Breaking down COVID-19 variants: Houston Methodist Hospital sequencing genomes

How can researchers tell what variant of COVID-19 is spreading in our area? It all begins in a laboratory.

In the Department of Pathology at Houston Methodist Hospital, their research group is skilled at sequencing different types of diseases.

"Yes, we have very large population-based collections of bacterial diseases, things like staph that cause common staph infections or group A strep, which causes strep throat and other things. We have a long history of really over a decade of doing work in genomics in bacteria, and we realized back in January 2020, at the start of the pandemic, that we needed to pivot our efforts to doing sequencing for all of our COVID-19 positive samples coming from patients," explains Dr. S. Wesley Long, the Medical Director of Diagnostic Microbiology at Houston Methodist.

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So how do they figure out if COVID-19 is Omicron, versus Delta, etc.?

"The analogy that I like to use is that when we sequenced the genome, the genome for a patient's COVID-19 is really like a book and the letters and the words and the paragraphs in that book are what tell the virus, how to make more virus, how to infect cells, how to do all the things that it does. What happens with these variants is that new mutations are really what you can think of as typos in the book that change letters, change the meanings of words and phrases, and hopefully change the behavior of the virus. So when we do sequencing of these samples, it's really like reading each patient's viral book and identifying what mutations or typos are there. And then when we see a certain set of typos or mutations, we know these mutations, means it's an Omicron variant, or these other set of mutations, some of which may overlap. But then we can also then study what's the effect of those changes on the behavior of the virus in patients," explains Dr. Long.

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Figuring out the variants is a very involved process.

"That happens in our research lab. We have a very dedicated team of research technologists, who work very hard, really 24/7 to process the sample. So after all of the clinical testing is done and the patient knows that they're positive, the leftover samples go to the research lab. There's some robotic automation, there's a lot of chemistry, a lot of enzymes and things that happen. We have to take the viral, what is actually RNA, make a DNA sequence and then prepare for sequencing. Then there's a large sort of washing machine size instrument that actually does the sequencing over about 36 hours, and then there's quite a bit of computational work that gets done on the back end to analyze that sequence. And then we of course, take that sequence data and go back and pull it, all of our patient data, and learn what we can from that, but it's really about a week-long process for the technologists to go from leftover positive sample, all the way through all the different enzymes and robotic steps to the final sequencing stuff and then to get the data and get it analyzed," states Dr. Long.

Parent to Parent: Protecting your children from COVID-19

As the omicron variant cases continue to rise, parents are becoming frustrated and worried about their kids going back to school where masking is not mandated.

It's important for researchers to keep up with the variants, so they can determine if vaccines and/or treatments will still respond or need to be tweaked to make them more beneficial.

"There is often different behavior that's ascribed to different variants. So as soon as there's a new variant of concern, a lot of work starts being done, usually in research laboratories, to look at how things might change in a lab dish, studying antibodies and things. Things change this way or that way in a test tube. We literally want to know, what does it mean for patients who are vaccinated, what are we seeing in terms of breakthrough severity, and then we want to do those downstream studies to really understand what the variant means, and to be able to communicate that with the public and communicate it with hospital leadership, so we know if we need to make changes to therapy or other things that we can do that in a timely manner," says Dr. Long.