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https://www.nature.com/articles/d41586-020-00895-8
24 March 2020

How blood from coronavirus survivors might save lives

New York City researchers hope antibody-rich 
plasma can keep people out of intensive care.


Amy Maxmen

EMS personnel work outside the Emergency Department at St. Barn



Hospitals in New York City are becoming 
overwhelmed with coronavirus cases.Credit: Misha Friedman/Getty

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.

[]

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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.

<https://www.nature.com/articles/d41586-020-00800-3>
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Podcast Extra: Coronavirus - science in the pandemic

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<https://www.nature.com/articles/d41586-020-00895-8?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&error=cookies_not_supported&code=c877c416-37d0-456f-b977-732a5cbef87c&utm_source=Nature+Briefing&utm_campaign=7fdc8b2aa7-briefing-dy-20200325&utm_medium=email&utm_term=0_c9dfd39373-7fdc8b2aa7-44889217#ref-CR1>1.

During the SARS outbreak in 2002–03, an 80-person 
trial<https://www.nature.com/articles/d41586-020-00895-8?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&error=cookies_not_supported&code=c877c416-37d0-456f-b977-732a5cbef87c&utm_source=Nature+Briefing&utm_campaign=7fdc8b2aa7-briefing-dy-20200325&utm_medium=email&utm_term=0_c9dfd39373-7fdc8b2aa7-44889217#ref-CR2>2 
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<https://www.nature.com/articles/d41586-020-00895-8?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&error=cookies_not_supported&code=c877c416-37d0-456f-b977-732a5cbef87c&utm_source=Nature+Briefing&utm_campaign=7fdc8b2aa7-briefing-dy-20200325&utm_medium=email&utm_term=0_c9dfd39373-7fdc8b2aa7-44889217#ref-CR3>3 
in the Democratic Republic of the Congo, but the 
study was small and not placebo controlled. A 
2015 
trial<https://www.nature.com/articles/d41586-020-00895-8?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&error=cookies_not_supported&code=c877c416-37d0-456f-b977-732a5cbef87c&utm_source=Nature+Briefing&utm_campaign=7fdc8b2aa7-briefing-dy-20200325&utm_medium=email&utm_term=0_c9dfd39373-7fdc8b2aa7-44889217#ref-CR4>4 
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.

A person donating plasma surrounded by medical workers in prote


A person who has recovered from coronavirus 
infection, donates blood plasma in Zouping, China.Credit: AFP/Getty

Casadevall corralled support for his idea through 
an editorial in the 
<https://www.wsj.com/articles/how-a-boys-blood-stopped-an-outbreak-11582847330>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.

<https://www.nature.com/articles/d41586-020-00760-8>
[]


How much is coronavirus spreading under the radar?

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.”

<https://www.nature.com/articles/d41586-020-00660-x>
[]


Why does the coronavirus spread so easily between people?

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.”
doi: 10.1038/d41586-020-00895-8


Reference

    * 1. Casadevall, A. and Pirofski, L. J. Clin. 
Invest. https://doi.org/10.1172/JCI138003 (2020).
    * 2. Cheng Y. et al. Eur. J. Clin. Microbiol. 
Infect. Dis. 1, 44–46 (2005).
    * 3. Mupapa, K. et al. J. Infect. Dis. 17, S18–S23 (1999).
    * 4. Van Griensven, J. et al. N. Engl. J. Med. 374, 33–42 (2015).