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.
Researchers at the university suggested their findings could lead to new genetic tests that could be offered by medical laboratories
New research conducted at the University of Utah suggests that clinical laboratories may someday be able to deploy genetic tests to indicate whether a couple has a higher-than-average risk of stillbirth.
This is yet another example of how researchers are cracking DNA’s code to understand how certain gene variants may affect the healthcare of offspring. The knowledge produced by this research, as confirmed by additional studies, may lead to genetic markers that medical laboratories can use to diagnose the risk of stillbirth using the parent’s DNA.
“Stillbirth is one of those problems that is so tragic and life-changing,” said study co-author Jessica Page, MD (above). “It is especially frustrating when you don’t have a good answer for why it happens. This knowledge may give us the opportunity to change how we risk stratify people and reduce their risk through prevention.” Should this research be validated, clinical laboratories may soon have new genetics tests to help doctors identify risk for stillbirth. (Photo copyright: Intermountain Healthcare.)
Can Stillbirth be Prevented?
Jessica Page, MD, an assistant professor in the Department of Obstetrics and Gynecology at the University of Utah School of Medical and co-author of the 2022 study, was lead author of a 2018 study that estimated nearly one-fourth of stillbirths are preventable.
“Stillbirth rate reduction has been slow in the US and we think many stillbirths may be potentially preventable,” she said in a university press release. “This is motivating us to look for those genetic factors so we can achieve more dramatic rate reduction.”
According to the press release, the University of Utah researchers found that stillbirth “can be inherited and tends to be passed down through male members of the family. That risk preferentially comes from the mother’s or father’s male relatives—their brothers, fathers, grandfathers, uncles, or male cousins. But the odds of a couple losing a baby to stillbirth are even greater when the condition comes from the father’s side of the family.”
The researchers made this discovery by analyzing data from the Utah Population Database (UPDB), which contains information on eight million people who were born in the state or have other connections there. The database is maintained by the Huntsman Cancer Institute at the University of Utah. It includes genealogical information and health records that allowed the researchers to trace incidence of stillbirths across multiple generations of families.
The researchers examined 9,404 stillbirth cases between 1978 and 2019, along with 18,808 live births that served as controls. They identified 390 multi-generational families with high numbers of stillbirths. Within that group, they looked at incidence of stillbirth among first-, second-, and third-degree relatives of stillborn babies. They then compared those numbers with data from unaffected families.
“We were able to evaluate multigenerational trends in fetal death as well as maternal and paternal lineages to increase our ability to detect a familial aggregation of stillbirth,” said genetic epidemiologist Tsegaselassie Workalemahu, PhD, lead author of the study. “Not many studies have examined inherited genetic risk for stillbirth because of a lack of data. The Utah Population Database allows for a more rigorous evaluation than has been possible in the past.”
Workalemahu described the research as “an important step toward identifying specific genes that increase the risk of stillbirth, which could one day lead to better diagnosis and prevention,” according to the university press release.
One caveat, the press release notes, is that Utah’s population is disproportionately of northern European descent. “Future studies will need to determine whether the trends hold true among people of different races and ethnicities,” it stated.
Call for More Testing
The University of Utah study is part of a larger effort to gain a greater understanding of the causes of stillbirths.
The story notes that “more than 20,000 pregnancies in the US end in stillbirth,” and in one in three of those cases, the cause is not determined.
Drucilla Roberts, MD, an obstetric and perinatal pathologist at Massachusetts General Hospital (MGH), told ProPublica that at a minimum, “the placenta should definitely be evaluated in every stillbirth.” But citing CDC data, the story notes that this is done in only 65% of stillbirths, and autopsies are performed in less than 20%.
“Experts blame the low rates on several factors,” the story states. “Because an autopsy often is performed in the days following a stillbirth, doctors and nurses have to ask families soon after they receive news of the death if they would like one. Many families can’t process the loss, let alone imagine their baby’s body being cut open. What’s more, many doctors aren’t trained in the advantages of an autopsy, or in communicating with parents about the exam.”
One consequence, ProPublica notes, is that clinicians are ill-equipped to advise patients on how to reduce risk in future pregnancies. The story describes the case of Karen Gibbins, MD, a maternal-fetal medicine specialist and an assistant professor of obstetrics and gynecology at the Oregon Health and Science University (OHSU) in Portland.
An Opportunity for Pathologists
Gibbins’ son was stillborn in 2018. She asked for an autopsy and learned that her son “had a rare disease caused by her antibodies attacking the cells in his liver,” the story states. When she became pregnant again, her doctor prescribed antibody infusions and she later gave birth to a healthy son. “If we had not had that autopsy, my third child would have died as well,” she told ProPublica.
This parent’s comment about the value of the autopsy done after her son’s stillbirth identifies an opportunity for the pathology profession. For several decades, health plans have become ever more reluctant to pay for autopsies. Yet, pathologists know the value that autopsies can provide.
The immediate value comes from revealing useful insights about all the health conditions of the deceased. The long-term value comes from the ability to gather the findings across a large number of autopsies that can contribute to new knowledge about health conditions that physicians use to improve the diagnoses of different health conditions.
Thus, with the publication of this peer-reviewed study about the connection between genetic variations and stillbirth, there is the opportunity for some of the nation’s pathology societies to advocate for funding a pilot program to fund more autopsies of stillborn babies, specifically to add more knowledge about the role of gene mutations as a causative factor in stillbirths.
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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.
“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.
“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.
Clinical laboratories and pathology groups can benefit from knowing how genetic testing is being used for other than medical testing purposes
It is useful for pathologists and clinical laboratory managers to be aware of the different ways genetic testing and DNA sequencing is being conducted. That’s because a genetic test for one purpose—such as identifying an individual’s relatives and connection to a region or a cultural group—might generate data that could become part of that person’s medical care.
Thus, an ongoing genetic study in South Africa highlighting the issue of so-called “helicopter research” will be informative for Dark Daily’s readers.
Also known as “neo-colonial science,” helicopter research describes when scientists from wealthy countries perform research in lower-income countries in ways that may be deemed exploitative or disrespectful to local populations.
“Scientists conduct helicopter research when they collect data from developing countries and marginalized communities with little to no involvement from local researchers and community members,” wrote researchers Dana Al-Hindi, and Brenna Henn PhD, in an article for The Conversation. “Helicopter research also occurs when researchers take data out of the country they collected it from without either providing benefit to or sharing the results with the community.”
In an article for The Conversation, UC Davis researchers Brenna Henn, PhD (left), and Dana Al-Hindi (right), wrote, “While we have learned a great deal from these communities, we have been unable to fulfill a common request: providing them their individual genetic ancestry result. In our attempts to overcome the logistical challenges of providing this information, we’ve grappled with the common question of how to ensure an equitable balance of benefits between researchers and the community they study. What we’ve found is that there is no easy answer.” Clinical laboratories will want to remember the term “Helicopter Research” in relation to these types of studies. (Photos copyright: UC Davis/The Conversation.)
The South Africa study, conducted over the past 12 years, aims to use genetic data “to help unravel the history and prehistory of southern Africans and their relationship to populations around the world,” the authors wrote in The Conversation.
The researchers have been using the genetic data to trace the ancestry of indigenous Khoekhoe and San peoples in South Africa as well as other populations that self-identify as “Colored.”
“Early European colonizers initially used this term to refer to indigenous Khoekhoe and San groups long before it was codified by the apartheid government in 1948,” the researchers wrote. “It persists today as an ethnic category, broadly encompassing Khoe-San groups, various East African, Indian, and Southeast Asian populations brought by the slave trade, and people of mixed ancestry.”
Challenges Sharing Genetic Data with Study Participants
Participants in the study have asked to see their personal genetic ancestry results, but the researchers noted several challenges, including local restrictions and the difficulty of presenting complex data in “an accessible and digestible form.” So, the researchers partnered with consumer-focused genetic testing company 23andMe (NASDAQ:ME).
23andMe provided additional funding for the research, assisted the researchers in community outreach, and “expanded our ability to ‘capacity-build’—that is, to make sure that the knowledge and skills we gain are shared with local institutions,” Henn and Al-Hindi wrote in The Conversation. They added that they are still dealing with questions about whether their efforts to provide equitable benefits are sufficient.
“Our research team, local collaborators, and 23andMe are all concerned about how to best address the risk of helicopter research, coercion, and any unknown risks that may arise from disclosing personal ancestry results,” they wrote.
Cape Town Statement on Fostering Research Integrity
The issue of helicopter research was a major focus at the 7th World Conference on Research Integrity (WCRI), held May 29-June 1 in Cape Town, South Africa. It was the first WCRI to be held in Africa and adopted the theme “Fostering Research Integrity in an Unequal World.”
One outcome of the conference will be an effort to produce what is known as the Cape Town Statement on Fostering Research Integrity. The statement will “highlight the importance of fairness in international research partnerships,” noted Research Professional News.
The statement “compels institutions and researchers alike to act on their responsibilities to promote equity, diversity, and fairness in research partnerships,” conference speaker Retha Visagie, DCur, told the publication. She leads the Research Integrity Office at the University of South Africa.
Conference co-chair Lyn Horn, PhD, director the Office of Research Integrity at the University of Cape Town, told the publication that it could take up to a year before a draft of the statement is ready for comment.
One overarching goal will be to “demonstrate why inequity and unfair practices in research collaborations and contexts is a research integrity (RI) matter,” the authors wrote. “Second it must identify some key values or principles and action guides that will address the issue of equity and fairness in research within the context of the complete research life cycle from research agenda setting and call to proposal development, through grant application, allocation and management of funding, data production, analysis, management and sharing, to outputs, translation, and evaluation.”
Another conference speaker, Francis Kombe PhD, told attendees the statement will offer guidance specifically to institutions such as universities, journals, and funding organizations, the journal Science reported. That stands in contrast to earlier statements on helicopter research, which were geared more toward individuals and small groups.
How any of this will impact clinical laboratories and pathology groups remains unclear. Nevertheless, it is worthwhile knowing how gene sequencing is being used by researchers for purposes other than to guide diagnoses and treatment of patients.
