As schools reopen, scientists say some children could spread COVID-19 even if they already have the antibodies


As schools and colleges reopen across the country, scientists say social distancing remains a critical public-health response to COVID-19. New research released Thursday sheds more light on children who test positive for COVID-19, and the contagiousness of coronavirus. Children often remain asymptomatic or display very few symptoms, and the research also offers insights into the course of the disease at an important time for families and communities.

A study published in the latest edition of the Journal of Pediatrics finds that the virus and antibodies can coexist in young patients. “With most viruses, when you start to detect antibodies, you won’t detect the virus anymore. But with COVID-19, we’re seeing both,” says Burak Bahar, lead author of the study and director of Laboratory Informatics at Children’s National Hospital in Washington, D.C. “This means children still have the potential to transmit the virus even if antibodies are detected.”


‘Children still have the potential to transmit the virus even if antibodies are detected.’


— Burak Bahar, director of Laboratory Informatics at Children’s National Hospital in Washington, D.C.

The researchers reviewed an analysis of 6,369 children tested for SARS-CoV-2, the virus that causes COVID-19, and 215 patients who underwent antibody testing at Children’s National between March 2020 and June 2020. Out of these 215 young patients, 33 tested positive for both the virus and antibodies during the course of the disease. Nine of those 33 also showed presence of antibodies in their blood while also later testing positive for the virus.

What’s more, researchers found that patients aged 6 years through 15 years old took a longer time (a median time of 32 days) to clear the virus, meaning that it had left their systems, versus patients aged 16 years through 22 years old (a median of 18 days). Females in the 6 to 15 age group also took longer to clear the virus than males: A median of 44 days for females versus 25.5 days for males. “We can’t let our guard down just because a child has antibodies or is no longer showing symptoms,” Bahar said.

The study also found that 25 days was the median time from viral positivity to negativity — the moment when the virus can no longer be detected; it took 18 days to go from viral positivity to seropositivity — or the presence of antibodies in the blood — and it took 36 days to reach adequate levels of neutralizing antibodies. These “neutralizing antibodies” are important in potentially protecting a person from reinfection of the same virus, the researchers wrote.

Four important caveats: Firstly, the study looked at a relatively small number of children. Secondly, the next phase of research will be to test whether coronavirus that is present along with the antibodies for the disease can be transmitted to other people. Thirdly, scientists need to explore whether antibodies correlate with immunity and, fourthly, they need to establish how long antibodies and potential protection from reinfection actually lasts. As such, Bahar reiterates the need for social distancing.

Related:Dr. Fauci: It’s ‘conceivable’ we’ll know by November if a safe, effective vaccine is coming

A separate study published this week in JAMA Pediatrics suggests that children can spread SARS-CoV-2, even if they never develop symptoms or even long after symptoms have cleared. It found a significant variation in how long children continued to “shed” the virus through their respiratory tract and, therefore, could potentially remain infectious. The researchers also found that the duration of COVID-19 symptoms also varied widely, from three days to nearly three weeks.

A recent systematic review estimated that 16% of children with a SARS-CoV-2 infection are asymptomatic, but evidence suggests that as many as 45% of pediatric infections are asymptomatic, according to the U. S. Centers for Disease Control and Prevention. The signs and symptoms of COVID-19 in children are similar to other infections and noninfectious processes, including influenza, according to the CDC.


A separate study in JAMA Pediatrics said children may spread SARS-CoV-2, even if they never develop symptoms or even long after symptoms have cleared.

Under pressure from the teachers union to delay the start of the school year, New York City Mayor Bill de Blasio announced Tuesday that in-person classes will be pushed back until Sept. 21, 11 days later than planned. Remote learning, also originally slated to start on Sept. 10, will now commence on Sept. 16. Other countries have not fared so well with school reopenings. Israel, which also reopened schools this week, experienced outbreaks when it reopened schools on May 17.

Bahar also advised teachers and students to wear masks. To reduce the risk of spreading COVID-19, it may be preferable to use high-quality cloth or surgical masks that are of a plain design instead of face shields and masks equipped with exhale valves, according to an experiment published Wednesday by Physics of Fluids, a monthly peer-reviewed scientific journal covering fluid dynamics that was first established by the American Institute of Physics in 1958.

As of Sunday, the U.S. still has the world’s highest number of COVID-19 cases (6,262,989), followed by Brazil (4,123,000), India (4,113,811) and Russia (1,022,228), according to data aggregated by Johns Hopkins University. California became the first state in the country to surpass 700,000 confirmed cases. COVID has killed 188,711 people in the U.S. Worldwide, cases are near 27 million.

AstraZeneca
AZN,
-1.07%

, in combination with Oxford University; BioNTech SE
BNTX,
-1.19%

and partner Pfizer
PFE,
-0.11%

; GlaxoSmithKline
GSK,
-1.38%

; Johnson & Johnson
JNJ,
-0.64%

; Merck & Co.
MERK,
-0.95%

; Moderna
MRNA,
-3.45%

; and Sanofi
SAN,
+5.09%

are among those currently working toward COVID-19 vaccines.

The Dow Jones Industrial Index
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-0.56%
,
the S&P 500
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-0.81%

and the Nasdaq Composite
COMP,
-1.26%

ended lower Friday. Doubts about traction for further fiscal stimulus from Washington may be one factor discouraging investors who have been betting on Republicans and Democrats striking a deal to offer additional relief to consumers and businesses.



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Johns Hopkins scientists examining weird side effects of COVID-19 suggest one way coronavirus ‘gains a foothold in the body’


It’s an odd side effect. But could it provide clues as to how coronavirus attacks the body?

Why do some people with COVID-19 lose their sense of smell? And what can be learned from that? Scientists studying tissue removed from patients’ noses during surgery believe they may have discovered the reason why so many people with COVID-19 lose their sense of smell, even when they have no other symptoms and, as a result, one way the virus enters the body.

In a study published in the European Respiratory Journal on Wednesday, the researchers found extremely high levels of “angiotensin converting enzyme II,” or ACE-2, only in the area of the nose responsible for smelling. The ACE-2 enzyme is thought to be the gateway that allows coronavirus to enter the cells of the body and cause an infection.


‘These results suggest that this area of the nose could be where the coronavirus is gaining entry to the body.’


— Dr. Mengfei Chen, a research associate at Johns Hopkins School of Medicine

Researchers at the Johns Hopkins University School of Medicine in Baltimore conducted the study, led by Professor Andrew Lane, director of the division of rhinology and skull base surgery, and Dr. Mengfei Chen, a research associate. They used fluorescent dyes on the tissue samples to detect and visualize the presence of ACE-2 in the nose cells.

The study used these samples from the back of the nose of 23 patients, removed during endoscopic surgical procedures for conditions such as tumors or “chronic rhinosinusitis,” an inflammatory disease of the nose and sinus. They also studied biopsies from the trachea (windpipe) of seven patients. None of the patients had been diagnosed with coronavirus.

“This technique allowed us to see that the levels of ACE-2 — the COVID-19 ‘entry point’ protein were highest in the part of the nose that enables us to smell,” Chen said. “These results suggest that this area of the nose could be where the coronavirus is gaining entry to the body.” They found the most ACE-2 on the lining cells of the “olfactory epithelium” at the back of the nose where we detect smells.

In fact, the levels of ACE-2 in these cells was between 200 and 700 times higher than other tissue in the nose and trachea, Chen said, and they found similarly high levels in all the samples of olfactory epithelium. The ACE-2 enzyme was not detected on olfactory neurons, the nerve cells that pass information about smells to the brain.

“The olfactory epithelium is quite an easy part of the body for a virus to reach, it’s not buried away deep in our body, and the very high levels of ACE-2 that we found there might explain why it’s so easy to catch COVID-19,” Chen said. Lane added that this research may enable doctors to tackle the infection with antiviral therapies delivered directly through the nose.

Related:COVID-19 and 1918 flu have one depressing thing in common: exacerbating social and economic inequality

Many common respiratory infections, such as coughs and colds, can make us temporarily lose our sense of smell, said Tobias Welte, professor of pulmonary medicine and director of the Department of Pulmonary and Infectious Diseases at Hannover University School of Medicine, Germany. Welte, who was not involved in this study, said this study may reveal why that happens in so many patients.

It could also be one reason why COVID-19 is so infectious and, he added, this theory could potentially offer more effective treatments. “It suggests that the part of our nose responsible for smelling could also be the place where the coronavirus gains a foothold in the body. This finding will need to be confirmed, but it offers possible new avenues for treating the infection.”


Another study found evidence of direct viral damage to the olfactory system in two patients who died from COVID-19.

A separate study released earlier this month and published in JAMA Otolaryngology — Head & Neck Surgery, a peer-reviewed journal, looked at the nasal cells of two patients who had died of SARS-CoV-2, the virus that causes the disease COVID-19, and found evidence of direct viral damage to the sensory system used for smelling in patients testing positive for SARS-CoV-2.

As of Sunday, COVID-19 has now killed at least 808,716 people worldwide. The U.S. has the world’s highest number of confirmed COVID-19 cases (5,703,561) and deaths (176,808). Worldwide, confirmed cases are now at 23,421,944, according to data aggregated by Johns Hopkins University, which does not, for the most part, account for asymptomatic cases.

Some younger COVID-19 patients who were otherwise healthy are suffering loss of taste and/or smell, blood clots and strokes. Many “long-haulers” — COVID-19 patients who show symptoms for months after the initial infection passed — report neurological problems including confusion, difficulty concentrating, headaches, extreme fatigue, mood changes and insomnia.

Coronavirus update:The Dow Jones Industrial Index
DJIA,
+0.68%
,
the S&P 500
SPX,
+0.34%

and the Nasdaq Composite
COMP,
+0.41%

ended lower Friday. This week, the Federal Reserve minutes urged Congress for more pandemic aid, underscoring the challenge to the country’s economic recovery as the world anxiously awaits a COVID-19 vaccine.

AstraZeneca
AZN,
-1.38%
,
in combination with Oxford University; BioNTech SE
BNTX,
+10.18%

and partner Pfizer
PFE,
+0.41%

; GlaxoSmithKline
GSK,
-0.93%

Johnson & Johnson
JNJ,
+0.88%

; Merck & Co.
MERK,
-1.24%

; Moderna
MRNA,
-2.00%

; and Sanofi
SAN,
-1.82%

are among those currently working toward COVID-19 vaccines.



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Scientists estimate the speed and distance of coronavirus transmission when people cough, sneeze, speak — and run


There’s a lot scientists know — and a lot they don’t.

In “Coughs and Sneezes: Their Role in Transmission of Respiratory Viral Infections, Including SARS-CoV-2,” released Tuesday, researchers describe the various types and sizes of virus-containing droplets present in sneezes and coughs, and how some medical procedures and devices may spread these droplets. “Coughs and sneezes create respiratory droplets of variable size that spread respiratory viral infections,” according to the article, which was published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.


‘While most respiratory droplets are filtered by the nose or deposit in the oropharynx, the smaller droplet nuclei become suspended in room air and individuals farther away from the patient may inhale them.’

“Because these droplets are forcefully expelled, they are dispersed in the environment and can be exhaled by a susceptible host. While most respiratory droplets are filtered by the nose or deposit in the oropharynx, the smaller droplet nuclei become suspended in room air and individuals farther away from the patient may inhale them,” said Rajiv Dhand, professor and chair of the Department of Medicine and associate dean of clinical affairs at University of Tennessee Graduate School of Medicine, and co-author of the paper.

Among the researchers’ recommendations: “Health care providers should stay six feet away from infected patients, especially when the patient is coughing or sneezing. For spontaneously breathing patients, placing a surgical mask on the patient’s face or using tissue to cover his or her mouth, especially during coughing, sneezing or talking, may reduce the dispersion distance or viral load. While ideally, infected patients should be in single rooms to prevent droplet dispersion, it is acceptable for two patients with the same infection that is spread by respiratory droplets to be in the same room.”

The contagiousness of speech droplets

“Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission,” a separate study published in the latest edition of the peer-reviewed Proceedings of the National Academy of Sciences, the official journal of the National Academy of Sciences, found. “Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second.”

In a closed, stagnant-air environment, droplets disappear from view after eight to 14 minutes, “which corresponds to droplet nuclei of ca. 4um diameter, or 12um to 21um droplets prior to dehydration,” the researchers wrote. One micrometer, um, is equivalent to one millionth of a meter. The coronavirus is 0.125 um. The scientists said that, while it’s long been recognized that respiratory viruses such as coronavirus can be transmitted via droplets generated by coughing or sneezing, it’s less widely known that normal speaking does too. High viral loads of SARS-CoV-2 have been detected in oral fluids of COVID-19−positive patients, including asymptomatic ones.

Related:5 critical mistakes that created the biggest public-health crisis in a generation

How far coronavirus droplets can travel

Social distancing has been defined for people that are standing still. “It does not take into account the potential aerodynamic effects introduced by person movement, such as walking fast, running and cycling,” researchers wrote in another study titled, “Towards aerodynamically equivalent COVID-19, 1.5 meters social distancing for walking and running.” Bert Blocken, a professor of civil engineering at Eindhoven University of Technology in the Netherlands and Katholieke Universiteit Leuven in Flanders, Belgium, and his co-authors recommend that people avoid walking or running in the slipstream of a walker or runner in the park and street.

“In the absence of head wind, tail wind and cross-wind, for walking fast at 4 kilometers per hour, this distance is about 5 meters (16 feet) and for running at 14.4 kilometers per hour, this distance is about 10 meters (32 feet),” the study, which has not been peer reviewed, found. The smaller the distance between the runners, the larger the fraction of droplets to which the trailing runner is exposed.” If people wish to run behind and/or overtake other walkers and runners with regard for social distance, “they can do so by moving outside the slipstream into staggered formation,” it added.

Letter from New York:‘When I hear an ambulance, I wonder if there’s a coronavirus patient inside. Are there more 911 calls, or do I notice every distant siren?’

Factors indoor contributing to contagion

Factors affecting whether the virus remains “stable” and contributing to transmission: Humidity and temperature of the room, air-conditioning, whether or not there are open windows, general air quality, size of the room and, of course, how many people are present and how close they are to each other. “In contrast to SARS-CoV-1, most secondary cases of the new SARS-CoV-2 transmission appear to be occurring in community settings rather than health-care settings,” a recent study published in the New England Journal of Medicine found.

The COVID-19 pandemic, which was first identified in Wuhan, China in December, had infected 9,154,232 people globally and 2,325,970 in the U.S. as of Tuesday. It had claimed at least 473,650 lives worldwide, 120,771 of which were in the U.S., according to Johns Hopkins University’s Center for Systems Science and Engineering. The Dow Jones Industrial Index
DJIA,
+0.95%

and the S&P 500
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+1.01%

were slightly higher Tuesday, as investors weighed progress in COVID-19 vaccine research amid fears of a surge of coronavirus in U.S. states that have loosened restrictions.

How COVID-19 is transmitted



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Scientists expect an acceleration of coronavirus cases as states reopen


The decision by states to end lockdowns on their populations will inevitably lead to a spread of the coronavirus and more deaths, experts said Sunday.

Christopher Murray, director of the University of Washington’s Institute for Health Metrics and Evaluation, said their model now forecasts 137,184 deaths. That’s up from 134,475 deaths projected on May 4.

Murray said the slight increase was due to cases and deaths going up more than expected in Illinois, Arizona, Florida and California. These increases were partially offset by better news from New Jersey and New York.

There is also an “explosive increase in mobility in a number of states that we expect will translate into more cases and deaths in 10 days from now,” Murray said on “Face the Nation” on CBS.

Jeffrey Shaman, chief science officer at Coriell Life Sciences, agreed there would be a “rebound” in cases as a result of the patchwork response from federal and state officials.

In an interview on NBC’s “Meet the Press,” Shaman said that, while it is difficult to be precise about the likely rise in cases, “one would imagine that with any loosening of restrictions there is only going to accelerate the growth of the virus.”

People who get infected today aren’t seen as confirmed cases for a couple weeks. So the growth of cases won’t be seen until the end of May, Shaman said.

“In a lot of the states in which they are loosening restrictions — they are barely hanging on. In some of them, they already have growth of the virus taking place,” he added.

Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, said 60%-70% of the public will ultimately be infected by the virus. At the moment, only 5%-15% of the population has been infected. “That is what we need a plan for,” he said.

“We are riding this tiger, we are not directing it,” Osterholm said. Governments can only nibble around the edges.

Osterholm said testing equipment across the country is already being run 24 hours a day and is starting to break down.

“The infrastructure is just not there,” he said. “We need a plan.”



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As pressure for coronavirus vaccine mounts, scientists debate risks of accelerated testing By Reuters


© Reuters. FILE PHOTO: U.S. NIH’s Fauci joins Pence for a news briefing on the administration response to the Coronavirus, at the White House in Washington

By Julie Steenhuysen

CHICAGO (Reuters) – Drugmakers are working as quickly as possible to develop a vaccine to combat the rapidly spreading coronavirus that has infected more than 100,000 people worldwide.

Behind the scenes, scientists and medical experts are concerned that rushing a vaccine could end up worsening the infection in some patients rather than preventing it.

Studies have suggested that coronavirus vaccines carry the risk of what is known as vaccine enhancement, where instead of protecting against infection, the vaccine can actually make the disease worse when a vaccinated person is infected with the virus. The mechanism that causes that risk is not fully understood and is one of the stumbling blocks that has prevented the successful development of a coronavirus vaccine.

Normally, researchers would take months to test for the possibility of vaccine enhancement in animals. Given the urgency to stem the spread of the new coronavirus, some drugmakers are moving straight into small-scale human tests, without waiting for the completion of such animal tests.

“I understand the importance of accelerating timelines for vaccines in general, but from everything I know, this is not the vaccine to be doing it with,” Dr Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, told Reuters.

Hotez worked on development of a vaccine for SARS (Severe Acute Respiratory Syndrome), the coronavirus behind a major 2003 outbreak, and found that some vaccinated animals developed more severe disease compared with unvaccinated animals when they were exposed to the virus.

“There is a risk of immune enhancement,” said Hotez. “The way you reduce that risk is first you show it does not occur in laboratory animals.”

Hotez testified last week before the U.S. House Committee on Science, Space and Technology about the need for sustained funding for vaccine research. There remains no vaccine for any of the new coronaviruses that have caused outbreaks in the past 20 years.

At least for now, the world’s experts have concluded that accelerated testing is a risk worth taking.

At a specially convened World Health Organization (WHO) meeting in mid-February, designed to co-ordinate a global response to the new coronavirus, scientists representing government-funded research organizations and drugmakers around the world agreed that the threat was so great that vaccine developers should move quickly into human trials, before animal testing is completed, four people who attended the meeting told Reuters.

“You want to have a vaccine as quickly as possible,” Dr Marie-Paule Kieny, former assistant director-general at the WHO, who co-chaired the meeting, told Reuters. “You have to balance this with the risk that you impose on a very small number of people, and do all you can do to mitigate this risk as much as possible.”

The conclusion of that meeting, which was not open to media, has not been officially publicized by the WHO. It does not reflect any official position adopted by the WHO, a United Nations body whose job it is to help shape global health policy.

Regulatory oversight of drugmakers and medical research is in the hands of national regulators. The most powerful of those, the U.S. Food and Drug Administration (FDA), has signaled that it is in agreement with the consensus and will not stand in the way of accelerated testing schedules.

“When responding to an urgent public health situation such as novel coronavirus, we intend to exercise regulatory flexibility and consider all data relevant to a certain vaccine platform,” FDA spokeswoman Stephanie Caccomo said in a statement. The agency had no comment specifically on animal testing for vaccine enhancement.

Coronavirus vaccine developers are still required to conduct routine animal testing to make sure the vaccine itself is not toxic and is likely to help the immune system respond to the virus.

SEATTLE RISK

Some 20 coronavirus vaccine candidates are being developed by research institutes and drugmakers including America’s Johnson & Johnson (NYSE:) and France’s Sanofi (PA:) SA. The U.S. government has earmarked more than $3 billion for coronavirus treatments and vaccines.

Biotechnology company Moderna Inc, which is working with the U.S.-funded National Institutes of Health (NIH), is the closest to human testing, announcing plans to start a trial with 45 people in Seattle this month.

Testing for the specific risk of vaccine enhancement in animals will proceed simultaneously with human trials, the NIH told Reuters, which it said should establish whether it is safe to expose larger numbers of people to the vaccine. Moderna did not respond to requests for comment.

The plan is consistent with the WHO consensus and FDA requirements, said Dr Emily Erbelding, director of the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. The trial is expected to take 14 months, a spokeswoman for the NIH said.

Dr Gregory Poland, a virologist and vaccine researcher with the Mayo Clinic in Rochester, Minnesota, expressed doubts about that approach. “This is important, but it has to be done in a way that reassures scientists and the public that these (vaccines) are not only efficacious, but safe,” he told Reuters.

Hotez said he was surprised human trials were going ahead. “If there is immune enhancement in laboratory animals vaccinated with the Moderna vaccine, that’s a showstopper,” he said.

U.S. immunotherapy company Inovio Pharmaceuticals Inc, which is developing a coronavirus vaccine in collaboration with a Chinese company, also expects to start human clinical trials in 30 U.S. volunteers in April rather than wait for animal studies on vaccine enhancement.

“The community as a whole weighed that and said we don’t want to delay the clinical process. We’ve been encouraged to go as rapidly as possible into Phase 1 studies,” Inovio Chief Executive Joseph Kim told Reuters.

The company plans to start human safety trials shortly thereafter in China and South Korea – two countries that have been hit hard by the virus. Kim said he expects to have an answer to the question of vaccine enhancement at some point this year.

The Moderna/NIH trial is enrolling patients at the Kaiser Permanente Washington Health Research Institute in Seattle. The choice of location, made several weeks ago, could prove to be problematic.

To reduce the risk to volunteers, scientists at the WHO meeting recommended that drugmakers restrict early clinical trials to small groups of healthy people and conduct them in places where the virus is not spreading, according to Kieny, who now works at French research institute Inserm. That lowers the chances that people who get the vaccine could encounter the virus and trigger a more severe reaction.

Since the location was chosen, the Seattle metro area has emerged as the epicenter of infections in the United States. Washington state has reported 162 coronavirus infections and 22 deaths, out of a total of 755 infections and 26 deaths in the country as of Tuesday, according to a tally by Johns Hopkins University.

Nevertheless, Moderna and the NIH plan to go ahead.

“We think there is no reason to have to change the site. If you change it, there might be community transmission in another site over the next couple of weeks,” Erbelding said. “Any risk of that to participants is very small. It would be manageable as the trial progresses. People are being observed very, very carefully.”

EARLY WARNING SIGNS

Tragic lessons from other vaccines and prior work on coronaviruses have raised some warning flags for developers.

The best-known example occurred in a U.S. trial in the 1960s of a vaccine created by the NIH and licensed to Pfizer Inc (NYSE:) to fight respiratory syncytial virus (RSV), which causes pneumonia in infants. The vast majority of babies who received the vaccine developed more severe disease, and two toddlers died. A more recent example occurred in the Philippines, where some 800,000 children were vaccinated with Sanofi’s dengue vaccine, Dengvaxia. Only afterward did the company learn that it could increase the risk of more severe disease in a small percentage of individuals.

Research, including that conducted by Hotez, has shown that coronaviruses in particular have the potential to produce this kind of response. But testing for the risk of vaccine enhancement is time-consuming because it requires scientists to breed mice that are genetically altered to respond to the virus like humans. Work on these and other animal models is just getting under way in several laboratories around the world.

Moderna, Inovio and several other vaccine developers are not waiting for that process to be completed and are planning to launch human trials in record time for a virus that was only discovered in December.

Both Moderna and Inovio say their vaccines are likely to have a lower risk of vaccine enhancement because they are made using newer technology that focuses on specific genes on the outer ‘spike’ portion of the virus. Coronavirus vaccines that caused vaccine enhancement were typically made using an inactivated version of the entire virus. Neither company has produced a licensed vaccine to date.

J&J said it is developing animal models to test for vaccine enhancement and hopes to have a vaccine candidate ready for human trials in October. A Sanofi spokeswoman said the company will examine this risk before testing the vaccine in clinical trials.

“People know how traumatic the RSV experience was,” said Dr Johan Van Hoof, global head of Janssen Vaccines, J&J’s vaccine unit. “When you see signals in animals like this, we should not ignore them.”





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