England’s National Health Service to Offer Widespread Rapid Whole Genome Sequencing for Children and Babies

Research in the UK and US into how rapid WGS can prevent deaths and improve outcomes for kids with rare genetic diseases may lead to more genetic testing based in local clinical laboratories

Genetic scientists with the National Health Service (NHS) in England have embarked on an ambitious plan to offer rapid whole genome sequencing (rWGS) for children and babies with serious illnesses, as part of a larger initiative to embrace genomic medicine in the United Kingdom (UK).

The NHS estimates that the plan will benefit more than 1,000 children and babies each year, including newborns with rare diseases such as cancer, as well as kids placed in intensive care after being admitted to hospitals. Instead of waiting weeks for results from conventional tests, clinicians will be able to administer a simple blood test and get results within days, the NHS said in a press release.

The press release notes that about 75% of rare genetic diseases appear during childhood “and are responsible for almost a third of neonatal intensive care deaths.”

Here in the United States, pathologists and clinical laboratory managers should see this development as a progressive step toward expanding access to genetic tests and whole genome sequencing services. The UK is looking at this service as a nationwide service. By contrast, given the size of the population and geography of the United States, as this line of medical laboratory testing expands in the US, it will probably be centered in select regional centers of excellence.

The NHS laid out its implementation plan in a strategy paper published on NHS England’s website titled, “Accelerating Genomic Medicine in the NHS.”

“This strategy sets out how more people will be empowered to take preventative action following risk-based predictions, receive life-changing diagnoses, and get the support needed to live with genomically-informed diagnoses alongside improved access to cutting-edge precision [medicine] treatments. It also outlines how the NHS will accelerate future high-quality genomic innovation that can be adopted and spread across the country, leading to positive impacts for current and future generations,” the NHS wrote.

Amanda Pritchard

“This global first is an incredible moment for the NHS and will be revolutionary in helping us to rapidly diagnose the illnesses of thousands of seriously ill children and babies—saving countless lives in the years to come,” said NHS chief executive Amanda Pritchard (above) in a press release announcing the program. (Photo copyright: Hospital Times.)

New Rapid Whole Genome Sequencing Service

The NHS announced the plan following a series of trials last year. In one trial, a five-day old infant was admitted to a hospital in Cheltenham, Gloucester, with potentially deadly levels of ammonia in his blood. Whole genome sequencing revealed that changes in the CPS1 gene were preventing his body from breaking down nitrogen, which led to the spike in ammonia. He was given life-saving medication in advance of a liver transplant that doctors believed would cure the condition. Without the rapid genetic test, doctors likely would have performed an invasive liver biopsy.

Following sample collection at NHS locations, the genetic tests will be performed at the new National Rapid Whole Genome Sequencing Service, part of the South West NHS Genomic Laboratory Hub run by the Royal Devon University Healthcare NHS Foundation Trust in Exeter, UK.

Using a simple blood test, the new newborn genetic screening service in England is expected to benefit more than 1,000 critically ill infants each year, potentially saving their lives. “The rapid whole genome testing service will transform how rare genetic conditions are diagnosed,” explained Emma Baple, PhD, Professor of Genomic Medicine at University of Exeter Medical School and leader of the National Rapid Whole Genome Sequencing Service in the press release. “We know that with prompt and accurate diagnosis, conditions could be cured or better managed with the right clinical care, which would be life-altering—and potentially life-saving—for so many seriously unwell babies and children,” Precision Medicine Institute reported.

According to The Guardian, test results will be available in two to seven days.

Along with the new rWGS testing service, the NHS announced a five-year plan to implement genomic medicine more broadly. The provisions include establishment of an ethics advisory board, more training for NHS personnel, and an expansion of genomic testing within the existing NHS diagnostic infrastructure. The latter could include using NHS Community Diagnostics centers to collect blood samples from family members to test for inherited diseases.

UK’s Longtime Interest in Whole Genome Sequencing

The UK government has long been interested in the potential role of WGS for delivering better outcomes for patients with genetic diseases, The Guardian reported.

In 2013, the government launched the 100,000 Genomes Project to examine the usefulness of the technology. In November 2021, investigators with the project reported the results of a large pilot study in which they analyzed the genomes of 4,660 individuals with rare diseases. The study, published in the New England Journal of Medicine (NEJM) titled, “100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care—Preliminary Report,” found “a substantial increase in yield of genomic diagnoses made in patients with the use of genome sequencing across a broad spectrum of rare disease.”

The study’s findings suggest that use of WGS “could save the NHS millions of pounds,” The Guardian reported.

Whole Genome Sequencing System for Newborns in the US

Researchers in the United States are also looking at the potential for WGS to improve health outcomes in children with genetic conditions. Last August, a research team led by Stephen F. Kingsmore, MD, DSc, President/CEO of Rady Children’s Institute for Genomic Medicine in San Diego, authored a study published in the American Journal of Human Genetics (AJHG) titled, “A Genome Sequencing System for Universal Newborn Screening, Diagnosis, and Precision Medicine for Severe Genetic Diseases,” that described a scalable prototype for a newborn screening system.

“This NBS-rWGS [newborn screening by rapid whole genome sequencing] system is designed to complement the existing newborn screening process and has the potential to eliminate the diagnostic and therapeutic odyssey that many children and parents face,” Kingsmore said in a press release. “Currently, only 35 core genetic disorders are recommended for newborn screening in the United States, but there are more than 7,200 known genetic diseases. Outcomes remain poor for newborns with a genetic disease because of the limited number of recommended screenings. With NBS-rWGS, we can more quickly expand that number and therefore potentially improve outcomes through precision medicine.”

A more recent 2023 study which examined 112 infant deaths at Rady Children’s Hospital found that 40% of the babies had genetic diseases. In seven infants, genetic diseases were identified post-mortem, and in five of them “death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission,” the authors wrote.

“Prior etiologic studies of infant mortality are generally retrospective, based on electronic health record and death certificate review, and without genome information, leading to underdiagnosis of genetic diseases,” said Christina Chambers, PhD, co-author of the study, in a press release. “In fact, prior studies show at least 30% of death certificates have inaccuracies. By implementing broad use of genome sequencing in newborns we might substantially reduce infant mortality.” 

Pioneering work with whole genome sequencing for newborns, such as that being conducted by the clinical laboratory and genetic teams at Rady Children’s Hospital and the UK’s NHS, could allow doctors to make timely interventions for our most vulnerable patients.

—Stephen Beale

Related Information:

Study Suggests DNA Sequencing Could Reduce Infant Deaths, Often Caused by Genetic Disease

Novel Newborn Screening System Uses Rapid Whole Genome Sequencing and Acute Management Guidance to Screen and Diagnosis Genetic Diseases

Study Finds Association of Genetic Disease and Infant Mortality Higher than Previously Recognized: 41% of Infant Deaths Associated with Genetic Diseases

Genome Sequencing Could Prevent Infant Deaths

A Genome Sequencing System for Universal Newborn Screening, Diagnosis, and Precision Medicine for Severe Genetic Diseases

Genetic Testing in the PICU Prompts Meaningful Changes in Care

Major Policy Event in United Kingdom Aligns National Genetic Screening Program Using Rapid Whole Genome Sequencing

World-First National Genetic Testing Service to Deliver Rapid Life-Saving Checks for Babies and Kids

Genome Sequencing Trial to Test Benefits of Identifying Genetic Diseases at Birth

New NHS Genetic Testing Service ‘Could Save Thousands of Children’ in England

NHS England Completes Move Towards Rapid Whole Genome Sequencing of All Critically Ill Infants

Whole Genome Sequencing for Children: An Information Guide for Parents, Carers, and Families

Another Milestone for CRISPR-Cas9 Technology: First Trial Data for Treatment Delivered Intravenously

Unlike most other CRISPR/Cas-9 therapies that are ex vivo treatments in which cells are modified outside the body, this study was successful with an in vivo treatment

Use of CRISPR-Cas9 gene editing technology for therapeutic purposes can be a boon for clinical laboratories. Not only is this application a step forward in the march toward precision medicine, but it can give clinical labs the essential role of sequencing a patient’s DNA to help the referring physician identify how CRISPR-Cas9 can be used to edit the patient’s DNA to treat specific health conditions.

Most pathologists and medical lab managers know that CRISPR-Cas9 gene editing technology has been touted as one of the most significant advances in the development of therapies for inherited genetic diseases and other conditions. Now, a pair of biotech companies have announced a milestone for CRISPR-Cas9 with early clinical data involving a treatment delivered intravenously (in vivo).

The therapy, NTLA-2001, was developed by Intellia Therapeutics (NASDAQ:NTLA) and Regeneron Pharmaceuticals (NASDAQ:REGN) for treatment of hereditary ATTR (transthyretin) amyloidosis, a rare and sometimes fatal liver disease.  

As with other therapies, determining which patients are suitable candidates for specific treatments is key to the therapy’s success. Therefore, clinical laboratories will play a critical role in identifying those patients who would most likely benefit from a CRISPR-delivered therapy.

Such is the goal of precision medicine. As methods are refined that can correct unwelcome genetic mutations in a patient, the need to do genetic testing to identify and diagnose whether a patient has a specific gene mutation associated with a specific disease will increase.

The researchers published data from a Phase 1 clinical trial of NTLA-2001 in the New England Journal of Medicine (NEJM), titled, “CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis.” They also presented their findings at the Peripheral Nerve Society (PNS) Annual Meeting.

What is NTLA-2001 and Why Is It Important?

Cleveland Clinic describes ATTR amyloidosis as a “protein misfolding disorder” involving transthyretin (TTR), a protein made in the liver. The disease leads to deposits of the protein in the heart, nerves, or other organs.

According to Intellia and Regeneron, NTLA-2001 is designed to inactivate the gene that produces the protein.

The interim clinical trial data indicated that one 0.3 mg per kilogram dose of the therapy reduced serum TTR by an average of 87% at day 28. A smaller dose of 0.1 mg per kilogram reduced TTR by an average of 52%. The researchers reported “few adverse events” in the six study patients, “and those that did occur were mild in grade.”

Current treatments, the companies stated, must be administered regularly and typically reduce TTR by about 80%.

“These are the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR,” said Intellia President and CEO John Leonard, MD, in a press release. “The interim results support our belief that NTLA-2001 has the potential to halt and reverse the devastating complications of ATTR amyloidosis with a single dose.”

He added that “solving the challenge of targeted delivery of CRISPR-Cas9 to the liver, as we have with NTLA-2001, also unlocks the door to treating a wide array of other genetic diseases with our modular platform, and we intend to move quickly to advance and expand our pipeline.”

Daniel Anderson, PhD

“It’s an important moment for the field,” MIT biomedical engineer Daniel Anderson, PhD (above), told Nature. Anderson is Professor, Chemical Engineering and Institute for Medical Engineering and Science at the Koch Institute for Integrative Cancer Research at MIT. “It’s a whole new era of medicine,” he added. Advances in the use of CRISPR-Cas9 for therapeutic purposes will create the need for clinical laboratories to sequence patients’ DNA to help physicians determine the best uses for a CRISPR-Cas9 treatment protocol. (Photo copyright: Massachusetts Institute of Technology.)

In Part 2 of the Phase 1 trial, Intellia plans to evaluate the new therapy at higher doses. After the trial is complete, “the company plans to move to pivotal studies for both polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis,” the press release states.

Previous clinical trials reported results for ex vivo treatments in which cells were removed from the body, modified with CRISPR-Cas9 techniques, and then reinfused. “But to be able to edit genes directly in the body would open the door to treating a wider range of diseases,” Nature reported.

How CRISPR-Cas9 Works

On its website, CRISPR Therapeutics, a company co-founded by Emmanuelle Charpentier, PhD, a director at the Max Planck Institute for Infection Biology in Berlin, and inventor of CRISPR-Cas9 gene editing, explained that the technology “edits genes by precisely cutting DNA and then letting natural DNA repair processes take over.” It can remove fragments of DNA responsible for causing diseases, as well as repairing damaged genes or inserting new ones.

The therapies have two components: Cas9, an enzyme that cuts the DNA, and Guide RNA (gRNA), which specifies where the DNA should be cut.

Charpentier and biochemist Jennifer Doudna, PhD, Nobel Laureate, Professor of Chemistry, Professor of Biochemistry and Molecular Biology, and Li Ka Shing Chancellor’s Professor in Biomedical and Health at the University of California Berkeley, received the 2020 Nobel Prize in Chemistry for their work on CRISPR-Cas9, STAT reported.

It is important to pathologists and medical laboratory managers to understand that multiple technologies are being advanced and improved at a remarkable pace. That includes the technologies of next-generation sequencing, use of gene-editing tools like CRISPR-Cas9, and advances in artificial intelligence, machine learning, and neural networks.

At some future point, it can be expected that these technologies will be combined and integrated in a way that allows clinical laboratories to make very early and accurate diagnoses of many health conditions.

—Stephen Beale

Related Information

Intellia and Regeneron Announce Landmark Clinical Data Showing Deep Reduction in Disease-Causing Protein After Single Infusion of NTLA-2001, an Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

Landmark CRISPR Trial Shows Promise Against Deadly Disease

CRISPR Milestone Pushes Gene Editing Toward Its Promise

CRISPR Clinical Trials: A 2021 Update

CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future

Diseases CRISPR Could Cure: Latest Updates on Research Studies and Human Trials

Faster, Better, Cheaper: The Rise of CRISPR in Disease Detection

The Potential of CRISPR-Based Diagnostic Assays and Treatment Approaches Against COVID-19

Two Female CRISPR Scientists Make History, Winning Nobel Prize in Chemistry for Genome-Editing Discovery

Multiple Studies Raise Questions About Reliability of Clinical Laboratory COVID-19 Diagnostic Tests

In the absence of a “gold standard,” researchers are finding a high frequency of false negatives among SARS-CoV-2 RT-PCR tests

Serology tests designed to detect antibodies to the SARS-CoV-2 coronavirus that causes the COVID-19 illness have been dogged by well-publicized questions about accuracy. However, researchers also are raising concerns about the accuracy of molecular diagnostics which claim to detect the actual presence of the coronavirus itself.

“Diagnostic tests, typically involving a nasopharyngeal swab, can be inaccurate in two ways,” said Steven Woloshin, MD, MS, in a news release announcing a new report that “examines challenges and implications of false-negative COVID-19 tests.” Woloshin is an internist, a professor at Dartmouth Institute, and co-director of the Geisel School of Medicine at Dartmouth.

“A false-positive result mistakenly labels a person infected, with consequences including unnecessary quarantine and contact tracing,” he stated in the news release. “False-negative results are far more consequential, because infected persons who might be asymptomatic may not be isolated and can infect others.”

Woloshin led a team of Dartmouth researchers who analyzed two studies from Wuhan, China, and a literature review by researchers in Europe and South America that indicated diagnostic tests for COVID-19 are frequently generating false negatives. The team published their results in the June 5 New England Journal of Medicine (NEJM).

For example, one research team in Wuhan collected samples from 213 hospitalized COVID-19 patients and found that an approved RT-PCR test produced false negatives in 11% of sputum samples, 27% of nasal samples, and 40% of throat samples. Their research was published on the medRxiv preprint server and has not been peer-reviewed.

The literature review Woloshin’s team studied was also published on medRxiv, titled, “False-Negative Results of Initial Rt-PCR Assays for COVID-19: A Systematic Review.” It indicated that the rate of false negatives could be as high as 29%. The authors of the review looked at five studies that had enrolled a total of 957 patients. “The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability,” they wrote. “Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection.”

Another literature review, published in the Annals of Internal Medicine, titled, “Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure,” estimated the probability of false negatives in RT-PCR tests at varying intervals from the time of exposure and symptom onset. For example, the authors found that the median false-negative rate was 38% if a test was performed on the day of symptom onset, versus 20% three days after onset. Their analysis was based on seven studies, five of which were peer-reviewed, with a total of 1330 test samples.

Doctors also are seeing anecdotal evidence of false negatives. For example, clinicians at UC San Diego Health medical center treated a patient with obvious symptoms of COVID-19, but two tests performed on throat samples were negative. However, a third test, using a sample from a bronchial wash, identified the virus, reported Medscape.

The lesson for clinicians is that they can’t rely solely on test results but must also consider their own observations of the patient, Joshua Metlay, MD, PhD, of Massachusetts General Hospital told Medscape.

Sensitivity and Specificity of COVID-19 Clinical Laboratory Tests

The key measures of test accuracy are sensitivity, which refers to the ability to detect the presence of the virus, and specificity, the ability to determine that the targeted pathogen is not present. “So, a sensitive test is less likely to provide a false-negative result and a specific test is less likely to provide a false-positive result,” wrote Kirsten Meek, PhD, medical writer and editor, in an article for ARUP Laboratories.

“Analytic” sensitivity and specificity “represent the accuracy of a test under ideal conditions in which specimens have been collected from patients with either high viral loads or a complete absence of exposure,” she wrote. However, “sensitivity and specificity under real-world conditions, in which patients are more variable and specimen collection may not be ideal, can often be lower than reported numbers.”

In a statement defending its ID Now molecular point-of-care test, which came under scrutiny during a study of COVID-19 molecular tests by NYU Langone Health, Northwell Health, and Cleveland Clinic, according to MedTech Dive, Abbott Laboratories blamed improper sample collection and handling for highly-publicized false negatives produced by its rapid test. An FDA issued alert about the test on May 14 noted that Abbott had agreed to conduct post-market studies to identify the cause of the false negatives and suggest remedial actions.

Issues with Emergency Use Authorizations

In their NEJM analysis, Woloshin et al point to issues with the FDA’s process for issuing Emergency Use Authorizations (EUAs). For example, they noted variations in how manufacturers are conducting clinical evaluations to determine test performance. “The FDA prefers the use of ‘natural clinical specimens’ but has permitted the use of ‘contrived specimens’ produced by adding viral RNA or inactivated virus to leftover clinical material,” they wrote.

When evaluating clinical performance, manufacturers ordinarily conduct an index test of patients and compare the results with reference-standard test, according to the Dartmouth researchers. For people showing symptoms, the reference standard should be a clinical diagnosis performed by an independent adjudication panel. However, they wrote, “it is unclear whether the sensitivity of any FDA-authorized commercial test has been assessed in this way.” Additionally, a reference standard for determining sensitivity in asymptomatic people “is an unsolved problem that needs urgent attention to increase confidence in test results for contact-tracing or screening purposes.”

Stephen Rawlings, MD, PhD
“To truly determine false negatives, you need a gold standard test, which is essentially as close to perfect as we can get,” Stephen Rawlings, MD, PhD, (above), a resident physician of internal medicine and infectious diseases fellow at UC San Diego’s Center for AIDS Research (CFAR), who has been working on SARS-CoV-2 test validation since March. “But there just isn’t one yet for coronavirus,” he told Medscape. (Photo copyright: University of California, San Diego.)

In a perspective for Mayo Clinic Proceedings, Colin P. West, MD, PhD; Victor M. Montori, MD, MSc; and Priya Sampathkumar, MD, offered four recommendations for addressing concerns about testing accuracy:

  • Continued adherence to current measures, such as physical distancing and surface disinfection.
  • Development of highly sensitive and specific tests or combinations of tests to minimize the risk of false-negative results and ongoing transmission based on a false sense of security.
  • Improved RT-PCR tests and serological assays.
  • Development and communication of clear risk-stratified protocols for management of negative COVID-19 test results.

“These protocols must evolve as diagnostic test, transmission, and outcome statistics become more available,” they wrote.

Meanwhile, clinical laboratories remain somewhat on their own at selecting which COVID-19 molecular and serology tests they want to purchase and run in their labs. Complicating such decisions is the fact that many of the nation’s most reputable in vitro diagnostics manufacturers cannot produce enough of their COVID-19 tests to meet demand.

Consequently, when looking to purchase tests for SARS-CoV-2, smaller medical laboratory organizations find themselves evaluating COVID-19 kits developed by little-known or even brand-new companies.

—Stephen Beale

Related Information:

New Report Examines Challenges and Implications of False-Negative COVID-19 Tests

Questions about COVID-19 Test Accuracy Raised Across the Testing Spectrum

COVID-19 Test Results: Don’t Discount Clinical Intuition

FDA Provides New Tool to Aid Development and Evaluation of Diagnostic Tests That Detect SARS-CoV-2 Infection

EUA Authorized Serology Test Performance

Emergency Use Authorization (EUA) Information and List of All Current EUAs 

Coronavirus (COVID-19) Update: FDA Provides Promised Transparency for Antibody Tests

Understanding Medical Tests: Sensitivity, Specificity, and Positive Predictive Value

Webinar Part 1: Quality Issues Your Clinical Laboratory Should Know Before You Buy or Select COVID-19 Serology Tests

Webinar Part 2: Achieving High Confidence Levels in the Quality and Accuracy of Your Clinical Lab’s Chosen COVID-19 Serology Tests, featuring James Westgard, PhD

Clinical Laboratories Should Be Aware of Potential Airborne Transmission of SARS-CoV-2, the Coronavirus That Causes COVID-19

‘Aerosol and Surface Stability’ study shows that the virus can remain infectious in aerosol form for hours and on surfaces for days

By now, clinical laboratory workers, microbiologists, and phlebotomists should be fully aware of the potential for transmission on surfaces of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes Coronavirus disease 2019 (COVID-19). The CDC’s latest Morbidity and Mortality Weekly Report revealed that the coronavirus “was identified on a variety of surfaces in cabins of both symptomatic and asymptomatic infected passengers up to 17 days after cabins were vacated on the Diamond Princess, but before disinfection procedures had been conducted,” the New York Post reported. That means the virus can survive on surfaces significantly longer than CDC previously believed.

But did you know a recent study published in the New England Journal of Medicine (NEJM) found that SARS-CoV-2 can also survive in the air for many hours, potentially allowing aerosolized transmission of the virus as well?

The NEJM study also showed that the stability of SARS-CoV-2 to survive on surfaces and in aerosolized form mirrors the stability of the SARS coronavirus (SARS-CoV) that caused the severe acute respiratory syndrome (SARS) outbreak of 2003.

This is critically important information for clinical laboratory professionals in open-space laboratories, phlebotomists collecting medical laboratory specimens, and frontline healthcare workers who come in direct contact with potentially infected patients. They should be aware of every potential COVID-19 transmission pathway.

Hospital infection control teams will be particularly interested in the possibility of airborne transmission, as they often visit infected patients and are tasked with tracking both the source of the infection as well as individuals who may be exposed to sick patients.

The NEJM study, titled “Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1” was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), an agency of the US Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention (CDC), Princeton University, and University of California, Los Angeles. The researchers concluded that SARS-CoV-2 remains in the air “up to three hours post aerosolization.”

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They also found the virus was detectable for up to four hours on copper and up to 24 hours on cardboard. The scientists concluded SARS-CoV-2 can remain on plastic and stainless-steel surfaces for two to three days, though the amount of the virus on surfaces decreases over time.

“Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days,” the study states. “These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, and they provide information for pandemic mitigation efforts.”

But Can COVID-19 Be Caught Through Air?

However, as noted in Wired, the researchers did not clearly state that infected persons can spread COVID-19 to others in the same airspace. Some experts have pointed out that there is a difference between a virus that can exist as an aerosol—defined as a liquid or solid suspended in gas under only limited conditions—and the measles virus, for example, which the CDC estimates “can live for up two hours in an airspace where the infected person has coughed or sneezed.”

“While the researchers tested how long the virus can survive in aerosols suspended in the air, they didn’t actually sample the air around infected people,” Wired noted. “Instead, they put the virus into a nebulizer and puffed it into a rotating drum to keep it airborne. Then, they tested how long the virus could survive in the air inside the drum.”

Neeltje van Doremalen, PhD, a research fellow at National Institutes of Health (NIH) and researcher at the NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, who coauthored the NEJM study, cautioned against an overreaction to this latest research. On Twitter she wrote, “Important: we experimentally generated [COVID-19] aerosols and kept them afloat in a drum. This is not evidence of aerosol transmission.”

Nonetheless, the World House Organization (WHO) took note of the study’s findings and on March 16, 2020, announced it was considering “airborne precautions” for healthcare workers, CNBC reported in its coverage of a virtual press conference on March 16, 2020, led by Maria Van Kerkhove, MS, PhD, Technical Lead for WHO’s Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Task Force.

Van Kerkhove emphasized that health officials were monitoring results from other studies investigating how environmental conditions such as humidity, temperature, and ultraviolet light affect the disease and its ability to live on different surfaces.

“When you do an aerosol-generating procedure like in a medical care facility, you have the possibility to what we call aerosolize these particles, which means they can stay in the air a little bit longer,” said Maria Van Kerkhove, MS, PhD (above), Technical Lead for WHO’s Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Task Force during a virtual press conference, CNBC reported. “It’s very important that healthcare workers take additional precautions when they’re working on patients and doing these procedures,” she added. [Photo copyright: World Health Organization/YouTube.)

To Be or Not to Be an Airborne Pathogen

Stanley Perlman, MD, PhD, Professor of Microbiology and Immunology at the University of Iowa, believes aerosol transmission ultimately will be found not to play a large role in COVID-19 transmission.

“I think the answer will be, aerosolization occurs rarely, but not never,” Perlman told STAT. “You have to distinguish between what’s possible and what’s actually happening.”

In an NEJM editorial, Perlman expanded on those thoughts. “Although specific anti-coronaviral therapies are still in development, we now know much more about how to control such infections in the community and hospitals, which should alleviate some of this fear,” he wrote. “Transmission of [SARS-CoV-2] probably occurs by means of large droplets and contact and less so by means of aerosols and fomites, on the basis of our experience with SARS-CoV and MERS-CoV. Public health measures, including quarantining in the community as well as timely diagnosis and strict adherence to universal precautions in healthcare settings, were critical in controlling SARS and MERS. Institution of similar measures will be important and, it is hoped, successful in reducing the transmission of [SARS-CoV-2].”

An NIH news release announcing the SARS-CoV-2 stability study highlighted two additional observations:

  • “If the viability of the two coronaviruses is similar, why is SARS-CoV-2 resulting in more cases? Emerging evidence suggest that people infected with SARS-CoV-2 might be spreading virus without recognizing, or prior to recognizing, symptoms. That would make disease control measures that were effective against SARS-CoV-1 less effective against its successor.
  • In contrast to SARS-CoV-1, most secondary cases of virus transmission of SARS-CoV-2 appear to be occurring in community settings rather than healthcare settings. However, healthcare settings are also vulnerable to the introduction and spread of SARS-CoV-2, and the stability of SARS-CoV-2 in aerosols and on surfaces likely contributes to transmission of the virus in healthcare settings.”

Clearly, the scientific community has not agreed on aerosolization as a definite source of infection. Nevertheless, clinical laboratory workers in settings where potential exposure to SARS-CoV-2 exists should take precautions against airborne transmission until scientists can definitively determine whether this latest coronavirus can be acquired through the airborne transmission.

—Andrea Downing Peck

Related Information:

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

Another Decade, Another Coronavirus

WHO Considers ‘Airborne Precautions’ for Medical Staff After Study Shows Coronavirus Can Survive in Air

Coronavirus Can Likely Remain Airborne for Some Time. That Doesn’t Mean We’re Doomed

New Coronavirus Stable for Hours on Surfaces

Vermont Medical School Ceases All Lectures from Curriculum and Adopts “Active Learning” Techniques for Teaching Next Generation of Physicians

Professor-led classroom lectures end as students are expected to do much of their traditional learning outside of class. Will this influence how many medical students go on to choose pathology for their residency?

Medical Colleges, hospital universities, and healthcare trade schools nationwide are considering “Active Learning” techniques to replace lectures. These bastions of higher education—where anatomic pathologists, medical laboratory scientists, doctors, nurses, clinical laboratory technicians, and other healthcare professionals learn their skills—are adopting evidence-based teaching styles that resonate with modern technology-savvy students.

In September, the University of Vermont Larner College of Medicine (UVM) became the latest institution to embrace this trend when it announced it would abolish lectures across all of its programs beginning in 2019. This makes UVM the first member of the Association of American Medical Colleges (AAMC) to drop lectures from its curriculum.

“What we know about learning in general is different than it was decades ago,” Lisa Howley, PhD, AAMC Senior Director of Strategic Initiatives and Partnerships, told Inside Higher Education. “Our medical students are of a generation that has grown up differently when it comes to technology and the impact that has on their ability to receive and retain information.”

Dubbed a “flipped classroom,” students do homework before classes rather than after, as would be done in a traditional education setting. They are expected to learn material online and through textbooks, and then complete self-assessments to gauge their understanding of what they’ve learned. Classroom time involves so-called “active learning,” which includes problem-solving in small groups, question-and-answer sessions, and group discussions.

UVM Not First to Drop Lectures

While UVM’s announcement has generated headlines and controversy, it is not the first medical school to abandon traditional lectures. Cleveland Clinic’s Lerner College of Medicine at Case Western Reserve University opened in 2004 with a no-lecture format.

A growing body of research, such as this study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), indicates that active learning improves student performances, especially in science, technology, engineering, and mathematics. With the specialties of pathology and medical laboratory medicine heavily dependent on technology and science, this may be a favorable development for medical students who decided to specialize in these fields.

“We teach evidence-based medicine all the time,” William Jeffries, PhD, Senior Associate Dean for Medical Education at UVM, stated in the Inside Higher Education article. “If you have the evidence to show one treatment is better than the other, you would naturally use that treatment. So, if we know that there are methods superior to lecturing, why are we lecturing at all?”

Kelly J. (McDonough) Butnor, MD (center), Surgical Pathologist and Professor of Pathology and Laboratory Medicine at University of Vermont College of Medicine, conducts a team-based learning session with second-year students. (Photo and caption copyright: The Washington Post, Erin Post, Larner College of Medicine.)

In 2112, Charles G. Prober, MD, Senior Associate Vice Provost for Health Education and Professor of Pediatrics at Stanford School of Medicine, and Chip Heath, PhD, Professor of Organizational Behavior in the Stanford Graduate School of Business, called for a “change in the way we educate doctors.”

In “Lecture Halls without Lectures—A Proposal for Medical Education,” published in the New England Journal of Medicine (NEJM), Prober and Heath wrote, “Students are being taught roughly the same way they were taught when the Wright brothers were tinkering at Kitty Hawk.” They suggested five years ago that active learning and short online videos were more effective and a better use of students’ limited time than auditorium-style mandatory lectures. Today, with mobile technologies and streaming Internet technologies, their argument is even more valid.

Lack of Funds Blocks Innovation

Jeffries contends the cost of making wholesale changes in how students are taught, which requires retraining faculty and renovating classrooms, keeps most medical schools from overhauling teaching methods. “Most schools do not have the resources to turn the battleship around,” he told Inside Higher Education.

At UVM, however, a $66-million gift last year by Robert Larner, MD, and his wife Helen, is helping fund the school retrain its medical school teaching staff and redesign classroom spaces to support active learning. Larner is a dual-degree alum whose name now adorns the medical school.

In a recent NEJM article, Richard M. Schwartzstein, MD, Professor, Beth Israel Deaconess Medical Center (BIDMC) at Harvard Medical School, and David H. Roberts, MD, Dean for External Education at Harvard Medical School, point out that “the movement away from traditional lecture-based courses has been under way in US medical schools for more than three decades.” They question, however, whether the push to do away with all lectures is “merely the latest fad in medical education” or is it truly evidence-based?

“We can often serve our students best by fusing elements of various methods, such as team-based or case-based learning and interactive large-group learning sessions, rather than feeling obliged to adhere to a particular format,” they wrote. “But we must also use evidenced-based approaches whenever possible and rigorously evaluate our innovations, acknowledging that important outcomes may include student engagement and problem-solving skills, team dynamics, and the learning environment as much as exam scores.”

Prober told the Washington Post that medical school students already vote with their feet for the type of teaching format they prefer.

“When you go into a lecture in medical schools across the nation, you will find a minority of students actually present,” he said. “Medical students are adults. One generally believes adults try to make decisions that are in their best interests. They have seemingly made the decision that it is not in the lectures.”

For the past two decades, many pathologists have regularly pointed out that advances in technologies and procedures in both anatomic pathology and clinical laboratory medicine have outpaced the ability of medical schools and residency programs to incorporate these new developments into training programs. Thus, clinical laboratory scientists and pathologists will be watching with interest to see if these new models for medical school education are capable of incorporating new advances in laboratory medicine into their training formats in a timely fashion.

—Andrea Downing Peck

Related Information:

Become a Doctor, No Lectures Required

Medical School Without the ‘Sage on a Stage’

Active Learning Increases Student Performance in Science, Engineering, and Mathematics

Lecture Halls without Lectures–A Proposal for Medical Education

Saying Goodbye to Lectures in Medical School–Paradigm Shift or Passing Fad?

UVM Names Robert Larner, MD, College of Medicine

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