This post will attempt to answer the following questions:
- What is convalescent plasma?
- How does donating plasma help?
- Will it help for COVID-19?
- What are the potential problems?
- Why isn’t this happening everywhere?
The idea of transfusing convalescent plasma into a sick patient is nothing new. Plasma is the part of the blood that does not have living white or red blood cells. It is mostly water but also contains electrolytes and proteins of various types. Some of those proteins are antibodies. The idea then is simple. People who recover from an infection have produced antibodies that are responsible for eliminating the pathogen. That plasma can be transfused it into someone who is seriously ill to help them fight off their infection.
The idea of taking the blood plasma from someone who had an infection and recovered and transfusing it into somebody who is sick was first done in the 1890s to treat the bacterial infection diptheria . This was a deadly (but now vaccine preventable disease that causes a coating along the back of the throat leading to breathing issues among other problems. In this first iteration they didn’t even use convalescent plasma from people. They infected horses and then transfused their plasma into infected people – and it worked! In fact, the very first Nobel prize in medicine was given to Emil von Behring for this discovery. Fortunately for us (and the horses) it was discovered how to do this using human plasma and was used in various outbreaks throughout history including in the Spanish flu pandemic of 1918-1919. It was abandoned in the 1950s after vaccines became more effective. As bloodborne pathogens like hepatitis and HIV came around this practice was nearly completely abandoned.
This changed in the past 20 years with improvements in screening and safety of the blood supply. It was actually used in both other major coronavirus outbreaks – SARSCoV1 in 2003 and MERS in 2012 with positive results.
This sounds like a game changer and it may be. There is also something beautiful and poetic of someone who has gone through a trial and prevailed giving a piece of themselves to someone else to help them through the ordeal. Unfortunately the solution is not perfect. First, it’s not clear if or how well it will work for COVID-19.
Why wouldn’t it work? The problem may be that the antibodies only work at an early point in the disease. It could be that the plasma is only effective before viral levels have reached a certain threshold. It could also be that when people become critically ill it is not the virus that is what’s making them so ill. There seems to be a period where the immune system starts to clear the viral particles but then expands its response out of control. At this point the virus itself is not causing the damage, the immune system is and getting antibodies to kill the virus at this point would be too late. To keep with our equine theme, the horse is out of the barn. This may be a problem with COVID-19 since we are seeing people who are critically ill later in the disease course when it may be too late for plasma to work.
There is also a problem of variability in plasma levels of virus fighting proteins and antibodies. It may be that the effectiveness of one donor’s plasma is different than another’s so it effectiveness would vary. This could cloud the research results and clinical response.
So why not give it earlier? The problem with giving it earlier is that you may be giving people the plasma who would have recovered anyway. There are significant risks. Plasma transfusions are associated with adverse events ranging from mild fever and allergic reactions to life-threatening bronchospasm, transfusion-related acute lung injury, and circulatory overload in patients with cardiorespiratory disorders. These must be carefully tracked. If the plasma is effective, the risks would be justified but it would be a shame to cause an adverse reaction in a patient that would have recovered without any treatment.
So it is not a guarantee that plasma donations will work but they may. There are early reports of effectiveness that are encouraging but can’t lead to conclusions. This is why we do science. There are trials underway that are giving convalescent plasma to people who are very sick, to patients early in the disease who are mildly at risk, and to healthcare workers who have a high exposure (to try and prevent disease).
If it is effective there are logistical issues. This is where I am in my personal plasma donation journey. I have filled out no less than 5 or 6 forms volunteering to donate my plasma but keep running into roadblocks. This is likely due to the fact that the systems to collect, check, and distribute the blood are not yet in place. These are the steps that need to be taken to make this happen:
- Donors need to be identified.
- Testing needs to be done to determine if they were infected and if they have recovered.
- There needs to be a location that they can go to donate.
- The supplies, staff, and equipment needs to be set up to collect their plasma.
- Recipients need to be identified. In this case the research trials need to be designed and approved and consent needs to be given.
- The plasma needs to typed, screened for communicable disease, and stored.
- Appropriate recipients need to be identified.
- The plasma needs to be delivered and administered.
Fortunately, our nation’s blood banks are set up to do steps 3-6 but they need to be mobilized for this. Thanks to a dedicated infectious disease specialist at my hospital I have finally been accepted to enter a clinical trial as a donor. The donation will be coordinated through the Red Cross and the Mayo Clinic. More than one administrator has contacted me. This has not been simple. I was all set to go but then found out I have to get tested again for coronavirus. I guess this is to make sure I am not still infected. I’m not sure why they can’t do antibody testing but I’m happy to comply. I just need to get a break to get down to get tested. I just used my only break in seeing so many COVID19 patients to write this. I’ll have to go tomorrow. I’ll let you know how it goes.