Monday, March 1

Can plasma from recovered COVID-19 patients treat the sick?

Since March 28, 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 (SN: 2/21/20). 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
(SN: 3/10/20) 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 in St. Louis.

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.

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 (SN: 2/3/20),
is a target of neutralizing antibody.

Researchers suspect that
this type of antibody is what makes convalescent plasma effective. And it also
hints at when using the plasma may be most beneficial.

Early on in the disease, the
virus is infecting cells and hijacking cell machinery to make many copies of
itself. “But as the disease progresses, the tissue damage done by the virus is
more difficult to reverse and isn’t necessarily reversed by something that is
solely targeted towards the virus itself,” such as antibodies, says Henderson. The
body’s inflammatory response can be contributing to the damage.

It doesn’t mean that passive antibody therapy wouldn’t help someone critically ill with COVID-19, he says. “We have so much to learn, of course, but we’re thinking the antibodies may prevent the virus from expanding its numbers.”

Clinical trials of convalescent plasma are beginning in other countries, too. As doctors await answers from completed trials, additional patients may receive the treatment under the FDA’s emergency authorization. It’s great that critically ill patients and their doctors have that option, Shoham says. In the meantime, “we’re trying to … find out if [convalescent plasma] actually works.