Read on Twitter
A very small sample size, but Dr. MacCannell shows 2 important findings here: 1. B.1.1.7 variant may not be very common in the US and 2. PCR is not a good substitute for sequencing when detecting variants. https://twitter.com/dmaccannell/status/1345081019225894912
On point 1, you can’t tell much from 31 samples. There are millions of cases of SARS-CoV-2 in the US and such a small sample size isn’t representative. Could be the variant is truly uncommon, could be that the samples only made it appear that way.
There could be much higher prevalence in other states or other communities than samples here. But that brings us to point 2, and calls for greatly expanding genomic sequencing efforts to find out.
Point 2 is related to the use of so called spike dropouts in PCR tests. PCR works by amplifying specific sequences in the viral genome, determined by specific primers and prove sets. If the sequence changes, primer/probes won’t bind and detect that target.
The B.1.1.7 variant has a deletion at positions 69 & 70 in S, and thus primer/probes directed at that site won’t yield a signal because of the deletion. However, 69/70del has emerged multiple times and is present in other variants.
Most notably, using S dropouts as a proxy for B.1.1.7, scientists in the UK made the claim that B.1.1.7 results in much higher viral loads, to the tune of 4 Cts. PCR amplification is exponential, so 4 cycles means that’s 4 orders of magnitude higher.
But this casts doubt on that finding. It’s clear that B.1.1.7 is more transmissible. Sequencing has confirmed that in the UK it became very prevalent, very quickly. What we don’t know is the mechanism for increased transmissibility.
Could be from increased fitness resulting in higher viral loads/increased shedding, could be better ACE2 binding, could be something else (better evasion of host antiviral immunity or interaction with a host factor enhancing replication or egress, for example).
This underscores the need for more research into the virological characteristics of B.1.1.7 but also reminds us that all assays have limitations. Based on the S dropout PCR data, I saw a lot of confident statements that “increased viral shedding” is responsible for transmission.
And that’s a big presumption even without the PCR issue. Viral load estimates can vary a lot anyway depending on when a sample is collected in the course of infection.
And, as Dr. MacCannell notes in his thread, the S dropouts in the US were largely other variants with the 69/70del and we shouldn’t rush to conclusions based on PCR alone.
The B.1.1.7 variant is concerning and we need to do a lot of work quickly to figure out some of these key questions: how is it more transmissible, will vaccines work against it, how prevalent is it in the US?
But overconfident statements and assumptions about data that itself is already based on assumptions (in this case that B.1.1.7 replicates to higher titers because of Ct values for S dropouts which are assumed to be B.1.1.7) can be harmful.
For example, assuming that because B.1.1.7 is more transmissible via higher viral loads, it is “a ticking time bomb” and we have to radically alter vaccination schedules without any evidence that doing so would provide protection against COVID-19.
Or thinking that travel restrictions will do a damn thing in places like the UK or US where transmission is widespread. You don’t need to worry about throwing a match into a burning building. You need to put the fire out.
Putting the fire out means stopping transmission. Bad news: there’s no way to do this with vaccines right now, given both limited supplies and major logistical issues with distribution. Switching to an (untested, unsupported) 1 shot regimen won’t solve distribution problems.
So what do we do? Good news: mutation doesn’t confer superpowers to the virus. It’s not more transmissible because B.1.1.7 can magically teleport into your respiratory tract. It’s not suddenly the viral equivalent of the X-Men.
Viruses don’t evolve to get around masks, distancing, or disruption of the virus particle by detergents or disinfectants. Mutation doesn’t defy the laws of physics.
B.1.1.7 is transmitted the same exact way as all the other variants of SARS-CoV-2 so you can reduce exposure risk with the same additive precautions:
-masks
-distancing
-stay home
-avoid gatherings/crowds
-avoid closed spaces/ventilate
-hygiene/disinfection
-masks
-distancing
-stay home
-avoid gatherings/crowds
-avoid closed spaces/ventilate
-hygiene/disinfection
Even if it turns out that increased shedding IS the means by which B.1.1.7 is more transmissible, that doesn’t change the path forward. Rather than tinkering with vaccine guidance or advocating for pointless travel restrictions, let’s emphasize precautions that we KNOW work.
Now before you say BUT ANGIE, they don’t work! They haven’t worked! No more lockdowns!...
They haven’t worked because people haven’t been doing them. People aren’t staying home. People got together for the holidays. People refuse to wear masks. Etc.
They haven’t worked because people haven’t been doing them. People aren’t staying home. People got together for the holidays. People refuse to wear masks. Etc.
So why do we think that, with widespread non-compliance with guidance, people are suddenly going to rush out for an untested vaccine regimen? It’s likely that not enough people will.
We need to redouble our efforts to encourage risk reduction. We need to get people on board with minimizing their exposure risk. We DON’T need to fearmonger about the unknowns about B.1.1.7 and use that to justify just winging it with something as important as vaccination.
So in conclusion:
-PCR doesn’t replace robust genomic surveillance
-we have a lot to learn about B.1.1.7
-this doesn’t justify new vaccine regimens
-stay home, stay safe, avoid the three Cs, Swiss cheese risk reduction
-PCR doesn’t replace robust genomic surveillance
-we have a lot to learn about B.1.1.7
-this doesn’t justify new vaccine regimens
-stay home, stay safe, avoid the three Cs, Swiss cheese risk reduction
