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Researchers Use Whole Genome Sequencing to Make Surprising Discovery about Hospital-Acquired C. Diff Infections

By analyzing strains of the bacterium from a hospital ICU, the scientists learned that most infections were triggered within patients, not from cross-transmission

Tracking the source of Hospital-acquired infections (HAI) has long been centered around the assumption that most HAIs originate from cross-transmission within the hospital or healthcare setting. And prevention measures are costly for hospitals and medical laboratories. However, new research puts a surprising new angle on a different source for some proportion of these infections.

The study suggests that most infections caused by Clostridioides difficile (C. Diff), the bacterium most responsible for HAIs, arise not from cross-transmission in the hospital, but within patients who already carry the bacterium.

The research team, led by immunologist Evan Snitkin, PhD, and microbiologist Vincent Young, MD, PhD, both from the University of Michigan (UM), and epidemiologist Mary Hayden, MD, of Rush University Medical Center in Chicago, analyzed fecal samples from more than 1,100 patients in Rush Medical Center’s intensive care unit over a nine-month period.

A researcher performed whole genome sequencing on 425 strains of the bacterium isolated from the samples and found “very little evidence that the strains of C. diff from one patient to the next were the same, which would imply in-hospital acquisition,” according to a UM news story.

“In fact, there were only six genomically supported transmissions over the study period. Instead, people who were already colonized were at greater risk of transitioning to infection,” UM stated.

Arianna Miles-Jay, PhD, a postdoctoral fellow in The Snitkin Lab at the University of Michigan and Manager of the Genomic Analysis Unit at the Michigan Department of Health and Human Services, performed the genomic sequencing. “By systematically culturing every patient, we thought we could understand how transmission was happening. The surprise was that, based on the genomics, there was very little transmission,” she said in the UM news story.

The researchers published their findings in the journal Nature Medicine titled, “Longitudinal Genomic Surveillance of Carriage and Transmission of Clostridioides Difficile in an Intensive Care Unit.”

Evan Snitkin, PhD

“Something happened to these patients that we still don’t understand to trigger the transition from C. diff hanging out in the gut to the organism causing diarrhea and the other complications resulting from infection,” said Evan Snitkin, PhD (above), Associate Professor of Microbiology and Immunology, and Associate Professor of Internal Medicine, Division of Infectious Diseases at University of Michigan, in a UM news story. Medical laboratories involved in hospital-acquired infection prevention understand the importance of this research and its effect on patient safety. (Photo copyright: University of Michigan.)

Only a Fraction of HAIs Are Through Cross-Transmission

In the study abstract, the researchers wrote that “despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States.”

Citing data from the US Centers for Disease Control and Prevention (CDC), HealthDay reported that “nearly half a million C. diff infections occur in the United States each year. Between 13,000 and 16,000 people die from the bacterium, which causes watery diarrhea and inflammation of the colon. Many of these infections and deaths have been blamed on transmission between hospitalized patients.”

The new study, however, notes that 9.3% of the patients admitted to the ICU carried toxigenic (produces toxins) C. diff, but only 1% acquired it via cross-transmission. The carriers, the study authors wrote, “posed minimal risk to others,” but were 24 times more likely to develop a C. diff infection than non-carriers.

“Our findings suggest that measures in place in the ICU at the time of the study—high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C. diff, and single patient rooms —were effective in preventing C. diff transmission,” Snitkin told HealthDay. “This indicates that to make further progress in protecting patients from developing C. diff infections will require improving our understanding of the triggers that lead patients asymptomatically carrying C. diff to transition to having infections.”

Recognizing Risk Factors

Despite the finding that infections were largely triggered within the patients, the researchers still emphasized the importance of taking measures to prevent hospital-acquired infections.

“In fact, the measures in place in the Rush ICU at the time of the study—high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C. diff, and single patient rooms—were likely responsible for the low transmission rate,” the UM news story noted.

One expert not involved with the study suggested that hospitals’ use of antibiotics may be a factor in causing C. diff carriers to develop infections.

“These findings suggest that while we should continue our current infection prevention strategies, attention should also be given to identifying the individuals who are asymptomatic carriers and finding ways to reduce their risk of developing an infection, like carefully optimizing antibiotic usage and recognizing other risk factors,” Hannah Newman, Senior Director of Infection Prevention at Lenox Hill Hospital in New York City, told HealthDay.

Snitkin, however, told HealthDay that other factors are likely at play. “There is support for antibiotic disruption of the microbiota being one type of trigger event, but there is certainly more to it than that, as not every patient who carries C. diff and receives antibiotics will develop an infection.”

Another expert not involved with the study told HealthDay that “many patients are already colonized,” especially older ones or those who have been previously hospitalized.

“A lot of their normal flora in their GI tract can be altered either through surgery or antibiotics or some other mechanism, and then symptoms occur, and that’s when they are treated with antibiotics,” said Donna Armellino, RN, Senior VP of Infection Prevention at Northwell Health in Manhasset, New York.

Whatever is taking place, hospital-acquired infections kill thousands of people every years. It’s on the federal Centers for Medicare and Medicaid Services’ (CMS) “never event” list of hospital-acquired conditions (HOC) that should never happen to hospital patients. This affects reimbursement to hospitals for treatment of infections under Medicare’s Hospital-Acquired Condition Reduction Program

This research also demonstrates the value of faster, cheaper, more accurate gene sequencing for researching life-threatening conditions. Microbiologists, Clinical laboratory scientists, and pathologists will want monitor further developments involving these findings as researchers from University of Michigan and Rush University Medical Center continue to learn more about the source of C. diff infections.

—Stephen Beale

Related Information:

The Surprising Origin of a Deadly Hospital Infection

Patient-to-Patient Transmission Not to Blame for Most C. Difficile Infections in Hospitals

Longitudinal Genomic Surveillance of Carriage and Transmission of Clostridioides difficile in an Intensive Care Unit

Millions of COVID-19 At-Home Tests Set to Flood Market as HHS Asks 12 Test Manufacturers to Produce 200 Million Tests

Free at home clinical-laboratory testing for COVID-19 has been provided in the past, but this time the federal government wants to manufacture as many tests as possible in the US

Pathologists and clinical laboratory managers may be interested to learn that the US market is about to be flooded with millions of at-home COVID-19 rapid tests. The federal government has contracted with 12 US-based test manufacturers to produce 200 million at-home self-tests aimed at detecting “currently circulating COVID-19 variants” through the end of this year, according to a US Department of Health and Human Services (HHS) news release.

Through the Administration for Strategic Preparedness and Response (ASPR), HHS is investing $600 million to fund the self-tests, which are available for delivery through a reopening of the COVID.Gov/Test website.

Federal officials want to head off “supply chain issues” that developed in the past with reliance on tests made overseas, and to address a possible COVID-19 surge during the fall and winter, the Associated Press (AP) reported.

In fact, 500 million tests have already been distributed through US government channels to long-term care facilities, schools, and low-income senior housing.

Dawn O’Connell, JD

“Manufacturing COVID-19 tests in the United States strengthens our preparedness for the upcoming fall and winter seasons, reduces our reliance on other countries, and provides good jobs to hardworking Americans,” said Assistant Secretary for Preparedness and Response Dawn O’Connell, JD (above), in an HHS news release. “ASPR’s investments in these domestic manufacturers will increase availability of tests in the future.” With the federal government preparing for what it expects to be a surge in demand for COVID-19 testing, clinical laboratories may want to track the CDC’s weekly reports on the number of positive COVID-19 cases as this year’s influenza season progresses. (Photo copyright: Administration for Strategic Preparedness and Response.)

In Vitro Diagnostics Test Makers Get Government Gigs

This is not the first time federal officials sent out free COVID-19 tests to consumers. According to the AP, more than 755 million tests went out to US households in previous efforts to fight the spread of infections. But unlike those tests, these tests will be manufactured entirely within the US.

The government’s latest wave of free tests is meant to “complement ASPR’s ongoing distribution of free COVID-19 tests to long-term care facilities, low-income senior housing, uninsured individuals, and underserved communities, with 500 million tests provided to date through these channels,” the HHS news release noted.  

Both large and lesser-known in vitro diagnostics (IVD) manufacturers were selected by the federal government to receive funding. They include:

HHS advises people to take the test at the first sign of symptoms (fever, sore throat, runny nose, others), after coming into contact someone who has COVID-19, or prior to gathering with a group, as a preventative to spread of the coronavirus.

Tracking New BA.2.86 COVID Variant

Currently, the federal Centers for Disease Control and Prevention (CDC) is tracking BA.2.86 (aka, Pirola), a new SARS-CoV-2 variant.

According to CDC’s latest Respiratory Viruses Update:

  • Reporting laboratories say existing antibodies work against the BA.2.86 variant.
  • The variant does not appear to be linked in the US with increasing infections or hospitalizations.
  • It is “unclear how easily BA.2.86 spreads” relative to other variants.
  • BA.2.86 has been detected in nine states: Colorado, Delaware, Michigan, Ohio, Pennsylvania, Virginia, Washington, and in wastewater in New York and Ohio, as well as in other countries. 

For week ending Sept. 23, the CDC reported the following statistics compared to the prior week:

  • 19,079 COVID-19 hospitalizations, down 3.1%.
  • Total hospitalizations: 6.3 million.
  • 2.7% of total deaths were due to COVID-19, up 8%.
  • COVID-19 test positivity rate was 11.6%, down 1.1%.
  • 1.8% of emergency department visits were diagnosed with COVID-19, down 11.7%.

According to Verywell Health, BA.2.86 carries more than 30 mutations.  

“Even with a lot of mutations, there are a lot of spots in the virus that can be recognized by our immune system, and there are many shared mutations as well. There will be some protection from new vaccine booster as well as prior infections,” Rajendram Rajnarayanan, PhD, Assistant Dean of Research and Associate Professor, Basic Sciences, Arkansas State University, told Verywell Health.

During an online media briefing conducted by the World Health Organization (WHO), Maria Van Kerkhove, PhD, COVID-19 Technical Lead at WHO, said that the variant could be classified by WHO as a “variant of concern” in the event of widespread circulation. 

COVID-19, an Endemic Disease?

It’s worth noting that the common cold, influenza, SARS, and SARS-CoV-2 are all in the coronavirus family, and thus closely related with similar symptoms. It would not be a surprise that SARS-CoV-2 joins those other viruses as an endemic virus with a similar yearly cycle of infection rates.

If that happens, and no surge in infections appears that would motivate orders for the new COVID-19 at-home tests, the government may find itself with a lot of unused tests at the end of the year. The US Food and Drug Administration (FDA) is aware of this possibility and provides a website where people can check to see if their test has an extended expiration date.

Plus, folks who are tired of the pandemic may not respond at all to the government’s insistence to prepare for possible surges in infection rates.

“Whether or not people are done with it, we know the virus is there, we know that it’s circulating. We know, if past is prologue, it’ll circulate to a higher degree and spread, and cases will go up in the fall and winter seasons,” said Assistant Secretary for Preparedness and Response Dawn O’Connell, JD, in the HHS new release. “Anticipating that that would be true again, or something similar, we want to make sure the American people have these tools.”

Clinical laboratories may want to prepare as well. Many people are not comfortable with at-home self-testing and prefer to have their local medical labs perform the tests.

—Donna Marie Pocius

Related Information:

Biden-Harris Administration Awards $600 Million to Bolster US Manufacturing of COVID-19 Tests and Announces the Re-Opening of COVIDTests.gov

Biden Administration Announces $600 Million to Produce COVID-19 Tests and Will Reopen Website to Order Them

Free COVID Testing Will Fade with US Health Emergency in May

CDC’s COVID-19 Variant Update

CDC’s COVID-19 Data Tracker

Why B.2.86 Stands Out from Other COVID-19 Variants

Healthcare Experts See Links Between COVID-19 and RSV as Tripledemic Pressures Ease on Hospitals and Clinical Laboratories

Some medical experts suggest an ‘immunity gap’ related to COVID-19 mitigation measures, while others point to alternative theories

Surge in fall/winter SARS-CoV-2, influenza (flu), and respiratory syncytial virus (RSV) hospitalizations and ensuing clinical laboratory test referrals—dubbed by some public health experts as a “tripledemic”—appear to have eased in the US, according to stats from the US Centers for Disease Control and Prevention (CDC), Becker’s Hospital Review reported. However, scientists are still left with questions about why the RSV outbreak was so pronounced.

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.

Asuncion Meijas MD, PhD

“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.”

Pediatrician and infectious disease expert Theresa Barton, MD, of UT Health San Antonio noted that there was also a big RSV surge in summer of 2021.

“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.

Stephen Beale

Related Information:

This Year’s RSV Surge: Bigger, Earlier, and Affecting Older Patients than Previous Seasonal Outbreaks

Experts Explain the ‘Perfect Storm’ of Rampant RSV and Flu

Flu, COVID-19 and RSV are All Trending Down for the First Time in Months

COVID, Flu, RSV Declining in Hospitals As ‘Tripledemic’ Threat Fades

COVID-19 May Be to Blame for the Surge in RSV Illness Among Children. Here’s Why.

Is Immunity Debt or Immunity Theft to Blame for Children’s Respiratory Virus Spike?

Don’t Blame ‘Immunity Debt’ If You Get Sick This Winter

Claims of an Immunity Debt in Children Owe Us Evidence

Some are Blaming ‘Immunity Debt’ for the ‘Tripledemic’—But Experts Disagree

Rapid Tests for COVID, RSV and the Flu are Available in Europe. Why Not in the US?

Breath Sample Is Used by Opteev Technologies’ Combined COVID/Influenza/RSV Screening Device with 95% Sensitivity and 90% Specificity

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.

ViraWarn is a pocket-size breath analyzer that detects COVID-19, influenza, and respiratory syncytial virus (RSV) in about a minute, according to an Opteev news release. The technology company just submitted ViraWarn to the US Food and Drug Administration (FDA) for Pre-Emergency Use Authorization (Pre-EUA).

“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. 

Conrad Bessemer

“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.”
  • In a biosensor chamber, virus particles create a change in “electrical resistivity.”
  • 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.

In “Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test,” Dark Daily reported on the FDA issuing an EUA in 2022 for the InspectIR COVID-19 Breathalyzer, the first test to detect compounds in breath samples linked to SARS-CoV-2 infection, an FDA statement noted.

And in “NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers,” we covered how researchers at JILA, a research center jointly operated by the National Institutes of Standards and Technology (NIST) and the University of Colorado Boulder, have developed a breath test that can detect and monitor four disease biomarkers at one time with the potential to identify six more.

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.  

Donna Marie Pocius

Related Information:

Pocket-Sized Breath Analyzer Detects COVID-19, RSV, Influenza in Under 60 Seconds

COVID-19, RSV, and Influenza Breath Analyzer, ViraWarn, Wins CES 2023 Innovation Award

Baltimore Company Launches Device That Detects COVID-19, Flu

ViraWarn Pre-EUA Application

The Missing Piece in the Fight Against the Pandemic is Finally Here: The Evolution of Screening for COVID-19

FDA Authorizes First COVID-19 Diagnostic Test Using Breath Samples

Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test

NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers

Early Appearance of RSV Cases, Combined with Influenza and COVID-19, Raises Concern about Possibility of a Tripledemic During This Flu Season

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.

Dean Blumberg, MD

“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. 

“Age by itself is a risk factor for more severe disease, meaning that the younger babies are usually the ones that are sick-sick,” Asuncion Mejias, MD, PhD, a principal investigator with the Center for Vaccines and Immunity at the Abigail Wexner Research Institute, Nationwide Children’s Hospital, in Columbus, Ohio, told MarketWatch. “We are also seeing older kids, probably because they were not exposed to RSV the previous season.”

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.

JP Schlingman

Related Information:

“Tripledemic” in US Could Bring Deluge of Patients to Hospitals

When COVID-19, Flu and RSV Meet. The Potential for a Tripledemic.

A Tripledemic Expected This Winter

CDC HAN Alert: Increased Respiratory Virus Activity, Especially Among Children, Early in the 2022-2023 Fall and Winter

CDC: Respiratory Syncytial Virus Infection (RSV)

6-Year-Old with RSV Dies as Hospitals See Alarming Rise in New Virus Cases

COVID-19 May Be to Blame for the Surge in RSV Illness Among Children. Here’s Why.

Influenza, COVID, and RSV Cases Continue to Rise with Andrea Garcia, JD, MPH

COVID-19 vs. Flu vs. RSV: How to Tell the Difference Between Respiratory Infections

Pandemic ‘Immunity Gap’ is Probably Behind Surge in RSV Cases, Scientists Say

R.S.V. Cases Are Rising. Here’s What You Need to Know

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