Immune response may be linked to AstraZeneca vaccine clot issue; death risk rising among young adults in Brazil

By Nancy Lapid

(Reuters) -The following is a roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.

Immune response may explain rare clots after AstraZeneca vaccine

Researchers may have found an explanation for the rare but serious blood clots reported among some people who received AstraZeneca’s COVID-19 vaccine. They believe the phenomenon is similar to one that rarely occurs with a blood thinning drug called heparin, called heparin-induced thrombocytopenia (HIT). In HIT, the drug triggers the immune system to produce antibodies that activate platelets, which cause blood to clot. Drugs other than heparin can cause clotting disorders that strongly resemble HIT, and researchers suspect that in rare cases, the AstraZeneca vaccine may be another such trigger. Four previously healthy individuals who got the AstraZeneca shot and developed life-threatening clots had the same kind of antibodies that activate platelets and initiate clotting in HIT, the researchers reported on Monday in a paper posted on Research Square ahead of peer review. Twenty individuals who received the vaccine but did not develop clots did not have these antibodies. An editorial comment posted with the study noted that drug-induced thrombocytopenia is treatable if identified promptly. Millions of people have received the vaccine without issues and European regulators and the World Health Organization say the benefits of the AstraZeneca shot outweigh its risks.

COVID-19 death risk rising for young adults in Brazil

Southern Brazil is seeing a sudden rise in COVID-19 deaths among young and middle-aged adults after the identification there of a concerning virus variant known as P.1, researchers said. They analyzed data from Parana – the largest state in southern Brazil – on 553,518 cases diagnosed from September 2020 through March 17, 2021. In all age groups, the proportion of patients who died either held steady or declined between September and January. Starting in February, however, fatality rates rose for almost all groups over age 20, according to a report posted on Friday on medRxiv ahead of peer review. From January to February, these rates tripled among patients aged 20 to 29, from 0.04% to 0.13%, and doubled among those aged 30 to 39, 40 to 49, and 50 to 59. “Individuals between 20 and 29 years of age whose diagnosis was made in February 2021 had an over 3-fold higher risk of death compared to those diagnosed in January 2021,” the researchers said. “Taken together, these preliminary findings suggest significant increases in case fatality rates in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil, and this should raise public health alarms.”

Pfizer, Moderna vaccines limit asymptomatic infections

Vaccines from Pfizer Inc and partner BioNTech SE and from Moderna Inc dramatically reduced the risk of infection by the new coronavirus within weeks after the first of two shots, according to data from a study of nearly 4,000 U.S. healthcare personnel and first responders in six states. Previous trials by the companies evaluated the vaccines’ efficacy in preventing illness from COVID-19, but would have missed infections that did not cause symptoms. In the new study, conducted from mid-December to mid-March, nearly 75% of participants had received at least one dose of vaccine, and everyone had weekly coronavirus testing for 13 consecutive weeks in order to pick up asymptomatic infections. According to a report published on Monday by the U.S. Centers for Disease Control and Prevention (CDC), the risk of infection fell by 80% two weeks or more after the first of two shots and by 90% by two weeks after the second shot. “The authorized mRNA COVID-19 vaccines provided early, substantial real-world protection against infection for our nation’s healthcare personnel, first responders, and other frontline essential workers,” CDC Director Rochelle Walensky said in a statement.

Pandemic has cut parents’ access to hospitalized children

Pediatricians have long endorsed the idea that babies and children in hospitals should not be separated from their families – a practice that in many facilities was restricted or discontinued to limit COVID-19 infections, according to new research. From mid-May through early July, researchers collected survey responses from 96 pediatric care units in 22 countries in Europe, Asia, and North America. The results – mostly from intensive care units for newborns – showed that before the pandemic, 87% of units welcomed families and 92% encouraged skin-to-skin care, according to a report published in Journal of Perinatology. After the onset of the pandemic, more than 83% of the hospital units restricted family presence, with additional restrictions placed on parental participation in their infant’s care, said study coauthor Ita Litmanovitz of Meir Medical Center in Kfar Saba, Israel. Hospitals’ decisions to limit family access did not depend on their previous rules, the availability of single-family rooms, or the virus infection rate in the hospital’s geographical area. “Restrictions during the pandemic increased separation between the infant and family,” the researchers found. These restrictions, Litmanovitz added, “go against psychological and neuroscienti´Čüc evidence in support of unrestricted parental presence and ability to care for their hospitalized infants.”

(Reporting by Nancy Lapid; Editing by Bill Berkrot)

Germany, Italy, France to halt AstraZeneca shots, further hitting EU vaccination campaign

By Thomas Escritt and Stephanie Nebehay

BERLIN/GENEVA (Reuters) – Germany, France and Italy said on Monday they would stop administering the AstraZeneca COVID-19 vaccine after several countries reported possible serious side-effects, throwing Europe’s already struggling vaccination campaign into disarray.

Denmark and Norway stopped giving the shot last week after reporting isolated cases of bleeding, blood clots and a low platelet count. Iceland and Bulgaria followed suit and Ireland and the Netherlands announced suspensions on Sunday.

The moves by some of Europe’s largest and most populous countries will deepen concerns about the slow rollout of vaccines in the region, which has been plagued by shortages due to problems producing vaccines, including AstraZeneca’s.

Germany warned last week it was facing a third wave of infections, Italy is intensifying lockdowns and hospitals in the Paris region are close to being overloaded.

German Health Minister Jens Spahn said that although the risk of blood clots was low, it could not be ruled out.

“This is a professional decision, not a political one,” Spahn said adding he was following a recommendation of the Paul Ehrlich Institute, Germany’s vaccine regulator.

France said it was suspending the vaccine’s use pending an assessment by the EU medicine regulator due on Tuesday. Italy said its halt was a “precautionary and temporary measure” pending the regulator’s ruling.

Austria and Spain have stopped using particular batches and prosecutors in the northern Italian region of Piedmont earlier seized 393,600 doses following the death of a man hours after he was vaccinated. It was the second region to do so after Sicily, where two people had died shortly after having their shots.

The World Health Organization appealed to countries not to suspend vaccinations against a disease that has caused more than 2.7 million deaths worldwide.

“As of today, there is no evidence that the incidents are caused by the vaccine and it is important that vaccination campaigns continue so that we can save lives and stem severe disease from the virus,” WHO spokesman Christian Lindmeier said.

The United Kingdom said it had no concerns, while Poland said it thought the benefits outweighed any risks.

“UNUSUAL” SYMPTOMS

AstraZeneca’s shot was among the first and cheapest to be developed and launched at volume since the coronavirus was first identified in central China at the end of 2019 and is set to be the mainstay of vaccination programs in much of the developing world.

Thailand announced plans on Monday to go ahead with the Anglo-Swedish firm’s shot after suspending its use on Friday but Indonesia said it would wait for the WHO to report.

The WHO said its advisory panel was reviewing reports related to the shot and would release its findings as soon as possible. But it said it was unlikely to change its recommendations, issued last month, for widespread use, including in countries where the South African variant of the virus may reduce its efficacy.

The European Medicines Agency (EMA) has also said there was no indication the events were caused by the vaccination and that the number of reported blood clots was no higher than seen in the general population.

The handful of reported side-effects in Europe have upset vaccination programs already under pressure over slow rollouts and vaccine skepticism in some countries.

The Netherlands said on Monday it had seen 10 cases of possible noteworthy adverse side-effects from the AstraZeneca vaccine, hours after the government put its vaccination program on hold following reports of potential side-effects in other countries.

Denmark reported “highly unusual” symptoms in a 60-year-old citizen who died from a blood clot after receiving the vaccine, the same phrase used on Saturday by Norway about three people under the age of 50 it said were being treated in hospital.

“It was an unusual course of illness around the death that made the Danish Medicines Agency react,” the agency said in a statement late on Sunday.

One of the three health workers hospitalized in Norway after receiving the AstraZeneca shot had died, health authorities said on Monday, but there was no evidence that the vaccine was the cause. They said they would continue their probe and that no more suspected cases had been reported since Saturday.

AstraZeneca said earlier it had conducted a review covering more than 17 million people vaccinated in the European Union and the UK which had shown no evidence of an increased risk of blood clots.

Investigations into potential side-effects are complicated as the history of each case and circumstances surrounding a death or illness are examined. Austrian authorities have said their review of the AstraZeneca batch will take about two weeks.

The EMA has said that as of March 10, a total of 30 cases of blood clotting had been reported among close to 5 million people vaccinated with the AstraZeneca shot in the European Economic Area, which links 30 European countries.

The WHO said that as of March 12, more than 300 million doses of COVID-19 vaccines had been administered around the world with no deaths found to have been caused by any of them.

(Reporting by Panarat Thepgumpanat in BANKOK and Andreas Rinke and Paul Carrel in BERLIN, Angelo Amante in ROME, Christian Lowe in PARIS, Toby Sterling in AMSTERDAM, Jacob Gronholt-Pedersen in COPENHAGEN and Stanley Widianto in JAKARTA; writing by Philippa Fletcher; editing by Nick Macfie)

WHO tries to quash nervousness about AstraZeneca vaccine

By Emma Farge and Emilio Parodi

GENEVA/MILAN/SOFIA (Reuters) – The World Health Organization squarely endorsed AstraZeneca’s coronavirus vaccine on Friday, as Thailand joined a number of smaller European countries in suspending use of the shot because of sporadic reports of blood clots among recipients.

Bulgaria also joined Denmark, Norway and Iceland, which all stopped using the vaccine on Thursday. Austria, Italy, Luxembourg, Estonia, Lithuania and Latvia stopped using certain batches.

“Until all doubts are dispelled…, we are halting inoculations with this vaccine,” Bulgarian Prime Minister Boyko Borissov said.

His health minister, Kostadin Angelov, said a 57-year-old woman had died of heart failure 15 hours after receiving an AstraZeneca shot, but urged those already inoculated to stay calm.

“We do not have any official data that proves a causal connection,” he said.

That line was reinforced by the WHO, which is keenly aware that AstraZeneca’s shot is by far the cheapest and most high-volume launched so far, and set to be the mainstay of vaccination programs in much of the developing world.

Spokeswoman Margaret Harris said the vaccine was “excellent”.

“It’s very important to understand that, yes, we should continue to be using the AstraZeneca vaccine,” she told a briefing. “All that we look at is what we always look at: Any safety signal must be investigated.”

The EU regulator, the European Medicines Agency (EMA), said on Wednesday that there had been 22 reports of embolisms from blood clots among 3 million people who had received the vaccine – no more than in the general population – but Bulgaria said it wanted to see that guidance in written form.

‘THIS NEEDS TO BE EXPLAINED’

Experts point to the difficulty of putting risks in perspective for a wider public that may be spooked by negative headlines.

In Sicily, where two people died shortly after being vaccinated, the regional health administrator said 7,000 inoculation appointments had been cancelled as a result.

Silvestro Scotti, a family doctor in Naples and head of the Italian Federation of General Practitioners, said he had been bombarded all day with inquiries from people nervous about getting the AstraZeneca shot.

“The crazy thing is that, even if the correlation between the vaccine and blood clots were proved, it would be a rate of 0.007 out of a thousand,” he said.

“To give an example: the birth control pill, which is used widely and doesn’t worry anyone, has a proven risk rate of 0.6 in a thousand. Even in the worst-case scenario, the risk/benefit ratio for this vaccine is extraordinarily favorable. That needs to be explained to people.”

The WHO’s Harris said 268 million doses of COVID-19 vaccines from various developers had been administered worldwide without being shown to have caused a single death.

In France, where distrust of vaccination is long-established, only 43% said they trusted the AstraZeneca shot in a Harris Interactive poll conducted on March 11-12, while 55% said they trusted COVID-19 vaccines in general.

Germany has also had to contend with substantial skepticism, to the extent that Health Minister Jens Spahn suggested that the AstraZeneca shot be given to the police force and army, after some health and other frontline workers baulked at receiving it.

However, German authorities’ main concern has been lack of supply, rather than lack of acceptance, as social and economic restrictions to limit transmission take their toll.

One doctor administering vaccinations in Berlin said recipients were now asking far fewer questions about the vaccine than two weeks ago.

(Additional reporting by Stephanie Nebehay in Geneva, Crispian Balmer in Rome, Paul Carrel in Berlin, Tsvetelia Tsolova in Sofia, Matthias Blamont in Paris; Writing by Kevin Liffey; Editing by Mark Heinrich)

Denmark, Norway temporarily suspend AstraZeneca COVID shots after blood clot reports

By Nikolaj Skydsgaard and Jacob Gronholt-Pedersen

COPENHAGEN (Reuters) – Health authorities in Denmark and Norway said on Thursday they had temporarily suspended the use of AstraZeneca’s COVID-19 vaccine shots after reports of the formation of blood clots in some who have been vaccinated.

The move comes after Austria stopped using a batch of AstraZeneca shots while investigating a death from coagulation disorders and an illness from a pulmonary embolism.

Danish health authorities said the country’s decision to suspend the shots for two weeks came after a 60-year old woman in Denmark, who was given an AstraZeneca shot from the same batch that was used in Austria, formed a blood clot and died.

Danish authorities said they had responded “to reports of possible serious side effects, both from Denmark and other European countries.”

“It is currently not possible to conclude whether there is a link. We are acting early, it needs to be thoroughly investigated,” Health Minister Magnus Heunicke said on Twitter.

The vaccine would be suspended for 14 days in Denmark.

“This is a cautionary decision,” Geir Bukholm, director of infection prevention and control at the Norwegian Institute of Public Health (FHI), told a news conference.

FHI did not say how long the suspension would last.

“We … await information to see if there is a link between the vaccination and this case with a blood clot,” Bukholm said.

Also on Thursday, Italy said it would suspend use of an AstraZeneca batch that was different to the one used in Austria.

Some health experts said there was little evidence to suggest the AstraZeneca vaccine should not be administered and that the cases of blood clots corresponded with the rate of such cases in the general population.

“This is a super-cautious approach based on some isolated reports in Europe,” Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told Reuters.

“The problem with spontaneous reports of suspected adverse reactions to a vaccine are the enormous difficulty of distinguishing a causal effect from a coincidence,” he said, adding that the COVID-19 disease was very strongly associated with blood clotting.

AstraZeneca on Thursday told Reuters in a written statement the safety of its vaccine had been extensively studied in human trials and peer-reviewed data had confirmed the vaccine was generally well tolerated.

The drugmaker said earlier this week its shots were subject to strict and rigorous quality controls and that there had been “no confirmed serious adverse events associated with the vaccine.” It said it was in contact with Austrian authorities and would fully support their investigation.

The European Union’s drug regulator, the European Medicines Agency (EMA), said on Wednesday there was no evidence so far linking AstraZeneca to the two cases in Austria.

It said the number of thromboembolic events – marked by the formation of blood clots – in people who have received the AstraZeneca vaccine is no higher than that seen in the general population, with 22 cases of such events being reported among the 3 million people who have received it as of March 9.

EMA was not immediately available for comment on Thursday.

Four other countries – Estonia, Lithuania, Luxembourg and Latvia – have stopped inoculations from the batch while investigations continue, the EMA said.

The batch of 1 million doses went to 17 EU countries.

Swedish authorities said they did not find sufficient evidence to stop vaccination with AstraZeneca’s vaccine. Sweden has found two cases of “thromboembolic events” in connection with AstraZeneca’s vaccine and about ten for the Pfizer-BioNTech vaccine.

“We see no reason to revise our recommendation,” Veronica Arthurson, head of drug safety at the Swedish Medical Products Agency, told a news conference. “There is nothing to indicate that the vaccine causes this type of blood clots.”

Spain on Thursday said it had not registered any cases of blood clots related to AstraZeneca’s vaccine so far and would continue administering the shots.

(Additional reporting by Ludwig Burger in Frankfurt, Johan Ahlander in Stockholm, Victoria Klesty in Oslo and Kate Kelland in London. Editing by Alex Richardson, Nick Macfie and Bernadette Baum)

WHO issues new clinical advice on treating COVID-19 patients

GENEVA (Reuters) – The World Health Organization (WHO) issued fresh clinical advice on Tuesday for treating COVID-19 patients, including those displaying persistent symptoms after recovery, and also said it advised using low-dose anti-coagulants to prevent blood clots.

“The other things in the guidance that are new are that COVID-19 patients at home should have the use of pulse oximetry, that’s measuring the oxygen levels, so you can identify whether someone at home is deteriorating and would be better off having hospital care,” WHO spokeswoman Margaret Harris told a U.N. briefing in Geneva.

The WHO advised clinicians to put patients into the awake prone position, on their front, shown to improve the oxygen flow, she said.

“Also we recommend, we suggest, the use of low-dose anti-coagulants to prevent blood clots forming in blood vessels. We suggest the use of lower doses rather than higher doses because higher doses may lead to other problems,” Harris said.

She added that a WHO-led team of independent experts, currently in the central Chinese city of Wuhan where the first human cases were detected in December 2019, is due to leave quarantine in the next two days to pursue its work with Chinese researchers on the virus origins.

She declined to comment on reports of delays in roll-out of vaccines in the European Union. She said she had no specific data and the WHO’s priority was for health workers in all countries to be vaccinated in the first 100 days of the year.

AstraZeneca, which developed its shot with Oxford University, told the EU on Friday it could not meet agreed supply targets up to the end of March.

(Reporting by Stephanie Nebehay and Emma Farge)