The company defended its claims of 79 percent efficacy for its coronavirus shot and said it would release more up-to-date trial results within 48 hours.LONDON — The announcement this week that the AstraZeneca shot, the workhorse of global vaccine rollouts, had achieved nearly 80 percent efficacy in a gold-standard American trial was met with relief by the many countries relying on it.“When you get the call, get the jab,” the British health secretary, Matt Hancock, urged, part of a campaign by European lawmakers to calm people’s nerves after a recent safety scare with the shot.But by Tuesday, that campaign had, once again, been thrown off course, at least for the moment. For AstraZeneca, it was seemingly another episode of public relations whiplash, part of a series of recent miscues and communication blunders by the company that scientists said had undercut the effort to sell one of the most potent and indispensable vaccines against the coronavirus.In a highly unusual move, American health officials said on Tuesday that the company’s account of its U.S. trial findings had not been entirely accurate, suggesting that AstraZeneca had used only the most favorable data to generate apparently spectacular efficacy results.Those comments created new friction between AstraZeneca and American officials even as the company vies for a coveted authorization from the Food and Drug Administration. But more urgently, they threw a wrench into the efforts of elected leaders around the world to rebuild trust in a shot whose low price and easy storage requirements have made it the backbone of many countries’ campaigns to end the pandemic.“It’s eroding confidence,” said Simon Clarke, an associate professor in cellular microbiology at the University of Reading. “When you pump things up, and then people not unreasonably question it, then that erodes confidence.”A vaccination center in Belgrade, Serbia, this month. Despite troubling news reports about the AstraZeneca vaccine, European and global regulators have deemed the shots safe and effective.Laura Boushnak for The New York TimesFaith in the vaccine had already plunged across Europe after recent reports that a very small number of recipients had developed unusual blood clots. In France, Germany, Italy and Spain, more people now believe that the vaccine is unsafe than that it is safe, polling has shown, a blow to a shot that remains the continent’s best hope for saving people’s lives during a mounting surge of new infections.Despite the drumbeat of troubling news reports about the vaccine, European and global regulators have deemed it safe and effective. More than 11 million doses have been administered in Britain alone, almost all of them without serious side effects, driving down hospitalizations and helping the country to emerge from a dreadful wintertime wave of infections.Nevertheless, AstraZeneca’s U.S. trial was hotly anticipated. The largest of its kind for the shot, it had been expected to provide the cleanest, most complete picture of the vaccine’s efficacy. American officials saw it as an incontrovertible test of the vaccine’s performance.And health officials around the world were looking to it as a crucial guide to their own rollouts: It would supply crucial data on older people, who had not been as well represented in earlier trials, and a more precise read on the vaccine’s overall efficacy, which had appeared from earlier trials to be lower than that of other leading shots.As soon as AstraZeneca announced its results on Monday, saying that the vaccine had 79 percent efficacy in preventing symptomatic Covid-19, lawmakers began citing it as part of their fledgling efforts to shore up public confidence in the vaccine.Prime Minister Boris Johnson of Britain received an AstraZeneca shot on Friday. “I literally did not feel a thing,” he later said. “I cannot recommend it too highly.”Pool photo by Frank AugsteinBy Tuesday, scientists said, it seemed as though AstraZeneca had punched a hole in those efforts. Rather than sewing up questions about the shot, it had called to mind communications problems that have dogged the company since last year, delaying the regulatory process in some regions and creating hesitation among some recipients.Scientists said that such a public dust-up between the American medical experts overseeing a trial and the company sponsoring it was extremely unusual.“It is usually done in private,” Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said of disagreements between a data and safety monitoring board — the experts overseeing the trial — and a vaccine maker. “So this is unprecedented, in my opinion.”In its first public comments, AstraZeneca said that the results published on Monday reflected its U.S. trial data up to Feb. 17. It said that its preliminary assessment of more complete trial data showed that “the results were consistent with the interim analysis,” but said that it would share more up-to-date efficacy results within 48 hours.Scientists said that the problem could yet turn out to be a technical matter that did not change their assessment of the vaccine. American officials did not suggest that any safety issues had been withheld, a subject of intense interest in the wake of the concerns in Europe.AstraZeneca said that the results published on Monday reflected its U.S. trial data up to Feb. 17.  American officials did not suggest that any safety issues had been withheld.Alessandro Grassani for The New York TimesNevertheless, it quickly took the wind out of the sails of European lawmakers’ public campaign to restore confidence in the shot. In recent days, a number of political leaders, including Prime Minister Boris Johnson of Britain and Prime Minister Jean Castex of France, have received the vaccine themselves in a bid to show people that it was safe.“I literally did not feel a thing,” Mr. Johnson told reporters. “I cannot recommend it too highly.”The stumble on Tuesday was the latest in a series of miscues that have made for a prickly relationship between AstraZeneca and American and European regulators — and, scientists said, created unnecessary public confusion about a vaccine that appears to be highly effective.In early September, the company quietly halted its global trials after a participant in Britain fell ill. But American regulators did not find out until the story broke publicly. Subsequently, the company’s slowness to provide the F.D.A. with evidence that its vaccine was not linked to any illnesses kept it grounded for nearly seven weeks. AstraZeneca has said it shared data in a timely manner.By late November, the company was again riding high: It released results from early clinical trials, including in Britain, showing that the vaccine was up to 90 percent effective.But those results, too, were quickly clouded by uncertainty. AstraZeneca later acknowledged that there had initially been confusion over the vaccine dosage received by some study participants, making it more difficult to interpret the findings.Britain, which has long championed the homegrown vaccine, authorized the shot in late December, relying on the earlier clinical trial results. The European Union’s medicine regulator did the same, but a month later.E.U. officials said that the delay had partly resulted from a back-and-forth between the regulators and AstraZeneca over the quality of the data.Waiting outside a vaccination center in Munich, Germany, on Sunday. Europe has seen a mounting surge of new infections recently.Laetitia Vancon for The New York TimesAnd even after the vaccine was authorized, a number of European countries initially restricted it to younger people, citing a lack of sufficient data about its efficacy in older people. That problem was supposed to be resolved by the American trial, in which older people were better represented.Neither European nor British regulators gave any indication on Tuesday that the problems with AstraZeneca’s American data would have any impact on rollouts there. Those agencies relied on a separate set of data from non-American trials to authorize the vaccine.“We are in contact with the company regarding this further information,” the European Medicines Agency said in a statement on Tuesday, “and E.M.A. will assess the data concerned as soon as the company submits it to us.”Matina Stevis-Gridneff contributed reporting from Brussels.

Many Americans know they’ve put on weight during the pandemic, but it’s been difficult for experts to detail the scope of the problem.Soon after the pandemic started over a year ago, Americans started joking about the dreaded “quarantine 15,” worried they might gain weight while shut in homes with stockpiles of food, glued to computer screens and binge-watching Netflix.The concern is real, but assessing the problem’s scope has been a challenge. Surveys that simply ask people about their weight are notoriously unreliable, and many medical visits have been virtual.Now a very small study using objective measures — weight measurements from Bluetooth-connected smart scales — suggests that adults under shelter-in-place orders gained more than half a pound every 10 days.That translates to nearly two pounds a month, said Dr. Gregory M. Marcus, senior author of the research letter, published on Monday in the peer-reviewed JAMA Network Open. Americans who kept up their lockdown habits could easily have gained 20 pounds over the course of a year, he added.“We know that weight gain is a public health problem in the U.S. already, so anything making it worse is definitely concerning, and shelter-in-place orders are so ubiquitous that the sheer number of people affected by this makes it extremely relevant,” said Dr. Marcus, a cardiologist and professor of medicine at University of California, San Francisco.While it is almost impossible to make generalizations based on the study — which included fewer than 300 people scattered across the United States — all participants were tracking their weight regularly.Many of these people were losing weight before shelter-in-place orders were issued in their states, Dr. Marcus noted. “It’s reasonable to assume these individuals are more engaged with their health in general, and more disciplined and on top of things,” he said. “That suggests we could be underestimating — that this is the tip of the iceberg.”Excess weight has been linked to a greater risk of developing more severe Covid-19 disease, and the United States already has among the highest rates of overweight and obesity in the world. Some 42 percent of American adults over age 20 have obesity, as defined by body mass index, while another 32 percent of Americans are simply overweight.The risk of severe illness has been documented among young adults who are overweight or have obesity, as well. Many states are prioritizing Americans with obesity for vaccination, along with those who have other chronic conditions like diabetes or hypertension.The new study analyzed data obtained from 269 participants who were involved in an ongoing cardiology study, the Health eHeart Study. They volunteered to report weight measurements from Bluetooth-connected smart scales and weighed themselves regularly; the researchers gathered 7,444 weight measurements over a four-month period, an average of 28 weight measurements from each participant.The group was not nationally representative, by any means, so the results are not generalizable: About three-quarters were white, and just 3.5 percent identified as Black or African-American; about 3 percent identified as Asian-American. The average age was 51, and they were split almost evenly among men and women.The participants were from 37 states and the District of Columbia. The researchers analyzed weight measurements taken between Feb. 1, 2020, and June 1, 2020, in order to look at weight changes both before and after shelter-in-place orders were issued for each state.While the participants mostly had been losing pounds before the orders were issued, their weights rose steadily at a rate of about six-tenths of a pound every 10 days after the orders were issued, regardless of where they were in the country and regardless of chronic medical conditions.The lockdowns have certainly had an effect on dietary patterns, on what people eat and how often they eat. But the restrictions also curtailed the humdrum physical activity that is part and parcel of daily living, the researchers said.“If you think about people commuting, even running to the subway or bus stop, or stepping in at the post office to mail a letter, or stopping at the store — we burn a lot of calories in non-exercise activities of daily living,” said Leanne Redman, a professor of clinical physiology at the Pennington Biomedical Research Center, part of Louisiana State University.Her research had found that people were eating a healthier diet during the initial days of the shutdown but were more sedentary.An earlier study by U.C.S.F. researchers looked at daily step counts, as tracked by smartphones, among nearly half a million people in nearly 200 countries. The number of steps people took declined by 27 percent a month after the World Health Organization declared the pandemic.The concern about exercise also extends to children, who are known to pack on unhealthy pounds during the summer recess months when they are not in school. The risk is even greater for Hispanic and Black children than for white children, said Andrew G. Rundle, an associate professor of epidemiology at Columbia University’s Mailman School of Public Health, author of a recent paper that expressed concern that school closings would exacerbate existing racial health disparities.“We argued that being out of school, which we thought would go on for six months and has gone on longer, was going to be like the summer recess but even worse, because everyone would be loading up on shelf-stable calorie-laden food, and staying indoors and not going out,” he said. “Everything that makes the summer dangerous for kids would be magnified by the lockdown.”

Serious complications due to blood clots, such as heart attacks and strokes, that are experienced by some COVID-19 survivors may be caused by a lingering immune response in the blood vessels after recovery, suggests a study published today in eLife.
The findings may help explain why some COVID-19 survivors, so-called ‘long-haulers’, report lasting COVID-19 symptoms or why some experience strokes or heart attacks weeks or months after recovery. They may also suggest potential strategies to help prevent these complications.
“During the initial stages of infection, SARS-CoV-2, the virus that causes COVID-19, may attack the lining of the blood vessels which can trigger inflammation and an immune response. This can result in blood vessel damage in the short term,” explains first author Florence Chioh, Research Assistant at the Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore. “For our study, we wanted to investigate what happens in the blood vessels of COVID-19 survivors over the longer term.”
Chioh and colleagues collected blood samples from COVID-19 survivors within a month of their recovery and discharge from the hospital. They found that, in comparison with healthy individuals, COVID-19 survivors have twice as many damaged blood vessel cells, called circulating endothelial cells, floating in their blood. Even more of these damaged blood vessel cells were found in survivors who had conditions such as hypertension or diabetes that can also damage the blood vessels.
In addition to signs of blood vessel damage, the team found that survivors had an abundance of inflammatory proteins called cytokines that are produced by immune cells. They also found unusually high numbers of immune cells called T cells, which help destroy viruses, despite the fact that the virus was already gone.
“We show that an overactive immune system is the likely cause of blood vessel damage seen in some COVID-19 survivors,” Chioh says. “This may cause ‘leakiness’ in the blood vessels that increases the risk of blood clots.”
“Our work suggests that COVID-19 patients, especially those with underlying chronic conditions, may benefit from close post-recovery monitoring,” adds senior author Christine Cheung, Assistant Professor and Provost’s Chair in Medicine at LKCMedicine. “This would help identify high-risk individuals who may need blood thinners or preventative therapy to protect them from debilitating blood-clotting complications.”
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Of the many perplexing questions surrounding SARS CoV-2, a mysterious new pathogen that has killed an estimated 2.6 million people worldwide, perhaps the most insistent is this: why does the illness seem to strike in such a haphazard way, sometimes sparing the 100 year old grandmother, while killing healthy young men and women in the prime of life?
A new study by Karen Anderson, Abhishek Singharoy and their colleagues at the Biodesign Institute at Arizona State University, may offer some tentative clues. Their research explores MHC-I, a critical protein component of the human adaptive immune system.
The research suggests that certain variant forms of MHC-I can help protect the body, by stimulating a strong immune response, while others may leave an individual susceptible to viral assault, severe illness and possibly, death.
“The implication of our findings is that the capacity to mount a strong and diverse T cell response to SARS-CoV-2 may be important to limit disease severity,” Anderson says. “The key to this work is using protein structure to predict individual MHC-I peptide binding capacity.”
Anderson is researchers at the Biodesign Virginia G. Piper Center for Personalized Diagnostics and professor at ASU’s School of Life Sciences. Singharoy is a researcher in the Biodesign Center for Applied Structural Discovery and assistant professor at ASU’s School of Molecular Sciences.
Cellular police
Humans, like all vertebrates, carry MHC-I molecules in all nucleated cells. A central role of MHC-I is to help the body clear infections from viruses and other pathogens. It does this by gathering fragments of the virus, ferrying them to the cell surface and presenting them to immune agents known as CD8+ T cells, which ceaselessly patrol the body.

The COVID-19 pandemic has had devastating effects in U.S. nursing homes and long-term care facilities, resulting in an estimated 1.2 million infections and 147,000 deaths as of early 2021. Yet even as mortality rates in the general population have decreased over time, little evidence has been uncovered to determine whether nursing home residences have experienced similar reductions.
Now, new data collected and analyzed by researchers at Brown University shows that mortality rates among nursing home residents with COVID-19 declined from March to November 2020, and that the deadliest period of time for nursing home residents followed the pandemic’s arrival, when the virus spiked in spring 2020.
The information fills an important evidence gap in accounting for death rates of nursing home residents from COVID over time, the researchers say.
“Understanding the mortality risk from COVID-19 among nursing home residents is critical for identifying the mechanisms that most significantly affect health outcomes in this vulnerable population,” said Cyrus Kosar, lead study author and a doctoral candidate in health services, policy and practice in Brown’s School of Public Health.
Kosar conducted the analysis with principal investigator and Brown professor Vincent Mor, who has been researching the impact of COVID-19 in nursing homes since the beginning of the pandemic.
Long-term care residents have accounted for approximately 40% of total U.S. deaths from COVID-19. While data showed that mortality rates from the virus in the general population have declined overall, there was no evidence that nursing homes had similarly turned a corner. What’s more, the researchers say, some of the factors contributing to reduced mortality rates in the general population, such as improved COVID-19 therapeutics and supportive care in hospitals, are not applicable to nursing home residents, who are often treated in the facilities where they reside instead of being admitted to a hospital.

Knee osteoarthritis is a painful condition that affects over 14 million U.S. adults, many of whom have extreme obesity, defined by body mass index (BMI) greater than 40kg/m2. Total knee replacement (TKR) is often recommended to treat advanced knee osteoarthritis, but surgeons may be hesitant to operate on patients with extreme obesity due to concerns about the increased risks of tissue infection, poor wound healing and higher risk of implant failure. Using an established, validated and widely published computer simulation called the Osteoarthritis Policy (OAPol) Model, researchers from Brigham and Women’s Hospital, together with collaborators from Yale and Boston University Schools of Medicine, quantified the tradeoff between the benefits and adverse events, taking into consideration costs of forgoing versus pursuing TKR. They found that across older and younger age groups, TKR is a cost-effective treatment for these patients. Findings are published in Annals of Internal Medicine.
“People with extreme obesity experience substantial pain reduction from TKR, leading to meaningful improvements in quality-adjusted life expectancy. High BMI should not serve as a barrier for people seeking this procedure,” said corresponding author Elena Losina, PhD, a founding director of the Policy and Innovation eValuation in Orthopedic Treatments Center and a co-director of the Brigham’s Orthopedic and Arthritis Center for Outcomes Research. “From a health policy perspective, this operation offers a very good value for the dollars spent.”
The computer model used by the researchers, OAPol, combines clinical and economic data from national datasets to forecast the clinical course of patients who decide to receive or forgo TKR. In the model, each treatment choice is associated with benefits (improvements in pain leading to better quality of life), drawbacks (surgery complications, continuous pain reducing quality of life) and costs. The model tallies the data from a large number of patients to calculate an incremental cost-effectiveness ratio of TKR, calculated as dollars for quality adjusted life year (QALY) gained. The researchers reported favorable cost-effectiveness ratios of $35,200 and $54,100 per QALY for patients younger and older than 65 years, respectively. The researchers noted that most patients with extreme obesity and advanced knee osteoarthritis considering TKR are in the younger age range. These data, they suggest, may help to diminish concerns regarding the value of TKR in these patients.
“Instead of questioning whether or not to do surgery for people with extreme obesity, the conversation should be about how to accommodate these patients and provide accurate information about what to expect post-surgery,” Losina said. “Ultimately, this study raises the question of how to do the operation in a way that addresses all of the challenges that may arise. This is a discussion that should take place between individual patients and physicians, discussing all the risks, complications, and benefits as well as considerations of operating room accommodations that would optimize the work of orthopedic surgeons performing TKR in these patients.”
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A pioneering study, published in Scientific Reports, found that the Parkinon’s gene PINK1 is important for the generation of dopamine-producing neurons throughout life, and is not just responsible for the premature death of these neurons The international research, led by University of Sheffield’s Neuroscience Institute, used two model systems to examine how neurons are produced throughout our lifetime Parkinson’s disease is a relentlessly progressive neurodegenerative disorder that affects around 145,000 people in the UK A gene defect linked to Parkinson’s disease may not only cause the early death of neurons, but also impair the process that generates neurons in the brain throughout our lifetime, a new study has revealed.
The international study, led by the University of Sheffield’s Neuroscience Institute, may have a significant impact on the future treatment of Parkinson’s patients who develop the illness due to PINK1 defect or similar gene defects.
The development of novel treatments and therapies to slow down disease progression, halt or reverse Parkinson’s may now focus on enhancing the generation of new dopamine-producing neurons, rather than just trying to protect these neurons from dying later.
The findings, published today (23 March 2021) in Scientific Reports, used two model systems to measure how inactivation of the PINK1 gene affects dopamine-producing neurons in the adult brain.
Dopamine-producing neurons are the most severely affected brain cells in Parkinson’s disease. It is typically thought that Parkinson’s genes, such as PINK1, cause early death of these neurons, with symptoms developing when neuron numbers fall. However, here, researchers found that a deficiency in PINK1 resulted in fewer dopamine-producing neurons being made throughout life.
Professor Oliver Bandmann, Professor of Movement Disorders Neurology at the Sheffield Institute for Translational Neuroscience (SITraN), said: “Neurogenesis is the process by which new neurons are formed in the brain. Recent evidence suggests that this process is ongoing throughout life but the relevance of this is poorly understood in neurodegenerative disorders such as Parkinson’s disease.”
“We know that mutations in the PINK1 gene cause an early onset, inherited form of Parkinson’s disease. If we can further our understanding about the impact of this genetic mutation on the dopamine-producing neurons we can develop new therapeutic approaches that aim to mitigate those effects.”

The company is preparing to apply for emergency authorization from the Food and Drug Administration. But the shot may not be needed in the United States.[Update: Federal health officials raised questions about the AstraZeneca trial results after they were announced. Read more here.]The coronavirus vaccine developed by AstraZeneca and the University of Oxford provided strong protection against Covid-19 in a large clinical trial in the United States, completely preventing the worst outcomes from the disease, according to results announced on Monday.Although no clinical trial is large enough to rule out extremely rare side effects, AstraZeneca reported that its study had turned up no serious safety issues. Government officials and public health experts expressed hope that the results would improve global confidence in the vaccine, which was shaken this month when more than a dozen countries, mostly in Europe, temporarily suspended the shot’s use over concerns about possible rare side effects.The trial, involving more than 32,000 participants, was the largest test of its kind for the shot. The AstraZeneca vaccine was 79 percent effective over all in preventing symptomatic infections, higher than observed in previous clinical trials, the company announced in a news release. The trial also showed that the vaccine offered strong protection for older people, who had not been as well represented in earlier studies.The fresh data may have arrived too late to make much difference in the United States, where the vaccine is not yet authorized and unlikely to become available before May. By then, federal officials predict, there will be enough vaccine doses for all of the nation’s adults from the three vaccines that have already been authorized.Even so, the better-than-expected results are a heartening turn for AstraZeneca’s shot, whose low cost and simple storage requirements have made it a vital piece of the drive to vaccinate the world.The results could also help ease concerns about the AstraZeneca vaccine in Europe. In an effort to boost waning public confidence, many European political leaders have gotten the injections in recent days.“The results from the U.S. trial of the Oxford-AstraZeneca vaccine give strong evidence that the vaccine is both safe and highly effective,” Matt Hancock, the British health secretary, said on Monday. “Vaccines are our way out of this, so when you get the call, get the jab.”How the Oxford-AstraZeneca Vaccine WorksAn adenovirus helps prime the immune system to fight the coronavirus.Regulators in Europe initiated a safety review of AstraZeneca’s vaccine this month after a small number of people who had recently been inoculated developed blood clots and abnormal bleeding. The trial did not turn up any sign of such problems, although some safety issues can be detected only in the real world, once a drug or vaccine has been given to millions of people.AstraZeneca said on Monday that it would continue to analyze the new data and prepare to apply in the coming weeks for emergency authorization from the Food and Drug Administration. The vaccine has already been approved in more than 70 countries, but clearance from American regulators would bolster its global reputation.Because the United States already has ample supply of vaccines from the three other manufacturers, however, F.D.A. regulators are unlikely to move on the accelerated timeline that they did with other vaccines.In November, Oxford and AstraZeneca reported that the vaccine was 70 percent effective across studies in Britain and Brazil. But those results were hard to interpret. The findings looked much different in participants who received the first dose of the vaccine at a strength that was not initially planned and then got their second dose many weeks later than originally intended. There were also relatively few older people in those trials. As a result, some public health experts and U.S. health officials viewed those studies as insufficient to tell how well the vaccine worked.“This was a very big, well-powered study that I think confirms now that this vaccine is a good vaccine,” said Dr. Anthony S. Fauci, the nation’s leading infectious-disease expert. He added that it was premature to say what the vaccine’s role would be in the United States.AstraZeneca has said it will release 30 million doses to the United States as soon as it receives authorization. Tens of millions of those doses are already ready to be shipped or close to it. U.S. officials have agreed to send four million of the doses to Canada and Mexico, in exchange for doses later in the future.Two-thirds of participants in the clinical trial were given the vaccine, with doses spaced four weeks apart, and the rest received a saline placebo. Volunteers were recruited from Chile and Peru in addition to the United States.The results announced on Monday were based on 141 Covid-19 cases that had turned up among the volunteers in the clinical trial.None of the volunteers who got the vaccine developed severe symptoms or had to be hospitalized. Five participants who were given the placebo developed severe Covid-19 by the time the interim data were analyzed, and more cases have since turned up in that group, Menelas Pangalos, an AstraZeneca executive, said at a news conference on Monday.Participants who received the vaccine in the trial had no increased risk of blood clots or related illnesses. And a specific search turned up no cases of cerebral venous sinus thrombosis — blood clots in the brain that can result in dangerous bleeding — that raised some of the most serious concerns in Europe.“Because of the slight battering the AstraZeneca vaccine has taken over the last few weeks — and particularly in the last week or two in Europe — new data showing it is safe and effective is, if you’ll excuse the phrase, a good shot in the arm,” said Michael Head, a senior research fellow in global health at the University of Southampton in Britain.The vaccine worked well across ethnicity and age groups, AstraZeneca said. And the vaccine was 80 percent effective in about 6,000 trial volunteers over age 65 — findings likely to quell concerns about insufficient clinical trial data on how well the vaccine works in older people.Even if the vaccine is not used in the United States, receiving emergency authorization from the F.D.A. — whose rigorous review process is considered the global gold standard — would be an important milestone for AstraZeneca.“The benefits of these results will mainly be for the rest of the world, where confidence in the AstraZeneca vaccine has been eroded,” said Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine.Although it is difficult to compare vaccines tested in different clinical trials at different points in the pandemic, the new results put AstraZeneca’s shot in the company of other leading vaccines.AstraZeneca’s vaccine can be stored for six months when refrigerated. Unlike the messenger RNA vaccines from Pfizer and Moderna, it uses an older approach similar to that of the shot from Johnson & Johnson. A delivery vehicle — a weakened version of a chimpanzee adenovirus — is used to transport coronavirus genes into human cells. That is meant to train the immune system to fight off attacks from the real coronavirus.A number of key data points that American regulators will need to scrutinize the vaccine were missing from the company’s news release.It was unclear, for example, how up to date the data are. If the analysis was conducted on data from a month or two ago, it is possible that a more current look would present a different picture of the vaccine’s effectiveness and safety. The company will provide the F.D.A. with a more comprehensive, recent set of data than what AstraZeneca disclosed on Monday.AstraZeneca’s relationship with U.S. authorities has been fraught since last year, when senior health officials believed the company was not forthright about the design of its clinical trials, its results and safety issues. That skepticism carried over to last week, when senior officials at a number of federal health agencies had grown even more suspicious.An analysis by the independent safety monitoring board helping to oversee the U.S. trial was delayed several times because the board had to ask for revised reports from those handling trial data on behalf of the company, according to a person familiar with the matter who was not authorized to discuss it publicly.It is often the case that such boards “can request new or clarifying analyses of data from the trial,” an AstraZeneca spokeswoman said. “This would enable them to ensure the robustness of their determinations.”Still, the holdup with the data again tested American officials’ trust in the company. Suspicion intensified so much last week that some government officials and vaccine experts were speculating about whether the company was sitting on its results or working to frame them in a more flattering light.In fact, the company did not yet have its results until this past weekend, Dr. Pangalos said.Sharon LaFraniere

According to federal officials, an independent panel of medical experts said the promising results announced by the company on Monday may have relied on “outdated information.”Federal health officials said early Tuesday that results from a U.S. trial of AstraZeneca’s Covid-19 vaccine may have relied on “outdated information” that “may have provided an incomplete view of the efficacy data,” casting doubt on an announcement on Monday that had been seen as good news for the British-Swedish company as well as the global vaccination drive.In a highly unusual statement released after midnight, the National Institute of Allergy and Infectious Diseases said that the data and safety monitoring board, an independent panel of medical experts under the National Institutes of Health that has been helping to oversee AstraZeneca’s U.S. trial, had notified government agencies and AstraZeneca late Monday that it was “concerned” by information the company had released that morning.The institute urged AstraZeneca to work with the monitoring board “to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.”AstraZeneca did not immediately return a request for comment early Tuesday.In a news release on Monday announcing the results of the U.S. trial, the company said that the vaccine it developed with the University of Oxford was 79 percent effective against Covid-19, higher than observed in previous trials, and completely prevented the worst outcomes from the disease. The long-anticipated results were seen as encouraging global confidence in the vaccine, which was shaken this month when more than a dozen countries, mostly in Europe, temporarily suspended the shot’s use over concerns about possible rare side effects.In recent days, the monitoring board’s analysis was delayed several times because the board had to ask for revised reports from those handling trial data on behalf of the company, according to a person familiar with the matter who was not authorized to discuss it publicly.Companies sponsoring drug or vaccine trials typically wait for the monitoring board to run analyses and conclude that the study has yielded an answer before they announce trial results. During the trial, an unblinded statistical analysis group that is walled off from the company acts as an intermediary to handle data requests and many other interactions with the monitoring board.Company executives are blinded to the results of the study until the monitoring board reports their study data back to them. The monitoring board ultimately conveyed the results of the study to AstraZeneca in a meeting over the weekend, leading to the company’s announcement Monday morning.An AstraZeneca spokeswoman, whom the company declined to name, said last week that it was “completely incorrect” that the trial data had formatting problems or had not been submitted to the monitoring board in a clean fashion.“As is often the case,” the spokeswoman said, monitoring boards “can request new or clarifying analyses of data from the trial. This would enable them to ensure the robustness of their determinations.”Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said it was “highly irregular” to see such a public display of friction between a monitoring board and a study sponsor, which are typically in close concordance.“I’ve never seen anything like this,” he said in an interview after the institute’s statement was released. “It’s so, so troubling.”AstraZeneca’s relationship with the U.S. authorities has been fraught since last year, when senior health officials believed the company was not being forthright about the design of its clinical trials, its results and safety issues. That skepticism carried over to last week, when senior officials at a number of federal health agencies grew suspicious about why AstraZeneca had not announced data from its U.S. study.That U.S. trial, which involved more than 32,000 participants, was the largest test of its kind for the shot. The results AstraZeneca released on Monday were from an interim look at the data after 141 Covid-19 cases had turned up among volunteers.The company did not disclose how up-to-date the data are. If the analysis was conducted on data from a month or two ago, it is possible that a more current look would present a different picture of the vaccine’s effectiveness and safety. The company has said it will provide the Food and Drug Administration with a more comprehensive, recent set of data than what it disclosed on Monday. Although no clinical trial is large enough to rule out extremely rare side effects, AstraZeneca reported that its study turned up no serious safety issues.The fresh data may have arrived too late to make much difference in the United States, where the vaccine is not yet authorized and is unlikely to become available before May. By then, federal officials predict, there will be enough vaccine doses for all of the nation’s adults from the three vaccines that have already been authorized: Pfizer-BioNTech, Moderna and Johnson & Johnson.Even so, the better-than-expected results were seen as a heartening turn for AstraZeneca’s shot, whose low cost and simple storage requirements have made it a vital piece of the drive to vaccinate the world.The results were also thought to ease concerns about the AstraZeneca vaccine in Europe. Regulators there said last week that the shot was “safe and effective,” having conducted a review after a small number of people who had recently been inoculated developed blood clots and abnormal bleeding. The U.S. trial did not turn up any sign of such problems, although some safety issues can only be detected in the real world, once a drug or vaccine has been widely used.Many millions of people have received the AstraZeneca shot worldwide, including more than 17 million in Britain and the European Union, almost all without serious side effects. In an effort to increase public confidence, many European political leaders have gotten the injections in recent days. The AstraZeneca vaccine has also been administered in the past week to leaders in South Korea, Taiwan and Thailand.AstraZeneca said on Monday that it would continue to analyze the new data and prepare to apply in the coming weeks for emergency authorization in the United States. The vaccine has already been approved in more than 70 countries, but clearance from American regulators would bolster its global reputation.The statement from the infectious disease institute comes after a series of miscues and communication blunders by AstraZeneca dating to last year that have eroded American officials’ trust in the company.Last summer, at least some top F.D.A. officials learned only from news reports that AstraZeneca had paused its Phase ⅔ vaccine trial in Britain after a participant developed neurological symptoms. Then in September, after another participant in the British study fell ill with similar symptoms, AstraZeneca halted its trials globally but failed to promptly notify the U.S. authorities.The U.S. study was ultimately paused for seven weeks last fall, in part because AstraZeneca was slow to provide the F.D.A. with evidence that the vaccine had not caused the neurological symptoms. Investigators ultimately concluded that the illnesses could not be linked to the vaccine. Still, the delay was a key reason that AstraZeneca fell so far behind the three other manufacturers whose vaccines have been granted emergency authorization in the United States.