AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction in participant in the U.K.

0



 A

large, Phase 3 study testing a Covid-19 vaccine being developed by AstraZeneca and the University of Oxford at dozens of sites across the U.S. has been put on hold due to a suspected serious adverse reaction in a participant in the United Kingdom.

A spokesperson for AstraZeneca, a frontrunner in the race for a Covid-19 vaccine, said in a statement that the company’s “standard review process triggered a pause to vaccination to allow the review of safety data.” 

In a follow-up statement, AstraZeneca said it initiated the study hold. The nature of the adverse reaction and when it happened was not immediately known, though the participant is expected to recover, according to an individual familiar with the matter. 

The spokesperson described the pause as “a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated, ensuring we maintain the integrity of the trials.” The spokesperson also said that the company is “working to expedite the review of the single event to minimize any potential impact on the trial timeline.”

An individual familiar with the development said researchers had been told the hold was placed on the trial out of “an abundance of caution.” A second individual familiar with the matter, who also spoke on condition of anonymity, said the finding is having an impact on other AstraZeneca vaccine trials underway — as well as on the clinical trials being conducted by other vaccine manufacturers.

Clinical holds are not uncommon, and it’s unclear how long AstraZeneca’s might last. But the progress of the company’s trial — and those of all Covid-19 vaccines in development — are being closely watched given the pressing need for new ways to curb the global pandemic. There are currently nine vaccine candidates in Phase 3 trials. AstraZeneca’s is the first Phase 3 Covid-19 vaccine trial known to have been put on hold.

Researchers running other trials are now looking for similar cases of adverse reactions by combing through databases reviewed by a so-called Data and Safety Monitoring Board, the second person said.

AstraZeneca only began its Phase 3 trial in the U.S. in late August. The U.S. trial is currently taking place at 62 sites across the country, according to clinicaltrials.gov, a government registry, though some have not yet started enrolling participants. Phase 2/3 trials were previously started in the U.K., Brazil, and South Africa.

There are a number of different reactions that can qualify as suspected serious adverse reactions, symptoms that require hospitalization, life-threatening illness and even death. It was also not immediately clear which clinical trial the adverse reaction occurred in, though a clear possibility is the Phase 2/3 trial underway in the U.K.

While it’s still unclear how severe and rare the adverse event may be, the finding could impact how quickly efficacy data from the U.K. trial will be available. Those data are considered integral to any bid to seek an emergency use authorization for the vaccine from the U.S. Food and Drug Administration — and potentially jeopardize President Trump’s efforts to fast-track a vaccine ahead of the November election.

A Phase 1/2 study published in July reported that about 60% of 1,000 participants given the vaccine experienced side effects. All of the side effects, which included fever, headaches, muscle pain, and injection site reactions, were deemed mild or moderate. All of the side effects reported also subsided during the course of the study. 

The vaccine  — known as AZD1222 — uses an adenovirus that carries a gene for one of the proteins in SARS-CoV-2, the virus that causes Covid-19. The adenovirus is designed to induce the immune system to generate a protective response against SARS-2. The platform has not been used in an approved vaccine but has been tested in experimental vaccines against other viruses, including the Ebola virus. 

The Phase 3 trial in the U.S. aims to enroll about 30,000 participants at 80 sites across the country, according to a release last week from the National Institutes of Health. 

It was not immediately clear what steps were being taken at study sites across the U.S. in response to the hold. Clinical holds in ongoing studies often involve a pause in recruiting new participants and dosing existing ones, unless it’s deemed in the interest of participant safety to continue dosing.

In the statement from AstraZeneca, the company spokesperson noted that “in large trials, illnesses will happen by chance but must be independently reviewed to check this carefully.” The spokesperson also said the company is “committed to the safety of our participants and the highest standards of conduct in our trials.”

Several states in the U.S. Midwest and Northeast have seen new COVID-19 cases increase for two weeks in a row, though nationally both new infections and deaths last week remained on a downward trend, a Reuters analysis showed.

The United States reported more than 287,000 new cases in the week ended Sept. 6, down 1.4% from the previous week and marking the seventh straight week of declines. More than 5,800 people died from COVID-19 last week, the third week in a row that the death rate has fallen.

Nevertheless, 17 states have seen cases rise for at least two weeks, according to the Reuters tally of state and county reports. They include Missouri, North Dakota, and Wisconsin, where between 10% and 18% of people tested had the new coronavirus.

In the Northeast, Delaware, New Hampshire, New Jersey, and New York also reported increases in new cases for at least two weeks, though the positive test rate ranged from a low of 0.9% in New York to a high of 4.3% in Delaware — below the 5% level the World Health Organization considers concerning.

In some states, testing has increased as schools reopened. New York City, for instance, is testing 10% to 20% of students and staff every month. The University of Illinois is testing students twice a week.

Nationally, the share of all tests that came back positive for COVID-19 fell for a fifth week to 5.5%, well below a peak of nearly 9% in mid-July, according to data from The COVID Tracking Project, a volunteer-run effort to track the outbreak.

The United States tested on average 741,000 people a day last week, up 5% from the prior week, but down from a peak in late July of over 800,000 people a day.


Job openings for blue-collar workers in the UK are recovering faster than demand for white-collar roles, according to a survey that suggests office support staff are among the main casualties of the shift to working from home after the coronavirus pandemic started. A monthly survey conducted by advisory firm KPMG and the Recruitment & Employment Confederation pointed to a strong pick-up in the hiring of temporary staff in August, with the reading on its temporary billings index rising to 55.6 from 45.1 the previous month. In contrast, there was only a slight rise in permanent staff appointments, with the permanent placements index rising from 44.7 to 50.9.

With restaurants and malls bustling, pre-pandemic life is slowly returning for people in Singapore -- except for the more than 300,000 migrant workers who make up much of the city’s low-wage workforce.

Since April, these workers have been confined to their residences with limited exceptions for work. After an extensive testing and quarantine campaign, the government cleared the dormitories where most of these workers live of Covid-19 in August, letting residents leave for several “essential errands,” like court appearances and doctor’s appointments.

The government said last month it was working toward relaxing more rules for workers. Those plans are now under threat, with new virus clusters emerging in the dorms, where workers from China, India, Indonesia, and elsewhere share bunks and tight living spaces.

“Some days I feel very upset and can’t take it,” said Mohd Al Imran, a Bangladeshi worker with a local engineering firm. After months of confinement at the dorms, he got Covid-19 anyway. He was sent to a coronavirus care facility and said it was “very free” by comparison. “At the dorm, you can’t go out from your room,” he said in a text message. “They treat it like a prison.”

Singapore has been saying it’s taking appropriate measures, considering that migrant workers have accounted for nearly 95% of the city’s coronavirus cases. But the resurgence, so soon after the dorms were declared Covid-free, is raising questions about whether Singapore’s conditions for its low-wage workforce undermine the efforts to stamp it out.

“If you’ve got relatively socio-economically deprived people in crowded housing, you’ll get Covid-19 transmission at a higher rate,” said Peter Collignon, an infectious diseases physician and a professor at the Australian National University Medical School. It’s not inappropriate to treat higher-risk groups differently, he added, but “it’s unreasonable to put restrictions on people when there are things you can fix-up.”


While experts say it’s reasonable to cordon off specific areas to quash an outbreak, they also say the conditions in the dorms are ripe for future transmission. The ventilation isn’t always good, and bathrooms are shared among a dozen or more. Government standards currently specify a minimum of 50 square feet of personal space, roughly equivalent to a third of a parking spot -- conditions that “will always pose a risk of outbreaks,” said Raina Macintyre, a professor of global biosecurity at the University of New South Wales in Australia.

Poor and disenfranchised populations around the world have borne the brunt of the global pandemic, highlighting wide social and economic inequalities that existed long before Covid-19. In the best of times, Singapore’s migrant workers live with more restrictions than citizens and white-collar ex-pats; with clusters rising again in the dorms, the prolonged lockdown-like conditions have brought new psychological stressors, along with a renewed debate about the city-state’s deep reliance on this part of the workforce.

relates to Singapore’s Poorest Stay in Lockdown While Others Move Freely

Social distancing markers are displayed on tables and stools at the canteen.

Photographer: Wei Leng Tay/Bloomberg

In local media and on Facebook, reports of self-harm and suicide attempts among migrant workers have circulated. When asked, Singapore’s Ministry of Manpower said these tend to be isolated incidents that reflect existing, underlying mental illness or trouble back home. Either way, social service groups say they’re swamped with calls for help from workers.

The situation “has definitely deteriorated in the last two months,” said Alex Au, vice president of the local migrant aid group, Transient Workers Count Too. “The tone of the conversations has changed a lot. There’s a lot of ‘I don’t care if you don’t even get me my salary, just get me out of here. I want to go home.’”

With overtime, a migrant worker could earn S$600 ($438) to S$1,000 a month, far less than the monthly cost of a typical three-room apartment. The dorms still eat up a chunk: For around S$350, a worker can get a bunk bed in a room shared with 12 to 16 others.

The amenities vary. There is typically some kind of health services, like a clinic or a sickbay, as well as recreation spaces, mini-marts, and indoor and outdoor seating areas.

Past the Worst?

Cases have fallen since Singapore put restrictions on dorm residents in April

Source: Singapore Ministry of Health

As of June, the government had moved more than 32,000 workers into temporary accommodations in response to the crisis. Longer-term, it plans to build 11 new dorms which will limit occupancy to 10 single beds per room; toilet, bathroom, and sink facilities will be shared by every five residents, down from 15 currently.


Close quarters are ideal for the spread of a highly contagious virus-like Covid-19. After officials instituted broad, city-wide restrictions in April, cases exploded in the dorms, eventually peaking at more than 1,000 a day. By May, with lockdown measures still in place, Singapore had one of the biggest outbreaks in the region.

relates to Singapore’s Poorest Stay in Lockdown While Others Move Freely

Security personnel stand at the entrance to the dorm building.

Photographer: Wei Leng Tay/Bloomberg

The country responded with an aggressive testing strategy and, as case counts began to fall, began the process of reopening in mid-June. Dorm residents, though remain on virtual lockdown, with exceptions for those who had jobs to go to -- some, but not all, of the city’s construction projects were allowed to start up again.

The dorm exits are monitored, and before workers can go to work or run one of the sanctioned errands, their employer must notify the government’s Ministry of Manpower. This is a trade-off many residents are willing to make. Many are owed wages, and the health costs may be worse back home. Out of more than 57,000 reported cases in Singapore, only 27 patients have died.

Ah Hlaing, a Burmese worker at an elder-care center, has been riding out her quarantine in a Holiday Inn since May. “I do morning exercise, eat breakfast, watch the news, movies,” she said. “I’m on Facebook, eat lunch, have a bath, dinner, pray, and sleep.”

Fewer people, though, have jobs to go to these days, cutting off the biggest allowable reason to leave the dorms. On an annualized basis, Singapore’s GDP dropped nearly 43% in the second quarter compared with the previous three months. Many construction projects are also on hold until employers can meet safe distancing and testing criteria.

relates to Singapore’s Poorest Stay in Lockdown While Others Move Freely

Pick-up and drop-off area outside a workers dormitory.

Photographer: Wei Leng Tay/Bloomberg

So they’re largely confined to their compounds. “I don’t know until when I will be quarantined, and I don’t have any income,” said Bob Bu, a 33-year-old Chinese national who worked as a restaurant manager until he lost his job in a salary dispute with his employer. “I was under great mental pressure and couldn’t sleep for a while, because of the uncomfortable environment of the dormitory.”

At construction company, Kori Holdings, Ltd., ten of the 200 migrant employees have told Chief Executive Officer Hooi Yu Koh that they’d like to go home.

“I could understand the concern of the workers in isolation, with family members worrying about their safety, being confined to the dormitories,” he said. “They just want to return home to their family as well as to ensure that the family knows they are safe.”

As outbreaks ebb and flow, the government has warned that the city-state won’t return to pre-Covid norms any time soon. Instead, the leaders are describing a “new normal,” where crowds and large gatherings are restricted until there’s a vaccine and social distancing is enforced.


relates to Singapore’s Poorest Stay in Lockdown While Others Move Freely

A worker uses the Trace Together app.

Photographer: Wei Leng Tay/Bloomberg

For Singapore’s migrant workers, that’s ushered in a series of safe living measures, including the mandatory use of a government contact-tracing app. Employers also have to ensure that dorm workers as well as those in sectors like construction go for routine testing every 14 days. In at least one dorm, residents have been allowed one 30-minute visit to the on-site amenities a day, otherwise they’re expected to be in their room or at work.

“This is not the ideal situation,” said Leong Hoe Nam, an infectious disease physician at Singapore’s Mount Elizabeth Hospital. “But let’s look at the facts. There’s little to no transmission in the [broader] community. If you need the economy to move, would you release the community people or the dormitory workers? The safety of others overrides the interest of an individual.”

Post a Comment

Previous Post Next Post