Pathology Laboratory

Convalescent Serum

Convalescent serum is an effective treatment for many diseases. Till 20th century, the treatment became known as convalescent plasma therapy.

What is Convalescent Serum?

In the 1890s, German scientist Emil Behring pioneered a novel treatment for diphtheria. Behring, along with a Japanese physician named Kitasato Shibasaburō, discovered that blood serum from animals infected with certain toxins could be infused into humans providing treatments for various illnesses.

Behring described these protective molecules at the time as “antitoxins,” and spent the rest of the decade optimizing the process. He ultimately found horses to be the most efficient animal for producing large volumes of serum antitoxins. In 1901, Behring won the very first Nobel Prize in Physiology or Medicine for his work in developing these diphtheria serum therapies.

Today, we understand how this kind of treatment theoretically works, as we understand how an organism’s immune system generates antibodies to fight off certain infectious agents. However, over a century ago, the field of immunology was still young, and scientists didn’t understand exactly how serum therapy could be working. Behring himself referred to blood as “a very special juice” and used terms such as disinfectant to describe how his serum therapy healed patients.

What is a Convalescent Plasma Therapy?

Across the first few decades of the 20th century, the treatment became known as convalescent plasma therapy, and was frequently used in times of infectious disease outbreak. Blood products from recovered patients were common treatments for everything from measles and mumps to polio.

The treatment was widely deployed during the Spanish flu pandemic in 1918. A 2006 meta-analysis examining eight studies published between 1918 and 1925 suggested convalescent plasma therapy significantly reduced mortality rates in cohorts receiving the treatment.

The 2006 study, of course, cites significant limitations in interpreting these results, as recorded case studies from the early 20th century do not have the methodological rigor of modern research practices. These were not blinded, randomized, or placebo-controlled trials. Control groups were calculated by simply counting untreated patients in the same hospital or ward.

Bearing all this in mind, the meta-analysis suggested the overall case-fatality rate among patients treated with convalescent plasma was 16 percent. The case fatality rate in the untreated control group was 37 percent.

This treatment method ultimately fell out of common use by the mid-20th century. From the discovery of antibiotics to the development of sophisticated vaccines, scientists eventually produced more effective modes of medical treatment. But new treatments take time to develop, trial and deploy. And when a new virus spreads through the population, we don’t really have the luxury of time.

COVID-19 treatment with convalescent plasma

Hospitals are gearing up to test if a century-old treatment used to fight off flu and measles outbreaks in the days before vaccines, and tried more recently against SARS and Ebola, just might work for COVID-19, too: using blood donated from patients who’ve recovered.

Doctors in China attempted the first COVID-19 treatments using what the history books call “convalescent serum” today, known as donated plasma from survivors of the new virus.

Now a network of U.S. hospitals is waiting on permission from the Food and Drug Administration to begin comprehensive studies of the infusions, both as a treatment for the sick and as vaccine-like temporary protection for people at high risk of infection. There’s no guarantee it will work.

“We won’t know until we do it, but the historical evidence is encouraging,” Dr. Arturo Casadevall of Johns Hopkins University’s School of Public Health told The Associated Press. Casadevall drew on that history in filing the FDA application. The FDA is “working expeditiously to facilitate the development and availability of convalescent plasma” a spokesperson said.

  1. What exactly is this convalescent plasma therapy?

    It may sound like back to the Stone Age but there’s good scientific reason to try using survivors’ blood, said Dr. Jeffrey Henderson of Washington University School of Medicine in St. Louis, who coauthored the FDA application with Casadevall and another colleague at the Mayo Clinic. When a person gets infected by a particular germ, the body makes specially designed proteins called antibodies to fight the infection. After the person recovers, those antibodies float in survivors’ blood, specifically plasma, the liquid part of blood for months, even years. One of the planned studies would test if giving infusions of survivors’ antibody-rich plasma to newly ill COVID-19 patients would boost their own body’s attempts to fight off the virus. To see if it works, researchers would measure if the treatment gave patients a better chance of living or reduced the need for breathing machines.
    One caution: While regular plasma transfusions are a mainstay of medicine, rarely they can cause a lung-damaging side effect.

  2. Could this also act like a vaccine?

    Sort of, but unlike a vaccine, any protection would only be temporary. A vaccine trains people’s immune systems to make their own antibodies against a target germ. The plasma infusion approach would give people a temporary shot of someone else’s antibodies that are short-lived and require repeated doses. Still, if FDA agrees, a second study would give antibody-rich plasma infusions to certain people at high risk from repeated exposures to COVID-19, such as hospital workers or first responders, said Dr. Liise-anne Pirofski of New York’s Montefiore Health System and Albert Einstein College of Medicine. That also might include nursing homes when a resident becomes ill, hoping to give the other people in the home some protection, she said. We need both things desperately, Pirofski said. We need to break the cycle of transmission and we also need to help people who are ill.

  3. How would hospitals or doctors get convalescent plasma?

    Blood banks take plasma donations much like they take donations of whole blood; regular plasma is used in hospitals and emergency rooms every day. If someone’s donating only plasma, their blood is drawn through a tube, the plasma is separated and the rest infused back into the donor’s body. Then that plasma is tested and purified to be sure it doesn’t harbor any blood-borne viruses and is safe to use. For COVID-19 research, the difference would be who does the donating people who have recovered from the coronavirus. Scientists would measure how many antibodies are in a unit of donated plasma – tests just now being developed that aren’t available to the public – as they figure out what’s a good dose, and how often a survivor could donate. Researchers aren’t worried about finding volunteer donors, but caution it will take some time to build up a stock. Get multiple emails a day from people saying, ‘Can I help? Can I give my plasma? Pirofski said.

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