Thread by @ASlavitt

COVID Update: How big a problem will future variants be?

I got an update from several top scientists. 1/

Quick review. Viruses continually mutate but can only mutate when they replicate. And so far we’re giving SARS-CoV-2 plenty of opportunities to replicate. 2/

Most mutations aren’t worth noting. They don’t increase hospitalizations. They don’t increase infectiousness. And they don’t cause problems for prior immunity. 3/

A fallacy pushed by anti-vaxxers is that vaccinations cause mutations.

It’s false. The more unvaccinated people, the more replication within cells as people mount a slow immune response— the more chances for the virus to mutate. 4/

So far the variants of concern that have taken hold in countries around the world have followed 1 of 2 paths for more cell replication— either evading vaccines or spreading more easily.

But so far none of these variants have combined both problems— evasiveness & contagiousness.5

Think of one path as going broad to more people (a more contagious variant is harder to catch) and another path as going deep (within a single individual to more cells).

One that had mutations to be the most rapidly growing & most evasive would be the most concerning. 6/

The vaccines that have caused the most trouble for vaccines in vitro & in reality (Beta, Iota, Delta+, Mu) have so far been outcompeted by the variants that spread more rapidly (Alpha and now Delta). 7/

Problematic variants that can’t grow as fast as Delta will be only a limited problem.

When we read about a Mu (0.1%) being a problem for vaccines, if it can’t outcompete Delta, it won’t take hold. 8/

So Delta, oddly, is defeating variants that would be more challenging for vaccines (and also monoclonals).

And until a variant that causes problems for the vaccine also spreads faster than Delta, it won’t become dominant. 9/

As an aside, Delta causes some problems for the vaccine but in a different way— because it replicates more virus so quickly that w/ lower antibody levels, immune response often isn’t fast enough to prevent symptoms. Cellular immunity does kick if to prevent hospitalizations. 10/

So why hasn’t a variant come along that has both negative characteristics? Will it?

The answer to the first question is largely randomness. There’s no reason why both types of mutations can’t exist in the same virus variant. 11/

The more opportunity, the more random things will happen. So it’s also the length of time of the pandemic, the spread & the too slow, too low vaccination rates that increases the odds. 12/

Will it happen?

We don’t know but we do know that vaccinating the globe and the US more quickly will reduce the odds.

In the scheme of viruses Delta already replicates very fast. Not close to measles, but arguably comparable to chicken pox. That’s a tall order for a mutant. 13/

So we could expect to see a lot of “problematic” mutations for the vaccines that never amount to much because Delta crushes them.

But what happens if we do see one that’s vaccine evasive that Delta doesn’t outcompete— or at least leaves room for it in some regions? 14/

There are a few key ingredients that must be ready: surveillance, vaccine development, regulatory & scaled manufacturing/distribution. 15/

We’ve taken a big step forward in surveillance with the CDC’s new forecasting center. Genetic sequencing need to occur however in many more regions of the US than it does now.

Countries around the world are also improving their ability to spot variants quickly. 16/

Once we identify a new variant, we can test its effectiveness against vaccines in the lab. If one is an evasive mutation, within 100 days we should have the capability to develop a new specialized booster.

By that time we should know if the variant is outcompeting Delta. 17/

The good news is that as long as a virus generates an immune response from the body, we should be able to make a vaccine that works (which is why HIV has been so challenging for scientists). 18/

Over the course of the year the Biden Admin has put together a pandemic resiliency plan that should allow for the rapid production & distribution of vaccines for new variants & new viruses.

The aim is 100 days for a vaccine & 100 days for full production. 19/

200 days sounds like a long time but if we have good surveillance & begin right away, remember how long it could be before a mutation is discovered & its proliferation depending on the origin. 20/

If the original COVID started circulating in China in the 4th quarter last year, it months before it started to spread significantly around the 🌏 .

If we are developing vaccines at pace, it could end up being only a short spike in most countries before a vax is ready. 21/

This will undoubtedly mean suffering in the place of the variant’s origin. And a lot of logistics (imagine a whole new global rollout). We will need to get better & better at it.

And of course each time face anew the challenges of vaccine hesitancy. 22/

Layered protections are essential. A vaccine plus a mask and good ventilation plus awareness of when spread is increasing in your community will keep everyone safest. 23:

Along with the development of an oral anti-viral, we are building the arsenal as a globe & as individuals to manage new variants but we have to use them.

24/

Right now Delta is the devil we know. And while not our friend, it is at least the enemy of our enemy.

If we don’t want to deal with worse variants we know how to reduce the odds. Slow the spread. Accelerate global vaccinations. Take its potential seriously. /end

One of the scientists who informed this thread is Tony Fauci. He’s my guest on @inthebubblepod tomorrow.