Viral reservoir could be behind persistence, says study, which also suggests a blood biomarker could be found for clinical laboratory testing
Microbiologists and virologists working closely with physicians treating long COVID-19 patients will gain new insights in a study that found coronavirus spike protein in COVID-19 patients’ blood up to 12 months after diagnosis. The researchers believe their findings could be used to develop a clinical laboratory biomarker for long COVID-19.
Researchers at Brigham and Women’s Hospital and Massachusetts General Hospital said medical experts are not sure why some people have unwelcome symptoms weeks and months after a positive COVID-19 diagnosis, while others clear the infection without lingering effects.
The scientists believe if this work is validated, clinical laboratories might gain an assay to use in the diagnosis of long COVID-19.
“The half-life of spike protein in the body is pretty short, so its presence indicates that there must be some kind of active viral reservoir,” said David Walt, PhD (above), Professor of Pathology, Brigham and Women’s Hospital, and lead author of the study that found coronavirus spike protein in long COVID patients. The study findings indicate a potential clinical laboratory biomarker for long COVID-19. (Photo copyright: Brigham and Women’s Hospital.)
Viral Reservoir Possibly Behind Long COVID-19
The study suggests that SARS-CoV-2 finds a home in the body, particularly the gastrointestinal tract, “through viral reservoirs, where it continues to release spike protein and trigger inflammation,” Medical News Today reported.
Lead author of the study David Walt, PhD, Professor of Pathology, Brigham and Women’s Hospital and the Hansjörg Wyss Professor Biologically Inspired Engineering at Harvard Medical School, told The Guardian he “was motivated to carry out the study after earlier research by his colleagues detected genetic material from the COVID virus (viral RNA) in stool samples from children with multisystem inflammatory syndrome (a rare but serious condition that often strikes around four weeks after catching COVID) as well as spike protein and a marker of gut leakiness in their blood.”
Long COVID—also known as long-haul COVID, post-COVID-19, or its technical name, post-acute sequelae of COVID-19 or PASC—can involve health problems continuing weeks, months, or even years after a positive diagnosis, according to the federal Centers for Disease Control and Prevention (CDC).
Symptoms of long COVID, according to the researchers, include:
fatigue,
loss of smell,
memory loss,
gastrointestinal distress, and
shortness of breath.
“If someone could somehow get to that viral load and eliminate it, it might lead to resolution of symptoms,” Walt told the Boston Globe, which noted that the researchers may explore a clinical trial involving antiviral drugs for treatment of long COVID-19.
Clues from Earlier Studies on Long COVID-19
Medical conditions that persisted following a COVID-19 infection have been studied for some time. In fact, in an earlier study, Walt and others found children who developed a multisystem inflammation syndrome weeks after being infected by SARS-CoV-2, according to their 2021 paper published in The Journal of Clinical Investigation, titled, “Multisystem Inflammatory Syndrome in Children Is Driven by Zonulin-Dependent Loss of Gut Mucosal Barrier.”
Although these earlier studies provided clues, the cause of PASC remains unclear, the researchers noted. They planned to take a more precise look at PASC biology by using appropriate sampling and patient recruitment.
“Disentangling the complex biology of PASC will rely on the identification of biomarkers that enable classification of patient phenotypes. Here, we analyze plasma samples collected from PASC and COVID-19 patients to determine the levels of SARS-CoV-2 antigens and cytokines and identify a blood biomarker that appears in the majority of PASC patients,” the researchers wrote.
Finding a Marker of a Persistent Infection
The researchers used plasma samples from 63 people with a previous SARS-CoV-2 diagnosis (37 also had PASC), Medical News Today reported. Over a 12-month period, the researchers’ findings included:
Detection in 65% of PASC samples of full-length spike, S1 spike, and nucleocapsid throughout the year of testing.
Spike detected in 60% of PASC patient samples, and not found in the COVID-19 samples.
In an interview with Scientific American, bioengineer Zoe Swank PhD, post-doctoral researcher, Brigham and Women’s Hospital, and co-author of the study, said, “Our main hypothesis is that the spike protein is not causing the symptoms, but it’s just a marker that is released because you still have infection of some cells with SARS-CoV-2.”
In that article, Swank shared the scientists’ intent to do more research involving hundreds of samples over the course of the COVID-19 pandemic from many hospitals and people.
COVID-19 Not the Only Virus That Hangs On
Having a long-haul COVID-19 marker is a “game-changer,” according to an infectious disease expert who was not involved in the study.
“There has not so far been a clear, objective marker that is measurable in the blood of people experiencing long COVID-19,” Michael Peluso, MD, Assistant Professor, Medicine, University of California San Francisco, told Scientific American. “I hope their findings will hold up. It really would make a difference for a lot of people if a marker like this could be validated,” he added.
However, COVID-19 is not the only virus that could persist. Ebola also may linger in areas that skirt the immune system, such as the eye interior and central nervous system, according to a World Health Organization fact sheet.
Thus, medical laboratory leaders may want to follow the Brigham and Women’s Hospital research to see if the scientists validate their finding, discover a biomarker for long-haul COVID-19, and pursue a clinical trial for antiviral drugs. Such discoveries could have implications for how diagnostic professionals work with physicians to care for long COVID patients.
Experts say it is time ‘to restore our confidence in vaccines’ as many medical laboratories take steps to support testing for the polio virus
Clinical laboratories and microbiologists in the state of New York will want to know that, in July, a man in New York was diagnosed with polio and subsequently the virus was detected in the wastewater of two New York counties.
The area, Rockland County, N.Y., just north of New York City, was also at the forefront of a measles outbreak that occurred in 2018 and 2019. The outbreak was attributed to low vaccination rates within the community.
The unidentified, immunocompetent young man was admitted to a New York hospital after experiencing a low-grade fever, neck stiffness, back and abdominal pain, constipation, and lower extremity weakness. He eventually developed paralysis from the disease, which is irreversible.
Poliomyelitis, commonly known as polio, is a disabling and life-threatening disease that is caused by the poliovirus. Though it rarely surfaces in the United States, there is now confirmation of the first US case since 2013.
“The polio vaccine is safe and effective, protecting against this potentially debilitating disease, and it has been part of the backbone of required, routine childhood immunizations recommended by health officials and public health agencies nationwide,” said Mary T. Bassett, MD (left), Health Commissioner at the New York Department of Health, in a press release. Clinical laboratories and microbiologists in New York may want to prepare for an increase in vaccination requests. (Photo copyright: Time.)
Is Polio Back in America? Clinical Laboratories Will Want to Be Prepared
“I think it’s concerning because it can spread,” epidemiologist Walter Orenstein, MD, Professor, Department of Medicine, Division of Infectious Diseases at Emory University School of Medicine told STAT. “If there are unvaccinated communities, it can cause a polio outbreak.”
According to the federal Centers for Disease Control and Prevention (CDC), public health experts are working diligently to discover how and where the infected individual contracted polio. The CDC website states that the risk for people who have received the polio vaccine is very low, but there is concern for those who have not received the recommended doses of the vaccine.
“Most of the US population has protection against polio because they were vaccinated during childhood, but in some communities with low vaccine coverage, there are unvaccinated people at risk,” the CDC noted. “Polio and its neurologic effects cannot be cured but can be prevented through vaccination.”
The US uses an injectable polio vaccine for the poliovirus which contains killed viruses. The vaccine “instructs” the immune system to recognize and combat the virus. This inactivated polio vaccine (IPV) is administered to children as a shot in the arm or leg and is typically given in four separate doses.
“The inactivated polio vaccine we have is very effective and very safe and could have prevented this,” Orenstein told STAT. “We need to restore our confidence in vaccines.”
“Based on what we know about this case, and polio in general, the (New York) Department of Health strongly recommends that unvaccinated individuals get vaccinated or boosted with the FDA-approved IPV polio vaccine as soon as possible,” said Mary T. Bassett, MD, Health Commissioner at the New York Department of Health in a press release.
Poliovirus Found in Wastewater via Use of Gene Sequencing
Poliovirus is very contagious and is transmitted through person-to-person contact. The virus lives in an infected person’s throat and intestines and can contaminate food and water in unsanitary conditions. According to the CDC, typical symptoms of the illness include flu-like symptoms such as:
Sore throat
Fever
Tiredness
Nausea
Headache
Stomach pain
Most of these symptoms will disappear within five days, but polio can invade the nervous system and cause more serious complications, such as meningitis, paralysis, and even death.
After confirmation of the new case of polio, wastewater surveillance detected the presence of the poliovirus in Rockland and Orange counties, New York.
Wastewater analysis can uncover pathogens within a community and has been used in the fight against other infectious diseases, including:
“In some regards, wastewater is a public health dream scenario,” said Mark Siedner, MD, an infectious disease doctor at Massachusetts General Hospital and associate professor at Harvard Medical School, in an interview with Fortune. “Everyone poops, and most people poop every day. It provides real-time data on infection rates. In that regard, it’s an extremely powerful tool, particularly good at detecting early warning signs. Before people get sick, we might get a signal.”
Wastewater analysis can provide insights regarding the types of viruses that people within a community are shedding and if the volume of those viruses are increasing. This information can provide scientists with an early marker for an outbreak of an illness that is on the verge of spreading.
Microbiologists and clinical laboratories should be aware of the specific types of infectious agents public health authorities are detecting in wastewater, even as they perform screening and diagnostic tests on their patients for similar infectious diseases.
Polio is Appearing Worldwide
The Global Polio Eradication Initiative (GPEI) has announced that new cases of polio have been reported in Israel and the United Kingdom. These are countries where polio cases are extremely rare.
This indicates that microbiologists and clinical laboratories managers will want to be on constant alert for uncommon infectious diseases that may appear suddenly, even if those illnesses are rare. Accurate and immediate diagnoses of such infectious diseases could play a major role in triggering a public health response to control potential outbreaks while they are in their earlier stages.
Clinical laboratories continue to report positive COVID-19 tests for individuals that have been vaccinated and even previously infected with the same variant of the coronavirus
Researchers across the globe continue to study the SARS-CoV-2 coronavirus and its many variants. Their goals are to curb the spread of the disease and develop new therapies and treatments for optimal patient outcomes. Now, a study conducted by scientists at the University of Missouri (UM) provides deeper insight into the processes the virus uses to mutate and overpower the human immune system. These findings could lead to improved antivirals and clinical laboratory tests for COVID-19.
The UM team identified specific mutations occurring within the virus’ spike protein that help Omicron subvariants evade existing antibodies and create an infection. These mutations may explain why some people who have had previous COVID-19 infections and/or who are fully vaccinated continue to test positive for SARS-CoV-2, and why the virus continues to evolve.
“Omicron now has more than 130 sublineages and they have been here for quite a while. We are now just finally able to detect them and differentiate among them with this research,” said Kamlendra Singh, PhD, associate research professor in the Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine, in a UM press release.
“Previous variants, including Alpha, Beta, Gamma, and Delta, contributed to many of the mutations occurring now with these Omicron variants. So, our research shows how the virus has evolved over time with new mutations,” he added.
“Throughout the pandemic, the [SARS-CoV-2] virus has continued to get smarter and smarter. Even with vaccines, it continues to find new ways to mutate and evade existing antibodies,” said Kamlendra Singh, PhD (above), Associate Research Professor, College of Veterinary Medicine at University of Missouri, in a UM press release. This research team’s findings may help clinical laboratories further develop their SARS-CoV-2 antibody tests. (Photo copyright: University of Missouri.)
Antibodies for One Variant, but Not for Another
The scientists began their investigation by researching online databases that track COVID-19 cases and analyzing the protein sequences from more than 10 million Omicron-related samples that were collected from around the world since November of last year.
They examined the available sequences, structures of spike/receptor and spike/antibody complexes of the samples, and then conducted molecular dynamics simulations. The team utilized 3D modeling to locate where mutations occur and created structures of the spike protein to determine how the mutations are affected by antibodies and vaccinations.
The researchers found that the Omicron variant continues to mutate and has become extremely efficient at adaptation. Reinfections are happening because many individuals do not possess the antibodies for the new subvariants that continue to develop.
“Vaccinated individuals, or those who have previously tested positive, may have the antibodies for one variant but not necessarily for any of the other variants,” Singh explained. “The various mutations may seem like only subtle differences, but they are very important.”
The UM scientists’ research shows it is possible to differentiate Omicron subvariants from each other and pinpoint how certain mutations might become problematic for patients. According to Singh, many people can be infected with multiple variants at the same time. He is hopeful that their work will make it possible for vaccines and other treatments to specifically target different strains of the virus.
Singh also believes that the coronavirus is most likely never going to disappear from society and that new variants and their sublineages will continue to appear and evolve.
“The ultimate solution going forward will likely be the development of small molecule, antiviral drugs that target parts of the virus that do not mutate,” Singh said. “While there is no vaccine for HIV, there are very effective antiviral drugs that help those infected live a healthy life, so hopefully the same can be true with COVID-19.”
Omicron Subvariants May Be Here to Stay
“I am proud of my team’s efforts, as we have identified specific mutations for various variants throughout the pandemic, and it feels good to be contributing to research that is assisting with the situation,” Singh said. “We will continue to help out, as there will surely be new variants in the future.”
Singh is also part of a team that developed a supplement called CoroQuil-Zn, which was designed to reduce a patient’s viral load after being infected with SARS-CoV-2. The drug is currently being used in parts of India and is awaiting approval from the US Food and Drug Administration (FDA).
Clinical laboratories that perform antibody testing for SARS-CoV-2 infections should be aware that the coronavirus will likely be moving among humans for many years to come. This recent research may aid in the development of new antivirals, treatments, and vaccines that target specific subvariants for the best patient outcomes.
Understanding why some mutations impair normal bodily functions and contribute to cancer may lead to new clinical laboratory diagnostics
New insight into the human genome may help explain the ageing process and provide clues to improving human longevity that can be useful to clinical laboratories and researchers developing cancer diagnostics. A recent study conducted at the Wellcome Sanger Institute in Cambridge, United Kingdom, suggests that the speed of DNA errors in genetic mutations may play a critical role in the lifespan and survival of a species.
To perform their research, the scientists analyzed genomes from the intestines of 16 mammalian species looking for genetic changes. Known as somatic mutations, these mutations are a natural process that occur in all cells during the life of an organism and are typically harmless. However, some somatic mutations can impair the normal function of a cell and even play a role in causing cancer.
“Aging is a complex process, the result of multiple forms of molecular damage in our cells and tissues. Somatic mutations have been speculated to contribute to ageing since the 1950s, but studying them had remained difficult,” said Inigo Martincorena, PhD (above), Group Leader, Sanger Institute and one of the authors of the study. Greater understanding of the role DNA mutations play in cancer could lead to new clinical laboratory tools and diagnostics. (Photo copyright: Wellcome Sanger Institute.)
Lifespans versus Body Mass
The mammalian subjects examined in the study incorporated a wide range of lifespans and body masses and included humans, giraffes, tigers, mice, and the highly cancer-resistant naked mole-rat. The average number of somatic mutations at the end of a lifespan was around 3,200 for all the species studied, despite vast differences in age and body mass. It appears that species with longer lifespans can slow down their rate of genetic mutations.
The average lifespan of the humans used for the study was 83.6 years and they had a somatic mutation rate of 47 per year. Mice examined for the research endured 796 of the mutations annually and only lived for 3.7 years.
Species with similar amounts of the mutations had comparable lifespans. For example, the small, naked mole-rats analyzed experienced 93 mutations per year and lived to be 25 years of age. On the other hand, much larger giraffes encountered 99 mutations each year and had a lifespan of 24 years.
“With the recent advances in DNA sequencing technologies, we can finally investigate the roles that somatic mutations play in ageing and in multiple diseases,” said Inigo Martincorena, PhD, Group Leader, Sanger Institute, one of the authors of the study in a press release. He added, “That this diverse range of mammals end their lives with a similar number of mutations in their cells is an exciting and intriguing discovery.”
The scientists analyzed the patterns of the mutations and found that the somatic mutations accumulated linearly over time. They also discovered that the mutations were caused by similar mechanisms and the number acquired were relatively similar across all the species, despite a difference in diet and life histories. For example, a giraffe is typically 40,000 times larger than a mouse, but both species accumulate a similar number of somatic mutations during their lifetimes.
“The fact that differences in somatic mutation rate seem to be explained by differences in lifespan, rather than body size, suggests that although adjusting the mutation rate sounds like an elegant way of controlling the incidence of cancer across species, evolution has not actually chosen this path,” said Adrian Baez-Ortega, PhD, postdoctoral researcher at the Sanger Institute and one of the paper’s authors, in the press release.
“It is quite possible that every time a species evolves a larger size than its ancestors—as in giraffes, elephants, and whales—evolution might come up with a different solution to this problem. We will need to study these species in greater detail to find out,” he speculated.
Why Some Species Live Longer than Others
The researchers also found that the rate of somatic mutations decreased as the lifespan of each species increased which suggests the mutations have a likely role in ageing. It appears that humans and animals perish after accumulating a similar number of these genetic mutations which implies that the speed of the mutations is vital in ascertaining lifespan and could explain why some species live substantially longer than others.
“To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising. But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate,” said Alex Cagan, PhD, Postdoctoral Fellow at the Sanger Institute and one of the authors of the study in the press release.
“This suggests that somatic mutations may play a role in ageing, although alternative explanations may be possible. Over the next few years, it will be fascinating to extend these studies into even more diverse species, such as insects or plants,” he noted.
Benefit of Understanding Ageing and Death
The scientists believe this study may provide insight to understanding the ageing process and the inevitability and timing of death. They surmise that ageing is likely to be caused by the aggregation of multiple types of damage to the cells and tissues suffered throughout a lifetime, including somatic mutations.
Some companies that offer genetic tests claim their products can predict longevity, despite the lack of widely accepted evidence that such tests are accurate within an acceptable range. Further research is needed to confirm that the findings of the Wellcome Sanger Institute study are relevant to understand the ageing process.
If the results are validated, though, it is probable that new direct-to-consumer (DTC) genetic tests will be developed, which could be a new revenue source for clinical laboratories.
The federal agency shipped tests to five commercial clinical laboratory companies, augmenting efforts by public health labs
Medical laboratories in the US are ramping up their efforts to respond to an outbreak of monkeypox that has been spreading around the globe. Microbiologists and clinical laboratory scientists will be interested to learn that this infectious agent—which is new to the US—may be establishing itself in the wild rodent population in this country. If proved to be true, it means Americans would be at risk of infection from contact with rodents as well as other people.
The Centers for Disease Control and Prevention (CDC) announced on May 18 that it had identified the infection in a Massachusetts resident who had recently traveled to Canada. As of August 3, the federal agency was reporting 6,617 confirmed cases in the US.
“Because there are no other non-variola orthopoxviruses circulating in the US, a positive test result is presumed to be monkeypox,” states the APHL press release.
“As we focus on the US response, we keep a close watch on the global outbreak. Infectious diseases don’t respect borders, as we know,” said Chris Mangal (above), director of public health preparedness and response, APHL, in a press release. “I am proud of how LRN member laboratories have rapidly and effectively responded to this emergency. This is precisely what the LRN was intended to do. Should this outbreak continue to grow, preparing for expanded testing and increasing capacity beyond LRN laboratories is important to ensuring we are ready for a surge in testing.” (Photo copyright: Association of Public Health Laboratories.)
Commercial Labs Get Involved
Seeking to bolster testing capacity, the federal Department of Health and Human Services (HHS) announced on June 22 that the CDC had begun shipping OrthopoxvirusPCR tests to five commercial lab companies. They include:
“By dramatically expanding the number of testing locations throughout the country, we are making it possible for anyone who needs to be tested to do so,” said HHS Secretary Xavier Becerra in an HHS press release.
Labcorp was first out of the gate, announcing on July 6 that it was offering the CDC-developed test for its customers, as well as accepting overflow from public labs. “We will initially perform all monkeypox testing in our main North Carolina lab and have the capacity to expand to other locations nationwide should the need arise,” said Labcorp chief medical officer and president Brian Caveney, MD, in a press release.
Mayo Clinic Laboratories followed suit on July 11, announcing that the clinic’s Department of Laboratory Medicine and Pathology would perform the testing at its main facility in Rochester, Minnesota.
“Patients can access testing through Mayo Clinic healthcare professionals and will soon be able to access testing through healthcare professionals who use Mayo Clinic Laboratories as their reference laboratory,” Mayo stated in a press release.
Then, Quest Diagnostics announced on July 13 that it was testing for the virus with an internally developed PCR test, with plans to offer the CDC test in the first half of August.
The lab-developed test “was validated under CLIA federal regulations and is now performed at the company’s advanced laboratory in San Juan Capistrano, Calif.,” Quest stated in a press release.
Public Health Emergency?
Meanwhile, the CDC announced on June 28 that it had established an Emergency Operations Center to respond to the outbreak. A few weeks later, on July 23, World Health Organization (WHO) Secretary-General Tedros Adhanom Ghebreyesus, PhD, declared that the outbreak represented “a public health emergency of international concern.”
He noted that international health regulations required him to consider five elements to make such a declaration.
“WHO’s assessment is that the risk of monkeypox is moderate globally and in all regions, except in the European region where we assess the risk as high,” he said in a WHO news release. “There is also a clear risk of further international spread, although the risk of interference with international traffic remains low for the moment. So, in short, we have an outbreak that has spread around the world rapidly, through new modes of transmission, about which we understand too little, and which meets the criteria in the International Health Regulations.”
Still, public health authorities have made it clear that this is not a repeat of the COVID-19 outbreak.
“Monkeypox virus is a completely different virus than the viruses that cause COVID-19 or measles,” the CDC stated in a June 9 advisory. “It is not known to linger in the air and is not transmitted during short periods of shared airspace. Monkeypox spreads through direct contact with body fluids or sores on the body of someone who has monkeypox, or with direct contact with materials that have touched body fluids or sores, such as clothing or linens. It may also spread through respiratory secretions when people have close, face-to-face contact.”
The New York Times reported that some experts disagreed with the CDC’s assessment that the virus “is not known to linger in the air.” But Professor of Environmental Health Donald Milton, MD, DrPH, of the University of Maryland, told The Times it is still “not nearly as contagious as the coronavirus.”
The Massachusetts resident who tested positive in May was not the first known case of monkeypox in the US, however, previous cases involved travel from countries where the disease is more common. Two cases in 2021—one in Texas and one in Maryland—involved US residents who had recently returned from Nigeria, the CDC reported. And a 2003 outbreak in the Midwest was linked to rodents and other small mammals imported to Texas from Ghana in West Africa.
“Labcorp and Quest don’t dispute that in many cases, their phlebotomists are not taking blood from possible monkeypox patients,” according to CNN. “What remains unclear, after company statements and follow-ups from CNN, is whether the phlebotomists are refusing on their own to take blood or if it is the company policy that prevents them. The two testing giants say they’re reviewing their safety policies and procedures for their employees.”
One symptom of monkeypox, the CDC states, is a rash resembling pimples or blisters. Clinicians are advised that two swabs should be collected from each skin lesion, though “procedures and materials used for collecting specimens may vary depending on the phase of the rash.”
“Effective communication and precautionary measures between specimen collection teams and laboratory staff are essential to maximizing safety when manipulating specimens suspected to contain monkeypox virus,” the CDC notes. “This is especially relevant in hospital settings, where laboratories routinely process specimens from patients with a variety of infectious and/or noninfectious conditions.”
Perhaps the negative reaction to the CDC’s initial response to the COVID-19 outbreak in the US is driving the federal agency’s swift response to this new viral threat. Regardless, clinical laboratories and pathology groups will play a key role in the government’s plan to combat monkeypox in America.
DNA analysis of early plague victims pinpoints Black Death’s start on Silk Road trading communities in mountain region of what is now modern-day Kyrgyzstan in Central Asia
Microbiologists and clinical laboratory scientists will likely find it fascinating that an international team of scientists may have solved one of history’s greatest mysteries—the origin of the bubonic plague that ravaged Afro-Eurasia in the mid fourteenth century. Also known as the Black Death, the plague killed 60% of the population of Europe, Asia, and North Africa between 1346-1353 and, until now, the original source of this disease has largely gone unsolved.
In their study published in the journal Nature, titled, “The Source of the Black Death in Fourteenth-Century Central Eurasia,” the authors outlined their investigation of cemeteries in the Chüy Valley of modern-day Kyrgyzstan. The tombstone inscriptions showed a disproportionally high number of burials dating between 1338 and 1339 with inscriptions stating “pestilence” as the cause of death.
Archeological evidence combined with ancient DNA analysis of early plague victims enabled scientists to pinpoint the Black Death’s origins in Kyrgyzstan. “We have basically located the origin in time and space, which is really remarkable,” geneticist Johannes Krause, PhD (above), Professor at the Max Planck Institute for Evolutionary Anthropology, who co-led the study, told The Guardian. “We found not only the ancestor of the Black Death, but the ancestor of the majority of the plague strains that are circulating in the world today.” These new research findings may help microbiologists and clinical pathologists gain new insights into how current strains of Yersinia pestis can be better diagnosed. (Photo copyright: Max Planck Institute.)
Big Bang of Plague
Using 30 skeletons that were excavated from these cemeteries in the late 1880s and moved to St. Petersburg, Russia, the scientists analyzed the DNA of ancient pathogens recovered from the remains of seven people. They discovered Yersinia pestis (Y. pestis) DNA in three burials from Kara-Djigach, which lies in the foothills of the Tian Shan mountains.
According to another article in Nature, the scientists showed that a pair of full Y. pestis genomes from their data were direct ancestors of strains linked to the Black Death, and that the Kara-Djigach strain was an ancestor of the vast majority of Y. pestis lineages circulating today.
“It was like a big bang of plague,” Krause stated at a press briefing, Nature reported.
The research team concluded that the Tian Shan region was the location where Y. pestis first spread from rodents to people, and that the local marmot colonies likely the prevalent rodent carriers of plague.
“We found that modern strains [of the plague] most closely related to the ancient strain are today found in plague reservoirs around the Tian Shan mountains, so very close to where the ancient strain was found. This points to an origin of Black Death’s ancestor in Central Asia,” Krause explained in a Max Planck Institute news release.
He told Nature that fleas likely passed the marmot-based infection on to humans, sparking a local Kyrgyzstan epidemic. The disease then spread along the Silk Road trade routes, eventually reaching Europe, where rats (and the fleas that they carried) spread the disease.
Understanding Context of Plague
Writing in The Conversation, Associate Professor of Medieval and Environmental History Philip Slavin, PhD, University of Stirling, who co-authored the study, explained that Kara-Djigach is unlikely to be “the specific source of the pandemic,” but rather that the “disaster started somewhere in the wider Tian Shan area, perhaps not too far from that site,” where marmot colonies were likely the source of the 1338-1339 outbreak.
Making a modern-day comparison, Krause told Nature, “It is like finding the place where all the strains come together, like with coronavirus where we have Alpha, Delta, Omicron all coming from this strain in Wuhan.”
Slavin maintains that understanding the “big evolutionary picture” is key when studying the phenomenon of emerging epidemic diseases.
“It is important to see how these diseases develop evolutionary and historically, and avoid treating different strains as isolated phenomena,” he wrote in The Conversation. “To understand how the diseases develop and get transmitted, it is also crucial to consider the environmental and socioeconomic contexts.”
Scientists have spent centuries debating the source of the Black Death that devastated the medieval world. The multidisciplinary process used by the Slavin/Krause-led team provides a lesson to clinical laboratory managers and pathologists on the important role they play when collaborating with colleagues from different fields on scientific investigations.
