Omicron was first reported in South Africa on November 24, 2021, and within days it was already making its rounds in the United States, increasing the number of SARS-CoV-2 cases as it spreads. infiltrated every school, restaurant and family gathering. But when exactly did omicron overthrow the delta variant to become dominant? And how quickly did it actually take over?
These are the questions a team led by researchers from Harvard Medical School set out to investigate in real time using a new, faster variant-finding technique to analyze SARS-CoV-2 samples. from screening programs at area universities.
Their analysis, published on May 25 in Clinical infectious diseasesshows that omicron arrived in Massachusetts earlier than expected by experts and took over within days; information that the study authors immediately presented to local hospitals and public health departments to inform preparations for an increase in COVID-19 cases.
Omicron’s rise to world domination has been extremely rapid, as has its emergence here in Boston. It moved so fast that we would have missed a lot of cases without these college-run screening programs, but with them we were able to document the takeover..”
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 their asymptomatic screening programs. They found that omicron accounted for more than 90% of SARS-CoV-2 infections as early as nine days after arriving in a community. Additionally, 10% of cases in college communities were from omicron up to 10 days before omicron hit the 10% mark in Massachusetts.
Omicron outperformed the delta variant in universities one to two weeks earlier than in the state as a whole. Additionally, patients infected with omicron had a lower viral load than those infected with delta-; indicating that the increased omicron transmission was due to characteristics of the variant itself, rather than the presence of more virus.
The research not only helped ring the alarm bells on omicron, but suggests that college campuses can offer valuable monitoring centers to set up surveillance programs for early detection of incipient infectious disease outbreaks.
“Universities are a bit of a melting pot that reflects the surrounding community, so they can be a good place to pick up things as they happen,” said lead author Michael Springer, associate professor of systems biology at the University. ‘HMS Blavatnik Institute.
A quick recovery
In early December, researchers began to see an increase in COVID-19 cases in testing programs at Boston-area universities, which coincided with an increase in cases across Massachusetts; and by mid-December, universities were inundated with positive cases. .
“We all saw that omicron was spreading around the world and was coming to Massachusetts,” Springer recalled, adding that at the same time “the number of positive cases we had in the testing lab was quite shocking.” , as it jumped exponentially from where it was a few weeks earlier.
The standard technique for determining whether a sample of SARS-CoV-2 is one variant or another is to sequence the entire viral genome; a process that often takes seven to 10 days. In fact, when the omicron arrived in Massachusetts, many labs that do SARS-CoV-2 gene sequencing had a backlog of samples, delaying them a week or two in understanding the true prevalence of omicron.
With the clock ticking and COVID-19 cases on the rise, researchers knew they needed a better way to tell the omicron apart from the delta, which until then had been more than 99 % of cases. They used a technique for variant determination recently developed by Nicole Welch, a doctoral candidate at HMS and the Broad Institute of MIT and Harvard and author of the paper. The technique combined PCR gene amplification and CRISPR gene editing technologies to target the specific genetic mutations that differentiate delta from omicron.
“Rather than sequencing the entire virus, we asked if there were defining mutations at particular locations that collectively served as markers of viral variants,” said first author Brittany Petros, MD candidate at HMS and at the Broad Institute.
The team found that omicron can be distinguished from delta within hours based on as few as three nucleic acid differences between the variants. Additionally, the researchers used GISAID, a database of SARS-CoV-2 sequences from around the world, to confirm that these three nucleotide changes differentiated the omicron from the delta more than 99% of the time.
“It really allowed us to say yes, the shortcut method is sensitive and specific for the variants we want to differentiate,” Petros said.
Using this technique, researchers determined that omicron completely outgrew delta within nine to 12 days in university communities. They also found that omicron was present and became dominant on local college campuses approximately one to two weeks earlier than in Massachusetts as a whole; and it was spreading rapidly despite patients with omicron having a lower viral load than those with delta.
“Studying these things is really important to understanding how transmissible new variants are, and how much of that is due to an ability to circumvent immunity that could mean we need to update vaccines,” said said Hanage.
spread the word
The researchers shared their data with hospitals and public health departments in real time, prompting some hospitals to suspend elective surgeries in anticipation of hospitalizing more people with COVID-19.
“We realized omicron wasn’t coming, omicron was already here, and we had to let everyone know,” Springer said.
“Showing our data to people in hospitals and in public health departments as we generated it enabled a rapid public health response,” Petros added.
Massachusetts Public Health has also begun implementing this variant determination technique to more quickly analyze SARS-CoV-2 samples.
“The state has taken over the sample processing pipeline, working at incredible speed to make it benefit the public,” Springer said.
Petros noted that the same platform can 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 Petros say that several factors have made universities the perfect place to profile omicron’s dynamics. Schools had comprehensive screening programs where everyone was tested once or twice a week, rather than only when showing symptoms and seeking clinical care. Additionally, college communities tend to include many people from the surrounding area. So, all of these tests from all of these different people resulted in a large and varied data set that could be easily studied.
People are often not hospitalized with COVID-19 until days or even weeks after being infected with SARS-CoV-2, but university samples, which are based on regular testing for everyone, regardless of symptoms, captured omicron as soon as he arrived.
“We’re talking about omicron having completely outperformed delta in nine days – at which time less than one person was infected and hospitalized with COVID-19,” Petros said.
Springer added, “There’s actually quite a big lag between when something hits and spreads and is a problem, and when it gets to hospitals.”
Logistically, universities had many SARS-CoV-2 samples, as well as many researchers and technologies. “Universities are hubs of innovation. We have new and useful technologies and everyone is open to collaboration, so it was about how we could help understand what was going on,” Springer said.
Many universities are now shutting down their SARS-CoV-2 testing programs, but Springer and Petros agree that similar programs could be a valuable tool in the future.
“Moving forward, we need to think about how we will stop future pandemics and how to better mitigate standard, endemic communicable diseases. Monitoring certain communities could be helpful for this because they give us a quick response,” Springer said.
“This points to universities as the place to monitor emerging infectious diseases and future outbreaks,” Petros added. Such surveillance, she said, could shed light on how an emerging disease spreads and how different strains of pathogens may compete.
Now Springer’s lab is working on developing large-scale diagnostic panels that will make it cheaper and easier to analyze for SARS-CoV-2 and other pathogens. Petros is investigating whether it is possible to modify technologies like those used in the study to sequence SARS-CoV-2 samples taken with rapid home antigen tests. Such tests are likely to become even more essential for understanding circulating SARS-CoV-2 strains or lineages, she noted, as asymptomatic screening programs are halted.
Both Springer and Petros emphasized that the research could not have been accomplished without substantial collaboration and rapid sharing of data between researchers and institutions – something they hope to continue in the future.
“Any study from these schools wouldn’t have been as strong as having data from several different schools together, where you can see the same reactions and the same trajectories,” Springer said. “We’re trying to solve a real-world problem, so we’re going to have to work together.”
Petros, BA, et al. (2022) Early introduction and increase of the Omicron SARS-CoV-2 variant in highly vaccinated academic populations. Clinical infectious diseases. doi.org/10.1093/cid/ciac413