The remarkably low number of influenza diagnoses makes it possible for clinical laboratories to stay focused on COVID-19
One positive note for clinical laboratories this winter is the fact that the number of biological samples being submitted for influenza (flu) testing have dropped significantly. This has given medical laboratories more resources for processing COVID-19 tests.
According to a feature published in Nature, the number of samples being submitted to medical laboratories for flu testing has dropped by 61%. More surprisingly, the number of positives has dropped by 98%. The combined flu/COVID-19 “twindemic” that some medical experts feared could crush our healthcare system has not materialized—yet, the Washington Examiner reported.
“In any given winter, hospitals are taxed by the flu,” Brian Garibaldi, MD, a pulmonologist and critical care specialist and Medical Director of the Johns Hopkins Biocontainment Unit told the Washington Examiner. “There’s always a concern that our emergency departments will be overwhelmed, and ICU capacity will be strained [due to the concurrence of flu and COVID-19 outbreaks], particularly with people who have coexisting conditions that then get influenza.”
The 2019-2020 flu season ended earlier than usual, likely because of precautions put in place in the spring to combat the coronavirus pandemic. Most years, the seasonal flu in the US peaks in February and trails off by May, Nature reported in “How Coronavirus Lockdowns Stopped Flu in Its Tracks.”
“Seasonal flu cases in the northern hemisphere usually peak in February and tail off by the end of May,” Nature wrote. “This year, unusually, lab-confirmed cases of influenza dropped precipitously in early April, a few weeks after the coronavirus pandemic was declared on 11 March. The data comes from tests of more than 150,000 samples from national influenza laboratories in 71 countries that report data to FluNet, a global surveillance system.”
Government Leaders and Health Experts Remain Concerned
Despite that encouraging data point, public health experts and political leaders were still concerned. In September, Arizona Governor Doug Ducey said, “The overlap of COVID-19 and flu season presents a perfect storm, and we aren’t taking any chances. We are approaching this fall with a proactive mindset and plan of action to limit the impact of the flu and preserve hospital resources,” the Washington Examiner reported.
The caution was certainly warranted. A normal flu season strains resources, but a severe flu season coupled with a global pandemic could have been disastrous. Luckily, Ducey’s “perfect storm” did not materialize.
Data from the World Health Organization’s FluNet Global Influenza Surveillance and Response System was used by Nature to develop the graphic above. It illustrates how the number of positive Influenza specimens in 2019-2020 declined compared to the previous two years. Some experts believe this is due to protocols implemented to combat the COVID-19 coronavirus by hospitals and clinical laboratories. (Graphic copyright: Nature.)
Why Is There Less Influenza?
So, why is there less flu and other respiratory infections?
Epidemiologist Lisa Lockerd Maragakis, MD, MPH, Associate Professor of Medicine and Senior Director of Infection Prevention at Johns Hopkins Health System, told U.S. News, widespread business and school closures provide fewer opportunities for influenza to spread. “We commonly see flu spread in communities, schools, businesses and through travel each year, so those changes are likely keeping the flu away.”
However, this may have a negative effect as well. Eili Klein, PhD, Associate Professor of Emergency Medicine at Johns Hopkins School of Medicine, warns that “Because of the current restrictions and precautions everyone is taking this season, far fewer people will be infected or exposed to the flu virus, and therefore won’t become immune to certain strains of the virus. So, the number of people who may have more severe infections next year is likely to be greater because immunity will be lower,” the Washington Examiner reported.
Other Viral Infections Also in Decline Due to COVID-19 Precautions, Vaccines
Masking, frequent handwashing, and social distancing certainly played a role in reducing the number of cases of flu reported this year. But influenza is not the only disease that saw reductions. “In Hong Kong, compared with previous years, the number of chickenpox cases dropped by about half to three-quarters,” Nature reported. “In April, cases of measles and rubella were their lowest, globally, since at least 2016, according to data available so far.”
Early in the COVID-19 pandemic, some public health officials were concerned that the decline in influenza cases was actually related to a lack of testing. “However, renewed efforts by public health officials and clinicians to test samples for influenza resulted in adequate numbers tested and detection of little to no influenza virus,” the Centers for Disease Control and Prevention (CDC) reported.
Another factor in the lower numbers of flu cases could be due to the fact that more people have gotten vaccinated this year. More than 188 million flu vaccines were distributed in 2020, an increase compared to the 169 million given in 2019.
“Flu vaccination in the community started earlier this year, as recommended by the CDC, and our community physicians report that vaccine uptake has been higher than usual,” Marie-LouiseLandry, MD, Clinical Virologist, Professor of Laboratory Medicine and of Medicine (Infectious Diseases), and Director of the Clinical Virology Laboratory at Yale School of Medicine, told Healthline.
It may also be that influenza diagnoses are fewer because people are not seeking treatment. Hospitals at or beyond capacity due to the pandemic, or fear of contracting COVID-19, may have motivated people with flu-like symptoms to stay home rather than seek treatment. However, most healthcare experts agree that public health measures to fight COVID-19 are likely the larger reason there is less flu.
“Public health measures such as movement restrictions, social distancing, and increased personal hygiene likely had an effect on decreasing influenza and other respiratory virus transmissions,” the World Health Organization (WHO) told Nature.
What About the Next Flu Season?
Experts are more conflicted regarding what all of this means for coming flu seasons. Some experts think that because there’s less flu this year, there will be less immunity next year, and severe illness will result. Others are more optimistic and hope that some strains of flu will disappear, which could mean less flu in the immediate future. It’s not a simple prediction to make.
Even if the low flu numbers this year mean some strains do not survive, it is unlikely that will remain the case. “I am sure that flu will come back with a vengeance at some stage in the future,” Robert Ware, PhD, a biostatistician, clinical epidemiologist, and Professor of Biostatistics with Griffith University in Queensland, Australia, told Nature.
Thus, clinical laboratories should remain vigilant for future influenza outbreaks. Hopefully by then the COVID-19 pandemic will have peaked and labs will be able to reallocate testing resources appropriately.
Liquid biopsy tests hold much promise. But inconsistencies in their findings provoke scrutiny and calls from researchers for further development before they can be considered reliable enough for diagnostic use
Many commercial developers of liquid biopsy tests tout the accuracy and benefits of their diagnostic technology. However, there are an equal number of medical laboratory experts who believe that this technology is not yet reliable enough for clinical use. Critics also point out that these tests are being offered as Laboratory Developed Tests (LDTs), which are internally developed and validated and have not undergone regulatory review.
Dark Daily has published several e-briefings on researchers who have sent the same patient samples to different genetic testing labs and received back materially different test results. Now, a new study by Johns Hopkins University concludes that liquid biopsy technology “must improve” before it should be relied upon for diagnostic and treatment decision making.
‘Certification for Medical Laboratories Must Improve’
Liquid Biopsy is the term for drawing whole blood and looking for cancer/tumor cells circulating in the blood stream. This is one factor in the imprecision of a liquid biopsy. Did the blood sample drawn actually have tumor cells? After all, only a limited number of tumor cells, if present, are in circulation.
Gonzalo Torga, MD (above left), and Kenneth J. Pienta, MD (above right), are the two Johns Hopkins Medicine doctors who conducted the recent study into the efficacy of liquid biopsy laboratory developed tests (LDTs) offered by different medical laboratory companies. They published their findings in JAMA Oncology. (Photos copyright: Johns Hopkins.)
In reporting the DNA findings and results from the two medical laboratory companies, researchers discovered that the results completely matched in only three of the 40 patients! The Johns Hopkins researchers are concerned that patients could be prescribed certain cancer treatments based on which lab company’s liquid biopsy test their physician orders, instead of an accurate identification of the unique mutations in their tumors.
“Liquid biopsy is a promising technology, with an exceptional potential to impact our ability to treat patients, but it is a new technology that may need more time and experience to improve,” Gonzalo Torga, MD, Postdoctoral Fellow and Instructor at Johns Hopkins, and the lead author of the study, told Forbes. “We can’t tell from these studies which laboratory’s panel is better, but we can say that certification for these laboratories must improve.”
Unlocking New View of Tumors
Two commercial tests were used for the study:
Guardant360 from Guardant Health, Inc., uses digital sequencing to analyze genomic data points at the single molecular level. It examines 73 genes, including all National Comprehensive Cancer Network (NCCN) listed genes. The test searches for DNA fragments among billions of cells and digitally tags each fragment. This process unlocks a view of tumors that is not seen with tissue biopsies, which helps doctors prescribe the best treatment options for a particular patient.
“As a simple blood test, it provides physicians with a streamlined, cost-effective method to identify genomic alterations that can comprehensively influence a patient’s therapy response,” Helmy Eltoukhy, PhD, co-founder and Chief Executive Officer at Guardant Health, told MDBR.
“The only way of keeping ahead of those diseases and tracking those mutations has been through surgery, through doing a tissue biopsy and physically cutting a piece of the tumor out and sequencing it,” Eltoukhy noted in an interview with Xconomy. “What we’re able to do is essentially get the same, or sometimes better performance to tissue biopsy, but through two teaspoons of blood.”
According to the Guardant Health website, it takes just 14 days for a full report from Guardant360 to reach the ordering physician. In addition, the blood test provides samples with an adequate level of cell-free DNA to test 99.8% of the time and reduces errors and false positives found in standard sequencing methods by 1,000 times. It is common for samples used for tissue sequencing to have insufficient DNA for testing 20% to 40% of the time.
“We believe that conquering cancer is at its core a big data problem, and researchers have been data-starved,” explained Eltoukhy in VentureBeat. “Our launch of the world’s first commercial comprehensive liquid biopsy sparked a boom in cancer data acquisition. Every physician who orders one of our tests, and every patient whose tumor DNA we sequence, adds to this larger mission by improving our understanding of this complex disease.”
PlasmaSELECT-R64, manufactured by Personal Genome Diagnostics (PGDx), evaluates a targeted panel of 64 genes that have biological and functional relevance in making treatment decisions. PGDx announced the expanded version of its PlasmaSELECT assay in March of 2017.
“We are proud to launch the revolutionary PlasmaSELECT 64 expanded assay just six months after we introduced the most accurate, clinically actionable liquid biopsy tumor profiling assay to the market,” said Doug Ward, Chief Executive Officer at PGDx, in a press release. “This update is the first liquid biopsy assay that includes MSI (microsatellite instability) testing as a biomarker for high tumor mutational load, thereby providing cancer patients and their oncologists with information on whether they might be candidates for immuno-oncology therapies. The ability to generate DNA tumor profiling non-invasively using blood or plasma offers many advantages and makes genomic testing more accessible and usable.”
Regulations of LDTs Could be Needed to Improve Liquid Biopsy Tests
There are pathologists and clinical laboratory professionals who believe the technology behind liquid biopsies is not yet reliable enough for clinical use. The tests are being offered as LDTs, which are internally developed and validated, and the Food and Drug Administration (FDA) allows LDTs to be sold without regulatory reviews at this time. However, there are discussions regarding if and how to regulate LDTs, the outcome of which could impact how clinical laboratories are allowed to market the LDTs they develop.
Clearly, liquid biopsies are still in their relatively early stages of development. More testing and evaluation is needed to determine their efficacy. However, their potential to revolutionize cancer detection and care is obvious and a strong motivator for LTD developers, which means there will be future developments worth noting.
