What’s the Difference Between Convalescent Plasma and Antibody-based Drugs?

In the early days of the COVID-19 epidemic, the opportunity to use Convalescent Plasma – the blood plasma from patients that have recovered from infections – got a fair amount of media attention, with Emergency Use Authorization and widespread use in hospitals, organized and led in large part by the National COVID-19 Convalescent Plasma Project.

Convalescent plasma has been primarily used in hospitals as a stop gap treatment in late stage Covid-19. Unfortunately, the data that has come back from these trials had indicated mixed success. Based on all that we’ve seen and learned about the virus’ pathogenesis, it should not be a surprise that its effectiveness has been limited.

How They Work

If you think of the virus like a fire, where antibodies – and immune response generally – works best is when the fire is small. Antibodies are given to “put out the fire”, and the same principles prevail. The bigger the fire and longer it has been going, the harder it is to put out the fire with an all-purpose agent – water(antibodies). So if you wait until late stage, severe illness – when the whole house is on fire – antibodies are not going to help nearly as much.

Respiratory infections are particularly difficult because the infections are really on the surface of the body – lung tissue. This means the blood can’t bring enough antibodies to be effective.

On top of that, a lot of studies and data have concluded that what is causing the very severe disease and death in most cases with Covid-19 is the immune response itself – those ‘cytokine storms.’ Why this varies so much is a mystery, but it seems clear that the bad outcomes are closely associated with this reaction. So, adding more antibodies is not going to help address this. The treatments that are having the most success in severe, late stage illness have been drugs that reduce the body’s over-active immune response.

The data that is most relevant to antibodies for the prevention use case are the vaccine trials. The consistent positive results of those together with the Phase 2 and Phase 3 antibody trials indicate that immune response is both strong and effective in putting that fire out when it first starts.

How They Are Administered

The other huge difference between Convalescent Plasma and antibody-based drugs are their method of delivery. Convalescent Plasma can only be administered in hospitals as a treatment, through an intravenous drip. So, by it’s very nature it is restricted to clinical settings and use cases – for people that are already sick.

Both major types of antibody-based drugs:

  1. Immuno Globulin and Hyper Immune Globulin;
  2. Monocolonal Antibodies;

Can be administered as shots, nasal sprays and similar methods. This means, of course, that they are much simpler and faster to give to people, and are suitable for delivery through clinics, doctor’s offices, public health centers, and so on.

That maps well to their use for both:

  1. prevention – given either prior to or immediately after exposure to the virus; and
  2. prophylaxis – given within a few days after exposure to reduce the severity of symptoms and disease.

These drugs can and are used as well for treatment of COVID-19 in later stages – and in fact much of the focus for development and production has been on that. But this misses the huge opportunity to apply them to give passive immunity now to a large segment of the population. As Dr. Scott Halstead, a global expert on infectious diseases and virology, and Science Advisor to Immunoprevention.org puts it:

We believe that antibodies could (should) be used to mitigate adverse COVID 19 outcomes and intervene in the chain of transmission by preventing infection of non-immunes. This is not a concept that has captured the public’s imagination. People understand the use of antibodies to reduce disease severity once the infection starts. Strange, we all know how to use antibodies against RSV to protect infants during their period of high risk to fatal infection. The long range solutions to the COVID 19 problem, clearly, are effective and safe vaccines. But, antibodies could be an effective interim tool.

Dr. Scott Halstead, Immunoprevention.org

What’s the Difference Between Convalescent Plasma and Antibody-based Drugs?
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