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How blood plasma from recovered patients could help treat the new coronavirus
By Matthew Herper @matthewherper and Adam Feuerstein @adamfeuerstein
March 5, 2020
Adobe
When it comes to creating treatments for Covid-19, the disease caused by the novel coronavirus, the first line of defense may be a century-old technology: purified blood plasma.
Medical literature published during the Spanish flu pandemic of 1918 includes case reports describing how transfusions of blood products obtained from survivors may have contributed to a 50% reduction in death among severely ill patients. In 1934, a measles outbreak at a Pennsylvania boarding school was halted when serum harvested from the first infected student was used to treat 62 fellow students. Only three of the 62 students developed measles — all mild cases.
More recently, plasma-derived therapy was used to treat patients during outbreaks of Ebola and avian flu. And on Wednesday the Japanese drugmaker Takeda Pharmaceutical Co. said it was developing a new coronavirus drug derived from the blood plasma of people who have recovered from Covid-19. Its approach is based on the idea that antibodies developed by recovered patients might strengthen the immune system of new patients.
Here’s what you need to know about how this old technology might help slow the coronavirus outbreak.
How is blood plasma turned into an infection-fighting drug?
Patients who have recovered from a disease have permanent antibodies generated by the immune system floating in their blood plasma, the liquid component of blood. To turn that into a drug, the plasma is harvested, tested for safety, and purified to isolate those protective antibodies. When injected into a new patient, the “plasma-derived therapy” — also known as convalescent plasma — provides “passive immunity” until the patient’s immune system can generate its own antibodies.
Mike Ryan, the head of the WHO’s emergencies program, has said convalescent plasma is a “very important area to pursue” as a potential treatment for patients with Covid-19. “It must be given at the right time because it mops up the virus in the system and it just gives the new patient’s immune system a vital push at the time it needs it — but it has to be carefully time and it’s not always successful.”
Is this approach already being used in this outbreak?
In February, doctors in Shanghai set up a special clinical to administer convalescent plasma to select patients who were newly infected with coronavirus.
“In China, we’ve only heard anecdotal reports of encouraging results. Nothing has been published yet,” said Greg Poland, a physician and infectious disease expert at the Mayo Clinic in Rochester, Minn. “But this approach is definitely worth trying.”
How is what Takeda is doing different?
Takeda already makes a medicine called intravenous immunoglobin, or IVIG, for treating patients who have immune disorders. It consists of antibodies of all types purified from the blood plasma of healthy people. Giving antibodies in this purified form is easier, because it requires a much lower volume of treatment; it’s safer, because there is no chance of transmitting other viruses; and it’s more efficient.
With its new treatment, TAK-888, Takeda hopes to create an IVIG from the blood of people who have been infected with the coronavirus and who have recovered. That could create a treatment or prophylactic relatively quickly. It might not need to go through phase I studies to demonstrate basic safety, or larger phase III studies to demonstrate efficacy. That means the treatment could be available sooner.
The other advantage of this approach is that researchers don’t need to figure out which antibodies work best at fighting off the novel coronavirus. They basically import the entire disease-fighting army of antibodies from patients whose bodies have already won. The antibodies in TAK-888 will be more narrowly selected to target coronavirus than those in garden variety IVIG.
How much of this new drug can Takeda make?
“We are not looking at this as a therapy that everyone should go on,” Julie Kim, the president of Takeda’s blood plasma unit, told STAT. “This will be targeted to patients who have severe disease.”
Kim said the hope is that a single donor might provide enough IVIG for a single patient. But it’s also possible that IVIG derived from several people would be needed to treat each patient. Takeda won’t know until it has taken steps to learn how many antibodies are present in patients who have recovered, and what dose of TAK-888 appears necessary to be effective. Those measures, Takeda said, could be discovered without large-scale trials.
Kim said that she could not comment on precise timelines until Takeda has had discussions with regulators like the Food and Drug Administration.
Are there others working with antibody treatments?
Yes. Among them is Regeneron, which is working on a mix of manufactured antibodies to attack the coronavirus. Vir Biotechnology, another biotech firm, has said it will have a similar approach.
The IVIG approach Takeda is using is known as “polyclonal antibodies,” which means, simply, that there are a lot of different types of antibodies in the mix. But many biotech drugs are what are known as monoclonal antibodies, single antibodies that can be originally generated in mice and then manufactured in huge tanks of cells.
One reason to be optimistic is that Regeneron has pulled it off before, manufacturing a treatment composed of three different monoclonal antibodies that appears to have some effectiveness against the Ebola virus.
Geoffrey Porges, an analyst at the investment bank SVB Leerink, said in an interview he was “very impressed” with the speed at which Regeneron developed an Ebola treatment. He said that the novel coronavirus might be harder, because it is not clear what parts of the rapidly mutating virus antibodies should target. “But if anyone can figure this out, it’s Regeneron,” he said.
Don’t vaccines also work by creating antibodies?
Vaccines work by teaching the body to make its own antibodies to an infectious agent without a person ever becoming infected. This is why they are among the most powerful weapons in public health.
But Porges, who worked at Merck’s vaccine division in the 1990s, said he thinks that creating a vaccine might be harder than companies expect, because this new virus is just not well enough understood. “You kind of need to have some fundamental understanding of the immunology and the virus before you can develop a vaccine,” he said. “It’s not clear to me that we have that.”
Many companies, including the biotechnology firm Moderna and the large pharmaceutical companies Johnson & Johnson and Sanofi, are working hard to develop vaccines quickly.
So which of these approaches is better?
That’s not the right question. Convalescent plasma, and then IVIG, could provide our first-line defense for people with Covid-19, especially those who are older and at much higher risk for complications. A monoclonal antibody drug could reach a greater number of patients. We also need antiviral drugs, such as remdesivir, being tested by Gilead Sciences. And a vaccine could do the most to slow or stop transmission.
“We need them all,” said Poland of the Mayo Clinic.
Andrew Joseph contributed reporting.
About the Authors
Matthew Herper
Senior Writer, Medicine
Matthew covers medical innovation — both its promise and its perils.
matthew.herper@statnews.com
@matthewherper
Adam Feuerstein
Senior Writer, Biotech
Adam is STAT’s national biotech columnist, reporting on the intersection of biotech and Wall Street.
adam.feuerstein@statnews.com
@adamfeuerstein
https://www.statnews.com/2020/03/05...overed-patients-could-help-treat-coronavirus/
We dont have a vaccine for Cornavirus yet
https://www.pharmaceutical-technology.com/news/vir-biotechnology-nih-biogen-coronavirus-antibodies/
Why don't children seem to get very ill from the coronavirus?
Health | Analysis 12 March 2020
By Layal Liverpool
Children seem to be much less affected by the coronavirus
RooM the Agency/Alamy
It has been widely reported that children are less likely to get severely ill and die from the new coronavirus. A recent study of 44,672 people with confirmed covid-19 infection found that children under 10 years old made up less than 1 per cent of those cases and none of the 1023 deaths.
“This is unlike flu,” says Akiko Iwasaki at Yale University. With flu, young children and older people are usually the most severely affected, so why is the new coronavirus different? It is a bit of a mystery.
A straightforward explanation would be that children are resisting infection in the first place, but that doesn’t seem to be the case. One recent study even found children to be just as likely as adults to get infected.
In any case, children that do become infected are still less likely to get sick with covid-19 and die – a similar trend to that seen with SARS or MERS, two other severe diseases caused by coronaviruses. So, what is protecting children?
No one has a good answer to that question yet,” says Iwasaki. But she and other experts suspect it may be down to the unique way children’s immune systems respond to these viruses.
A common complication of covid-19, SARS and MERS in adults is acute respiratory distress syndrome, where the immune response against the coronavirus becomes overzealous and causes life-threatening damage to the lungs.
The resulting leakage of fluid and immune cells into the lungs causes big problems, says Chris van Tulleken at University College London. Even if those immune responses are trying to help by attacking the virus, they can end up blocking oxygen uptake in the lungs, he says.
Because children’s immune systems are still developing, one suggestion is that they are shielded from this type of dangerous immune response – called a cytokine storm – when they get covid-19 or similar diseases. During the SARS outbreak, two studies found children produced relatively low levels of inflammation-driving cytokines, which may have been what protected their lungs from serious damage.
That doesn’t explain why children’s immune systems react differently to coronaviruses compared with flu. It might be due to differences in the type of cytokine response produced against each virus, says Iwasaki.
Children may also be benefiting from their lack of past exposure to coronaviruses generally. Because they have lived longer, adults are more likely than children to have encountered other coronaviruses in their lives, such as those that cause coughs and cold, and to already have antibodies against these milder viruses.
There is a suggestion that these existing antibodies could actually leave adults worse off, because they aren’t exactly matched to the new coronavirus. “Sometimes unmatched antibodies can be more harmful than good,” says Wendy Barclay at Imperial College London.
Understanding why children are being spared is about more than scientific curiosity. “If we can somehow mimic the children’s immune system, using therapeutics or drugs, maybe it just becomes a mild infection even in adults,” says Iwasaki.
And just because children aren’t getting severely ill, doesn’t mean they aren’t contributing to the spread of the new coronavirus. “There’s a danger of being complacent about the children not getting severely ill,” says Iwasaki.
There is already some indication that infected adults without symptoms can spread the virus and the same could be true of children. “It may be a good preventative measure to start closing schools,” says Iwasaki.
A recent case study described a young child with covid-19 who had high levels of virus but no symptoms. Whether or not children in this condition are infectious isn’t yet known, but finding out will be critical to tackling this pandemic.
Read more: https://www.newscientist.com/articl...-very-ill-from-the-coronavirus/#ixzz6Gbqo7I8B
