Posts Tagged ‘coronavirus’

Hospitals in New York City are gearing up to use the blood of people who have recovered from COVID-19 as a possible antidote for the disease. Researchers hope that the century-old approach of infusing patients with the antibody-laden blood of those who have survived an infection will help the metropolis — now the US epicentre of the outbreak — to avoid the fate of Italy, where intensive-care units (ICUs) are so crowded that doctors have turned away patients who need ventilators to breathe.

The efforts follow studies in China that attempted the measure with plasma — the fraction of blood that contains antibodies, but not red blood cells — from people who had recovered from COVID-19. But these studies have reported only preliminary results so far. The convalescent-plasma approach has also seen modest success during past severe acute respiratory syndrome (SARS) and Ebola outbreaks — but US researchers are hoping to increase the value of the treatment by selecting donor blood that is packed with antibodies and giving it to the patients who are most likely to benefit.

A key advantage to convalescent plasma is that it’s available immediately, whereas drugs and vaccines take months or years to develop. Infusing blood in this way seems to be relatively safe, provided that it is screened for viruses and other infectious agents. Scientists who have led the charge to use plasma want to deploy it now as a stopgap measure, to keep serious infections at bay and hospitals afloat as a tsunami of cases comes crashing their way.

“Every patient that we can keep out of the ICU is a huge logistical victory because there are traffic jams in hospitals,” says Michael Joyner, an anaesthesiologist and physiologist at the Mayo Clinic in Rochester, Minnesota. “We need to get this on board as soon as possible, and pray that a surge doesn’t overwhelm places like New York and the west coast.”

On 23 March, New York governor Andrew Cuomo announced the plan to use convalescent plasma to aid the response in the state, which has more than 25,000 infections, with 210 deaths. “We think it shows promise,” he said. Thanks to the researchers’ efforts, the US Food and Drug Administration (FDA) today announced that it will permit the emergency use of plasma for patients in need. As early as next week, at least two hospitals in New York City — Mount Sinai and Albert Einstein College of Medicine — hope to start using coronavirus-survivor plasma to treat people with the disease, Joyner says.

After this first rollout, researchers hope the use will be extended to people at a high risk of developing COVID-19, such as nurses and physicians. For them, it could prevent illness so that they can remain in the hospital workforce, which can’t afford depletion.

And academic hospitals across the United States are now planning to launch a placebo-controlled clinical trial to collect hard evidence on how well the treatment works. The world will be watching because, unlike drugs, blood from survivors is relatively cheap and available to any country hit hard by an outbreak.

Scientists assemble

Arturo Casadevall, an immunologist at Johns Hopkins University in Baltimore, Maryland, has been fighting to use blood as a COVID-19 treatment since late January, as the disease spread to other countries and no surefire therapy was in sight. Scientists refer to this measure as ‘passive antibody therapy’ because a person receives external antibodies, rather than generating an immune response themselves, as they would following a vaccination.

The approach dates back to the 1890s. One of the largest case studies occurred during the 1918 H1N1 influenza virus pandemic. More than 1,700 patients received blood serum from survivors, but it’s difficult to draw conclusions from studies that weren’t designed to meet current standards.

During the SARS outbreak in 2002–03, an 80-person trial of convalescent serum in Hong Kong found that people treated within 2 weeks of showing symptoms had a higher chance of being discharged from hospital than did those who weren’t treated. And survivor blood has been tested in at least two outbreaks of Ebola virus in Africa with some success. Infusions seemed to help most patients in a 1995 study in the Democratic Republic of the Congo, but the study was small and not placebo controlled. A 2015 trial in Guinea was inconclusive, but it didn’t screen plasma for high levels of antibodies. Casadevall suggests that the approach might have shown a higher efficacy had researchers enrolled only participants who were at an early stage of the deadly disease, and therefore were more likely to benefit from the treatment.

Casadevall corralled support for his idea through an editorial in the Wall Street Journal, published on 27 February, which urged the use of convalescent serum because drugs and vaccines take so long to develop. “I knew if I could get this into a newspaper, people would react, whereas if I put it into a science journal, I might not get the same reaction,” he says.

He sent his article to dozens of colleagues from different disciplines, and many joined his pursuit with enthusiasm. Joyner was one. Around 100 researchers at various institutes self-organized into different lanes. Virologists set about finding tests that could assess whether a person’s blood contains coronavirus antibodies. Clinical-trial specialists thought about how to identify and enroll candidates for treatment. Statisticians created data repositories. And, to win regulatory clearance, the group shared documents required for institutional ethical-review boards and the FDA.

Tantalizing signs

Their efforts paid off. The FDA’s classification today of convalescent plasma as an ‘investigational new drug’ against coronavirus allows scientists to submit proposals to test it in clinical trials, and lets doctors use it compassionately to treat patients with serious or life-threatening COVID-19 infections, even though it is not yet approved.

“This allows us to get started,” says Joyner. Physicians can now decide whether to offer the therapy to people with very advanced disease, or to those that seem to be headed there — as he and other researchers recommend. He says hospitals will file case reports so that the FDA gets a handle on which approaches work best.

Researchers have also submitted to the FDA three protocols for placebo-controlled trials to test the plasma, which they hope will take place at hospitals affiliated with Johns Hopkins, the Mayo Clinic and Washington University in St. Louis, along with other universities that want to take part.

Future directions

The US tests of convalescent plasma aren’t the first. Since early February, researchers in China — where the coronavirus emerged late last year — have launched several studies using the plasma. Researchers have yet to report on the status and results of these studies. But Liang Yu, an infectious-disease specialist at Zhejiang University School of Medicine in China, told Nature that in one preliminary study, doctors treated 13 people who were critically ill with COVID-19 with convalescent plasma. Within several days, he says the virus no longer seemed to be circulating in the patients, indicating that antibodies had fought it off. But he says that their conditions continued to deteriorate, suggesting that the disease might have been too far along for this therapy to be effective. Most had been sick for more than two weeks.

In one of three proposed US trials, Liise-anne Pirofski, an infectious-disease specialist at Albert Einstein College of Medicine, says researchers plan to infuse patients at an early stage of the disease and see how often they advance to critical care. Another trial would enrol severe cases. The third would explore plasma’s use as a preventative measure for people in close contact with those confirmed to have COVID-19, and would evaluate how often such people fall ill after an infusion compared with others who were similarly exposed but not treated. These outcomes are measurable within a month, she says. “Efficacy data could be obtained very, very quickly.”

Even if it works well enough, convalescent serum might be replaced by modern therapies later this year. Research groups and biotechnology companies are currently identifying antibodies against the coronavirus, with plans to develop these into precise pharmaceutical formulas. “The biotech cavalry will come on board with isolating antibodies, testing them, and developing into drugs and vaccines, but that takes time,” says Joyner.

In some ways, Pirofski is reminded of the urgency she felt as a young doctor at the start of the HIV epidemic in the early 1980s. “I met with medical residents last week, and they are so frightened of this disease, and they don’t have enough protective equipment, and they are getting sick or are worried about getting sick,” she says. A tool to help to protect them now would be welcomed.

Since becoming involved with the push for blood as a treatment, Pirofski says another aspect of the therapy holds her interest: unlike a pharmaceutical product bought from companies, this treatment is created by people who have been infected. “I get several e-mails a day from people who say, ‘I survived and now I want to help other people’,” she says. “All of these people are willing to put on their boots and brush their teeth, and come help us do this.”

Viruses like the novel coronavirus are shells holding genetic material

As the novel coronavirus causing COVID-19 spreads across the globe, with cases surpassing 284,000 worldwide today (March 20), misinformation is spreading almost as fast.

One persistent myth is that this virus, called SARS-CoV-2, was made by scientists and escaped from a lab in Wuhan, China, where the outbreak began.

A new analysis of SARS-CoV-2 may finally put that latter idea to bed. A group of researchers compared the genome of this novel coronavirus with the seven other coronaviruses known to infect humans: SARS, MERS and SARS-CoV-2, which can cause severe disease; along with HKU1, NL63, OC43 and 229E, which typically cause just mild symptoms, the researchers wrote March 17 in the journal Nature Medicine.

“Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” they write in the journal article.

Kristian Andersen, an associate professor of immunology and microbiology at Scripps Research, and his colleagues looked at the genetic template for the spike proteins that protrude from the surface of the virus. The coronavirus uses these spikes to grab the outer walls of its host’s cells and then enter those cells. They specifically looked at the gene sequences responsible for two key features of these spike proteins: the grabber, called the receptor-binding domain, that hooks onto host cells; and the so-called cleavage site that allows the virus to open and enter those cells.

That analysis showed that the “hook” part of the spike had evolved to target a receptor on the outside of human cells called ACE2, which is involved in blood pressure regulation. It is so effective at attaching to human cells that the researchers said the spike proteins were the result of natural selection and not genetic engineering.

Here’s why: SARS-CoV-2 is very closely related to the virus that causes severe acute respiratory syndrome (SARS), which fanned across the globe nearly 20 years ago. Scientists have studied how SARS-CoV differs from SARS-CoV-2 — with several key letter changes in the genetic code. Yet in computer simulations, the mutations in SARS-CoV-2 don’t seem to work very well at helping the virus bind to human cells. If scientists had deliberately engineered this virus, they wouldn’t have chosen mutations that computer models suggest won’t work. But it turns out, nature is smarter than scientists, and the novel coronavirus found a way to mutate that was better — and completely different— from anything scientists could have created, the study found.

Another nail in the “escaped from evil lab” theory? The overall molecular structure of this virus is distinct from the known coronaviruses and instead most closely resembles viruses found in bats and pangolins that had been little studied and never known to cause humans any harm.

“If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness,” according to a statement from Scripps.

Where did the virus come from? The research group came up with two possible scenarios for the origin of SARS-CoV-2 in humans. One scenario follows the origin stories for a few other recent coronaviruses that have wreaked havoc in human populations. In that scenario, we contracted the virus directly from an animal — civets in the case of SARS and camels in the case of Middle East respiratory syndrome (MERS). In the case of SARS-CoV-2, the researchers suggest that animal was a bat, which transmitted the virus to another intermediate animal (possibly a pangolin, some scientists have said) that brought the virus to humans.

In that possible scenario, the genetic features that make the new coronavirus so effective at infecting human cells (its pathogenic powers) would have been in place before hopping to humans.

In the other scenario, those pathogenic features would have evolved only after the virus jumped from its animal host to humans. Some coronaviruses that originated in pangolins have a “hook structure” (that receptor binding domain) similar to that of SARS-CoV-2. In that way, a pangolin either directly or indirectly passed its virus onto a human host. Then, once inside a human host, the virus could have evolved to have its other stealth feature — the cleavage site that lets it easily break into human cells. Once it developed that capacity, the researchers said, the coronavirus would be even more capable of spreading between people.

All of this technical detail could help scientists forecast the future of this pandemic. If the virus did enter human cells in a pathogenic form, that raises the probability of future outbreaks. The virus could still be circulating in the animal population and might again jump to humans, ready to cause an outbreak. But the chances of such future outbreaks are lower if the virus must first enter the human population and then evolve the pathogenic properties, the researchers said.

By Anette Breindl

The first attempt at using existing drugs to treat patients infected with SARS-CoV-2 has yielded disappointing results.

In 200 hospitalized patients with severe COVID-19, a 14-day regimen of twice-daily treatment with Kaletra/Aluvia (lopinavir/ritonavir, Abbvie Inc.) did not hasten recovery when added to the standard of care. Chinese clinicians led by Bin Cao of the National Clinical Research Center for Respiratory Diseases reported their findings in the March 19, 2020, issue of The New England Journal of Medicine.

Lopinavir is a protease inhibitor, while ritonavir increases the half-life of lopinavir by inhibiting its metabolism. The drug was tested because screening studies had flagged it as having activity against MERS-CoV, which has led to a clinical trial of a combination of Kaletra/Aluvia and interferon-beta for the treatment of MERS-CoV in the Kingdom of Saudi Arabia.

In the COVID-19 trial, 199 patients were treated, split evenly between drug and standard-of-care groups. The study’s primary endpoint, time to improvement, was the same between the two groups, both of which took 16 days to improve. Mortality and viral load at various time points were also not different.

In an editorial published alongside the paper, Lindsey Baden, of Harvard Medical School, and Eric Rubin, of the Harvard TH Chan School of Public Health, wrote that “the results for certain secondary endpoints are intriguing,” but also acknowledged that those results were hard to interpret, due to a mix of trial size, possible differences in illness severity at baseline, and the fact that the trial was randomized but not blinded.

And if certain endpoints were intriguing, others were discouraging. In particular, viral loads did not differ between the groups, tellingly so, according to Baden and Rubin. “Since the drug is supposed to act as a direct inhibitor of viral replication, the inability to suppress the viral load and the persistent detection of viral nucleic acid strongly suggest that it did not have the activity desired,” they wrote. “Thus, although some effect of the drug is possible, it was not easily observed.”

It is possible that larger trials will yet uncover an effect of Kaletra/Aluvia. But for now, perhaps the best hope is that other drugs will work better – in particular, remdesivir (Gilead Sciences Inc.), which was originally developed for Ebola virus disease, but proved less effective there than several other options.

A paper in the Jan. 10, 2020, issue of Nature Communications investigated the effects of Aluvia on MERS-CoV in mouse experiments, where it showed ho-hum effects. The authors of the Nature Communications paper reported that “prophylactic [Kaletra/Aluvia plus interferon-beta] slightly reduces viral loads without impacting other disease parameters.”

But remdesivir was more effective. “Both prophylactic and therapeutic [remdesivir] improve pulmonary function and reduce lung viral loads and severe lung pathology” in a mouse model of MERS, the authors reported.

Remdesivir is in both an NIH-sponsored clinical trial and a Japanese-Chinese trial as potential COVID-19 treatment, after a January case report of a patient who showed rapid improvement after he was treated with the drug for COVID-19.

Though the Kaletra/Aluvia trial’s results were not as hoped, Baden and Rubin noted that the trial itself was an encouraging bit of news, as well as a “heroic effort…. As we saw during the 2014 Ebola outbreak in West Africa, obtaining high-quality clinical trial data to guide the care of patients is extremely difficult in the face of an epidemic, and the feasibility of a randomized design has been called into question. Yet Cao’s group of determined investigators not only succeeded but ended up enrolling a larger number of patients (199) than originally targeted.”

A woman falsely claimed she had coronavirus at a security checkpoint at Cleveland Hopkins International Airport, shutting down the checkpoint for 20 minutes, officials said.

By Adam Ferrise

A Los Angeles woman caused the temporary closure of a security checkpoint at Cleveland Hopkins Airport Sunday after she told a TSA agent that she contracted the coronavirus.

The woman licked her fingers as she handed her driver’s license to the agent, Cleveland police and the TSA said.

The 63-year-old woman was not arrested and criminal charges were not filed as of Monday afternoon. Police reports say the woman could face a charge of inducing panic.

The incident caused the checkpoint to close for 20 minutes for the area to be cleaned, according to police and a TSA spokeswoman. The TSA spokeswoman said the agency plans to pursue a civil citation against the woman, which could result in a fine.

The incident happened as coronavirus continues to spread in Ohio and Cuyahoga County. Of the 50 confirmed coronavirus cases in Ohio so far, 24 are in Cuyahoga County.

Airport spokeswoman Michele Dynia referred questions about airport operations to Cleveland’s Joint Information Center. A woman answering the phone there said she could not immediately answer any questions about the woman’s encounter with the agent.

The incident happened about 5:20 p.m. Sunday. The woman walked up to the TSA checkpoint, licked her fingers just before handing her driver’s license to a TSA agent, and said: “Good thing you are wearing gloves because I just licked my fingers and I have coronavirus,” according to police reports.

TSA agents called for the Cleveland fire and medics posted at the airport to respond. The woman denied telling the TSA agent she had coronavirus, but said she did lick her fingers and told the agent she was glad he was wearing gloves, police reports say. She told officers she had no health issues and did not have coronavirus.

An airline banned her from flying on Sunday, according to the TSA. TSA agents prohibited the woman from entering the airport for 24 hours, according to the police report.

Infected children may harbor SARS-CoV-2 while showing less-severe symptoms than adults. Their young immune systems, ACE2 receptor levels, and even exposure to other coronaviruses might play a role in their resilience.

by Anthony King

Since SARS-CoV-2, the virus responsible for the COVID-19 pandemic, was first recognized as a close cousin of the virus that caused the SARS outbreak of 2003, scientists have looked to the experience of that earlier epidemic to glean insight into the current global health crisis.

Kids were largely unaffected in the original SARS outbreak. In Hong Kong, no one under the age of 24 years died, while more than 50 percent of patients over 65 succumbed to the infection. Globally, less than 10 percent of those diagnosed with SARS were children, and only 5 percent of them required intensive care.

“There were repeated incursions from animals to humans, with both SARS and MERS, and the assumption by many was maybe children are just not exposed to the infected civet cats or camels,” says virologist Kanta Subbarao of the Doherty Institute in Melbourne, Australia.

A very similar pattern has been observed with the new outbreak of COVID-19. Within Wuhan, no children tested positive between November 2019 and the second week of January, and the elderly proved particularly vulnerable. The Chinese Centers for Disease Control and Prevention reported in mid-February that out of 44,672 confirmed cases of COVID-19, 86.6 percent were between 30 and 79 years of age. The oldest among them were at greatest risk of death. And in a study of 1,099 patients in China, just 0.9 percent of confirmed cases were under the age of nine, while only 1.2 percent were between 10 and 19 years old.

Now, evidence is emerging that while few children suffer severely from COVID-19, they do get infected. A recent study even found evidence of viral excretion in children from rectal swabs. “At the moment it doesn’t seem to be causing much in the way of serious disease in young people, particularly children,” says virologist Robin Shattock of Imperial College London. However, he adds, “it is quite likely that children are an important source of the virus.”

“There is good evidence that children get infected and have a fairly high titre of virus but just don’t have serious disease,” agrees Ralph Baric, a coronavirus researcher at the University of North Carolina at Chapel Hill. He saw a similar phenomenon in his mouse studies with the original SARS coronavirus (SARS-CoV). Although SARS-CoV can replicate fairly well, “younger animals are really resistant to infection in terms of the disease,” he says. When Baric tested older animals, he says, the severity of SARS illnesses rose. In one experiment, one-fifth of mice infected with SARS aged 3–4 weeks died, whereas all of the mice 7–8 weeks old died.

Subbarao has also found that young adult mice, at six weeks old, can clear SARS-CoV with no significant clinical symptoms. “When we used the same virus in 12-month-old mice, which is by no means really old, there were more clinical signs,” she says. These results indicate that both the original SARS-CoV and the one circulating now may infect children, but not make them ill. “The animal data supports the idea that they are infected but do not develop disease, because our young mice have the same levels of virus as old mice but do not get sick,” says Stanley Perlman, an immunologist at the University of Iowa. “It is not a question of infection.”

The work on mice is now being supported by emerging epidemiological data. A preprint posted to medRxiv on March 4 analyzed 391 COVID-19 cases and 1,286 of their close contacts. The authors concluded that children are at a similar risk of infection as the general population, though less likely to have severe symptoms.

An aging immune system

One explanation for the correlation between age and disease severity is that as humans’ immune systems age, more cells become inactive. “As you age, your immune system undergoes senescence and loses its capacity to respond as effectively or be regulated as effectively,” says Baric.

Another explanation, which Perlman favors, is tied to the aging lung environment. In order for individuals not to easily develop asthma or overreact to environmental irritants such as pollen or pollution, aged lungs counter the usual immune reaction with some tamping down of inflammation. As a result, says Perlman, the lungs do not respond quickly enough to a viral infection. For instance, when his group makes the lungs of older mice more like those of young mice by altering prostaglandins, compounds that respond to tissue injury, “then the mice do well and they can clear the [SARS] infection and don’t get sick,” says Perlman.

In experiments reported in 2010, Perlman and his colleagues showed that T cells are especially important in clearing viruses from mice infected with SARS-CoV. “It is almost certain we need both an antibody- and T cell–response to do well” against COVID-19 infection, says Perlman. His suspicion is that the young immune system and its efficient T cells do a superior job of responding to SARS-CoV-2. A 2010 study led by Subbarao also stressed the importance of CD4+ helper T cells, which stimulate B cells to make antibodies against pathogens, in controlling SARS-CoV infection in mice.

“It could be that the type of T cell that dominates early in life is better at repelling this virus,” says immunologist Kingston Mills of Trinity College Dublin. He also proposes that young children’s higher production of a type of T cell called Th2 might guard against runaway inflammatory responses to SARS-CoV-2. Perlman doesn’t support the proposed role of a bias toward Th2 cells in the case of this viral infection, but he does agree that an immune overreaction is problematic.

“The innate response is delayed in the elderly, so ends up playing catch-up and is exuberant,” Perlman writes in an email to The Scientist.

ACE2 receptor

SARS-CoV and SARS-CoV-2 both use the same keyhole to enter cells, the ACE2 receptor. There’s an abundance of this receptor in cells in the lower lung, which may explain the high incidence of pneumonia and bronchitis in those with severe COVID-19 infection. A recent study showed that ACE2 is also highly expressed in the mouth and tongue, granting the virus easy access to a new host. ACE2 receptor abundance goes down in the elderly in all these tissues, but, counterintuitively, this might place them at a greater risk of severe illness.

This is because the ACE2 enzyme is an important regulator of the immune response, especially inflammation. It protects mice against acute lung injury triggered by sepsis. And a 2014 study found that the ACE2 enzyme offers protection against lethal avian influenza. Some patients with better outcomes had higher levels of the protein in their sera, and turning off the gene for ACE2 led to severe lung damage in mice infected with H5N1, while treating mice with human ACE2 dampened lung injury.

A fall in ACE2 activity in the elderly is partly to blame for humans’ poorer ability to put the brakes on our inflammatory response as we age, according to emailed comments from Hongpeng Jia of Johns Hopkins Medicine. Reduced abundance of ACE2 receptors in older adults could leave them less able to cope with SARS-CoV-2, says Baric, though the hypothesis still needs more research.

Exposure to other coronaviruses

There are four other coronaviruses that infect humans, with symptoms typical of a common cold. These viruses are common in children. “We don’t know which of them, if any, might provide some cross immunity,” says Subbarao. It could be that immunity to viral proteins, obtained from circulating “common cold” viruses, moderates the course of COVID-19.

This is a “hand-waving hypothesis,” Subbarao adds, but one that is worth testing. Recently, it has been suggested that plasma from people who’ve recovered from COVID-19 could be transfused into patients infected with SARS-CoV-2 to treat them.

“I don’t think anyone in the field knows why the disease is less robust in extremely young animals or humans,” Baric tells The Scientist. It is also still too early to know how much learned from the first SARS coronavirus applies to SARS-CoV-2. “SARS-CoV-1 will tell us a lot, but I think there is new information we are going to learn about SARS-CoV-2,” Perlman acknowledges.

Dive Brief:

Rheumatoid arthritis drug Kevzara will be used in an international study of patients infected with the new coronavirus and suffering from acute respiratory distress syndrome, Regeneron Pharmaceuticals and Sanofi announced Monday.

The trial will kick off in disease hotspot New York City, expanding to a total of 16 U.S. sites and enrolling 400 patients. The companies aim to study whether Kevzara can reduce fever and the need for supplemental oxygen in patients severely affected by COVID-19, the illness caused by the virus.

Roche’s Actemra, which has a similar mechanism of action, has been tested in Chinese patients and led to a decrease in fever and oxygen use, prompting the country to include it in treatment guidelines. The drug’s use shows the speed with which global public health officials are willing to consider using drugs off-label in order to address the coronavirus pandemic.

Dive Insight:

A vaccine to prevent infections of the novel coronavirus SARS-CoV-2 is likely a year or more away — at best — and treatments specifically designed to fight this virus or its complications are similarly far off.

Possible treatments, however, could already be available in the form of marketed or existing experimental drugs. Global public health officials, eager for a weapon to use in the midst of a global pandemic, are showing a willingness to be flexible in terms of the clinical trials and the evidence needed to prove treatments’ effectiveness.

Earlier this month, China OK’d the use of Actemra in patients with lung complications and high levels of interleukin-6, or IL-6, a protein that mediates inflammatory and immune response. High levels of IL-6 have been associated with a greater risk of death in patients with community-acquired pneumonia.

Actemra and Kevzara both block IL-6 and are prescribed for rheumatoid arthritis, a disorder in which an overactive immune system creates joint-damaging inflammation and pain. Actemra is similarly approved in conjunction with cancer cell therapy, which can sometimes trigger an immune reaction known as cytokine release syndrome.

The U.S.-based Kevzara trial is a two-part design that will initially evaluate fever and oxygen use in patients with acute respiratory distress syndrome, or ARDS. Two different dose levels will be used and compared to a placebo.

Longer-term, the trial hopes to measure prevention of death, use of ventilation, supplemental oxygen or hospitalization, but the design will be “adaptive” to determine the number of patients that will be followed and the endpoints to be used. ARDS often causes permanent lung damage and can lead to early death.

The trial aims to enroll 400 patients in the U.S. Regeneron’s partner Sanofi will handle international trial sites, naming Italy as one likely location for testing in coronavirus patients.

To get the trial underway quickly, Regeneron and Sanofi worked closely with the Food and Drug Administration and the Biomedical Advanced Research and Development Authority, the division of HHS involved in preparing for natural and man-made biological threats.

By David Ho and Cornelia Zou

HONG KONG – As drug developers are racing to find a cure for the new coronavirus, researchers in Hong Kong claim to have made major headway in the development of a vaccine for the virus that has so far killed 132.

Yuen Kwok-yung, the chair of infectious diseases at the University of Hong Kong’s (HKU) department of microbiology, said in a press briefing at Hong Kong’s Queen Mary Hospital that his team had successfully isolated the novel virus from the first imported case in Hong Kong.

But he said the vaccine still needs months to be tested on animals and an additional year for human trials before it is fit for use.

The vaccine is based on a nasal spray influence vaccine invented by Yuen, a severe acute respiratory syndrome (SARS) expert, and his team.
The race to find a cure is on.

“It will normally take 15 to 18 months to go from obtaining the DNA of a virus to getting an IND for neutralizing antibodies,” Chris Chen, CEO of Wuxi Biologics Cayman Inc. (HK: 2269), told BioWorld. “Because of the possibilities of unexpected mutations, we cannot afford to follow the normal procedures, so we decided to compress the process to four or five months, while complying to all the international standards.”

The company said on Jan. 29 that it has stepped up its efforts in enabling the development of multiple neutralizing antibodies for the novel coronavirus.

Having respectively completed all preclinical CMC for the world’s first yellow fever antibody and the worlds’ first Zika virus antibody in a record timeline of seven and nine months previously, the company is aiming at a five-month mark for the development of new antibodies for the 2019 coronavirus.

“We obtained the virus DNA this week, we will produce the first batch of sample antibodies in the next few weeks, then we’ll ask authorized institutes to test the efficacy of our antibodies before communicating with the National Medical Products Administration and the Chinese Academy of Inspection and Quarantine regarding moving the antibodies forward into clinical study,” said Chen. “And in March, hopefully we’ll be able to start the mass production for human use.”

HKU’s Yuen told media that the coronavirus in SARS and Middle East Respiratory Syndrome (MERS) are in the same family of virus as the new strain.

Consequently, previous drugs used to battle those indications, such as the protease inhibitor Kaletra [lopinavir/ritonavir for HIV-1] and interferon beta, may be tested to see if they are effective treatments.

He added that they would investigate whether the antiviral ribavirin may also be added to those two candidates to improve them.

“We hope we can tell everyone if the drugs are effective in the laboratory after several weeks,” he said.

Yuen recently warned that the virus is entering its third wave of transmission, which would be human-to-human.

The first wave of transmission is believed to be from animal-to-human while the second wave spread from a seafood market in Wuhan to neighboring areas.

“Unlike the 2003 SARS outbreak, the improved surveillance network and laboratory capability of China was able to recognize this outbreak within a few weeks and announced the virus genome sequences that would allow the development of rapid diagnostic tests and efficient epidemiological control,” wrote Yuen and team in a recently published article in The Lancet.

“Our study showed that person-to-person transmission in family homes or hospitals, and intercity spread of this novel coronavirus are possible, and therefore vigilant control measures are warranted at this early stage of the epidemic.”

Global development work underway

Yuen’s HKU team is not the only one in the rush to develop a coronavirus vaccine.

The University of Queensland (UQ) in Australia is also aiming to develop one at an unprecedented speed.

“The team hopes to develop a vaccine over the next six months, which may be used to help contain this outbreak,” said Paul Young, the head of UQ’s school of chemistry and molecular biosciences, in a statement.

“The vaccine would be distributed to first responders, helping to contain the virus from spreading around the world.”

The speedy development is credited to a novel ‘molecular clamp’ technology invented by UQ researchers.

“The University of Queensland’s molecular clamp technology provides stability to the viral protein that is the primary target for our immune defense,” said Keith Chappell, a senior research fellow at UQ’s school of chemistry and molecular biosciences, in a statement.

“The technology has been designed as a platform approach to generate vaccines against a range of human and animal viruses and has shown promising results in the laboratory targeting viruses such as influenza, Ebola, Nipah and MERS coronavirus.”

Oslo, Norway based-public private coalition The Coalition for Epidemic Preparedness Innovations (CEPI) is supporting UQ’s development efforts. It is also working with biotech firms like Inovio Pharmaceuticals, Inc. and Moderna, Inc. on vaccines.

Rockville, Maryland-based Novavax Inc. is also working on one.

Others like Salt Lake City-based Co-Diagnostics Inc. claims to have finished the principle design work for a diagnostic.

Some expect that the health care system in China will bear the economic brunt of the virus.

“There is a risk that China’s health care system will not have sufficient resources to control the outbreak, which would mean that economic disruption could spiral further. Health care costs will also increase,” Imogen Page-Jarrett, a research analyst for the Access China division of the Economist Intelligence Unit, told BioWorld.

“The government added drugs used to treat the virus to the drug reimbursement list on January 21st, although patients will still face some out-of-pocket costs. Consumers may be forced to cut their spending, especially on non-essential items, in order to afford treatment or to save money as part of contingency planning,” she added.

Despite the dire situation, there is a silver lining for the pharmaceutical industry: “More positively, pharmaceutical companies will see strengthened demand for vaccines and antibiotics,” said Page-Jarrett.