Promising targeted antibody discovered for SARS-CoV-2 may prevent or treat COVID-19!

A paper was just published in Cell, a top biological journal, presenting results from a study that has identified a targeted antibody that can attack and kill the virus for infected mice and prevent infection for un-infected mice who are exposed to the virus. Here is an article discussing the paper with comments from authors from the Thailand medical news that provides a more digestible summary of the paper.

The approach is pretty exciting! They started with "convalescent plasma", or blood samples taken from individuals who were previously infected but recovered, from a set of 60 recovered patients and identified 14 potent "neutralizing antibodies" (i.e. antibodies are immune system generated proteins that bind specifically to the virus, and neutralizing antibodies can effectively kill the virus or keep it from replicating), with the most potent antibody called "BD-368-2", which has non-overlapping characteristics with some of the other most potent neutralizing antibodies, so could potentially be used together. They used cutting-edge single-cell-sequencing methods to identify and characterize these antibodies. They characterize how this antibody works, overlapping with the ACE2 binding site that is the mechanism by with SARS-CoV-2 invades host cells and replicates.

This antibody showed strong therapeutic and preventative capabilities in a mouse model that is relevant for studying SARS-CoV-2. The mice injected with BD-368-2 antibodies 2 hours after infection showed 2400x less viral load than control mice injected with unrelated antibodies, and there was no viral load detected for mice injected 2 hours before infection.

This is exciting for a number of reasons:

  1. The most promising treatment so far is infusion of convalescent plasma from recovered patients (which is the "oldest trick in the book" vs. infectious disease).

  2. This strategy is limited by number of plasma donors, variability and uncertainty in potency and effectiveness of the antibodies from each donor, and logistical issues in using this as a general treatment strategy over a broad geographic region.

  3. This paper shows success in isolating antibodies from convalescent plasma, selecting out the most potent ones, and utilizing these in treatment and prevention of the disease. The results in mice are really impressive, and it will be interesting to see what happens when they try to move to clinical application of this idea. Clinical trials have already started

  4. This could be a very biologically smart and targeted approach to treatment, and especially prevention -- the authors of the paper suggest that their neutralizing antibody could be available by the winter.

  5. Their deeper characterization of this antibody provides a mechanistic explanation for its efficacy, which makes it more likely that these results will hold up in further studies.

Some points of caution:

  • There is always a leap going from mice to human models, as some strategies that work well in mouse models don't end up working in humans for a variety of reasons.

  • The "therapeutic" part of the study involved injecting mice with the antibodies 2 hours after infection. It is infeasible in real world settings to know when someone is infected and treat immediately, and there is no data even in mice on whether this would have efficacy say 12 hours or 24 hours after infection, so it is not clear that it can be used as a treatment.

  • Additionally, once the infection takes root in a patient and their COVID-19 disease is advanced, it seems like the body's imbalanced and overactive immune response is responsible for the life-threatening symptoms -- thus in these cases it is not clear that such an antibody would be effective in preventing/stopping/reversing these effects, and there is even potential for antiviral antibodies to increase the severity of these responses. This means care needs to be taken in trying strategies like these in advanced patients.

However, this is very exciting to me -- using cutting-edge technology and basic science to take something we know can work (convalescent plasma), taking the targeted antibodies that human's clever and effective natural immune system has learned to produce that might be the key to its efficacy, and then figuring out how to produce this natural antibody and utilize it for treatment and prevention. Clever work, and encouraging results!

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