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 (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?
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.
Even more impressive is that the automated testing lab can reportedly process (with results in four hours) up to 3,000 patient samples daily for SARS-CoV-2, the coronavirus that causes the COVID-19 illness.
“All of our laboratories do PCR every day. But for this test we need to go above and beyond to ensure accurate detection,” said Jennifer Doudna, PhD, IGI Executive Director and UC Berkeley Professor of Molecular and Cell Biology, in an IGA news release.
“We put in place a robotic pipeline for doing thousands of tests per day,” she continued, “with a pipeline for managing the data and getting it back to clinicians. Imagine setting that up in a couple of weeks. It’s really extraordinary and something I’ve never seen in my career.”
Robert Sanders, UC Berkeley’s Manager Science Communications, told Dark Daily the COVID-19 lab performs about 180 tests per day and has tested 1,000 people so far—80% of the samples came from the campus community. About 1.5% to 4% of the tests were found to be positive for the SARS-CoV-2 coronavirus among the groups tested.
“We hope other academic institutions will set up testing labs too,” he said.
How Did Berkeley Set Up a COVID-19 Diagnostic Lab So Fast?
To get up and running quickly, university officials drew from the campus and surrounding business community to equip and operate the laboratory, as well as, train researchers to do clinical analysis of patient samples.
Though the methodology to test for the coronavirus—isolating RNA from a biological sample and amplifying it with PCR—is standard fare in most research labs worldwide, including at UC Berkeley, the campus’ research labs were shuttered due to the spread of the coronavirus.
IGI reached out to the idle labs for their high-throughput PCR systems to start-up the lab. Through its partnership with University Health Services and local and national companies, IGI created an automated sample intake and processing workflow.
Additionally, several research scientists who were under government-mandated stay-at-home orders made themselves available. “My own research is shut down—and there’s not very much I can do other than stay in my home … finally I’m useful,” said PhD candidate Holly Gildea in a Berkeleyside article which noted that about 30 people—mostly doctoral students and postdoctoral researchers—are being trained to oversee the process and monitor the automated equipment.
Postdoctoral fellows Jenny Hamilton (left) and Enrique Shao (right) with an automated liquid-handling robot (Hamilton Microlab STAR), which will be used to analyze swabs from patients to diagnose COVID-19. Hamilton and Shao volunteered to train to become CLIA certified so as to process patient samples. When analyzing real samples from patients, they would be wearing full personal protective equipment (PPE), including mask, face shield, gown and gloves. (Photo and caption copyright: Max and Jules Photography/UC Berkeley.)
Federal and State Authorities Remove Hurdles
In her article, “Blueprint for a Pop-up SARS-CoV-2 Testing Lab,” published on the medRxiv servers, Doudna summarized “three regulatory developments [that] allowed the IGI to rapidly transition its research laboratory space into a clinical testing facility.
“The second was California Governor Newsom’s Executive Order N-25-20, which modified the requirements for clinical laboratory personnel running diagnostic tests for SARS-CoV-2 in a certified laboratory.
“The third was increased flexibility and expediency at the state and federal levels for certification and licensure requirements for clinical laboratory facilities under the Clinical Laboratory Improvement Amendments (CLIA) program. Under these emergency conditions, the California Department of Public Health (CDPH) was willing to temporarily extend—once the appropriate regulatory requirements have been fulfilled—an existing CLIA certificate for high-complexity testing to a non-contiguous building on our university campus.”
“These developments,” wrote Doudna, “enabled us to develop and validate a laboratory-developed test (LDT) for SARS-CoV-2, extend the UC Berkeley Student Health Center’s clinical laboratory license to our laboratory space, and begin testing patient samples.”
Lessons Learned Implementing a Pop-Up COVID-19 Testing Laboratory
“Our procedures for implementing the technical, regulatory, and data management workstreams necessary for clinical sample processing provide a roadmap to others in setting up similar testing centers,” she wrote.
Learned strategies Doudna says could aid other academic research labs transform to a “SARS-CoV-2 Diagnostic Testing Laboratory include:
Leveraging licenses from existing CLIA-certified labs;
Following FDA authorized testing procedures;
Using online HIPAA training;
Managing supply chain “bottlenecks” by using donated equipment;
Adopting in-house sample barcoding;
Adapting materials, such as sampling tubes, to work with donated equipment;
Cost of equipment and supplies (not including staff) was $550,000, with a per test cost of $24, Doudna noted.
“As the COVID-19 pandemic continues, our intention is to provide both PCR-based diagnostic testing and to advance research on asymptomatic transmission, analyze virus sequence evolution, and provide benchmarking for new diagnostic technologies,” she added.
Medical laboratory leaders understand that the divide between clinical and research laboratories is not easy to surmount. Nevertheless, UC Berkley’s IGI pulled it off. The lab marshaled resources as it took on the novel coronavirus, quickly developed and validated a test workflow, and assembled and trained staff to analyze tests with fast TAT to providers, students, and area residents. There’s much that can be learned from UC Berkeley IGI’s accomplishments.
Cloud-based platform—IDseq—shows potential to track the causes and spread of infectious diseases worldwide using metagenomic data
Here’s the latest example of how big data and related technologies can give physicians—as well as microbiologists and clinical pathologists—a new tool for understanding infectious disease and tracking outbreaks anywhere in the world. This project is being funded and organized by well-known Silicon Valley entrepreneurs.
The project is known as IDseq. It was announced recently in a press release issued by Chan Zuckerberg Biohub (CZ Biohub), Chan Zuckerberg Initiative (CZI), and the Bill and Melinda Gates Foundation. IDseq is a platform designed to support global disease surveillance and prevention. It will make use of gene sequencing and analysis of metagenomic data. This data will be made accessible to the global medical community.
The system leverages the power of cloud computing to streamline the process of transmitting and analyzing metagenomic data, as well as sharing results with other platform users.
“That will be incredibly valuable. Information sharing is one of the most powerful public-health interventions in an outbreak,” Jennifer Gardy, PhD, an epidemiologist at the University of British Columbia, told The Atlantic.Designed by Engineers to Be Easily Used by Healthcare Providers and Medical Laboratory Technicians
Coverage in The Atlantic notes that IDseq isn’t the first tool to offer similar features. Joseph DeRisi, PhD, a biochemist at the University of California San Francisco and co-president of CZ Biohub, states, however, that IDseq is one of the first designed by a large team of engineers, security experts, and other tech and medical researchers.
Many tools see their origins in academic research and are less friendly to those without advanced academic expertise. The research team’s goal, according to DeRisi, is for IDseq “To enable people in under-resourced areas to do what we’ve been trying to do in San Francisco.”
“It’s easy for us to sit in our labs dreaming up tools and platforms,” Jennifer Gardy, PhD (above), an epidemiologist at the University of British Columbia, told The Atlantic. “But we need to make sure we’re designing them in a way that makes sense to the doctors, nurses, lab techs, and epidemiologists out there in an outbreak.” (Photo copyright: Michelle Thorpe/University of British Columbia.)
Two Trials Show Promise for IDseq Use
While the software is already available for free as a collection of open source tools, the IDseq platform is now in a “soft launch” phase. The Bill and Melinda Gates Foundation is funding training for clinicians at CZ Biohub’s labs in San Francisco through its Grand Challenges Explorations Initiative.
However, the platform has already achieved success in two noted scenarios—one at Dhaka Shishu Hospital in Dhaka, Bangladesh, and another in Tororo District Hospital in Uganda. Both used the system to analyze the samples of children admitted for fevers for which they found no known cause.
In the Dhaka cases, Senjuti Saha, PhD, a microbiologist from Child Health Research Foundation, used the platform to trace unexplained cases of meningitis to an earlier chikungunya virus outbreak. Saha explained to The Atlantic that her colleagues previously thought chikungunya could not cause meningitis. The platform found otherwise, allowing her to analyze a further 478 samples and detect an additional 17 cases of potential chikungunya-related meningitis.
In the Uganda cases, the researchers used metagenomic next-generation sequencing (mNGS) data and the IDseq platform to investigate unknown causes of fever in children.
“As progress is made toward elimination of malaria in sub-Saharan Africa, it will be increasingly important to understand the landscape of pathogens that account for the remaining burden of morbidity and mortality,” researchers state in their study, currently in early access at bioRxiv. “The use of mNGS can contribute importantly to this understanding, offering unbiased identification of infecting pathogens.”
Wide-Spread Use of IDseq Not Without Challenges
While an article in Medium by Charles de Bourcy, PhD, Software Engineer at Chan Zuckerberg Initiative, outlines how the IDseq platform can process up to 480GB in approximately 10 minutes, it doesn’t account for the initial data input, which can be daunting.
For areas with weak infrastructure and/or slow connection speeds, this could add significant delays as medical laboratories and healthcare workers at remote sites attempt to transfer data to the nearest IDseq-enabled location. Saha told The Atlantic, “If the transfer is too slow or the data too large, we just [ship] hard drives.”
Sequencing requirements create additional concerns. Bulky equipment and the skills required to run sequencers could limit the ability to use the IDseq platform to analyze and share results. Clinicians might also face difficulties in sourcing sequencing reagents due to customs and supply chain concerns.
Finally, the platform still requires an expert to interpret findings. “IDseq is an excellent tool, but it needs to be paired with people who have substantive knowledge to guide its use,” Saha told The Atlantic.
Regardless of these issues, Saha believes IDseq can help remote/resource-challenged medical labs chase diseases. “It doesn’t solve all the problems, but it means that groups like ours don’t have to spend time to build up [sequencing] capacity. And anything is better than nothing.”
IDseq might offer an excellent opportunity for microbiology laboratories, clinical laboratories, and medical researchers around the world to share data surrounding outbreaks, track disease on global and community level, and better determine the strains and probable sources of infectious diseases.
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