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There has been a lot of speculation that plasma therapy - the process of transfusing blood plasma from a person who has recovered from COVID-19 to a sick person – could be the solution to the pandemic, removing the need for other treatments or a vaccine.
Let’s take a look at plasma therapy, how it works and what we know about how effective it is against COVID-19.
1) What is plasma therapy and how does it work?
Plasma therapy, also called convalescent plasma transfer, takes advantage of molecules called antibodies. Antibodies are made by your body when you get infected or get a vaccine, and these molecules help fight against the infection. Antibodies are found in one component of your blood: the plasma. Plasma can be separated from the other bits of blood by centrifugation (spinning the liquid really fast so the different phases separate out) or filtering. You can tell the plasma is different from the rest of your blood because its yellow rather than red (shown in the test tube in the picture below).
The approach of using plasma therapy has been around since we first learnt about antibodies in the 1890s and since then it has been used intermittently. The process of giving someone antibodies that they can use to fight infection is called ‘passive immunisation’, this is different from vaccines where the body is stimulated to make its own antibodies so is called ‘active immunisation’. Antibodies from passive immunisation eventually get cleared out of the blood system. That means that if you get plasma therapy or antibodies, your protection against the disease will only be temporary. This is different from active immunisation. In active immunity your body’s own cells make the antibodies and ‘remember’ how to make them for the future, which means immunity can last for a lifetime. Because active immunisation needs your body to make the antibodies itself, immunisation can take some weeks to build up. Passive immunisation is giving you the antibodies directly, so protection is immediate. The exact timings of when you’re immune after passive or active immunisation vary depend on the disease.
Rabies is an example of a disease we tackle by both active and passive immunisation. You can become infected with rabies if you’re bitten by a rabid animal. Once you start getting the nasty symptoms of fever and hallucinations, the disease is almost always fatal. Luckily, we have developed ways to protect ourselves from rabies using both active and passive immunity. If you’re at risk of getting the rabies (e.g. you handle animals like dogs or bats) you can get the rabies vaccine, which gives you long-lasting active immunity. If you get bitten by a suspected rabid animal, you can get immunoglobulins i.e. antibodies to give you fast-acting passive immunity. By tacking the deadly disease in both ways, we have managed to significantly reduce the number of people dying from rabies.
2) Does plasma therapy work against COVID-19?
We know that plasma therapy works for a few diseases, and there is also evidence that it works against COVID-19’s sister disease: SARS, but do we know it works against COVID-19?
The only way to really test whether plasma therapy works against COVID-19 is to do a clinical trial. This means we need to:
1) Recruit hundreds (if not thousands) of volunteers with COVID-19
2) Divide them randomly into two groups
3) Give one group plasma therapy as well as normal treatment, and the other group (called the ‘control group’) the normal treatment. You have to do this without telling them which group they are in
4) See if the people who got the new treatment do better than the other guys
Every medicine you see in the pharmacy has gone through some form of clinical trial. The trial checks that the medicine does what it claims it does, as well as identifies any side-effects.
Here is the good news: there has been a huge international effort to get these clinical trials running to test plasma therapy. As of today, none of the clinical trials have yet finished, which means we don’t have their results. Luckily we should be getting results soon, this trial in Paris is set to finish on 15th May.
So, we have not yet got any results from clinical trials stating that plasma therapy helps people who have COVID-19. But, as is obvious from the number of trials that are being set up, we seem to be pretty optimistic that it will. The reason for this is that we have ‘preliminary case studies’ that show it works. Case studies are not the same as clinical trials because they use far fewer people and they do not have a ‘control’ group to compare against. Interviews from patients and doctors in Italy have highlighted success stories of plasma treatment. This study in South Korea reported that two patients with COVID-19 improved after being treated with convalescent plasma. Another study, from Wuhan, recorded 10 people that had reduced virus levels and improved symptoms after receiving plasma therapy. These are not the only studies to show these results, but case studies are not the same as a clinical trial. In these examples, patients who received plasma treatment could have got better for other reasons, such as other medication they were using or because their body had started fighting the infection. As clinical trials compare plasma therapy vs no plasma therapy, they are the only way to say for sure that plasma therapy is the thing that is making people get better. On top of this, they can establish the best protocol for treatment: how early should a patient get plasma therapy and how much plasma do they need.
Despite not having all the information yet, on the 23rd March the FDA approved plasma therapy to be used for compassionate or emergency use. Hospitals can get plasma from volunteers and current evidence suggests that the risks of plasma therapy are low, so if it could work it would be unethical not to use it for the very sick people when we have no alternatives.
On the other hand, plasma therapy is not without drawbacks. One issue would be how to scale up the treatment – the logistical challenge of getting enough plasma from volunteers to treat all the sick people. The other issue is that that these clinical trials are currently testing to see is plasma therapy works on people who are already sick with COVID-19. If we get positive results from that (great!) we have a potential treatment, but we haven’t got a way to immunise people so they do not get it in the first place, which might be essential due to the scale-up issue and because some people might die even with plasma therapy. For long-term immunity we would need a vaccine (look at the two strategies we have against rabies). Plasma therapy is a potential treatment, a vaccine is a potential preventative measure – they fulfil complementary roles.
Hedging all our bets on one ‘solution’ is unfortunately not possible, because any one of the ‘solutions’ of today could end up being proved useless in a clinical trial tomorrow. Luckily, scientists and health care workers across the globe are using their different expertise to explore every angle of attack against COVID-19.
Useful links:
Clinical trials website is where you can search for clinical trials and see all the information about them for yourself.
Nature article with a table that summarises current clinical trials
Click on underlined words in the text to view sources
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