Good morning and welcome to COVID Transmissions.
It has been 424 days since the first documented human case of COVID-19.
Today, a couple of headlines and a brief in-depth about why it’s important to sequence virus genomes.
As usual, bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
The deadliest week yet for the US
Last week was the deadliest week of the pandemic for the US, with more than 22,000 deaths.
Details here: https://www.cbsnews.com/news/covid-us-deadliest-week-2020-01-12/
We have not sequenced enough SARS-CoV-2 genomes in the US
As it turns out, up until quite recently, in the US we had only sequenced about 51,000 SARS-CoV-2 genomes. This may sound like a lot, but we’ve had at least 23,000,000 infections to date, and 17,000,000 infections at the time that the 51,000 number was released. 51,000 genomes is less than 3 tenths of 1 percent of the total number of cases that we could have sequenced virus from. Considering that there are many many viruses present in each infected person, it’s a vanishingly small number of the total virus genomes that have existed in the US altogether.
This stat comes from a CDC information page on the new B.1.1.7 variant: https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-emerging-variant.html
Here’s the information in context:
The VOC 202012/01 variant has not been identified through sequencing efforts in the United States, although viruses have only been sequenced from about 51,000 of the 17 million US cases.
Note that at the time the variant hadn’t yet been detected in the US.
This is a problem, and I’ll expand on why in today’s in-depth.
Travelers to the US will now need to be tested
Likely motivated by international variants appearing, travelers to the US from abroad will need to provide negative results of a COVID-19 test within 3 days of their departure, effective January 26th: https://www.cdc.gov/media/releases/2021/s0112-negative-covid-19-air-passengers.html
This isn’t a perfect solution, and the CDC acknowledges that. However it may filter out some cases that we wouldn’t have detected otherwise, and every little bit helps.
What am I doing to cope with the pandemic? This:
Deadlifting
I tried out deadlifting properly for the first time last night. I’ve been training up for quite awhile to where I could learn to do this. I have very little to say about it except this: wow, that’s not easy. I expect to be sore today.
What’s the deal with sequencing? (Apologies to Jerry Seinfeld)
Lately, we’ve had a lot to discuss regarding variants and genomes and detection. I told you before that it’s a bad thing that the US has not sequenced many of the SARS-CoV-2 genomes circulating in our population. Now, let me tell you why. We’re also going to walk through how sequencing is different from testing, in a practical sense.
New variants are detected via routine genome sequencing. Genome sequencing is talked about a lot in the popular press, but the difference between it and other analysis techniques is often dashed past without explanation. Both sequencing and PCR tests, which are used for most COVID-19 testing, rely on analysis of nucleic acids like RNA or DNA.
PCR tests are different from sequencing; these tests target and detect a certain general sequence, but they don’t need that sequence to match 100% every time. This is very useful for detecting things that mutate, like viruses. However, this type of test doesn’t tell us much about what mutations may be present.
PCR relies on the use of predefined “primers,” and copies anything from the target sequence that shows up between those primers. The primers need to match pretty well, but they don’t need to be a 100% match to the sequence—and they only need to recognize a small part of the genome. It doesn’t matter if anything besides whether primer actually attaches has changed. If the primers still attach, the PCR test can detect the virus—no matter how many mutations are present elsewhere.
This is good and bad. If the virus mutates, we can still detect it, especially if we use multiple redundant primer sets that detect different parts of the virus genome. However, it also means PCR can’t tell us very easily if the virus mutates. It will still give us a “yes” answer.
As it turns out, for B.1.1.7, we got a little lucky here—one of the mutations in that variant actually did affect one primer set, but not all of the primer sets in PCR tests. This made it somewhat easier to detect the variant, but didn’t really tell us anything specific about how the variant was different. For that, we needed sequence data.
Sequencing is a more intensive technique. It tells us the precise molecular composition of the chains of RNA or DNA present in a sample. We call this a “sequence” because RNA and DNA both use variations of 4 specific molecular units to form the “genetic code.” We’ve assigned these molecules letters, and when we sequence, the output is a string of those letters representing which molecules appear in which order. The reason I explain this in such detail is to offer a reminder that these strings of letters are not really letters—they represent chemicals that occupy 3 dimensional space, and have real chemical properties. This happens to matter in biochemistry and is often forgotten.
Anyway, sequencing is a little more complicated and a little more time consuming than PCR. If PCR takes two hours to detect something in a sample, sequencing might take a day or two—and we’re just talking about turnaround time on the actual process, not the work of shipping and setting up the sample in the workflow, etc. So if PCR tests are taking a few days to come back now, if we relied on sequencing for our testing, we would expect it to potentially take weeks. So while in theory, we could use sequencing as a way to test for COVID-19, in practice, it isn’t a good option.
For this reason, the US hasn’t sequenced a lot of SARS-CoV-2 genomes. I understand the priorities involved, but in the end, this hurts our surveillance. Other countries frequently sequence genomes of circulating viruses—and in fact, the US does it quite frequently for things like influenza virus—but we have deprioritized this in favor of other things.
The B.1.1.7 variant detected in the UK was detected because they sequenced a large share of genomes over there. To get accurate surveillance, you need to sequence genomes routinely. The US hasn’t been doing that.
We probably need to start. I’ve heard some reports that we are, but this will be a slow effort. No matter what, we need better intelligence on the nature of the epidemic raging in the United States.
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See you all next time.
Always,
JS
You saw the reports that Johnson and Johnson can't produce their vaccine until April, even if it shows great effectiveness when they report on their Phase 3 trial this month? Apparently, they are having trouble getting manufacturing set up. Not that surprising, commercializing these processes is hard, but disappointing.