Thread by @nanogenomic

I am concerned about sub-threshold neutralizing antibodies tied to disease enhancing antibodies leading to greater persistence of COVID. Those with long COVID are canaries in the coalmine and we should be directing far more attention to the pathogenesis underlying these cases.

For example, we know omicron is ~40x less potently neutralized by antibodies against the original SARS-CoV-2 strain, which we based our vaccines off. So our strategy is a booster to boost levels 25x, breaking past this threshold.

But what happens when those antibodies wane? Where are the studies examining the disease-enhancing thresholds for Group IV and other infection-enhancing antibodies?

If overall neutralizing titers go down while disease enhancing antibodies, with stronger affinity to new strains, increase in titer, we could have an entirely new wave of chronic pandemic.

I am not by any means against vaccination. The evidence is clear that vaccines boost titers well beyond natural recovery. But it is time to update our vaccines to encompass new strains, and we need to engineer next-generation vaccines without disease-enhancing antibody epitopes.

Also, the @CDC and @WhiteHouse should prioritize testing neutralizing antibody titers just as much as giving people boosters, since there is so much COVID in the wild. Someone vaccinated who recovers from COVID post-vaccination may have a better, more up to date immune response.

This is controversial because of the outright vaccine hesitancy our nation is facing, and I am not trying to stoke fear or discourage anyone from getting vaccinated. We must, however, take on a more proactive strategy to eliminating COVID. We are not currently on that path.

Antibody therapies were originally funded by DARPA as “stopgap” therapies to offset a pandemic while vaccines and other therapeutics are developed. Administering antibodies certainly is effective at reducing disease severity and hospitalization, and this is an amazing tech.

The problem with “stopgap” approaches is that they do not train your own immune system. And there has been an absence of studies, as far as I’m aware, looking at antibody levels after these externally administered antibodies wear off.

ieeexplore.ieee.org/stampPDF/getPD…

Now we are seeing that Merck’s drug is only 30% effective and that omicron is leading to breakthrough cases in vaccinated individuals. The disease severity and hospitalization incidence is greatly reduced, which is great news.

reuters.com/business/healt…

Unfortunately, we are learning that mRNA vaccines are not generating robust upper respiratory / nasal mucosal and IgA antibody mediated immunity, meaning that while you are protected from severe illness and lower respiratory disease, you can still transmit.

It doesn’t take a lot of imagination to understand that we are all scared of this pandemic, and that despite a lot of amazing science and rapidly translated vaccines and therapeutics that are saving tens of millions of lives, we aren’t through the woods yet.

From a public health policy perspective, we should continue encouraging vaccination, while also making efforts to test for antibody levels and paying attention to disease-enhancing antibody thresholds as antibodies wane. Our next wave of boosters should include omicron.

Finally, we need to create approaches such as SARS-BLOCK that are designed to stimulate upper respiratory mucosal immunity and promoting robust clearance and immune learning from infections. COVID is everywhere. You likely cannot go on a bus or airplane without being exposed.

We have a chance of incorporating everything we know and have learned to offset this pandemic, but our diagnostic and therapeutic approaches are currently not accounting for vaccine hesitancy and extraordinary transmission among vaccinated individuals.