Undergraduate screening programs have given scientists early insights into the spread of the omicron

Omicron was first reported in South Africa on November 24, 2021, and within a few days it was already making the rounds in the US, sending the number of SARS-CoV-2 cases soaring as it infiltrated every school, restaurant and family gathering. But when exactly did Omicron displace the delta variable to become dominant? And how quickly did he actually take it?

These are the questions that a team led by researchers at Harvard Medical School set out to study in real time using new, faster, and changing technology to analyze SARS-CoV-2 samples from screening programs at universities in the region.

Their analysis was published on May 25 in Clinical Infectious Diseases, shows that the omicron arrived in Massachusetts earlier than experts had expected, and took over the task within days–; Information the study authors immediately provided to local hospitals and public health departments to report on preparations for an increase in COVID-19 cases.

Omicron’s rise to global dominance was very rapid, and so was her appearance here in Boston. It moved so quickly that we would have missed out on a lot of cases had it not been for these college-run screening programs, but with it we were able to document the acquisition.. “


Bill Hanage, lead study author and associate professor of epidemiology, Chan School of Public Health, Harvard Medical School

Researchers from Boston University, Harvard University, and Northeastern University collaborated to analyze SARS-CoV-2 samples from asymptomatic screening programs. They found that omicron is responsible for more than 90 percent of SARS-CoV-2 infections as early as nine days after it reaches the community. Furthermore, 10 percent of cases in college communities were omicon up to 10 days before omicron reached the 10 percent mark in Massachusetts.

Omicron outperformed the delta variant in universities one to two weeks earlier than in the state as a whole. In addition, patients infected with omicron had lower viral loads than those infected with delta-; Suggesting that the increased omicron transmission was due to characteristics of the variant itself, rather than the presence of more viruses.

Not only has the research helped sound the alarm about omicron, but it suggests that campuses may provide valuable monitoring centers for establishing surveillance programs for early detection of impending infectious disease outbreaks.

“Universities are a kind of crucible that reflects on the community around them, so they can be a good place to pick up things as they arrive,” said senior author Michael Springer, associate professor of systems biology at HMS’s Blavatnik Institute.

quick takeover

In early December, researchers began seeing an increase in COVID-19 cases in screening programs at Boston-area universities that coincided with an increase in cases in Massachusetts as a whole; By mid-December, universities were overwhelmed with positive cases.

“We all saw Omicron spreading all over the world and was about to come to Massachusetts,” Springer recalls, adding that at the same time “the number of positive cases we had in the testing lab was absolutely shocking,” adding that it had jumped exponentially from what it had been weeks before. Only few.

The standard technique for determining whether a SARS-CoV-2 sample is one variant or another involves sequencing the entire viral genome—a process that often takes seven to 10 days to complete. In fact, when the omicron arrived in Massachusetts, many of the labs running the SARS-CoV-2 genetic sequencing had a backlog of samples, delaying them by a week or two in understanding the true spread of the omicron.

With the clock ticking and cases of COVID-19 rising, researchers realized they needed a more efficient way to distinguish between omicron and delta, which until that point had accounted for more than 99 percent of cases. They used a variant identification technique recently developed by Nicole Welch, a doctoral student at HMS, the Broad Institute of MIT, Harvard University and an author on the paper. This technology combined PCR gene amplification and CRISPR gene-editing techniques to identify specific genetic mutations that distinguish delta from omicron.

“Instead of sequencing the entire virus, we asked if there were specific mutations at specific sites that collectively act as markers for viral variants,” said first author Brittany Petros, a doctoral candidate at HMS and the Broad Institute.

The team found that an omicron could be distinguished from a delta within hours based on at least three nucleic acid differences between the variants. Furthermore, the researchers used GISAID, a database of SARS-CoV-2 sequences from around the world, to confirm that these three nucleotide changes distinguish umicron from delta more than 99 percent of the time.

“It really allowed us to say yes, the shortcut method is sensitive and specific to the variables we want to characterize,” Petros said.

Using this technique, the researchers determined that Omicron completely bypassed Delta within nine to 12 days in the university’s communities. They also discovered that omicron was present and became dominant on local college campuses about one to two weeks earlier than it was in Massachusetts as a whole—and was spreading rapidly even though patients with omicron had a lower viral load than those with delta.

“Studying these things is really important for understanding how new variants are transmitted, and how much of that is down to being able to evade immunity that may mean we need to update the vaccines,” Hanage said.

spread the word

The researchers shared their data with hospitals and public health departments in real time, prompting some hospitals to pause elective surgeries in anticipation of more people being hospitalized with COVID-19.

“We just realized Omicron was not coming, Omicron is already here, and we have to tell everyone,” Springer said.

“Showing our data to people in hospitals and public health departments as we created it allowed a rapid public health response,” Petros added.

Massachusetts public health departments have also begun implementing this variant identification technology to analyze SARS-CoV-2 samples faster.

“The state took over the sample processing pipeline, and worked incredibly quickly to make it happen for the public good,” Springer said.

Petros noted that the same platform could easily be adapted to differentiate new variants of SARS-CoV-2, which will be important as the COVID-19 pandemic continues and the virus continues to evolve.

Springer and Petrus say several factors have made universities the ideal place to learn about Omicron’s dynamics. Schools had comprehensive screening programs where everyone was tested once or twice a week, not just when they developed symptoms and sought clinical care. Additionally, university communities tend to include many people from the surrounding area. Thus, all those tests from all these different people led to a large and diverse data set that can be easily studied.

People often aren’t hospitalized with COVID-19 until days or even weeks after they contract SARS-CoV-2, but the university’s samples, which are based on testing everyone regularly regardless of symptoms, caught Omicron as soon as they arrived.

“We’re talking about omicron completely outperforming delta in nine days—turning less than a full cycle for one person to get infected and hospitalized with COVID-19,” Petros said.

“There’s really a significant lag between when something happens and it’s widespread and problematic, and when it gets to hospitals,” Springer added.

On the logistical side, the universities had a lot of SARS-CoV-2 samples, a lot of researchers and technology. “Universities are centers of innovation,” said Springer. “We have new, useful technologies and everyone is open to collaboration, so it’s about how we can help figure out what’s going on.”

Many universities are now discontinuing SARS-CoV-2 screening programs, but Springer and Petros agree that similar programs could be a valuable tool in the future.

“Going forward, we need to think about how we can stop future epidemics, how we can better mitigate standard, endemic and infectious diseases,” Springer said. “Screening specific communities may be useful for this because they give us an early response.”

“This points to universities as the right place to conduct surveillance for emerging infectious diseases and future disease outbreaks,” Petros added. She said such monitoring could shed light on how an emerging disease spreads and how different strains of pathogens can compete with each other.

Now, the Springer lab is developing large-scale diagnostic panels that make analyzing SARS-CoV-2 and other pathogens cheaper and easier. Petros is exploring whether techniques such as those used in the study could be changed to sequence SARS-CoV-2 samples taken through rapid at-home antigen tests. Such testing will likely become even more important for understanding the circulating SARS-CoV-2 strains or strains, she noted, with asymptomatic screening programs closed.

Springer and Petros emphasized that the research could not have been accomplished without significant collaboration and rapid data sharing between researchers and institutions – something they hope will continue into the future.

“None of the studies from this school alone would be as robust as having data from several different schools together, where you can see the same reactions and the same pathways,” Springer said. “We’re trying to solve a real-world problem, so we have to work together.”

source:

Journal reference:

Petros, BA, and others. (2022) Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university communities. Clinical Infectious Diseases. doi.org/10.1093/cid/ciac413

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