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Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
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February COVID-19 Superspreader Event in Boston Confirmed by Use of Genetic Sequencing as Next-Gen Sequencing Is Put to Novel Uses, including in Clinical Laboratories

Gene sequencing is enabling disease tracking in new ways that include retesting laboratory specimens from before the SARS-CoV-2 outbreak to determine when it arrived in the US

On February 26 of this year, nearly 200 executives and employees of neuroscience-biotechnology company Biogen gathered at the Boston Marriott Long Wharf hotel for their annual leadership conference. Unbeknownst to the attendees, by the end of the following day, dozens of them had been exposed to and become infected by SARS-CoV-2, the coronavirus that causes the COVID-19 illness.

Researchers now have hard evidence that attendees at this meeting returned to their communities and spread the infection. The findings of this study will be relevant to pathologists and clinical laboratory managers who are cooperating with health authorities in their communities to identify infected individuals and track the spread of the novel coronavirus.

This “superspreader” event has been closely investigated and has led to intriguing conclusions concerning the use of genetic sequencing to revealed vital information about the COVID-19 pandemic. Recent improvements in gene sequencing technology is giving scientists new ways to trace the spread of COVID-19 and other diseases, as well as a method for monitoring mutations and speeding research into various treatments and vaccines. 

Genetic Sequencing Traces an Outbreak

“With genetic data, a record of our poor decisions is being captured in a whole new way,” Bronwyn MacInnis, PhD, Director of Pathogen Genomic Surveillance at the Broad Institute of MIT and Harvard, told The Washington Post (WaPo) during its analysis of the COVID-19 superspreading event. MacInnis is one of many Broad Institute, Harvard, MIT, and state of Massachusetts scientists who co-authored a study that detailed the coronavirus’ spread across Boston, including from the Biogen conference.

Titled, “Phylogenetic Analysis of SARS-CoV-2 in the Boston Area Highlights the Role of Recurrent Importation and Superspreading Events,” the paper explains how the researchers “sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region” in order to investigate how the virus was introduced and spread through the area. They traced a specific mutation in the virus—“a simple switch of two letters in the virus’ 30,000-character genetic code,” WaPo reported.

What they discovered is both surprising and enlightening. According to WaPo’s report, at least 35 new cases of the virus were linked directly to the Biogen conference, and the same strain was discovered in outbreaks in two homeless shelters in Boston, where 122 people were infected. The variant tracked by the Boston researchers was found in roughly 30% of the cases that have been sequenced in the state, as well as in Alaska, Senegal, and Luxembourg.

“The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission,” the researchers noted in their study abstract.

“The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into [Massachusetts] early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data,” they concluded.

Anthony Fauci, MD
Some experts think humankind may be entering a period of increased pandemics. In their report published in Cell, titled, “Emerging Pandemic Diseases: How We Got to COVID-19,” Anthony Fauci, MD (above) Director of the National Institute of Allergy and Infectious Diseases (NIAID), and David Morens, MD, a senior associate professor at Johns Hopkins School of Public Health and Senior Advisor to Fauci, wrote, “One can conclude from this recent experience that we have entered a pandemic era. The causes of this new and dangerous situation are multifaceted, complex, and deserving of serious examination.” (Photo copyright: NIAID.)

Genetic Sequencing and Mutation Tracking

The use of genetic sequencing to trace the virus could inform measures to control the spread in new ways, but currently, only about 0.33% of cases in the United States are being sequenced, MacInnis told WaPo, and that not sequencing samples is “throwing away the crown jewels of what you really want to know.”

Another role that genetic sequencing is playing in this pandemic is in tracking viral mutations. One of the ways that pandemics worsen is when viruses mutate to become deadlier or more easily spread. Scientists are using genetic sequencing to monitor SARS-CoV-2 for such mutations.

A group of scientists at Texas A&M University led by Yue Xing, PhD, published a paper titled, “MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences,” which explains that “Although most mutations are expected to be selectively neural, it is important to monitor if SARS-CoV-2 will eventually evolve to be a stronger or weaker infectious agent as time goes on. Therefore, it is vital to track mutations from newly sequenced SARS-CoV-2 genome.”

Another group of researchers have identified such a mutation. “A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional, and municipal,” Bette Korber, PhD and her colleagues wrote in “Tracking Changes in SARS-CoV-2 Spike: Evidence That D614G Increases Infectivity of the COVID-19 Virus,” published in Cell. Korber is a Laboratory Fellow at Los Alamos National Laboratory and visiting faculty at Santa Fe Institute.

Korber’s findings are important because the mutation the scientists identified appears to have a fitness advantage. “Our data show that, over the course of one month, the variant carrying the D614G Spike mutation became the globally dominant form of SARS-CoV-2,” they wrote. Additionally, the study noted, people infected with the mutated variant appear to have a higher viral load in their upper respiratory tracts.

Genetic Sequencing, the Race for Treatments, Vaccines, and Managing Future Pandemics

A vaccine is the best hope for stopping a pandemic, but short of a vaccine, an effective clinical laboratory treatment is the next best thing. And as Dark Daily reported in “Advances in Gene Sequencing Technology Enable Scientists to Respond to the Novel Coronavirus Outbreak in Record Time with Medical Lab Tests, Therapies,” genetic sequencing is quickly becoming a critical tool to develop both.

If, as Fauci and Morens predict, future pandemics are likely, improvements in gene sequencing and analysis will become even more important for tracing, monitoring, and suppressing outbreaks. Clinical laboratory managers will want to watch this closely, as medical labs that process genetic sequencing will, no doubt, be part of that operation.

—Dava Stewart

Related Information:

Genetic Data Show How a Single Superspreading Event Sent Coronavirus Across Massachusetts and the Nation

How the Biogen Leadership Conference in Boston Spread the Coronavirus

How a Premier U.S. Drug Company Became a Virus ‘Super Spreader’

This Cambridge Drug Company Inadvertently Spread the Coronavirus. Now, It’s Creating A ‘Biobank’ To Hopefully Treat the Disease

Phylogenetic Analysis of SARS-CoV-2 in the Boston Area Highlights the Role of Recurrent Importation and Superspreading Events

MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences

Tracking Changes in SARS-CoV-2 Spike: Evidence That D614G Increases Infectivity of the COVID-19 Virus

The D614G Mutation in the SARS-CoV-2 Spike Protein Reduces S1 Shedding and Increases Infectivity

Emerging Pandemic Diseases: How We Got to COVID-19 Advances in Gene Sequencing Technology Enable Scientists to Respond to the Novel Coronavirus Outbreak in Record Time with Medical Lab Tests, Therapies

How Clinical Laboratories Can Avoid COVID-19 Superspreaders, Protect Their Customers and Their Hospital Networks

Understanding how superspreading occurs can help clinical lab leaders slow and even prevent the spread of SARS-CoV-2 within their communities and health systems

Clinical laboratories understand the critical importance of preventing the spread of infection. However, according to the Boston Globe, researchers worldwide are learning that roughly 80% of new COVID-19 cases are caused by just 10% of infected people. Those people are called superspreaders.

It’s critical that medical laboratory managers are aware of the role superspreaders play in transmitting SARS-CoV-2, the coronavirus that causes the COVID-19 illness.

Clinical lab leaders who understand how superspreading occurs can take steps to protect staff, patients, and anyone who visits the facility. Because lab personnel such as couriers and phlebotomists, among others, come into contact with large numbers of people daily, understanding how to identify superspreaders could limit transmissions of the coronavirus within the laboratory, as well as within hospital networks.

Superspreading versus Plodding

Influenza and other viruses tend to spread in a way that epidemiologists call “plodding.” One person infects another, and the virus slowly spreads throughout the population. However, scientists around the globe are finding that SARS-CoV-2 transmission does not fit that pattern. Instead, a few infected people appear to be transmitting the virus to dozens of other people in superspreading events, Boston Globe reported.

“You can think about throwing a match at kindling. You throw one match, it might not light the kindling. You throw another match, it may not light the kindling. But then one match hits the right spot and all of a sudden the fire goes up,” Ben Althouse, PhD, principal scientist and co-chair of epidemiology at the Institute for Disease Modeling in Bellevue, Wash., told the Boston Globe.

But because roughly 90% of infected people aren’t spreading the virus, identifying who the superspreaders are can be a challenge. Nevertheless, limiting situations in which superspreading is likely to occur could greatly reduce the spread of infection.

Samuel Scarpino, PhD Assistant Professor in the Network Science Institute at Northeastern University writing at the class board
Samuel Scarpino, PhD (above), Assistant Professor in the Network Science Institute at Northeastern University, says that “preventing superspreader events could go a long way toward stopping COVID-19,” Scientific American reported. “All of the data I’m seeing so far suggest that if you tamp down the superspreader events, the growth rate of the infections stops very, very quickly,” Scarpino said. (Photo copyright: University of Vermont.)

Examples of Superspreading Events

One of the first big outbreaks in the United States was an example of a superspreading event. The Biogen (NASDAQ:BIIB) leadership conference in late February in Boston resulted in at least 99 cases of COVID-19 just in Massachusetts, reported the Boston Globe.

Several superspreading events have occurred in houses of worship. One well-documented example prompted a CDC Morbidity and Mortality Weekly Report, titled, “High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice—Skagit County, Washington.” The 122-member choir met for practice twice in March. On March 3 no one had symptoms, but one person had cold-like symptoms at the March 10 practice. Eventually, 53 members tested positive for SARS-CoV-2.

On May 30, a Texas family held a birthday party, Medical Xpress reported. Twenty-five people attended the party, which only lasted a few hours. The family followed the state’s guidelines for gatherings, however one of the hosts was infected with the SARS-CoV-2 coronavirus and wasn’t aware of it. Seven attendees contracted it, and those seven spread the virus to an additional 10 family members. A total of 18 members of a single family were infected.

There are commonalities among the documented superspreading events. Most occur indoors, often in poorly ventilated areas. Some activities cause more respiratory droplets to be expelled than others, such as singing. Some respiratory droplets are released simply by breathing, and many more are expelled when a person talks. Talking louder expels even more droplets into the air.

Are Some People More Likely to Spread the Coronavirus than Others?

The fact that so few people are responsible for the majority of transmissions of the virus raises questions. Do some people simply have more virus particles to shed? Is biology a factor?

“I think the circumstances are a lot more important,” Kristin Nelson, MPH, PhD, Assistant Professor of Epidemiology at Emory University told the Boston Globe.

One factor may be how long the SARS-CoV-2 coronavirus is in the body before symptoms of the COVID-19 illness manifest.

“If people got sick right away after they were infected, they might stay at home in bed, giving them few opportunities to transmit the virus,” noted Scientific American in “How ‘Superspreading’ Events Drive Most COVID-19 Spread.” However, CDC states on its website that “The incubation period for COVID-19 is thought to extend to 14 days, with a median time of 4-5 days from exposure to symptoms onset. One study reported that 97.5% of persons with COVID-19 who develop symptoms will do so within 11.5 days of SARS-CoV-2 infection.”

During that time, infected individuals may transmit the virus to dozens of other people. The CDC estimates that about 40% of transmission occurs in pre-symptomatic people, Scientific American reported.

But it’s not all bad news. The fact that circumstances may be more important than biology might be good news for clinical laboratories. “Knowing that COVID-19 is a superspreading pandemic could be a good thing. It bodes well for control,” Nelson told the Boston Globe.

Clinical laboratory managers are encouraged to follow CDC recommended safety protocols, titled, “Guidance for General Laboratory Safety Practices during the COVID-19 Pandemic.” They include social distancing, setting up one-way paths through lab areas, sanitizing shared surfaces such as counters and benchtops, and implementing flexible leave policies so that sick employees can stay home.

Following these guidelines, and being aware of superspreaders, can help medical laboratories and anatomic pathology groups keep staff and customers free of infection.

—Dava Stewart

Related Information:

Most People with Coronavirus Won’t Spread It. Why Do a Few Infect So Many?  

Birthday Party Leaves 18 in Texas Family with Coronavirus

How the Biogen Leadership Conference in Boston Spread the Coronavirus

Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19)

COVID-19 Pandemic Planning Scenarios Guidance for General Laboratory Safety Practices during the COVID-19 Pandemic