Disclaimer: This blog post is intended to help you understand the controversy and reporting around convalescent plasma treatment for COVID-19 and to give you reasons to thank God for this treatment. It is not meant to take the place of advice from your doctor if you or a loved one are sick.
Introduction
I’m writing on a topic that is admittedly out of my main fields of expertise (which would be biblical interpretation and living the Christian the life). I’ve been hesitant to do this, but have felt (subjectively) that the Spirit was nudging me to take this risk. I feel that many people are likely confused by the mixed signals that are in the news about convalescent plasma treatment of COVID-19 and I think maybe I can help a little. I am not an expert on medical therapies in general or on immunology in specific, but I am good at reading and studying so that I can understand complex subjects and gifted to write in such a way that helps other people understand them as well. God has often graciously used me in this way. My goal is to help you understand and sort out apparently conflicting statements in the news about convalescent plasma treatment for the coronavirus. In doing so, I hope to provide you with a little good news regarding progress in fighting the pandemic and give you one more thing to thank God for. I pray God will use this blog post for that purpose.
Background
On August 23, the FDA issued an emergency use authorization for convalescent plasma to be used in the treatment of COVID-19. First, let me explain what convalescent plasma treatment is. When we get sick, our immune systems make antibodies to fight off the infection. After we get better, some of those antibodies remain in our blood, sometimes even for the rest of our lives. For more than a hundred years, doctors have used blood from people who have recovered from certain diseases to help treat people who are newly infected with the same disease. The newly infected person’s own immune system might not be making the right antibodies fast enough to beat the infection, especially if a newly infected person is especially vulnerable to the disease. So, giving them someone else’s antibodies can sometimes help a lot. These days, instead of simply giving blood from a recovered person, we have ways to separate out the part of the blood that contains the anti-bodies and just give that. This part of the blood is called plasma. It is called convalescent plasma because it comes from a person who has recovered from the disease.
Based on past experience with infections and antibody treatments, doctors wanted to try this treatment to help patients with COVID-19. . Due to the novelty of COVID-19, there was no specific evidence that this type of treatment would work, but historically convalescent plasma therapy has been effective in treating similar types of respiratory diseases. So in late March, with the approval of the FDA, they started what is called the Expanded Access Program (EAP). This program was overseen by one of the top hospitals and medical research centers in the world, the Mayo Clinic. Their main goal was to create a system where they could get plasma with antibodies to as many severely sick patients as possible as quickly and easily as possible in the midst of a pandemic. They focused on helping severely sick patients because they knew the supply of plasma would be limited. Basically, any hospital in the US that was willing to follow the program guidelines could sign up to be part of the program. Many hospitals (2,807, to be exact) did sign up.
Lots of people have received plasma with antibodies through the EAP. Over 35,000 people have received this treatment so far and the program continues! In addition to getting to plasma to them quickly, part of the EAP’s goal was to collect data. They wanted to use this data to determine first if the treatment was safe, and second if the treatment actually helps people. They did determine that that treatment is safe. There was a small chance that the antibodies would make things worse, but thankfully that has not happened. However, just because the treatment does not cause people harm, doesn’t mean that it works. That required additional research to answer the question: “Do the antibodies in the plasma help sick people?”
The group of top scientists and doctors associated with the Mayo clinic who were running the EAP examined data they had collected and they found evidence that the plasma was indeed helping sick people. They found evidence that indicates those antibodies in the plasma were working the way antibodies are supposed to work. They wrote a paper explaining this evidence in detail. This paper is a major reason that the FDA decided on August 23rd to grant an emergency use authorization (EUA) for convalescent plasma to treat COVID-19.
Now doctors and hospitals anywhere in the US can use this treatment. They do not have to be part of a specific program like the EAP. This emergency use authorization is likely to increase the use of plasma. Because of the additional publicity and additional confidence that FDA approval brings, it is likely that more patients who have recovered from COVID-19 will donate plasma, and more very sick patients will get that plasma. It is likely that the plasma will save the lives of some of those patients and will help others recover more quickly and have less severe symptoms and less suffering. This is something to celebrate! It is not a magic cure that completely and quickly heals everyone who gets it. It will not be available to everyone who gets diagnosed with COVID-19, but will likely continue to be given to those patients who are most at risk of dying from the disease. While it will not end the pandemic, or heal everyone, it is very likely to save lives and help many people.
Not Everyone is Celebrating
Surprisingly (or perhaps, predictably, in our broken society in 2020), quite a few scientists and pundits are not celebrating this important victory in the ongoing war against COVID-19. Some of them are instead focusing on criticizing the FDA and attacking President Trump, who made the announcement about the EUA. The language these critics use is likely to cause people to doubt whether convalescent plasma is a good, helpful treatment that we should be thankful for. Here are a few examples of negative comments and statements in the news:
1. Yesterday (September 2, 2020), CNN ran an article that began with these words:
“A National Institutes of Health panel said there's no evidence backing the use of convalescent plasma to treat coronavirus patients . . .”
In fact, as you will see below, there are multiple lines of strong evidence, provided by one of the top hospitals and medical research centers in the world, that convalescent plasma is an effective treatment.
2. The AP produced an article that was run by Fox News and other news outlets. Fox ran the article with this headline:
“FDA chief apologizes for overstating plasma effect on coronavirus: Scientists and medical experts have been pushing back against the claims about the treatment”
Technically, the FDA chief did misstate the effect and he did apologize. The specific mistake he made was that “Hahn and other Trump administration officials presented the difference as an absolute survival benefit, rather than a relative difference between two treatment groups.” This is a matter of detail that I would not care about if someone I loved was dying of COVID-19 and they were offered convalescent plasma. The headline, and especially the subtitle, is likely to cause people to doubt that the treatment is effective at all. This is especially true when the article includes lines like the one below. The bold emphasis is my own, is a statement I believe to be untrue, and one that I fear could cause people to doubt the effectiveness of this treatment.
“The FDA made the decision based on data the Mayo Clinic collected from hospitals around the country that were using plasma on patients in wildly varying ways -- and there was no comparison group of untreated patients, meaning no conclusions can be drawn about overall survival.” (You may read the article here for as long as the link works, or Google the above quote to quickly find it)
3. An article ran on the Politico news site had this headline:
“FDA authorizes plasma treatment despite scientists’ objections”
Would you want a treatment that scientists object to? The article is likely to discourage people from using this treatment, especially when it also includes quotes like this one:
“The data from the expanded access program is not a randomized controlled clinical trial, making it difficult for scientists to eliminate other factors in patients' recovery.” (The part of the quote in bold will be discussed in detail below. You may read the article here)
Looking at the Evidence
I wanted to look at the evidence for myself. So I searched for and quickly found the Mayo Clinic study that is available online (I’ve already provided a link above, but here it is again).
When I carefully read and reread the study, I thought the evidence for convalescent plasma being effective was quite strong. Since I am not professionally trained in this area, I asked a friend who is to read the Mayo Clinic article and also this blog post to see if he agrees with my understanding. My friend is a licensed veterinary doctor who graduated from the University of Maryland with a dual major in Biochemistry and Microbiology and then later earned his Doctor of Veterinary Medicine from VMRCM. He has an extensive background in research and analysis of technical papers. He has corroborated my understanding and has checked this blog post for any scientific errors or misstatements on my part.
Perhaps the most common criticism of the Mayo study is that it was not a randomized placebo control trial (RCT). But the Mayo study was very similar to a RCT and there is no good reason to reject its analysis. Let me explain the difference between a RCT and the Mayo study.
When someone gets sick there are a vast host of factors that can
contribute to how severe their illness is and whether or not they recover. As
with many infections, most people who get COVID-19 recover without needing
hospitalization. Most people will probably recover even if they are given no
treatment at all. Further, when doctors are trying to save someone’s life who
is critically ill, they often give multiple medicines (have you ever known
anyone in an ICU who only received one type of medicine or treatment?). If
one of those many treatments is new or untested, it can be difficult to
determine if that is actually the treatment that is helping the patient. If a
patient is given convalescent plasma and they get better, how do you know they
would not have gotten better anyways? How do you know that the
antibodies in the plasma helped them? To deal with this issue, the very best
method for testing new therapies, when possible, is to use a RCT.
In a RCT, you separate a population of sick patients into two groups. This is done randomly so that the two comparison groups are as similar as possible. Then you likewise treat both groups as similarly as possible with one important exception. One group gets the treatment you want to test. The other group gets a placebo. Further, neither the patients nor the doctors and nurses treating them know who is getting the placebo and who is getting the real drug (or the real antibodies). Then you see what happens. If more patients who received the real drug (or antibodies) get better than patients who received the placebo, that is evidence the drug, or treatment, works. Statistical analysis is done to make sure there was a big enough difference between the patients who got the real drug and the ones who got the placebo to prove that the difference was not just due to luck.
The Mayo Clinic agrees that a RCT is the very best kind of study for the purpose of precisely testing whether a new treatment works. They explain why they did not use a RCT. They had really good reasons that had to do with wanting to help as many people as possible as quickly as possible under the additional difficulties created by doing the study during a worldwide pandemic that is killing thousands of people every day. They explain these reasons in detail in their research paper. The reasons made a lot of sense to me.
Thankfully, there are some really smart people at the Mayo clinic who figured out two ways to test whether the convalescent plasma was helping even though they were not using a RCT. The first of these two methods I will explain is quite similar to a RCT in important ways.
When a pill is made by a pharmaceutical company, the dose in the pill is tightly controlled so that every patient who takes that pill gets the same dose of the medicine. But convalescent plasma is not made in a pharmaceutical facility. It is made in human bodies. It turns out that some people who have recovered from COVID-19 and who donate plasma have a lot of antibodies in their plasma, and some have relatively few antibodies. You cannot tell by looking at a person how many antibodies are in their plasma. A small sample of each plasma donation was sent to labs to measure the amount of antibodies in the plasma. However (this is important!) neither the doctors and nurses administering the plasma nor the patients receiving it knew whether they were receiving a bag of plasma with a lot of antibodies or with relatively few antibodies. But the researchers overseen by the Mayo clinic knew because they used a coding system to keep track of this. Then, they compared how many patients who received a low number of antibodies got better to how many patients who received a high number of antibodies got better (getting better for this research simply meant that they did not die, which is probably important to them and their families). It turns out that more people who got the higher number of antibodies recovered compared to people who got the lower number of antibodies. They did statistical analysis and it indicated that this was not the result of pure chance. The antibodies were really working. (Thank God, a little good news in this long pandemic.)
I hope you notice how similar the Mayo study was to the “gold standard” RCT. To reinforce this, here are two graphics comparing the two research methods:
Notice how closely the Mayo Clinic study approximates the “gold standard” RCT. In an emergency, in a pandemic killing thousands of people each day, until RCTs can be completed, doesn’t it make sense to use the promising, encouraging results of the Mayo study? That is what the FDA did. That is what Trump announced (without giving all the details, which are available publicly online). Why are pundits being so critical of the FDA and this announcement? Shouldn’t we be celebrating and thanking God for a treatment that, while it does not cure everyone, appears to be saving many lives? Shouldn’t we want to promote this so that more people who have recovered will be eager to donate their plasma and more sick people will be saved?
The Mayo clinic used a second method to test whether the antibodies were working. They knew based on history and medical experience that if antibody treatments for respiratory illnesses like COVID-19 work at all, they usually work best if the treatment is given earlier in the illness rather than waiting. If the antibodies do not work, it should not matter if they are given early or late. If they do work, it should matter. They found that giving the antibodies early did matter. This is additional evidence that supports the evidence found by comparing those who received low doses to those who received high doses. All the data points in the same direction: the antibodies in the convalescent plasma treatment help sick people.
So why are some people, including some medical professionals, so negative towards this treatment? I don’t know. Perhaps some just honestly do not understand the nature of the research. Perhaps some are politically motivated (consciously or subconsciously) and do not want to see any victory for the efforts of the Trump administrations to combat the pandemic. You decide.
Conclusions, Praise, and Prayer
Convalescent plasma is not a miracle cure. Some people who get it still die (this is true for many proven treatments for many diseases). We still need better treatments and vaccines. The pandemic is not over. But we can thank God that there is good evidence that one treatment that has already been used for tens of thousands of patients is working. It is saving lives and helping sick people get better.
In today’s climate, it feels like everything is politicized. We need to pray for wisdom and be discerning to sort out the truth.
We should keep praying for even better treatments and the scientists and doctors working on them and the FDA and other agencies involved in evaluating and approving treatments. One very promising treatment is called monoclonal antibodies. Our bodies produce many antibodies when fighting an infection like COVID-19. Scientists work to determine which of these many antibodies work the best. Then, instead of waiting for them to be produced in human bodies, they produce them in labs and similar facilities. They can produce consistently high doses of the very best antibodies. They are doing this today. These treatments are currently in phase 3 human testing. The fact that the Mayo study provided good evidence that antibodies from convalescent plasma are effective, gives us hope that these artificially produced monoclonal antibodies will work even better. Keep praying!
And while we are praying, let’s give God thanks for our immune systems. Our immune systems are amazing. Convalescent plasma treatment makes direct use of antibodies produced by human immune systems. Monoclonal antibodies can be mass produced to supplement the work of the immune system. If vaccines are developed that work, they will work because they have successfully equipped our own immune systems to fight the disease when it shows up.
I hope you will join me in thanking God for one treatment that is helping people in this pandemic: convalescent plasma.
Hebrews 13:16 And do not forget to do good and to share with others . . .
For further reading, thought, and edification:
1. Blog posts specifically related to the coronavirus:
How viruses strengthen the scientific case for a Creator
The Coronavirus and the Lord’s Prayer
7 Ways the Lord may use the Coronavirus Pandemic for Good.
2. Blog posts about scientific evidence for God as our Creator:
God Created the Earth to be Inhabited
Nuclear Submarines and Living Cells
Behe’s Three Mighty Blows Against Darwinism
How the Smallest Cells Give BIG Evidence for God
3.) Blog posts about other topics that thinking Christians might be blessed
by:
Create in Me a Clean Heart, O God
What does Paul Mean by a “Spiritual Body”?
The Three Ways Jesus Saves Us from our Sins
A Model for Intercessory Prayer
Practical Advice for Battles with Sin and Temptation
What’s so Great about the Great Commission?
Do we Kneel and Bow Down Enough?
The Book of Revelation is Practical and Applicable
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