numbers after mice receive immune-destroying treatments akin to those given to patients about to receive a blood stem cell transplant.

Conversely, extra zinc speeds this process, and T cells recover faster than normal. The team saw a similar result in a mouse model of blood stem cell transplant.

"So we had a consistent result of a better reconstitution of the thymus and also a better reconstitution of T cells in the peripheral blood after zinc supplementation," Iovino said. "But we still didn't know how exactly zinc was working."

Iovino discovered that it was the change in zinc levels around cells that release a key regenerative factor that seemed to kick off the thymus' renewal processes. T cells accumulate zinc as they develop, but release it after a damaging event -- like a burst of radiation -- kills them off.

Cells use a molecule called GPR39 to sense a change in external zinc, and Iovino found that an experimental compound that mimics rising external zinc levels by stimulating GPR39 could also promote renewal factor release and thymic regeneration.

"What we think is going on is, as you give zinc supplementation, that gets accumulated within the developing T cells. It gets stored and stored and stored, then the damage comes along and the zinc is released," Dudakov said. "Now you have more zinc than you normally would, and it can instigate this regenerative pathway. With the experimental compound we can just directly target GPR39 and basically get the same effect without any of that pretreatment."

Getting to the clinic

There's still a lot to learn before they can turn their findings to therapeutic strategies, the scientists said.

Transplant patients already receive mineral supplements, so if extra zinc were to be incorporated into their treatment regimens, it would be important to make sure that anyone receiving it is truly zinc-deficient. Iovino thinks many patients might be, but right now there isn't a good test to assess this. He's currently working on developing one, which would first be used to help researchers determine whether patients' zinc status correlates with immune recovery after blood stem cell transplant.

Dudakov will pursue GPR39-stimulating compounds as therapies to improve thymic recovery after acute injuries like pre-transplant radiation. The team is currently screening similar compounds to find any that may be more effective.

He and Iovino are also working to determine whether such compounds could help with thymic regeneration in other settings. Unfortunately, our thymuses also slowly shrink and reduce their T-cell output as we age. Dudakov and Iovino would also like to know whether this chronic degeneration could be slowed by boosting the organ's regenerative processes.

"Our lab is continuing to piece together the molecular players that contribute to thymus regrowth," Dudakov said. "Ultimately, we aim to develop therapies that trigger natural regeneration and restore immune health."

The study was funded by the National Institutes of Health, the American Society of Hematology and The Rotary Foundation.

---

Story Source:

Materials provided by Fred Hutchinson Cancer Research Center. Original written by Sabrina Richards. Note: Content may be edited for style and length.

---

Journal Reference:

1. Lorenzo Iovino, Kirsten Cooper, Paul deRoos, Sinead Kinsella, Cindy Anggelica Evandy, Tamas Ugrai, Francesco Mazziotta, Kathleen S. Ensbey, David Granadier, Kayla Hopwo, Colton W Smith, Alex Gagnon, Sara Galimberti, Mario Petrini, Geoffrey R Hill, Jarrod A Dudakov. Activation of the Zinc-sensing receptor GPR39 promotes T cell reconstitution after hematopoietic cell transplant in mice. Blood, 2022; DOI: 10.1182/blood.2021013950

https://www.sciencedaily.com/releases/2022/03/220331185359.htm

Are COVID-19-linked arrhythmias caused by viral damage to heart's pacemaker cells?

 The SARS-CoV-2 virus can infect specialized pacemaker cells that maintain the heart's rhythmic beat, setting off a self-destruction process within the cells, according to a preclinical study co-led by researchers at Weill Cornell Medicine, NewYork-Presbyterian and NYU Grossman School of Medicine. The findings offer a possible explanation for the heart arrhythmias that are commonly observed in patients with SARS-CoV-2 infection.

In the study, reported Apr. 1 in Circulation Research, the researchers used an animal model as well as human stem cell-derived pacemaker cells to show that SARS-CoV-2 can readily infect pacemaker cells and trigger a process called ferroptosis, in which the cells self-destruct but also produce reactive oxygen molecules that can impact nearby cells.

"This is a surprising and apparently unique vulnerability of these cells -- we looked at a variety of other human cell types that can be infected by SARS-CoV-2, including even heart muscle cells, but found signs of ferroptosis only in the pacemaker cells," said study co-senior author Dr. Shuibing Chen, the Kilts Family Professor of Surgery and a professor of chemical biology in surgery and of chemical biology in biochemistry at Weill Cornell Medicine.

Arrhythmias including too-quick (tachycardia) and too-slow (bradycardia) heart rhythms have been noted among many COVID-19 patients, and multiple studies have linked these abnormal rhythms to worse COVID-19 outcomes. How SARS-CoV-2 infection could cause such arrhythmias has been unclear, though.

In the new study, the researchers, including co-senior author Dr. Benjamin tenOever of NYU Grossman School of Medicine, examined golden hamsters -- one of the only lab animals that reliably develops COVID-19-like signs from SARS-CoV-2 infection -- and found evidence that following nasal exposure the virus can infect the cells of the natural cardiac pacemaker unit, known as the sinoatrial node.

To study SARS-CoV-2's effects on pacemaker cells in more detail and with human cells, the researchers used advanced stem cell techniques to induce human embryonic stem cells to mature into cells closely resembling sinoatrial node cells. They showed that these induced human pacemaker cells express the receptor ACE2 and other factors SARS-CoV-2 uses to get into cells and are readily infected by SARS-CoV-2. The researchers also observed large increases in inflammatory immune gene activity in the infected cells.

The team's most surprising finding, however, was that the pacemaker cells, in response to the stress of infection, showed clear signs of a cellular self-destruct process called ferroptosis, which involves accumulation of iron and the runaway production of cell-destroying reactive oxygen molecules. The scientists were able to reverse these signs in the cells using compounds that are known to bind iron and inhibit ferroptosis.

"This finding suggests that some of the cardiac arrhythmias detected in COVID-19 patients could be caused by ferroptosis damage to the sinoatrial node," said co-senior author Dr. Robert Schwartz, an associate professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine and a hepatologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Although in principle COVID-19 patients could be treated with ferroptosis inhibitors specifically to protect sinoatrial node cells, antiviral drugs that block the effects of SARS-CoV-2 infection in all cell types would be preferable, the researchers said.

The researchers plan to continue to use their cell and animal models to investigate sinoatrial node damage in COVID-19 -- and beyond.

"There are other human sinoatrial arrhythmia syndromes we could model with our platform," said co-senior author Dr. Todd Evans, the Peter I. Pressman M.D. Professor of Surgery and associate dean for research at Weill Cornell Medicine. "And, although physicians currently can use an artificial electronic pacemaker to replace the function of a damaged sinoatrial node, there's the potential here to use sinoatrial cells such as we've developed as an alternative, cell-based pacemaker therapy."

---

Story Source:

Materials provided by Weill Cornell Medicine. Note: Content may be edited for style and length.

---

Journal Reference:

1. Yuling Han, Jiajun Zhu, Liuliu Yang, Benjamin E. Nilsson-Payant, Romulo Hurtado, Lauretta A. Lacko, Xiaolu Sun, Aravind R. Gade, Christina A. Higgins, Whitney J. Sisso, Xue Dong, Maple Wang, Zhengming Chen, David D. Ho, Geoffrey S. Pitt, Robert E. Schwartz, Benjamin R. tenOever, Todd Evans, Shuibing Chen. SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells. Circulation Research, 2022; 130 (7): 963 DOI: 10.1161/CIRCRESAHA.121.320518

https://www.sciencedaily.com/releases/2022/04/220401122230.htm

EasyJet cancels 100 flights due to Covid absences

 EasyJet has cancelled around 100 flights on Monday, including 62 from the UK, blaming higher than usual levels of staff absence due to Covid.

The airline said it had tried to offset the problem by using standby crew but was forced "to make some cancellations in advance".

It comes amid rising demand for travel as the Easter school holidays begin.

Airports are also struggling with staff shortages that have led to long queues for security and check-in.

EasyJet, one of Europe's biggest airlines, said the cancellations were a small part of its schedule on Monday, which is around 1,645 flights.

"As a result of the current high rates of Covid infections across Europe, like all businesses, easyJet is experiencing higher than usual levels of employee sickness," a spokesman said.

"Unfortunately it has been necessary to make some additional cancellations for today and tomorrow. We are sorry for any inconvenience this may cause."

He said affected customers had been contacted and could rebook on alternative flights or receive a voucher or refund.

Airports have also seen staff shortages at time when demand for travel is picking up following the end of travel restrictions.

Passengers at Manchester Airport have faced long queues for check-in and security, leading some to miss their flights at the start of the Easter holidays.

There have also been complaints about extensive waits in the baggage reclaim halls.

On Sunday, traveller Donna Mayfield told the BBC the situation was "horrendous", while another said they had seen "customers and staff in tears".

Manchester Airport apologised and admitted passengers' experiences fell "below the standard we aim to provide".

"Our whole industry is facing staff shortages and recruitment challenges at present, after the most damaging two years in its history," a spokesperson said.

"The removal of all travel restrictions after two years, coupled with the start of the summer travel season, has seen a rapid increase in passenger numbers, which is putting an enormous strain on our operation."

There were also long queues to enter Terminal 2 at Heathrow Airport on Sunday morning. The airport blamed Covid checks required by destination countries and "high passenger volumes".

But there were also reports of staff shortages and problems with the e-gate passport checks, with some travellers saying they had waited hours to take off.

"Our teams are supporting our airline partners to get passengers away on their journeys as quickly as possible and we apologise for any inconvenience this has caused," a spokesperson said.

Gatwick told the BBC it was also having a busy weekend as the Easter holidays kicked off.

It said it has not seen big queues in its security area but that some check-in areas run by individual airlines were very busy.

https://www.bbc.com/news/business-60976958

Shanghai lockdown: Economy shaken by zero-Covid measures

 From Tesla's giga factory to a huge Disney resort, many multinational companies have their Chinese foothold in Shanghai. But in recent days the usually bustling financial centre has been stopped in its tracks after a spike in coronavirus cases.

With little notice, officials imposed two staggered waves of lockdowns on the city's more than 26m residents. The eastern side of Shanghai has just been through four days of tight restrictions. The western part began its four-day isolation on 1 April.

The latest round of quarantining is China's largest since the coronavirus outbreak was first identified in Wuhan at the end of 2019.

This lockdown could turn out to be particularly costly for the world's second largest economy.

As well as being a major focus of the financial industry, Shanghai is a hub for semiconductor, electronics and car manufacturing. It is also the world's busiest shipping port.

Xu Tianchen, China economist for the Economist Intelligence Unit said short-term supply chain disruptions will have an impact on China's economy as a whole.

"There will also be ripple effects elsewhere because of the interconnectedness between Shanghai and other regions of China, especially the manufacturing hub of the Yangtze River Delta," he said.

On a more local level, the city known for its high-end storefronts like Gucci and Louis Vuitton has already seen consumer spending slump.

Lost business at retailers, hotels, and restaurants could directly cost Shanghai 3.7% of its annual Gross Domestic Product (GDP), according to Mr Xu.

GDP is a key measure of the health, or otherwise, of an economy.

China's growth target

The Chinese government has set a target for the country's GDP to grow by 5.5% this year. But some analysts have said it will struggle to meet that goal.

At the end of last week, data pointed to a slowdown in March for China's manufacturing and services sectors.

It came after the technology hub Shenzhen and Jilin in China's industrial north-east last month also faced lockdowns so that officials could conduct mass coronavirus testing and try to curb the spread of the highly transmissible Omnicron variant of Covid-19.

"We have seen PMI data, which shows that both manufacturing and services sectors are actually hit hard. And that has not included the Shanghai lockdown. So I think qualitatively we're seeing more downside pressure for the first and second quarters of GDP data," according to Peiqian Liu, China economist for NatWest Markets.

PMI data is a summary of market conditions gathered through surveying senior executives in key industries about their expectations for a number of factors including new orders, production and employment.

With the number of coronavirus cases rising, there could also be more trouble ahead if there are further lockdowns, especially for small business owners.

"The focus is much more on how employment is going to hold up in a prolonged lockdown or extended period of uncertainties of lockdown due to outbreaks.

"So I think the service sector is not only facing a short-term pressure from a three-week lockdown from Shenzhen or a one-week lockdown from Shanghai, but facing much more pressure from the uncertainty that's going down the road with current set of Covid management policies," Ms Liu said.

'Closed-loop living'

While some companies in Shanghai have decided to close during the lockdown, others in industries like financial services and car manufacturing have implemented so-called "closed-loop" systems, according to Ms Liu.

Essentially, this means that employees have to live as well as work at their offices or factories.

"Imagine what happened in the Winter Olympics. It was also a closed-loop management, just to ensure that things within the bubble works operationally normal, and that they isolate people from outside or from the rest of China."

However, Mr Xu points out that it is not a strategy that can be sustained in the long-term.

"There's a concern that if lockdowns become prolonged and disruptions to the transportation to the supply chain persist, businesses will be unable to source supplies.

"So they are having an impact on road transport. The obvious risk is that Shanghai fails to eliminate the current outbreak quickly," he said.

Will Beijing stick to the plan?

Even as much of the rest of the world opens borders and eases restrictions, China still looks unlikely to shift away from its strict approach to the coronavirus.

"The policy has been a political source of legitimacy. The low levels of infections and deaths in China are often compared to other countries in the domestic media. As a result, the majority of the population within China still favour the zero-Covid policy, despite the increasing economic costs," Mr Xu said.

But Ms Liu believes there is a possible silver lining as Beijing has pledged to support the economy to meet its ambitious growth target.

"The government has been responsive with a set of easing policies from both fiscal and monetary front.

"That will hopefully stabilise the domestic growth momentum for this for the time being, and to ensure China's smooth running of the supply chain to minimise the global interruption of supply chain at this short term," she said.

https://www.bbc.com/news/business-60950507

Don’t take COVID advice from new fed Web site

 The White House just unveiled a brand-new Web site — COVID.gov — to help people “find COVID guidance.” Problem is, the feds’ atrocious advice all through the pandemic makes Uncle Sam the last place to go for guidance. 

Look at the latest big news from the CDC: its move to a “community levels” metric to govern indoor-masking rules. That shift — correct but long, long overdue — was prompted not by any change in the science around COVID but by the fact that mask mandates had become a politically disastrous issue for Democrats. 

And the agency still hasn’t updated its absurd guidance that kids in pre-K, literally the lowest-risk group for COVID on the planet, should have to mask “regardless of vaccination status.”

Speaking of schools, consider the dismal CDC record on closures. Even after months of data showed that 1) COVID was never a real risk to school-age kids unless they have serious comorbidities and 2) schools are not major vectors of transmission, the agency still slow-walked its re-opening guidance, largely at the behest of teachers unions (another Dem powerhouse). New reporting even reveals that the United Federation of Teachers actually had “line-by-line” influence on the language of the guidance itself.

The Food and Drug Administration, meanwhile, mandated a disastrous “pause” on the Johnson & Johnson vaccine. After the miraculous arrival on the US market of not one but three COVID vaccines in an unprecedented amount of time, the FDA stepped on the J&J jab over concerns around an extremely rare side effect — in just six cases out of 7 million doses administered. 

The Food and Drug Administration’s decision to pause the Johnson & Johnson COVID vaccine was disastrous.

Photo by ROBYN BECK/AFP via Getty Images

Vaccine uptake had been steadily climbing before the pause; after, it crashed. 

Heck, even Supreme Court justices managed to get the basic facts of COVID wrong. Justice Sonia Sotomayor suggested that “over 100,000 children” were hospitalized with COVID during the Omicron surge. (About 7,900 under-18’s in total have been hospitalized for COVID since March 2020.) 

When it comes to COVID rules — and the science behind them — the federal government has displayed a mixture of brute incompetence and political opportunism that has hurt millions in ways that may prove irreparable. 

Anyone who takes suggestions from COVID.gov does so at his own peril. 

https://nypost.com/2022/04/03/dont-take-covid-advice-from-new-fed-web-site/

Russian soldiers reportedly killed by Ukrainians’ poison-laced pastries

Two Russian soldiers have died and dozens more became sick after they were apparently poisoned by stuffed buns given to them by Ukrainians near the city of Kharkiv, Ukraine intelligence officials said.

The soldiers from the 3rd Motor Rifle Division were served the delicacies by citizens in the city of Izium, the Main Intelligence Directorate of Ukraine said Saturday.

“As a result, two invaders were killed at once, another 28 went to intensive care,” officials wrote in a Facebook post.

The conditions of the hospitalized soldiers were unclear.

The report came as another 500 soldiers fighting for Russian President Vladimir Putin were hospitalized because of alcohol poisoning, Ukraine asid. It’s unclear whether the Russian troops obtained the alcohol from Ukrainian citizens.

Russia has written off the incidents as “non-combat losses,” Ukrainian officials said.

Meanwhile, Russia on Sunday launched strikes on the Ukrainian cities of Kharkiv and Odesa

Oleh Synyehubov, the regional governor in Kharkiv, said Russian forces launched more than 20 strikes on the city and its outskirts in the country’s northeast over the past day. 

A missile strike on the city of Lozovo wounded four people, and Russian tanks bombarded a hospital in the town of Balakliia, Synyehubov said.

On Sunday morning, Russian forces also launched an airstrike on the Black Sea port of Odesa in southern Ukraine. The Russian military said the targets were an oil-processing plant and fuel depots around Odesa, which is the country’s largest port and home to its navy.

Ukrainian officials said they also have found brutalized bodies of women, children and local officials in the small city of Bucha near Kyiv, as Russian troops withdrew from the capital and its suburbs. Ukraine claimed some of the women had been raped and set on fire.

“There are murdered men whose bodies bear signs of torture,” added Oleksiy Arestovych, an aide to Ukrainian President Volodymyr Zelensky. “Their hands were tied, and they were killed by shots to the back of the head.”

Sergey Nikiforov, a spokesman for Zelensky, told the BBC that the gruesome discoveries look “exactly like war crimes.”

The Kremlin has previously denied committing war crimes in what it calls its “special military operation” in Ukraine.

Russia had promised last week that it would “radically” reduce its attacks around Kyiv and Chernihiv, though Ukraine has warned that it does not mean the cities wouldn’t become targets again, and the US and its allies predicted the move could simply mean Putin is regrouping.

https://nypost.com/2022/04/03/russian-soldiers-killed-by-pastries-poisoned-by-ukrainians/