Convalescent serum for Covid-19

Using convalescent plasma to bolster immune defences against Covid-19
28 April 2020

Interview with 

Robert Lechler, King's College London


Man giving blood


Here in the UK, the National Health Service have begun asking coronavirus survivors to donate blood plasma, to see if it can be used to treat those who currently have the infection. "Convalescent plasma" trials like these are also being carried out in other countries too. But does this work? Robert Lechler is an immunologist at Kings College London and is part of the UK initiative. He spoke to Chris Smith about the plan...

Robert - Good evening. Well, as you imply, this is a very simple concept really. It's taking plasma, which is the liquid component of blood, from patients who have recovered from Covid-19, and donating that or transfusing that into patients grappling with the virus, but failing to clear it.

Chris - Why do you think that will be useful?

Robert - The theory here is that a key component of clearing the virus is the part of the immune response called antibodies. These are circulating proteins that bind to foreign particles like viruses and help the immune system clear them. And one of the features of making an immune response against the virus is that, almost always, you do make antibodies and those, if you transfer them, they circulate in plasma. If you can transfer those into a patient who's grappling with a virus, those donated antibodies will help the patient to clear the virus.

Chris - Are there enough people who have actually caught and recovered from coronavirus to make this practical though? Because we estimate that the number of people in the population, in percentage terms, who have had it and recovered is still quite low.

Robert - Well, that's a fair point. Depends very much on how you choose to apply this treatment, which patient population you donate the plasma to, and there are three options. One is patients in intensive care, ventilated at risk of losing their lives; the second option is patients who are ill enough to be in hospital but not yet ventilated, and you're aiming to help them clear the virus in order to prevent them needing ventilation. The third option is that you go into care homes for an elderly person who tests positive even before they're ill, you try to prevent the development of the disease. Now I would say based on prior experience, probably the second of those three options is the most attractive. And in that case then the numbers I think work because we do now have hundreds of patients who have recovered around the country and in the hospitals that I worked with, at Guys and St Thomas' and King's College Hospital, we have well over a hundred patients who are, in theory, eligible to donate plasma.

Chris - So how does it work? What's the nuts and bolts? A person comes in and does, to all intents and purposes, the same thing as we would do when we do a blood transfusion donation. You would take the donation of blood and then skim off the plasma, which has got the antibody in it?

Robert - Roughly speaking, yes. I mean one way to do it is literally to take a pint of blood and then spin the cells out and give the plasma. Probably more appropriate is to use a technique called plasmapheresis; when the blood is taken out of a vein through a machine that spins out the cells, returns the cells to the donor, and the plasma then is taken and transfused into another person.

Chris - One consideration with these coronavirus infections though is that we think it falls into a range of different phases, where the initial phase is the virus growing in the patient's lungs and doing damage to the lung tissue, and then there's a second phase, which some people tend to develop. I don't think it's fair to say, we really don't understand why that happens, but in that second phase, we think the immune system is doing more damage. So is there not a risk that if you give people more immune factors you could actually intensify this? It would be almost like pouring oil on the fire.

Robert - You're quite right that it does look as though some of the terminal phases of this illness are, if you like, an over-exuberant immune response causing collateral damage. The point I'd make however is that antibodies are not really an important part of that collateral damage - that's much more driven by things called cytokines, which are like circulating immune hormones, and I don't think there's a risk of it causing greater inflammation in this way. The other point I'd make is that, as you implied in your introduction, this approach, it was used in China. In fact in some Covid patients, hundreds of patients have now been treated in the US, they really shot off and got into gear to do this, and talking to my American colleagues they haven't seen adverse effects of the kind that you are alluding to.

Chris - That's reassuring. And just to finish, Robert, is it clear when we need to intervene with this therapy? Or is that what the trial is going to help us to understand: whether it's good to give this therapy early on in the disease course or do you wait for someone to be extremely unwell and then you try this as a rescue therapy?

Robert - You wouldn't, I think, do this on every patient who gets the virus. Because for many people it is a relatively mild or moderate illness. No, this would be for patients who are ill enough to be in hospital, maybe their oxygen saturation levels are dropping a little bit, but they're not compromised enough to need ventilation. So you're trying to help them turbo charge their immune system to clear the virus before they reach the point of needing ventilation. I think that's the attractive moment to intervene.


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