News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

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?

Will ‘Flurona” Be an Issue for Clinical Laboratories This Flu Season?

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.

Stephen McMullan, MD

“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.)

.

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.

Ashley Croce

Related Information:

What Is ‘Flurona’? Israel Reports First Case of Rare Double Covid and Flu Infection

Similarities and Differences between Flu and COVID-19

What Is ‘Flurona’ and Why a Mayo Clinic Expert Says Flu Cases Are Rising

What Is ‘Flurona’? Coronavirus and Influenza Co-Infections Reported as Omicron Surges

CDC: COVID Data Tracker Weekly Review

The Double-Whammy COVID-Flu

What to Know about ‘Flurona’

Getting COVID-19 and the Flu at the Same Time: What Are the Risks?

Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens

AHA: Flurona and Its Impact on Flu Season

COVID-19 and Influenza Co-infection: A Systematic Review and Meta-Analysis

What Is ‘Flurona’? Why Are People Talking about It Now?

Fact Check-‘Flurona’ Is Not the Name of a New SARS-CoV-2 Variant

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

Monkeypox Outbreak Subsides in US, Europe, But Public Health Concerns Remain

Experts cite high vaccination rates and behavioral changes among at-risk groups, but warn about complacency; clinical laboratories should remain vigilant

In July, Scott Gottlieb, MD, Commissioner of the US Food and Drug Administration (FDA) from May 2017 to April 2019, wrote an op-ed in The New York Times titled, “Monkeypox Is About to Become the Next Public Health Failure.” In it, he wrote, “Our country’s response to monkeypox has been plagued by the same shortcomings we had with COVID-19.” But has it improved? Clinical laboratory leaders and pathology group managers will find it informative to find out what has taken place since Gottlieb made his stark prediction.

The global monkeypox outbreak that emerged last spring appears to have subsided in the US and Europe, though it remains to be seen if the disease can be completely eradicated, according to multiple media reports. As of Oct. 26, 2022, the Centers for Disease Control and Prevention (CDC) reported a 7-day rolling average of 30 cases per day in the US, down from a peak of nearly 440/day in early August.

Cases are also down in cities that earlier reported heavy outbreaks. For example, the New York City Health Department reported a 7-day average of just two cases per day on Oct. 25, compared with 73/day on July 30.

And the San Francisco Department of Public Health announced on Oct. 20 that it would end the city’s public health emergency on monkeypox (MPX) effective on Oct. 31. “MPX cases have slowed to less than one case per day and more than 27,000 San Franciscans are now vaccinated against the virus,” the agency stated in a press release.

Tedros Adhanom Ghebreyesus, PhD

“Once again, we caution that a declining outbreak can be the most dangerous outbreak, because it can tempt us to think that the crisis is over and to let down our guard,” said World Health Organization (WHO) Director-General Tedros Adhanom Ghebreyesus, PhD, in an Oct. 12 global press briefing. “That’s not what WHO is doing. We are continuing to work with countries around the world to increase their testing capacity, and to monitor trends in the outbreak.” Clinical laboratories should not assume the outbreak has passed but continue to be vigilant and prepared for increased demand in monkeypox testing. (Photo copyright: ITU Pictures.)

Changing Behavior Lowers Infection Rates

In addition to high vaccination rates, public health experts have attributed the decline to behavioral changes among at-risk groups. “There were really substantial changes among men who have sex [with] men,” infectious disease physician Shira Doron, MD, of Tufts Medical Center in Boston, told ABC News.

On September 2, the CDC published the results of a survey indicating that about half of men who have sex with men “reported reducing their number of sex partners, one-time sexual encounters, and use of dating apps because of the monkeypox outbreak.”

Another likely factor is the disease’s limited transmissibility. “Initially, there was a lot of concern that monkeypox could spread widely at daycares or in schools, but, overall, there has been very little spread among children,” NPR reported.  

But citing multiple studies, the NPR story noted “that often there isn’t very much virus in the upper respiratory tract,” where it might spread through talking or coughing. “Instead, the highest levels of virus occur on sores found on the skin and inside the anus.”

These studies, along with earlier research, “explain why monkeypox is spreading almost exclusively through contact during sex, especially anal and oral sex, during the current outbreak,” NPR reported.

Monkeypox Could Mutate, experts say

Despite the promising numbers, public health experts are warning that monkeypox could remain as a long-term threat to public health. According to an article in Nature, “At best, the outbreak might fizzle out over the next few months or years. At worst, the virus could become endemic outside Africa by reaching new animal reservoirs, making it nearly impossible to eradicate.”

In addition to the limited transmissibility of the virus, Nature noted that the outbreak stems from a relatively mild form of the pathogen and is rarely fatal. As of Oct. 28, the CDC reported a total of just six confirmed deaths in the US out of a total of 28,302 confirmed cases since the first infections were reported in May.

It is possible that the virus could mutate into a more contagious form, but Nature noted that monkeypox is a DNA virus, and that they tend to mutate more slowly than RNA viruses such as SARS-CoV-2 and HIV. Nevertheless, University of Alabama at Birmingham School of Medicine bioinformatician Elliot Lefkowitz, PhD, warned that a “worrisome mutation” could arise if the outbreak continues for much longer.

Another expert, Jessica Justman, MD, infectious disease specialist, epidemiologist, and associate professor at Columbia University Mailman School of Public Health, cautioned that declining case numbers might not reflect the true prevalence of the disease.

“I have no confidence that all the people who need to be tested are being tested,” she told Nature. She expressed concerns that people could resume risky behavior if they think the danger has passed.

Another question is whether currently available vaccines offer long-lasting protection. And though reported case numbers are down in the US and Europe, they are rising in parts of Africa and South America, Nature noted.

Gottlieb’s Dire Prediction

The decline in new infections followed dire warnings last summer about the possible consequences of the outbreak. In his New York Times op-ed, former Gottlieb criticized the CDC for being slow to test for the virus. He wrote, “[I]f monkeypox gains a permanent foothold in the United States and becomes an endemic virus that joins our circulating repertoire of pathogens, it will be one of the worst public health failures in modern times not only because of the pain and peril of the disease but also because it was so avoidable.”

At the time of his writing, Gottlieb was right to be concerned. On July 29, the CDC reported a seven-day moving average of 390 reported cases per day. According to the federal agency, a reported case “Includes either the positive laboratory test report date, CDC call center reporting date, or case data entry date into CDC’s emergency response common operating platform, DCIPHER.”

Quashing the outbreak, Gottlieb estimated, would have required about 15,000 tests per week among people presenting symptoms resembling monkeypox. But between mid-May and the end of June, he noted, the CDC had tested only about 2,000 samples, according to the federal agency’s July 15 Morbidity and Mortality Weekly Report (MMWR).

As a remedy, Gottlieb called on the Biden administration to re-focus the CDC’s efforts more on disease control “by transferring some of its disease prevention work to other agencies,” including the FDA.

Perhaps his suggestions helped. Confirmed monkeypox case are way down. Nevertheless, clinical laboratory leaders should continue to be vigilant. Growing demand for monkeypox testing could indicate an increase in reported cases as we enter the 2022 influenza season, which is predicted to be worse than previous years. Dark Daily covered this impending threat in “Australia’s Severe Flu Season Could be a Harbinger of Increased Influenza Cases in US and Canada Straining Already Burdened Clinical Laboratories.”

Stephen Beale

Related Information:

Monkeypox Cases in the US Are Way Down—Can the Virus Be Eliminated?

What Does the Future Look Like for Monkeypox?

NYC Has Almost Eliminated Monkeypox. An NYU Biology Prof on What the City Needs to Reach Zero

New York and Nevada Announce First Monkeypox Deaths as Official CDC Tally Rises to Four

Monkeypox Update: FDA Takes Significant Action to Help Expand Access to Testing

Gottlieb Predicts Monkeypox Will Become Public Health Failure

Monkeypox Is About to Become the Next Public Health Failure

Australia’s Severe Flu Season Could be a Harbinger of Increased Influenza Cases in US and Canada Straining Already Burdened Clinical Laboratories

Danish Study Finds Anti-Viral Paxlovid May Be Triggering Drug-to-Drug Interactions, Particularly in Elderly COVID-19 Patients

These findings may be useful to clinical laboratory professionals when physicians want guidance in effective treatments for COVID-19 patients, particularly when there are concerns about a rebound of the infection

Drug interactions are a major concern for physicians and clinical laboratories. That is especially true given the push for nearly universal COVID-19 vaccinations and boosters. Now, a study conducted in Denmark may show that the use of Paxlovid as an antiviral drug to treat early SARS-CoV-2 infection could trigger drug-drug interactions (DDI) in some patients.

For clinical laboratory managers, insights into the issues associated with Paxlovid may be useful in helping client physicians diagnose their patients and anticipate possible negative drug reactions where other anti-viral drugs are involved.

Also of interest to medical laboratory leaders is the fact that the federal Centers for Disease Control and Prevention (CDC) in May released a Health Alert Network (HAN) Health Advisory about the potential for COVID-19 rebound after Paxlovid treatment.

COVID-19 Rebound, according to the CDC, “has been reported to occur between two and eight days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative.”

The Danish researchers published their findings in the International Journal of Infectious Diseases, titled, “Assessing the Proportion of the Danish Population at Risk of Clinically Significant Drug-Drug Interactions with New Oral Antivirals for Early Treatment of COVID-19.”

Joan Susan Bregstein, MD

In an article she penned for STAT, Joan Susan Bregstein, MD (above), a pediatric emergency medicine physician and professor of pediatrics at Columbia University Irving Medical Center in New York, wrote, “Is Paxlovid worth it? The CDC advisory states in black, bold, and no uncertain terms that, despite the risk of rebound COVID, ‘Paxlovid continues to be recommended for early-stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease.’ But the definition of ‘high risk’ in this situation has been a moving target since the first days of COVID-19.” Clinical laboratory leaders can attest to the accuracy of that statement. (Photo copyright: Columbia University.)

Do Anti-Viral Drugs Interact with Other Medications?

Paxlovid is the retail name for a combination of two anti-viral drugs: nirmatrelvir and ritonavir. The medication for COVID-19 was developed by American pharmaceutical company Pfizer (NYSE:PFE) and received Emergency Use Authorization from the US Food and Drug Administration in August of this year.  

The drug is taken orally for five days by people who test positive for the SARS-CoV-2 coronavirus to head off disease progression as well as serious illness, according to the CDC advisory.

But a “sizeable proportion” of elderly people are on medications that could interact with Paxlovid, Reuters reported.

“Two oral antiviral drugs—nirmatrelvir/ritonavir (NMV/r) and molnupiravir—have been approved for early outpatient treatment of COVID-19 to prevent severe disease. Ritonavir, contained in NMV/r is known to have significant DDI with several drugs frequently used by the elderly. This communication puts the problem with DDI with oral antiviral COVID-19 treatment into perspective,” the study authors wrote.

Their analysis of prescription data from Denmark residents found “extensive use of drugs likely to interact with NMV/r” as follows:

  • Anticoagulants (blood thinners): used by 20% of people over age 65 and by 30% of people over 80.
  • Statins (cholesterol-lowering medications): taken by 15% to 18% of people over 65.
  • Analgesics (for pain), calcium channel blockers (used to decrease blood pressure in patients with hypertension), or digoxin (used to treat heart conditions): taken by 20% of those studied.

In their paper, the researchers offered guidance to physicians. “Before prescribing NMV/r, the patient’s full medical history, including herbals and over-the-counter and recreational drugs, must be known and co-treatment carefully managed by the treating physician or by a specialist to avoid detrimental effects.” 

However, one infectious disease specialist told Scientific American it may just take the elderly who were taking Paxlovid more time to completely get over COVID-19.

“Being of an elderly age and then having other risk factors—like diabetes, heart disease, kidney disease, or some sort of cancer—does put you at higher risk of rebound,” Aditya Shah, MBBS, Mayo Clinic Infectious Disease Physician and Researcher, told Scientific American.

Rebounding after Molnupiravir, Too

COVID-19 rebound is not exclusive to people who took Paxlovid, according to a paper published on medRxiv, titled, “Rebound after Paxlovid and Molnupiravir during January-June 2022.”

That study’s researchers retrospectively reviewed 92 million electronic health records (EHR) from US patients. They found most people (11,270) had been treated with Paxlovid. However, 2,374 patients took molnupiravir, which also was granted EUA status by the FDA and is marketed as Lagevrio.

That COVID-19-rebound study found:

  • After nirmatrelvir/ritonavir (Paxlovid) treatment: 3.53% had rebound infections, 2.3% with rebound symptoms, and .44% were hospitalized.
  • After molnupiravir (Lagevrio) treatment: 5.86% had rebound infections, 3.75% with rebound symptoms, and .84% were hospitalized.

“Patients who took molnupiravir were significantly older and had more comorbidities than those who took Paxlovid,” the researchers wrote. “Results further suggest that rebound was not unique to Paxlovid and may be associated with persistent viral infection in some patients treated with either of these two antivirals. There has been more attention to COVID-19 rebound following Paxlovid treatment than molnupiravir, which may be attributable to more people being treated with Paxlovid,” they concluded.

Clinical Laboratories Can Guide Doctors

In an article she penned for STAT, titled, “Paxlovid Rebound Happens, Though Why and to Whom Are Still a Mystery,” Joan Susan Bregstein, MD, a pediatric emergency medicine physician and professor of pediatrics at Columbia University Irving Medical Center in New York, wrote of COVID-19 rebound, “My emergency medicine physician colleagues are seeing tons of it. Although people tend to think of medical care as something that is certain, it is actually a real-time experiment. Paxlovid, like a lot of COVID-19 care, is a reminder of this.”

Similarly, Mayo Clinic’s Shah acknowledged difficulty in identifying a COVID-19 rebound case. “You need real documentation of three tests—a positive, a negative, a positive—and clear documentation of symptoms—all symptoms gone, symptoms come back,” Shah told Scientific American.

Thus, clinical laboratories play a vital role in diagnosing and treating COVID-19 rebound patients, because that is what clinical labs do: test, document, and report. And as the study of the Danish population pointed out, doctors need guidance as they prescribe oral antivirals to COVID-19 patients who are on other drugs and at possible risk of drug-drug interactions. 

Donna Marie Pocius

Related Information:

Assessing the Proportion of the Danish Population at Risk of Clinically Significant Drug-Drug Interactions with New Oral Antivirals for Early Treatment of COVID-19

CDC Health Advisory: COVID-19 Rebound after Paxlovid Treatment

Wastewater Study Technique Finds Virus Variants Sooner; Many Patients Are Using Meds Affected by Paxlovid

What Is Paxlovid Rebound and How Common Is It?

COVID-19 Rebound after Paxlovid and Molnupiravir during January-June 2022

Paxlovid Rebound Happens, Though Why and To Whom are Still a Mystery

;