Some healthcare experts point to an “immunity gap” tied to the COVID-19 pandemic, while others suggest alternative theories such as temporary immunodeficiency brought on by COVID-19. In most cases, RSV causes “mild, cold-like symptoms,” but the CDC states it also can cause serious illness, especially for infants, young children, and older adults, leading to emergency room visits, hospitalizations, and an increased demand for clinical laboratory testing.
Pulmonology Advisor reported that the disease typically peaks between December and February, but hospitalizations this season hit their peak in November with numbers far higher than in previous years. In addition to infants and older adults, children between five and 17 years of age were “being hospitalized far in excess of their numbers in previous seasons,” the publication reported.
“Age by itself is a risk factor for more severe disease, meaning that the younger babies are usually the ones that are sick-sick,” pediatrician Asuncion Mejias, MD, PhD (above), a principal investigator with the Center for Vaccines and Immunity at Nationwide Children’s Hospital in Columbus, Ohio, told MarketWatch. Now, she added, “we are also seeing older kids, probably because they were not exposed to RSV the previous season.” Clinical laboratories in hospitals caught the brunt of those RSV inpatient admissions. (Photo copyright: Nationwide Children’s Hospital.)
Did COVID-19 Cause Immunity Gap and Surge in Respiratory Diseases?
CDC data shows that hospitalization rates linked to RSV have steadily declined since hitting their peak of 5.2 per 100,000 people in mid-November. In contrast, hospitalizations linked to the flu peaked in late November and early December at 8.7 per 100,000. Hospitalizations linked to COVID 19—which still exceed those of the other respiratory diseases—reached a plateau of 9.7 per 100,000 in early December, then saw an uptick later that month before declining in the early part of January, 2023, according to the CDC’s Respiratory Virus Hospitalization Surveillance Network (RESP-NET) dashboard.
Surveillance by the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) revealed a similar pattern: An early peak in weekly numbers for emergency room visits for RSV, followed by a spike for influenza and steadier numbers for COVID-19.
So, why was the RSV outbreak so severe?
Respiratory diseases tend to hit hardest in winter months when people are more likely to gather indoors. Beyond that, some experts have cited social distancing and masking requirements imposed in 2020 and 2021 to limit the spread of COVID 19. These measures, along with school closures, had the side effect of reducing exposure to influenza and RSV.
“It’s what’s being referred to as this ‘immunity gap’ that people have experienced from not having been exposed to our typical respiratory viruses for the last couple of years, combined with reintroduction to indoor gatherings, indoor venues, indoor school, and day care without any of the mitigation measures that we had in place for the last couple of years,” infectious disease expert Kristin Moffitt, MD, of Boston Children’s Hospital told NPR.
Term ‘Immunity Debt’ Sparks Controversy
Other experts have pushed back against the notion that pandemic-related public health measures are largely to blame for the RSV upsurge. Many have objected to the term “immunity debt,” a term Forbes reported on in November.
“Immunity debt is a made-up term that did not exist until last year,” pediatrician Dave Stukus, MD, wrote on Twitter. Stukus is a Professor of Clinical Pediatrics in the Division of Allergy and Immunology at Nationwide Children’s Hospital in Columbus, Ohio.
An article published by Texas Public Radio (TPR) suggests further grounds for skepticism, stating that “the immunity debt theory doesn’t seem to hold up to scrutiny.”
“That was sort of the great unmasking, and everybody got viral illnesses,” she told TPR. “Now we’re past that. We’ve already been through that. We should have some immunity from that and we’re having it again.”
She added that “the hospital is filled with babies who are less than a year of age who have RSV infection. Those children weren’t locked down in 2020.”
The story also noted that not all Americans complied with social distancing or masking guidelines.
“We’re not seeing [less viral illness in] states in the United States that were less strict compared to states that were stricter during mask mandates and things like that. All the states are being impacted,” Barton told TPR.
Perfect Storm of Demand for Clinical Laboratory Testing
Barton suggested that COVID-19 might have compromised people’s immune systems in ways that made them more susceptible to other respiratory diseases. For example, a study published in Nature Immunology, titled, “Immunological Dysfunction Persists for Eight Months following Initial Mild-to-Moderate SARS-CoV-2 Infection,” found that some patients who survived COVID-19 infection developed post-acute long COVID (LC, aka, COVID syndrome) which lasted longer than 12 weeks. And that “patients with LC had highly activated innate immune cells, lacked naive T and naive B cells, and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at eight months after infection.”
Experts speaking to The Boston Globe said that multiple factors are likely to blame for the severity and early arrival of the RSV outbreak. Pediatric hospitalist and infectious disease specialist Chadi El Saleeby, MD, of Massachusetts General Hospital, said the severity of some cases might be tied to simultaneous infection with multiple viruses.
Clinical laboratories experienced a perfect storm of infectious disease testing demands during this tripledemic. Hopefully, with the arrival of spring and summer, that demand for lab tests will wane and allow for a return to a normal rate of traditional laboratory testing.
Clinical laboratories and point-of-care settings may have a new diagnostic test if this novel handheld device and related technology is validated by clinical trials
Efforts to develop breath analyzers that accurately identify viral infections, such as SARS-CoV-2 and Influenza, have been ongoing for years. The latest example is ViraWarn from Opteev Technologies in Baltimore, Maryland, and its success could lead to more follow-up PCR tests performed at clinical laboratories.
“Breath is one of the most appealing non-invasive sample types for diagnosis of infectious and non-infectious disease,” said Opteev in its FDA Pre-EUA application. “Exhaled breath is very easy to provide and is less prone to user errors. Breath contains a number of biomarkers associated with different ailments that include volatile organic compounds (VOCs), viruses, bacteria, antigens, and nucleic acid.”
Further clinical trials and the FDA Pre-EUA are needed before ViraWarn can be made available to consumers. In the meantime, Opteev announced that the CES (Consumer Electronic Show) had named ViraWarn as a 2023 Innovation Award Honoree in the digital health category.
“ViraWarn is designed to allow users an ultra-fast and convenient way to know if they are spreading a dangerous respiratory virus. With a continued increase in COVID-19 and a new surge in RSV and influenza cases, we’re eager to bring ViraWarn to market so consumers can easily blow into a personal device and find out if they are positive or negative,” said Conrad Bessemer (above), Opteev President and Co-Founder, in a news release.
Opteev is a subsidiary of Novatec, a supplier of machinery and sensor technology, and a sister company to Prophecy Sensorlytics, a wearable sensors company.
The ViraWarn breath analyzer uses a silk-based sensor that “traces the electric discharge of respiratory viruses coupled with an artificial intelligence (AI) processor to filter out any potential inaccuracies,” according to the news release.
Here is how the breath analyzer (mouthpiece, attached biosensor chamber, and attached printed circuit board chamber) is deployed by a user, according to the Opteev website:
The user turns on the device and an LED light indicates readiness.
The user blows twice into the mouthpiece.
A carbon filter stops bacteria and VOCs and allows virus particles to pass through.
As “charge carriers,” virus particles have a “cumulative charge.”
Electrical data are forwarded to the AI processor.
The AI processer delivers a result.
Within 60 seconds, a red signal indicates a positive presence of a virus and a green signal indicates negative one.
“The interaction of the virus with a specially designed liquid semiconductive medium, or a solid polymer semiconductor, generates changes in the conductivity of the electrical biosensor, which can then be picked up by electrodes. Such electrical data can be analyzed using algorithms and make a positive or negative call,” explains an Opteev white paper on the viral screening process.
While the ViraWarn breath analyzer can identify the presence of a virus, it cannot distinguish between specific viruses, the company noted. Therefore, a clinical laboratory PCR test is needed to confirm results.
Other Breath Tests
Opteev is not the only company developing diagnostic tests using breath samples.
For clinical laboratory managers and pathologists, Opteev’s ViraWarn is notable in breath diagnostics development because it is a personal hand-held tool. It empowers people to do self-tests and other disease screenings, all of which would need to be confirmed with medical laboratory testing in the case of positive results.
Further, it is important to understand that consumers are the primary target for this novel diagnostic device. This is consistent with investor-funding companies wanting to develop testing solutions that can be used by consumers. At the same time, a device like ViraWarn could be used by clinical laboratories in their patient service centers to provide rapid test results.
Epidemiologists warn that elderly and other individuals may be at high-risk for co-infection by strains of both SAR-CoV-2 and influenza
As of October, the influenza (flu) season has begun in North America. With the COVID-19 pandemic still prevalent, clinical laboratories must be prepared not only for increased demand for SARS-CoV-2 tests, but also for an increased number of orders for flu tests as well. In fact, virologists are sounding the alarm that some patients may present with an uncommon double infection of both viruses.
The potential for contracting the co-infection was dubbed “flurona” by the Israeli Outbreak Management Advisory Team in 2020. The Israeli Team coined the term flurona to describe the potential of contracting both COVID-19 and influenza after two young Israeli pregnant women were diagnosed with influenza and COVID-19. Since then, cases of co-infections have been confirmed in multiple countries around the world, according to The Washington Post.
The symptoms of influenza and COVID-19 are extremely similar. According to the Centers for Disease Control and Prevention (CDC), symptoms for both influenza and COVID-19 include fever, cough, chills, sore throat, and body aches. However, without a clinical laboratory test it is nearly impossible to distinguish one virus from the other.
Therefore, during this cold and flu season, clinical laboratory testing will be extremely important. And though co-infection with COVID-19 and the flu is rare, lab leaders should be on the lookout for spikes in testing.
“Co-infection is rare with COVID-19 and the flu, or COVID-19 and other types of infections that you might get as far as upper respiratory infections, because COVID-19 tends to take over,” Stephen McMullan, MD, a Mayo Clinic family medicine physician, told Mayo Clinic News. “Once COVID-19 is in your body, it’s going to be the predominant virus, but there are some rare cases where we have seen people getting both COVID-19 and the flu. So, it is possible, but it’s certainly not common.” Clinical laboratories should prepare for a spike in viral infections this winter that could indicate flurona. (Photo copyright: Mayo Clinic.)
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What Exactly Is a Flurona?
Although it is possible—albeit rare—to contract the flu and COVID-19 at the same time, flurona does not appear to be a “twindemic,” nor is it a distinct disease or a mutation of the two viruses, The Washington Post reported.
“The name seems to suggest that the viruses have somehow combined—and that’s not the case. It’s just that a person may get infected with two respiratory viruses at the same time or in short succession,” epidemiologist Judith O’Donnell, MD, Director, Department of Infection Prevention and Control, and Section Chief, Division of Infectious Diseases at Penn Presbyterian Medical Center, told an NPR affiliate in Pittsburg.
“It’s rare, but it’s not surprising that during a typical influenza season—which here in the northern hemisphere is right now during the winter months—that you will see multiple respiratory viruses circulating at the same time, and that people can get infected with more than one respiratory virus at the same time,” she added.
Though flurona may not be a hybrid virus, that does not mean it is of no concern.
“Although a low proportion of COVID-19 patients have influenza co-infection, the importance of such co-infection, especially in high-risk individuals and the elderly, cannot be ignored,” wrote the authors of a study published in Frontiers of Medicine titled, “COVID-19 and Influenza Co-infection: A Systematic Review and Meta-Analysis.”
Did COVID-19 Lockdowns, Social Distancing Cause Flurona?
According to the Washington Post, the US had record lows of influenza during the 2020-2021 flu season, however this was likely due to lockdown measures. With lockdown measures and social distancing even less prevalent this flu season, there is a risk of individuals being at risk for multiple respiratory viruses.
“We’re all a little bit more back together than we were a year ago,” McMullan told Mayo Clinic News. “The kids are back in school, and we have more events that people are attending, which could explain why we’re seeing flu cases rise.”
Thus, clinical laboratories should prepare for not only a higher number of flu tests, but also COVID-19 tests as well. That is because patients will not be able to distinguish which virus they are sick with based on symptoms alone. Further, because COVID-19 and the flu have similar symptoms, individuals may seek out multiple tests, or test for one virus and not the other.
McMullan asserts that a co-infection of the flu and COVID-19—though rare—is not impossible. For the best chance to avoid both diseases he suggests high-risk individuals “Get vaccinated against COVID-19, including your booster if eligible, and make sure to get your flu vaccine, continue to do the same strategies to protect yourself and others, such as wearing a mask in high-risk situations, washing your hands, and staying home if you feel ill.”
Meanwhile, clinical laboratory managers will want to track developments during this flu season. For example, flurona may be uncommon at this time, but emerging variants of SARS-CoV-2 and different strains of influenza might increase the number of patients diagnosed as infected with both COVID-19 and influenza.
Experts advise clinical laboratories to prepare now for a marked increase in demand for RSV, COVID-19, and influenza testing
Are the COVID-19 lockdowns responsible for the increase in cases of respiratory syncytial virus (RSV)? Some physicians believe that may be the case and it has hospitals, clinical laboratories, and pathology groups scrambling to prepare for a possible “tripledemic,” according to UC Davis Health.
The addition of RSV as we move into what is predicted to be a bad influenza (flu) season has prompted the Centers for Disease Control and Prevention (CDC) to issue a Health Alert Network (HAN) advisory which states, “Co-circulation of respiratory syncytial virus (RSV), influenza viruses, SARS-CoV-2, and others could place stress on healthcare systems this fall and winter.” This is especially true of clinical laboratories that still struggle to keep pace with demand for COVID-19 testing.
“COVID cases are expected to rise during the winter. This will be occurring at the same time we expect to see influenza rates increase while we are already seeing an early start to RSV season,” said Dean Blumberg, MD (above), chief of pediatric infectious diseases at UC Davis Children’s Hospital. “With all three viruses on the rise, we are worried about an increase in the rates of viral infection that may lead to an increase in hospitalizations.” Clinical laboratories should prepare for a marked increase in demand for RSV testing, as well as COVID-19 and influenza. (Photo copyright: UC Davis Health.)
Masking, Lockdowns, and Social Distancing Could be Responsible
Every winter in the United States, outbreaks of the flu and RSV occur. However, this year the RSV outbreak appears to be more serious. The CDC warns that “surveillance has shown an increase in RSV detections and RSV-associated emergency department visits and hospitalizations in multiple US regions, with some regions nearing seasonal peak levels.”
The current spread of RSV infections taking place in the US varies from prior outbreaks in notable ways:
Incidents are happening in the fall, whereas RSV outbreaks usually peak starting in late December.
Older children as well as infants are being hospitalized.
Current cases appear to be more severe.
Episodes are rising at a time when pediatric hospitalizations are already higher than usual due to other illnesses like COVID-19, influenza, and biennial enteroviruses.
Some experts believe that masking and social distancing due to the COVID-19 pandemic resulted in a respite of RSV infections in 2020. However, cases intensified in 2021, most likely a result of fewer young children being exposed to RSV during the previous year.
Most children typically have had at least one RSV infection before the age of two and the illness becomes less troublesome as children get older.
“The theory is that everyone’s now back together and this is a rebound phenomenon,” Jeffrey Kline, MD, Associate Chair of Research, Wayne State University School of Medicine in Detroit, told MarketWatch. “If we think about the relative increase—ninefold increase—that’s not nothing, especially in the pediatric [emergency departments]. Holy mackerel.”
Most RSV Infected Children Require Hospitalization
Kline is in charge of a surveillance network that aggregates information regarding incidents of viral infections from 70 US hospitals. The data shows that more children are being hospitalized with COVID-19 than with RSV, but that 5% of children are testing positive for both illnesses. About 60% of children in that group require hospitalization.
According to the CDC, individuals with RSV will typically begin to experience symptoms within four to six days after getting infected. Symptoms of RSV, which tend to appear in stages, include:
Runny nose
Decrease in appetite
Coughing
Sneezing
Fever
Wheezing
“RSV causes a mild cold illness in most people. But it can be very dangerous for very young children and older adults. And young infants are usually the most at risk of hospitalizations in what physicians would call their first RSV season,” said Andrea Garcia, JD, Vice President, Medicine and Public Health, American Medical Association (AMA), in a November 2 AMA update on the current flu season.
“In a pre-pandemic year,” she added, “we would see 1% to 2% of babies younger than six months with an RSV infection maybe needing to be hospitalized. And virtually all children have gotten an RSV infection by the time they’re two-years-old.”
Infants are at a much higher risk of experiencing severe disease due to RSV because their immune systems are not fully developed, and those under six months old are unable to breathe through their mouths if they are congested.
Mejias is studying whether prior exposure to COVID-19 alters how a baby’s immune system reacts to RSV, and if it may lead to more severe illness in those babies.
“That is something to work on and understand,” she said.
Comorbidities and Compromised Immune Systems also a Factor
Older adults and adults with weakened immune systems are predisposed to RSV infections, but there are things people can do to mitigate their chances of becoming ill from RSV.
“[RSV] is spread through contact with droplets from the nose and throat of infected people when they cough or sneeze. It can also be spread through respiratory secretions on surfaces,” said Garcia in the AMA update. “So, it’s a really good idea to clean and disinfect surfaces, especially in areas where young children are constantly touching things. Handwashing is always important. And if you are sick, please stay home.”
She added, “Premature infants, children with certain medical conditions, are also eligible to take a monthly monoclonal antibody treatment during RSV season, and that can help them stay out of the hospital.”
Most RSV infections typically go away on their own within a week or two. But such infections can lead to more severe illnesses, such as bronchiolitis and pneumonia. The more serious cases may require hospitalization with additional oxygen, IV fluids, and even intubation with mechanical ventilation. In most cases, hospitalization only lasts a few days, according to the CDC.
Be Prepared for a Tripledemic
“Health officials are concerned that this could be a sign of what’s to come,” stated Garcia in the AMA update. “A difficult winter, with multiple respiratory viruses circulating.”
For clinical laboratory managers, the early arrival of RSV cases at the front end of this influenza season provides an opportunity to position their labs to better meet the demand for RSV testing. They should also advise their client physicians that there may be a surge of respiratory illnesses during this flu season.
End of social distancing, masking, and other COVID-19 pandemic mitigations may lead to more severe flu-like infections in northern hemisphere, experts say
Clinical laboratory professionals in the United States and Canada should prepare now for a severe flu season. That is according to infectious disease experts at Johns Hopkin’s Center for Health Security who predict the rise in influenza (flu) cases in Australia signals what will likely be higher than normal numbers of flu-like infections starting this fall in the Northern Hemisphere.
As a Southern Hemisphere nation, Australia experiences winter from June through August. The land down under just concluded its worst flu season in five years. The flu arrived earlier than usual and was severe. Surveillance reports from the Aussie government’s Department of Health and Aged Care noted that influenza-like illness (ILI) peaked in May and June, but that starting in mid-April 2022 the weekly number of flu cases exceeded the five-year average.
If the same increase in flu cases happens here, healthcare systems and clinical laboratories already burdened with continuing COVID-19 testing and increasing demand for monkeypox testing could find the strain unbearable.
Amesh Adalja, MD (above), Infectious Disease Expert and Senior Scholar at the Johns Hopkin’s Center for Health Security, told Prevention that Australia’s flu season is typically a harbinger of what will follow in the US, Canada, and other Northern Hemisphere countries. “The planet has two hemispheres which have opposite respiratory viral seasons,” he said. “Therefore, Australia’s flu season—which is just ending—is often predictive of what will happen in the Northern Hemisphere.” Clinical laboratories in the United States should review their preparations as North America enters its influenza season. (Photo copyright: Johns Hopkins Bloomberg School of Public Health.)
Consequences of Decline in Flu Vaccinations and Social Distancing, Masks
The New York Times noted that in 2017, when Australia suffered through its worst flu season since modern surveillance techniques were adopted, the US experienced a deadly 2017-2018 flu season a half-year later that took an estimated 79,000 lives.
While the number of flu cases in this country is currently low, according to the weekly US Centers for Disease Control and Prevention’s (CDC) “Flu View,” that is expected to change as temperatures cool.
During the height of the COVID-19 pandemic in the US, influenza was nearly nonexistent. Pandemic-mitigation efforts such as masking, social distancing, and quarantining slowed the spread of the annual respiratory illness. But pandemic mitigation efforts are no longer the norm.
“Many have stopped masking,” said Abinash Virk MD, an Infectious Diseases Specialist at Mayo Clinic College of Medicine and Science, in a Mayo Clinic news blog that urged patients to get vaccinated for flu. “For the large part, we will see the re-emergence of influenza in the winter. In comparison, in 2020 winter … there was literally no influenza. But now that has all changed.”
Diminished Immunity Will Lead to More Severe Flu Cases
A CDC report published in July also noted that last winter’s flu season broke from the traditional pattern of arrival of the flu in the fall followed by a peak in cases in February.
During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June. It featured two distinct waves, with A(H3N2) viruses predominating for the entire season. But the overall case counts were the lowest in at least 25 years preceding the COVID-19 pandemic.
Thomas Russo, MD, Professor and Chief of Infectious Disease at the University at Buffalo in New York, said the past two mild flu seasons could set the stage for a difficult year in 2022-23.
“Immunity to respiratory viruses, including the flu, wanes over time,” Russo told Prevention. “People have not seen the virus naturally for a couple of years and many individuals don’t get the flu vaccine.” That, he says, raises the risk that people who are unvaccinated against the flu will develop more severe cases if they do happen to get infected.
“People are interacting closely again and there are very few mandates,” he added. “That’s a set-up for increased transmission of influenza and other respiratory viruses.”
“The Southern Hemisphere has had a pretty bad flu season, and it came on early,” Fauci, told Bloomberg in late August. “Influenza, as we all have experienced over many years, can be a serious disease, particularly when you have a bad season.”
CNN reported that US government modeling predicts flu will peak this year in early December.
CDC Advises Public to Get Flu Vaccine
Because COVID-19 and Influenza have many symptoms in common, such as fever, cough, shortness of breath, fatigue, sore throat, runny nose, headache, and muscle aches, the Mayo Clinic points out on its blog that testing is the only way to discern between the two when symptoms overlap.
According to the CDC, the best way to reduce risk from seasonal flu and its potentially serious complications is to get vaccinated every year. The best time to get vaccinated for the flu is in September and October before the flu starts spreading in communities, the CDC states. However, vaccination after October can still provide protection during the peak of flu season.
Yet, many people fail to get the flu vaccine even though it is recommended for everyone over the age of six months. CNN reported that just 45% of Americans got their flu shots last season. Flu vaccination rates fell for several at-risk groups, including pregnant women and children.
Though flu seasons are often unpredictable, clinical laboratories should prepare now for an influx of influenza test specimens and higher case rates than the past two pandemic-lightened flu seasons. Coupled with COVID-19 and monkeypox testing, already strained supply lines may be disrupted.
