Using quantitative genomics to track and understand COVID-19

Emma Hodcroft-PQG conference
Emma Hodcroft of the University of Bern outlined efforts to sequence SARS-CoV-2 samples in order to understand the virus’s spread and evolution

November 3, 2021 – Tracking variants of SARS-CoV-2, understanding which mutations make the virus more dangerous, and figuring out where the virus originally came from were some of the topics highlighted at the 15th annual Program in Quantitative Genomics (PQG) conference.

Held virtually October 28-29, 2021, the conference—“From COVID-19 Genomics to Spread, Vaccine, and Therapy”—featured a dozen experts. More than 70 participants from around the world viewed the live proceedings.

After opening remarks from Xihong Lin, professor of biostatistics and PQG coordinating director, participants heard from keynote speaker Emma Hodcroft, postdoctoral researcher at the University of Bern’s Institute of Social and Preventive Medicine, who outlined experts’ efforts since early 2020 to sequence SARS-CoV-2 samples in order to understand the virus’s spread and evolution.

After countries around the world began sharing sequencing data, scientists were able to distinguish between imported and locally transmitted infections, Hodcroft said. So, for example, screening samples collected in the spring of 2020 in the Seattle area, where there was an initial cluster of COVID-19 cases in the U.S., showed closely related sequences indicating that the cases weren’t only the result of travel, but represented ongoing local transmission.

Soon after, experts began tracking mutations in the virus. “For a long time these were more of a curiosity used to mark different clusters that were of interests to scientists, but didn’t seem to have much epidemiological or transmission impact,” Hodcroft said. “But this changed. Now we are very certain that there are impacts from different mutations on how the virus behaves. It is through being able to track these mutations and identify them in sequences that has allowed us to see the different variants of concern and of interest, and to track them.”

Mutations are only one piece of the puzzle in determining whether a dangerous new variant is cropping up, Hodcroft said. A rise in cases could also be due to seasonality, a super-spreader event, a change in local COVID-19 restrictions, or an increase in travel, she said. Sometimes a lack of complete information makes it difficult to tell what’s behind a surge in cases, she said.

Even if researchers find concerning properties in a new variant in the lab—such as the ability to evade immunity—it might not turn out to be a danger in the population at large, Hodcroft noted. “If we only detect it in a handful of people and it doesn’t seem to spread very well, then it may not be something that we would put at the top of our list as a variant of concern,” she said, adding, “We’re working at the edge of scientific knowledge, with new data coming in at an unprecedented rate and in unprecedented amounts. We’re trying to predict really complex outcomes from imperfect and often delayed data.”

Scientists are currently keeping watch on a new Delta variant dubbed “AY.4.2,” seen primarily in the United Kingdom. Hodcroft said that the proportion of AY.4.2 has gone up quite sharply in the U.K., and now represents about 11% of all cases there. “What does it mean? Should we be concerned about AY.4.2? I think at the moment it’s difficult to say,” she said.

Hodcroft urged continued global investment in sequencing and in sequencing expertise. “We still have blind spots around the world where we’re not regularly getting good numbers of sequences that allow us to have a really clear picture of what’s going on in [a particular] country and to know whether new variants are rising, or what variants are being imported there, and what impact they’re having.”

The conference featured two other keynote speakers. Benjamin Neale, co-director of the Program in Medical and Population Genetics at the Broad Institute and Director of Genetics at the Stanley Center for Psychiatric Research, spoke about the COVID Host Genetics Initiative, a consortium of roughly 3,000 scientists from more than 54 countries working collaboratively to generate, share, and analyze data to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes. Bette Korber, laboratory fellow at Los Alamos National Laboratory, spoke about her and her colleagues’ efforts to track the evolution and variants of SARS-CoV-2.

Georg Hahn, research associate in Harvard Chan School’s Department of Biostatistics and an abstract award winner at the conference, spoke about his genome-wide association analysis, conducted with Christoph Lange, professor of biostatistics, that accurately flagged a more deadly SARS-CoV-2 variant, found mostly in Brazil, known as P.1 or gamma.

Kristian Anderson, professor of immunology and microbiology at Scripps Research, discussed the major hypotheses about the origins of SARS-CoV-2, that it leaked from a lab or jumped from animals to humans. “What is the evidence for a lab leak?” he asked. “I will posit that there is none.” Most of the evidence points to the idea that the virus emerged from animals that were sold at wet markets in Wuhan, China, he said.

Other speakers covered topics including the evolution and spread of the B.1.1.7 variant in the U.K., the pathology and cellular targets of SARS-CoV-2, and the risk that SARS-CoV-2 could escape vaccine-induced immunity. The conference also included a virtual poster session featuring the work of junior researchers.

Karen Feldscher