Whether plasma from COVID-19 recovered patients treat the sick - Million Dollar Question
Clinical trials will test if antibodies against the
coronavirus prevent infection, aid survival
Since April 8th, at least 11 patients critically ill with
COVID-19 at hospitals in New York City and Houston became the first in the
United States to receive a promising experimental treatment. But the therapy,
newly authorized for emergency use by the U.S. Food and Drug Administration,
wasn’t concocted in a pharmaceutical laboratory. It came from the blood of
other patients, those who have recovered from the coronavirus infection.
The treatment is convalescent plasma, the liquid
component of blood taken from someone who has survived an infection, in this
case COVID-19. With the United States now leading the world in confirmed cases
of the disease — and no proven treatments yet — researchers here are racing to
set up clinical trials to test how effective convalescent plasma is against
SARS-CoV-2, the virus that causes COVID-19. If the treatment is beneficial,
that could lead to FDA approval for wider use.
A vaccine against SARS-CoV-2 is at best more than year
away. In trying to manage COVID-19 over the next several months,
the question is, “what kind of treatments could we administer that could
truncate this pandemic?” says pathologist John Roback of Emory University
School of Medicine in Atlanta, who does research on transfusion medicine. The top
candidates are drugs already approved to treat diseases such as malaria that
might be repurposed for COVID-19 and convalescent plasma, he
says.
Antibody defense
To fight a virus, the immune system develops antibodies,
proteins that bind to parts of the virus and impede the infection. When a
person makes antibodies in response to an infection or upon getting a vaccine,
it’s called active immunity. The initial ramp up to antibody production can
take about a week or two, but once that has occurred, the immune system will be
able to quickly respond to the next exposure to the virus. For some viruses and
vaccines, active immunity can last decades or even lifelong.
Convalescent plasma, also called passive antibody
therapy, is a type of passive immunity. It can provide antibodies immediately,
but the proteins will last only for a short amount of time, weeks to possibly a
few months.
“We’re using the antibody-rich plasma from the
convalescent patient to prevent infection or treat infection in another
patient,” says Jeffrey Henderson, an infectious disease physician and scientist
at Washington University School of Medicine. 
Setting up clinical trials
Henderson is part of a group of U.S. researchers working
to set up clinical trials for convalescent plasma, called the National COVID-19
Convalescent Plasma Project. There are plans to test the plasma in three
different groups.
One randomized clinical trial is designed to investigate
whether plasma can prevent infection in people exposed to COVID-19 by a close
contact, such as a family member, says project member Shmuel Shoham, an
infectious disease physician at Johns Hopkins University School of Medicine.
The trial will test plasma from recovered COVID-19 patients against a placebo —
plasma taken from patients prior to the December 2019 start of the epidemic, he
says.
Another trial is planned to test whether plasma can keep
people with moderate disease who are in the hospital from needing intensive
care, Shoham says. And a third trial aims to study whether the therapy helps
the most critically ill patients. The project is waiting on a green light from
the FDA to start enrolling patients in all of the trials.
2019 novel coronavirus
outbreak
Controlled clinical trials are necessary to get
definitive answers on whether convalescent plasma can stop disease or improve
symptoms of COVID-19, and which people it could help the most. But a look at
the history of infectious diseases, described in a commentary April 1 in the
Journal of Clinical Investigation, provides many instances in which passive
antibody therapy appeared to prevent or ameliorate infections. Convalescent
plasma was used to help stop outbreaks of measles and mumps before vaccines
were available, and there’s some evidence that those who got the plasma during
the 1918 influenza pandemic were less likely to die.
Convalescent plasma has also been put to use against SARS
and MERS, the two other coronavirus epidemics. But studies that showed some
benefit didn’t compare how the treatment worked against a placebo. That’s also
true for the first studies on using the plasma to treat COVID-19. In one, five
patients critically ill with COVID-19 and on mechanical ventilation received
convalescent plasma 10 to 22 days after being admitted to a hospital in
Shenzhen, China. As of March 25, three of the patients had been discharged,
after a little over 50 days in the hospital, and two were in stable condition
37 days after the transfusion, researchers report March 27 in JAMA. Although
the patients improved, they had also gotten antiviral medications, so it’s
unclear which therapy, if any, had an impact.
Plasma questions
In the United States, some blood banks and hospitals are
gearing up to collect plasma from people who’ve recovered from COVID-19. The
Red Cross has set up a donor request form for people who would like to contribute
plasma. The National COVID-19 Convalescent Plasma Project also has information
on how to register to donate plasma.
For the U.S. clinical trials, the researchers will be
scrutinizing the donated plasma to determine whether it contains neutralizing
antibodies, Henderson says. This type of antibody prevents the virus from
entering a host cell, thereby stopping the infection. Data so far suggest that
the spike protein, a particular protein in SARS-CoV-2 which the virus uses to
bind to a protein on human cells, is a target of neutralizing
antibody.
