Authors Dr. Angela Rasmussen
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Hard agree. And if this is useful, let me share something that often gets omitted (not by @kakape).
Variants always emerge, & are not good or bad, but expected. The challenge is figuring out which variants are bad, and that can't be done with sequence alone.
You can't just look at a sequence and say, "Aha! A mutation in spike. This must be more transmissible or can evade antibody neutralization." Sure, we can use computational models to try and predict the functional consequence of a given mutation, but models are often wrong.
The virus acquires mutations randomly every time it replicates. Many mutations don't change the virus at all. Others may change it in a way that have no consequences for human transmission or disease. But you can't tell just looking at sequence alone.
In order to determine the functional impact of a mutation, you need to actually do experiments. You can look at some effects in cell culture, but to address questions relating to transmission or disease, you have to use animal models.
The reason people were concerned initially about B.1.1.7 is because of epidemiological evidence showing that it rapidly became dominant in one area. More rapidly that could be explained unless it had some kind of advantage that allowed it to outcompete other circulating variants.
Variants always emerge, & are not good or bad, but expected. The challenge is figuring out which variants are bad, and that can't be done with sequence alone.
Feels like the next thing we're going to need is a ranking system for how concerning "variants of concern\u201d actually are.
— Kai Kupferschmidt (@kakape) January 15, 2021
A lot of constellations of mutations are concerning, but people are lumping together variants with vastly different levels of evidence that we need to worry.
You can't just look at a sequence and say, "Aha! A mutation in spike. This must be more transmissible or can evade antibody neutralization." Sure, we can use computational models to try and predict the functional consequence of a given mutation, but models are often wrong.
The virus acquires mutations randomly every time it replicates. Many mutations don't change the virus at all. Others may change it in a way that have no consequences for human transmission or disease. But you can't tell just looking at sequence alone.
In order to determine the functional impact of a mutation, you need to actually do experiments. You can look at some effects in cell culture, but to address questions relating to transmission or disease, you have to use animal models.
The reason people were concerned initially about B.1.1.7 is because of epidemiological evidence showing that it rapidly became dominant in one area. More rapidly that could be explained unless it had some kind of advantage that allowed it to outcompete other circulating variants.
This is a must-read article by @mlipsitch and @kesvelt and I strongly agree with the central points: we urgently need to step up genomic surveillance & get transmission down now in the US while these are rare.
But a couple things to expand on from a virology point of view.
The piece talks about the B117 variant as if it’s not SARS-CoV-2, but it is. B117 is distinguished by 23 changes across the genome, but it’s still fundamentally the same virus. It’s a different variant (some are calling it a strain depending on how that’s defined).
But 23 nucleotide changes aren’t sufficient to make this a completely different virus. So we are still fighting SARS-CoV-2. Just a new and improved version. Improved how? Well it’s more transmissible but the mechanism isn’t yet known.
When viruses become more transmissible it can happen in a few different ways:
-virus can be more fit (replicate to higher titers, hence more shedding)
-virus can replicate more efficiently in specific tissues (like the nose)
-spike can bind the receptor more efficiently and...
...thus infect host cells more efficiently
-virus can get better at evading/antagonizing innate host antiviral defenses
-increased environmental stability
-people can shed virus for longer periods of time
But a couple things to expand on from a virology point of view.
The article and the accompanying thread from @kakape are well worth a read https://t.co/32c8l66eTV
— Jason Kindrachuk, PhD (@KindrachukJason) January 9, 2021
The piece talks about the B117 variant as if it’s not SARS-CoV-2, but it is. B117 is distinguished by 23 changes across the genome, but it’s still fundamentally the same virus. It’s a different variant (some are calling it a strain depending on how that’s defined).
But 23 nucleotide changes aren’t sufficient to make this a completely different virus. So we are still fighting SARS-CoV-2. Just a new and improved version. Improved how? Well it’s more transmissible but the mechanism isn’t yet known.
When viruses become more transmissible it can happen in a few different ways:
-virus can be more fit (replicate to higher titers, hence more shedding)
-virus can replicate more efficiently in specific tissues (like the nose)
-spike can bind the receptor more efficiently and...
...thus infect host cells more efficiently
-virus can get better at evading/antagonizing innate host antiviral defenses
-increased environmental stability
-people can shed virus for longer periods of time