Case Report: COVID-19 Patient Recovers After Receiving Donated Plasma

Researchers at the University of Alabama (UAB) have announced that an immunodeficient patient who received a single intravenous infusion of convalescent plasma has now recovered from a month’s-long battle with COVID-19.

The patients’ physicians at UAB attribute her recovery to the high virus-neutralizing antibody titer present in the donated plasma, which the patient received from her son-in-law. 

The case adds to a growing body of research that the quality of the convalescent plasma—which is typically determined by the donor’s course of infection—matters.

“It turns out they have to get pretty sick to generate a good immune response and good antibodies against the virus if you’re naturally infected,” Randall Davis, MD, a professor in the UAB Department of Medicine and senior scientist at the O’Neal Comprehensive Cancer Center, tells Verywell. Davis treated the patient and reported his findings on the case in the journal Cell Reports Medicine. 

“We have found that even screening patients that were in the intensive care unit, those patients had the highest titers,” Davis says. “The sickest people were generating the highest antibody levels.” 

The Case

The 72-year-old woman, who has chronic lymphocytic leukemia, was admitted to the hospital for a cough and tested positive for COVID-19. After receiving initial treatments, she was discharged, but her condition continued to decline. She was later readmitted to the hospital after she developed severe pneumonia and was still testing positive for the virus.

“She was just generating virus for weeks,” Davis says. “And she had zero immunity against it and could not generate any antiviral immunity.”

Davis explains that when someone develops an infection or gets vaccinated, their B-cells are responsible for processing their body’s response to either the pathogen or the vaccine. B-cells then retain a memory of the infection or the inoculation, which helps them provide future defense against a virus.

However, Davis’ patient’s B-cells were not up to the task. “She has got a problem where all of her B-cells are leukemic. And so they are basically useless in the sense of defending her against infection.” 

In addition to B-cells, T-cells also play an important role in the body’s immune response to vaccines and infection. Davis says that he and the other researchers involved in the case tested the patient’s ability to make an antibody against multiple proteins in SARS-CoV-2. “She had plenty of time to generate antibodies if she was going to, and she did not,” says Davis.

Finding a Match

Two of the patient’s family members had already recovery from severe COVID-19 that had required hospitalization. Both of the individuals were tested at a local blood donation center.

The patient’s son-in-law turned out to be a compatible donor. His donated convalescent plasma was then designated to go to the patient. She received the infusion 33 days from the time that she first developed COVID-19 symptoms.

“She promptly recovered,” Davis says. “She had no fever within 48 hours. She hadn’t been eating and had lost about 15 pounds. And she was craving brownies the next day.”

Within three days of the infusion, SARS-CoV-2 was no longer detectable in her respiratory swabs. And she was discharged on the fourth day. “[She] went home and has been doing great ever since,” Davis says.

Her recovery is unusual because of the timeframe from symptom onset to infusion with convalescent plasma on day 33. 

“The sooner people get infused with neutralizing antibodies, either the ones that are recombinant now from Lilly or Regeneron or good convalescent plasma, the better these people are going to do,” Davis says.

Not All Convalescent Plasma Is Created Equal

Compared to other plasma donors, the patient’s son-in-law’s donated convalescent plasma was of extremely high virus-neutralizing antibody titer, which Davis says is what helped the woman make a full recovery.

Last August, the Food and Drug Administration (FDA) granted emergency use authorization (EUA) for convalescent plasma in cases of COVID-19. However, its use as a treatment for the virus has been controversial because there is a lack of evidence showing its benefit. For example, an editorial published in the British Medical Journal last October stated that “convalescent plasma is ineffective.”

“Unfortunately, there’s been a lot of plasma roulette,” Davis says. One issue is that not everyone who has had COVID-19 will have high enough virus-neutralizing antibody titers for their donated convalescent plasma to be useful.

For Davis’ study, researchers looked at titers from 64 remnant convalescent plasmas collected by two blood banks. Of the remnant plasmas from one blood bank, they found that only 37% had titers above 250. From the second blood bank, only 47% of the remnant plasmas made that cut. Eight remnant plasmas from the second blood bank had a titer above 1,000 (for comparison, the patient’s son-in-law’s extremely high titer was 5,700).

The researchers also looked at titers among 17 other patients, in addition to the 72-year-old woman, before and after convalescent plasma infusion. Of the 16 patients that researchers were able to analyze, convalescent plasma had no impact on their existing neutralizing antibodies. However, in the patient who received her son-in-law’s plasma, the researchers reported that they detected an “obvious rise.”

The Latest Research on Convalescent Plasma

“What we’ve learned so far is that if you have high-titer convalescent plasma and it is given very early in the patient’s course, there appears to be efficacy,” Claudia Cohn, MD, PhD, associate professor, Department of Laboratory Medicine and Pathology at the University of Minnesota Medical School and M Health Fairview, tells Verywell. 

Cohn specifically points to a small randomized, controlled, double-blind trial led by researchers in Buenos Aires, Argentina, and published in the New England Journal of Medicine. “It was a really well-run trial,” Cohn says, “and they found quite a bit of benefit for convalescent plasma in that trial.”

In the study, researchers screened outpatient older adults. If they were within 48 hours from developing their COVID-19 symptoms, the researchers enrolled the individuals in the trial, which allowed them to receive convalescent plasma within 72 hours of symptom onset.

The researchers concluded that early infusion of high-titer convalescent plasma in adults with mild COVID-19 illness reduced the progression of the disease. 

“There’s pretty good evidence that the virus is cleared from our bodies within 9 to 10 days,” Cohn says. “And so if there’s no virus, there’s nothing for the antibodies to remove.”

Cohn adds that an individual’s body eventually mounts its own immune response against SARS-CoV-2. “If you start to have your own immune response, it may be that convalescent plasma isn’t going to add that much extra.”

Developing Treatment Guidelines

Cohn also points to research from the Mayo Clinic published in the New England Journal of Medicine in January. The study found that in patients hospitalized with COVID-19 who were not receiving mechanical ventilation, high-titer convalescent plasma was associated with a lower risk of death. They also found a correlation between the benefit of convalescent plasma if it was administered early in the course of the disease. 

“First, it’s the virus infecting the cells, and then it’s the inflammatory response to the virus,” Cohn says. “And once the inflammatory response has started cascading in the wrong direction, the antibodies aren’t going to help.”

Cohn is also the chief medical officer for the American Association of Blood Banks and is part of a joint effort through the AABB to release guidelines for convalescent plasma use. The interim guidelines will be available in the coming weeks.

“The ultimate guidelines that will be based on all of the studies won’t come out until late spring, early summer,” Cohn says. “But we understand that since there’s a need, we are developing interim recommendations. They are a consensus of expert opinion, and there are about 20 or so people on the panel.” 

Donating Plasma If You’ve Had COVID-19

Both Davis and Cohn urge people who have had COVID-19 to donate convalescent plasma because of the growing need for it.

“The amount of convalescent plasma is going off the shelf faster than the number of COVID patients who might benefit from it,” Cohn says. “If you’ve had COVID and then received a vaccination, I urge you, even more, to donate because the vaccine will boost your antibody response. So your titer will probably be higher.”

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