New Life for an Old Therapy: Convalescent Plasma

April 4, 2020
Simon Murray, MD

By giving patients plasma or serum from patients who have developed antibodies to a particular virus or bacteria, an infected patient is given a massive boost to their adaptive immune system, which confers passive immunity.

The US Food and Drug Administration (FDA) announced that they are facilitating access to coronavirus disease 2019 (COVID-19) convalescent plasma for use in patients with serious or life-threatening COVID-19 infections. Clinical trials are underway but the FDA has granted permission for clinicians to use investigational plasma under single-patient emergency Investigational New Drug applications since there is no known cure or vaccine.

In the March 27, 2020 issue of JAMA, researchers from China reported the results of 5 patients treated for severe COVID-19 infections with post convalescent serum taken from recovered patients. All patients treated were on ventilators and were males, and they ranged in age from 36-73 years. Within 12 days of receiving convalescent serum, viral titers dropped dramatically to zero. All patients recovered.

Before and during treatment the patients also received interferon and lopinavir/ritonavir. It is questionable what role the addition of the antivirals played. The combination of lopinavir/ritonavir has now been discredited as a valid treatment for the COVID-19 infection.

The use of convalescent plasma is not a new concept. By giving patients plasma or serum from patients who have developed antibodies to a particular virus or bacteria, an infected patient is given a massive boost to their adaptive immune system, which confers passive immunity. It has been used since the 1800s.

The first valid trial was done in 1892 with diphtheria using blood serum initially. It was produced from animals who were infected with Diptheria, but soon whole blood or plasma recovered from donors with specific humoral immunity were identified as a possible source of specific antibodies of human origin. In the 1920s, it was used to treat scarlet fever. It was also used to treat and pertussis until about 1970. Horse serum was used to treat tetanus until the 1970s as well.

During the Spanish influenza pandemic of 1918 convalescent plasma was used as a potential therapy with mixed results. It has been used in a variety of viral infections, although studies have been small and inconclusive. One success was the use of convalescent serum to treat Ebola virus.

For COVID-19, the potential risks of receiving convalescent plasma remain unknown. In the case of the dengue virus, getting convalescent serum makes the patient’s paradoxically worse, as it causes the virus to replicate. Other known complications include transfusion-associated reactions seen with any blood transfusion. There is also the possibility that other known or unknown pathogens could be introduced into the patients.

Other considerations are that there are no large long-term trials that have proven the value of using the serum. There is a risk for laboratory workers handling the serum. A practical way to measure which individuals have the highest titer of antibodies needs to be established, and the use of supportive therapies in addition to plasma will need to be investigated as well.

The FDA has issued guidelines about the treatments with plasma. COVID-19 convalescent plasma can only be collected from recovered individuals if they are eligible to donate blood and undergo required testing. They have to have had proven COVID-19 infection and have been shown to be recovered. Potential donors are going to be screened like all blood donors are screened. At the University of Washington School of Medicine in Seattle, Terry B Gernsheimer, MD, and her colleagues are recruiting recovered COVID-19 patients to donate plasma. “The thought of using convalescent plasma makes sense; it something that we can try to give people to help them recover.”

Gernsheimer said, “it is not going to be any less safe than any unit of plasma that’s on the shelf that comes from our volunteer donors. There are always transfusion reactions that we have to worry about, and there potentially unknown pathogens that we don’t yet know about and are not testing for. It is a risk we see with any unit of plasma.”

COVID-19 survivors appear to start increasing the titer of antibody around day 28; therefore, suitable donors will not be selected unless they have had a documented infection that began 28 days before they can donate plasma. The FDA states that to be eligibile for donation, there should be a proven diagnosis of COVID 19 by a laboratory test, complete resolution of symptoms for at least 14 days before donation. Female donors must be negative for HLA antibodies. Donors must test negative to COVID-19 either by nasopharyngeal swabs or by molecular diagnostic tests from the blood. The FDA also advises that donors have defined SARS COV-2 neutralizing antibody titers with a titer greater than 1/320.

Eligible patients must have severe or immediately life-threatening infections with laboratory-confirmed COVID 19. The agency defines a life-threatening disease as one that causes acute respiratory distress with increased respiratory rate and decreased blood oxygenation.

One of the ways to avoid complications associated with transfusion of plasma would be to use only purified antibodies derived from the serum of patients who have recovered from COVID 19.

The views expressed are the author's and not reflective of the publication or its owners.