Antibodies are produced by the immune system as a way to fight off foreign invaders like viruses. Convalescent plasma uses antibody-rich plasma donated by COVID-19 survivors as a treatment for seriously ill patients who need an antibody boost. More than 70,000 people with COVID-19 have already received convalescent plasma. The current scientific evidence suggests this therapy may be effective in treating COVID-19, with the potential benefits outweighing the risks, according to the FDA’s press release. By granting the EUA for convalescent plasma, the government has made it easier for doctors and hospitals to use the treatment on more patients, according to Janis L. Abkowitz, MD, the division head of hematology at the University of Washington School of Medicine in Seattle. “The positive here is that this is one more thing that’s been allowed in the fight against COVID-19,” she says. “The EUA makes the use of convalescent plasma less experimental and it provides a way for doctors to access the therapy for individual patients who aren’t involved in clinical trials. It could also make it easier for different institutions to do related studies that use convalescent plasma on COVID-19 patients,” says Dr. Abkowitz. RELATED: Coronavirus Alert: The Latest News, Data, and Expert Insights on the COVID-19 Pandemic

Convalescent Plasma, Explained

To understand what convalescent plasma is, let’s look at each word. Plasma is the liquid part of the blood, and convalescent means “recovering.” As Abkowitz explains, “When someone gets COVID-19 or another infection, their body is working to get over it. Part of that process is making antibodies that attack the virus, and those antibodies are in the plasma.” Antibodies not only help us recover from an illness, they also protect us from getting the infection another time, which is why they remain in the plasma even after we get better. Giving plasma that contains coronavirus-fighting antibodies to a sick person is a way to take advantage of those lingering antibodies. “The thought is that if someone’s having a hard time recovering, if they can’t make antibodies against the virus, maybe we can give them the plasma of someone who did that successfully in order to help them to fight COVID-19,” she says. RELATED: Kids and COVID-19: What We Know Now

Convalescent Plasma Treatment Is Time-Tested

Doctors have used convalescent plasma therapy for a very long time, according to Abkowitz. “It was used to fight the Spanish flu in 1918, and it was used most successfully in people with Ebola fairly recently. It’s something that’s generally not a cure, but it can help out while we find more directed therapies that can be more efficacious,” she says.

What’s the Proof That Convalescent Plasma Is Effective Against COVID-19?

The FDA’s decision was largely based on a Mayo Clinic study designed to determine if convalescent plasma reduced mortality (the number of people who died) among hospitalized COVID-19 patients. The research took place during a three-month period at 2,807 acute-care facilities across the United States and included a total of 35,222 subjects. The study, which has not yet been peer reviewed or published in a journal, was posted on the MedRxiv website on August 12. The Mayo Clinic study has certain limitations. “It wasn’t designed as a blinded or placebo-controlled study where there is a control group who would get a different product or a placebo to see which has better outcomes,” says Abkowitz. “In this trial they gave the plasma to everyone to see if they could glean any insights on its effects on the 35,000 people they treated. They really didn’t have any comparator,” she says. The Mayo investigators found that people who were given high concentrations of antibodies did better than those who received lower concentrations of antibodies, says Abkowitz. “They also found that people who got the convalescent plasma earlier, that is, day 3 versus day 4 after being identified as being sick enough to receive it, tended to do better,” she says. These findings are more “early signals” than proof of efficacy, because of the way the trial was designed, says Abkowitz. “It’s a very early study — it’s appropriate that it’s been released because it [includes] a large number of patients, and it suggests that there might be some efficacy; it’s worth [doing] real studies to figure this out,” she says. “One thing we do know is that convalescent plasma is not a ‘cure-all,’ because you would know that right away. Most everyone would get better who was treated with it, and things would look so different for patients who were treated with this versus patients who weren’t. The researchers didn’t see that,” says Abkowitz. RELATED: Scientists Fast-Track Research for Coronavirus Treatment and Vaccine

Controversy About Convalescent Plasma

At the news conference on Sunday announcing the EUA, President Donald Trump, the U.S. secretary of health and human services, Alex M. Azar II, and the FDA commissioner Stephen Hahn, MD, all cited a striking statistic — that convalescent plasma had reduced deaths by 35 percent. An FDA tweet on August 23 at 6:29 p.m. stated: “A 35 percent improvement in survival is a pretty substantial clinical benefit,’ said FDA Commissioner @SteveFDA in relation to the convalescent plasma emergency use authorization issued today.” Many doctors and scientists criticized this characterization of the findings as exaggerated or even misleading. The backlash led Dr. Hahn to clarify the 35 percent reduction statistic on a CBS This Morning interviewand on Twitter. “Comparing those patients who got high concentrations of antibodies versus those who got low concentrations of antibodies — when you look at those data, the survival benefit of those two groups, there was a relative benefit of 35 percent,” said Hahn in the interview. “As I mentioned, I could have done a better job of explaining that at the press conference yesterday.” In a tweet issued by Hahn on late Monday night he wrote, “I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.” Absolute risk is the percentage chance of something happening over a certain time period, while relative risk involves the odds of something happening in two different groups compared with each other. The 35 percent benefit statistic comes from comparing two different groups who were both receiving plasma in the trial, which makes it relative rather than absolute. RELATED: Trump vs. Biden: Whom Do You Trust With Your Health?

What You Need to Know About Convalescent Plasma

Have questions about convalescent plasma? Here’s the what the FDA and experts say about the experimental therapy.

Where Does Convalescent Plasma Come From?

Convalescent plasma must be obtained from an FDA-registered blood establishment that follows the agency’s donor eligibility criteria, according to the FDA. For a donor to be eligible, evidence of COVID-19 can be shown in one of two ways: the prospective donor must have had a positive diagnostic test documented by a lab; or, if they never took a test while they were ill, they must have a positive serological test for SARS-CoV-2 antibodies after recovery. Before plasma donation, the donor must be completely free of COVID-19 symptoms for 14 days.

What Are the Risks or Side Effects of Convalescent Plasma?

The EUA requires that fact sheets that explain convalescent plasma and any potential side effects be made available to patients and healthcare providers. Possible side effects of COVID-19 convalescent plasma include allergic reactions, transfusion-associated circulatory overload, and transfusion-associated lung injury, as well as the potential for transfusion-transmitted infections, according to the FDA.

How Does a COVID-19 Patient Get Convalescent Plasma?

Now that the EUA has been granted, there are essentially two avenues for a patient to be treated with convalescent plasma. Clinical Trial Medical institutions and doctors apply to the FDA to conduct a clinical trial using convalescent plasma through what’s called an IND (investigational new drug) regulatory pathway. If a patient is being treated at that institution and fits the criteria for the trial, they may be treated with convalescent plasma. Currently there are 141 trials listed for convalescent plasma and COVID-19 at ClinicalTrials.gov. Single Patient Emergency IND (eIND) The FDA provides guidance to healthcare providers on who is eligible to be treated with convalescent plasma. The patient must have a lab-confirmed case of COVID-19 and have a severe or immediately life-threatening case of the virus which can include shortness of breath, respiratory frequency at or below 30 per minute, low blood oxygen saturation, respiratory failure, septic shock, or multiple organ dysfunction or failure. The treating physician must request and complete an eIND form by email. The form includes information about the patient’s medical history and diagnosis, and the doctor’s rationale for requesting the use of convalescent plasma. This process may be circumvented and expedited in certain circumstances. RELATED: From Nose to Toes, the List of COVID-19 Symptoms Keeps Growing

What Do Researchers Hope to Gain by Studying Convalescent Plasma?

Even given some of the positive signals found in the Mayo Clinic trial, it’s likely that convalescent therapy won’t make sense for the large majority of patients, but will help a subset of people, says Abkowitz. “Even if it doesn’t work in everyone, studying convalescent plasma will provide us with lots of learning about next steps in the fight against COVID-19,” she says. “For example, we may find what component of the plasma makes people recover faster and what component might make people immune, which is what you want to reproduce to create a treatment such as synthetic antibodies or a vaccine,” she says. “I think there’s a huge amount of science that’s going to come out of the study of convalescent plasma, which is a good thing. That’s not always the case when you do scientific trials on drugs,” says Abkowitz. RELATED: Life After Lockdown: COVID-19 Safety Tips for Offices, Restaurants, and Hair Salons