Findings are ‘a vital first step in discovering potentially valuable targets for development of new [COVID-19] treatments,’ noted co-first author of the study
Researchers at King’s College London (KCL) have determined that levels of certain blood proteins specific to each person’s blood type can be “causally linked” to an increased risk of hospitalization and death from a COVID-19 infection. The scientists also found that a person’s genetics play a key role in establishing the levels of those proteins in the blood.
This is relevant for clinical laboratories—particularly hospital/health system laboratories—because testing for specific proteins in the blood by medical laboratories could help flag incoming patients at higher risk for an acute COVID-19 infection.
Also, “By identifying this suite of proteins, the research has highlighted a number [of] possible targets for drugs that could be used to help treat severe COVID-19,” noted a KCL news release.
Identifying certain drugs that would be more effective for specific individuals or healthcare groups is a core goal of precision medicine.
“We have used a purely genetic approach to investigate a large number of blood proteins and established that a handful have causal links to the development of severe COVID-19,” said Alish Palmos, PhD (above), Postdoctoral Research Associate, King’s College London Social, Genetic and Developmental Psychiatry Center, and co-first author of the study. “Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.” Medical laboratories may soon be able to use this knowledge as a way to determine risk for severe COVID-19 hospitalization, as well as to guide decisions on how to use new precision medicine drugs for combating the infection. (Photo copyright: Twitter.)
Genetic Variants Linked to Causality
Since the COVID-19 pandemic began in late 2019, scientists and researchers have been vigorously trying to understand the SARS-CoV-2 coronavirus and determine why some patients have more severe symptoms than others.
To conduct their study, the KCL researchers screened more than 3,000 blood proteins to identify which proteins have a causal link to hospitalization risk, the need for respiratory support, and death from a severe COVID-19 infection.
“Causality between exposure and disease can be established because genetic variants inherited from parent to offspring are randomly assigned at conception similar to how a randomized controlled trial assigns people to groups,” said Vincent Millischer, MD, PhD, Medical University of Vienna and co-first author of the study in the KCL news release.
“In our study, the groups are defined by their genetic propensity to different blood protein levels, allowing an assessment of causal direction from high blood protein levels to COVID-19 severity whilst avoiding influence of environmental effects,” he added.
The scientists selected genetic variants, known as single nucleotide polymorphisms, that were strongly associated with blood protein levels. They then performed their analysis using Mendelian randomization to test the causal associations of those blood proteins with the development of severe COVID-19 infections.
“Mendelian randomization uses genetic variants associated with a trait [e.g., protein level] and measures their causal effect on disease outcomes, [avoiding] environmental confounding factors, such as lifestyle, being physically ill, etc.,” Alish Palmos, PhD, told Medical News Today. Palmos is a Postdoctoral Research Associate at King’s College London’s Social, Genetic, and Developmental Psychiatry Center and co-first author of the study.
Blood Groups Linked to COVID-19 Hospitalization, Death
One of the most important findings of the KCL research is a causal association between COVID-19 severity and an enzyme called ABO, which determines blood type. This discovery suggests that blood groups perform an instrumental role in whether individuals develop severe forms of the illness.
“The enzyme helps determine the blood group of an individual and our study has linked it with both risk of hospitalization and the need of respiratory support or death,” said Christopher Hübel, PhD, Postdoctoral Research Associate, King’s College and co-last author of the study in the press release. “Our study does not link precise blood group with risk of severe COVID-19, but since previous research has found that proportion of people who are group A is higher in COVID-19 positive individuals, this suggests that blood group A is more likely candidate for follow-up studies.”
The KCL researchers uncovered several compelling findings regarding blood proteins and COVID-19, including:
The discovery of six blood markers that were significantly associated with an elevated risk of hospitalization.
The discovery of nine blood markers that were significantly associated with a decreased risk of hospitalization.
Consistent results indicating hospitalization being significantly associated with decreased levels of macrophage inflammatory protein.
Five blood markers associated with the need for respiratory support or death.
Eight blood markers causally associated with a statistically significantly decreased risk of need for respiratory support or death.
Consistent results with respiratory support or death being significantly causally associated with decreased levels of neprilysin.
Developing New COVID-19 Treatments and Preventative Therapies
“What we have done in our study is provide a shortlist for the next stage of research,” said Gerome Breen, PhD, in the KCL news release. Breen is Professor of Psychiatric Genetics at King’s College London’s Institute of Psychiatry, Psychology and Neuroscience, and co-last author of the study.
“Out of 1000s of blood proteins we have whittled it down to about 14 that have some form of causal connection to the risk of severe COVID-19 and present a potentially important avenue for further research to better understand the mechanisms behind COVID-19 with an ultimate aim of developing new treatments but potentially also preventative therapies,” he added.
Further research and clinical investigation are needed to validate the King’s College London researchers’ findings. However, their insights could result in new clinical laboratory tests and personalized treatments for COVID-19.
Supplychain shortages involving clinical laboratory products may not ease up any time soon, as China’s largest shipping province is once again in COVID-19 lockdown
Following two years of extremely high demand, pathology laboratories as well as non-medical labs in the United Kingdom (UK) and Europe are experiencing significant shortages of laboratory resources as well as rising costs. That’s according to a recently released survey by Starlab Group, a European supplier of lab products.
In its latest annual “mood barometer” survey of around 200 lab professionals in the UK, Germany, Austria, Italy, and France, Starlab Group received reports of “empty warehouses” and a current shortage of much needed lab equipment, reportedly as a result of rising costs, high demand, and stockpiling of critical materials needed by pathology laboratories during the COVID-19 pandemic, according to Laboratory News.
The survey respondents, who represented both medical laboratories and research labs, noted experiencing more pressure from staff shortages and insufficient supplies required to meet testing demands in 2021 as compared to 2020. For example, only 23% of respondents said they had enough liquid handling materials—such as protective gloves and pipettes—in 2021, down from 39% who responded to the same question in 2020.
“The entire laboratory industry has been in a vicious circle for two years. While more and more materials are needed, there’s a lack of supplies. At the same time, laboratories want to stockpile material, putting additional pressure on demand, suppliers, and prices,” Denise Fane de Salis, Starlab’s UK Managing Director and Area Head for Northern Europe, told Process Engineering. “Institutes that perform important basic work cannot keep up with the price competition triggered by COVID-19 and are particularly suffering from this situation,” she added.
“COVID-19 is the largest, but by no means the only challenge facing Europe’s laboratories,” Denise Fane de Salis (above), Starlab’s UK Managing Director and Area Head for Northern Europe, told Laboratory News. “The mood barometer we commissioned once again clearly shows that we need to look at the entire range of laboratory work. The laboratory sector is not only essential in medicine and research. Diagnostics have long since encompassed almost all areas of life and the economy.” Those in this country responsible for clinical laboratory supply chains should consider what Salis is advising. (Photo copyright: Starlab UK.)
Lab Supply Shortages Worsen in 2021
With a UK office in Milton Keynes, Starlab’s network of distributors specialize in liquid handling products including pipette tips, multi-channel pipettes, and cell culture tubes, as well as PCR test consumables and nitrile and latex gloves.
According to Laboratory News, Starlab’s 2021 annual survey, released in March 2022, found that:
64% cited late deliveries contributing to supply woes.
58% noted medical labs getting preference over research labs, up from 46% in 2020.
57% said demand for liquid handling products was the same as 2020.
30% of respondents said material requirements were up 50% in 2021, compared to 2020.
76% reported dealing with rising prices in lab operations.
29% expect their need for materials to increase by 25% in 2022, and 3% said the increase may go as high as 50%.
17% of respondents said they foresee challenges stemming from staff shortages, with 8% fearing employee burnout.
UK-European Medical Laboratories on Waiting Lists for Supplies
Could import of lab equipment and consumables from Asia and other areas outside UK have contributed to the shortages?
“A substantial portion of the world’s clinical laboratory automation, analyzers, instruments, and test kits are manufactured outside UK. Thus, UK labs may face a more acute shortage of lab equipment, tests, and consumables because governments in countries that manufacture these products are taking ‘first dibs’ on production, leaving less to ship to other countries,” said Robert Michel, Editor-in-Chief of Dark Daily and our sister publication The Dark Report.
Indeed, a statement on Starlab’s website describes challenges the company faces meeting customers’ requests for supplies.
“The pandemic also has an impact on our products that are manufactured in other countries. This particularly affects goods that we ship from the Asian region to Europe by sea freight. Due to the capacity restrictions on the ships, we expect additional costs for the transport of goods at any time. Unfortunately, the situation is not expected to ease for the time-being,” Starlab said.
Furthermore, economists are forecasting probable ongoing supply chain effects from a new SARS-CoV-2 outbreak in China.
Lockdown of China’s Largest Shipping Province Threatens Supply Chains Worldwide
According to Bloomberg News, “Shenzhen’s 17.5 million residents [were] put into lockdown on [March 13] for at least a week. The city is located in Guangdong, the manufacturing powerhouse province, which has a gross domestic product of $1.96 trillion—around that of Spain and South Korea—and which accounts for 11% of China’s economy … Guangdong’s $795 billion worth of exports in 2021 accounted for 23% of China’s shipments that year, the most of any province.”
Bloomberg noted that “restrictions in Shenzhen could inflict the heaviest coronavirus-related blow to growth since a nationwide lockdown in 2020, with the additional threat of sending supply shocks rippling around the world.”
“Given that China is a major global manufacturing hub and one of the most important links in global supply chains, the country’s COVID policy can have notably spillovers to its trading partners’ activity and the global economy,” Tuuli McCully, Head of Asia-Pacific Economies, Scotiabank, told Bloomberg News.
Wise medical laboratory leaders will remain apprised of supply chain developments and possible lockdowns in Asia while also locating and possibly securing new sources for test materials and laboratory equipment in anticipation of future supply shortages.
Smaller cities and rural towns are finding the NWSS a useful early warning tool for tracking COVID-19 in their communities
In a move that mirrors similar programs around the world, the federal Centers for Disease Control and Prevention (CDC) now monitors sewage nationwide and records levels of SARS-CoV-2 in an effort to prevent new outbreaks of COVID-19 and spot any new variants of the coronavirus.
Advances in gene sequencing technologies are enabling the CDC’s National Wastewater Surveillance System (NWSS), and in many communities, clinical laboratories and health system laboratories have worked with local health authorities to test wastewater since onset of the pandemic.
“What started as a grassroots effort by academic researchers and wastewater utilities has quickly become a nationwide surveillance system with more than 34,000 samples collected representing approximately 53 million Americans,” noted epidemiologist Amy Kirby, PhD (above) during the telebriefing.
Kirby is a Senior Service Fellow in the Waterborne Disease Prevention Branch at the CDC.
“Currently, CDC is supporting 37 states, four cities, and two territories to help develop wastewater surveillance systems in their communities. More than 400 testing sites around the country have already begun their wastewater surveillance efforts,” she added.
“Estimates suggests between 40% and 80% of people with COVID-19 shed viral RNA in their feces, making wastewater and sewage an important opportunity for monitoring the spread of infection,” said epidemiologist Amy Kirby, PhD (above), a Senior Service Fellow in the Waterborne Disease Prevention Branch at the CDC. The NWSS’ findings could enable public health officials to better allocate mobile clinical laboratory testing and COVID-19 vaccination sites around the country. This would be especially beneficial in rural and underserved healthcare populations. (Photo copyright: Center for Global Safe Water, Sanitation, and Hygiene.)
Genetic Sequencing Enables Tracking of Virus and Bacteria
At the time of the telebriefing, the federal agency anticipated having an additional 250 sites online within a few weeks and even more sites added within the coming months. Many of the participating sites are sequencing the genes of their biological samples and reporting that data to the CDC.
“So, we’ve seen from very early days in the pandemic that rates of detection in wastewater correlate very well with other clinical indicators, like pace rates and hospitalization and test positivity,” Kirby stated. “That data continues to come in and it continues to be a very solid indicator of what’s going on in the community.”
Wastewater, also referred to as sewage, includes water from toilets, showers, and sinks that may contain human fecal matter and water from rain and industrial sources. To use the CDC’s wastewater surveillance system:
Wastewater is collected from a community area served by the surveillance system as it flows into a local water treatment plant.
Collected samples are sent to an environmental or public health laboratory where they are tested for SARS-CoV-2.
Health departments submit the testing data to the CDC through the online NWSS Data Collection and Integration for Public Health Event Response (DCIPHER) portal.
The DCIPHER system then analyzes the data and reports the results back to the health department for use in their COVID-19 response.
Beginning in February 2022, members of the public can view the results of collected data online through the CDC’s COVID Data Tracker.
Wastewater Sampling Is a ‘Critical Early Warning System’
According to the CDC NWSS website, there are many advantages to using wastewater surveillance in the fight against COVID-19, including:
Wastewater can capture the presence of the virus shed by people both with and without symptoms.
Health officials can determine if infections are increasing or decreasing within a certain monitoring site.
Wastewater surveillance does not depend on people having access to healthcare or the availability of COVID-19 testing.
It is possible to implement wastewater surveillance in many communities as nearly 80% of the US population are served by municipal wastewater collection systems.
“These built-in advantages can inform important public health decisions, such as where to allocate mobile testing and vaccination sites,” Kirby said. “Public health agencies have also used wastewater data to forecast changes in hospital utilization, providing additional time to mobilize resources and preparation for increasing cases.”
The wastewater sampling represents a critical early warning system for COVID-19 surges and variants, and the CDC hopes this type of sampling and research can be utilized in the future for other infectious diseases.
“Wastewater surveillance can be applicable to a wide variety of health concerns. And so, we are working to expand the National Wastewater Surveillance platform to use it for gathering data on other pathogens, and we expect that work to commence by the end of this year,” Kirby said. “Our targets include antibiotic resistance, foodborne infections like E. Coli, salmonella, norovirus, influenza, and the emerging fungal pathogen Candida Auris.”
Critical Surveillance Tool for Microbiology Laboratories
Independent of the nation’s network of public health laboratories, expansion of this program may give microbiology and clinical laboratories in smaller cities and rural towns an opportunity to test wastewater specimens in support of local wastewater monitoring programs.
As the CDC develops this surveillance network into a more formal program, microbiology labs may find it useful to learn which infectious diseases are showing up in their localities, often days or weeks before any patients test positive for the same infectious agents.
That would give pathologists and clinical laboratory leaders an early warning to be on the alert for positive test results of infectious diseases that wastewater monitoring has confirmed exist in the community.
Though the variant poses low risk thanks to modern HIV treatments, the scientists stress the importance of access to early clinical laboratory testing for at-risk individuals
With the global healthcare industry hyper focused on arrival of the next SARS-CoV-2 variant, pathologists and clinical laboratories may be relieved to learn that—though researchers in the Netherlands discovered a previously unknown “highly virulent” strain of HIV—the lead scientist of the study says there’s “no cause for alarm.”
In a news release, researchers at the University of Oxford Big Data Institute said the HIV variant got started in the Netherlands in the 1990s, spread quickly into the 2000s, and that prior to treatment, people with the new virulent subtype B (VB variant) had exceptionally high viral loads compared to people with other HIV variants.
Fortunately, the scientist also found that around 2010, thanks to antiretroviral drug therapy, the severe variant began to decline.
In an interview with NPR, Chris Wymant, PhD, the study’s lead author, said, “People with this variant have a viral load that is three to four times higher than usual for those with HIV. This characteristic means the virus progresses into serious illness twice as fast, and also makes it more contagious.”
Fortunately, he added, “Existing medications work very well to treat even very virulent variants like this one, cutting down on transmission and reducing the chance of developing severe illness.
“Nobody should be alarmed,” he continued. “It responds exactly as well to treatment as HIV normally does. There’s no need to develop special treatments for this variant.”
Wymant is senior researcher in statistical genetics and pathogen dynamics at the Big Data Institute (BDI).
Epidemiologist Chris Wymant, PhD (above), lead author of the Big Data Institute study at Oxford University, says today’s modern HIV antiretroviral drug therapies effectively treat for the “highly viral” HIV VB variant he and his team discovered. “Nobody should be alarmed,” he told NPR. “It responds exactly as well to treatment as HIV normally does.” Nevertheless, he stressed the importance of access to early clinical laboratory testing for at-risk individuals. (Photo copyright: Oxford Big Data Institute.)
In their published study, the BDI researchers reported that their analysis of genetic sequences of the VB variant suggested it “arose in the 1990s from de novo (of new) mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
“By the time, they were diagnosed, these individuals were vulnerable to developing AIDS within two to three years. The virus lineage, which has apparently arisen de novo since around the millennium, shows extensive change across the genome affecting almost 300 amino acids, which makes it hard to discern the mechanism for elevated virulence,” the researchers noted.
The researchers analyzed a data set from the project BEEHIVE (Bridging the Epidemiology and Evolution of HIV in Europe and Uganda). They found 15 of 17 people positive for the VB variant residing in the Netherlands. That prompted them to focus on a cohort of more than 6,700 Dutch HIV positive people in the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort database, where they found 92 more individuals with the VB variant, bringing the total to 109.
According to a Medscape report on the study’s findings, people with the VB variant showed the following characteristics:
Double the rate of CD4-positive T-cell declines (indicator of immune system damage by HIV), compared to others with subtype-B strains.
Increased risk of infecting others with the virus based on transmissibility associated with variant branching.
Wymant says access to clinical laboratory testing is key to curtailing the number of people who contract the VB variant. “Getting people tested as soon as possible, getting them onto treatment as soon as possible, has helped reduce the numbers of this variant even though we didn’t know that it existed,” he told NPR.
The University of Oxford Big Data Institute study is another example of how constantly improving genome sequencing technology allows scientists to dig deeper into genetic material for insights that can advance the understanding of many diseases and health conditions.
This new knowledge about the human genome may lead to a new set of biomarkers and clinical laboratory tests for predisposition to this health condition
Researchers across the globe are working to understand why some people who become infected with the SARS-CoV-2 coronavirus experience loss of smell (anosmia) and taste (ageusia) often for months following recovery from COVID-19 infection.
Now, pathologists and medical laboratory managers will be interested to learn that scientists from DNA testing company 23andMe believe they have identified a genetic risk factor associated with the condition. The discovery could lead to a new set of biomarkers for predisposition to loss of taste or smell that could help experts develop improved precision medicine treatments for similar conditions.
“Early data suggests that supporting cells of the olfactory epithelium are the ones mostly being infected by the virus and presumably this leads to the death of the neurons themselves. But we don’t really know why and when that happens, and why it seems to preferentially happen in certain individuals,” he added.
To perform their study, the 23andMe researchers examined the genetic tests of 69,841 individuals who self-reported that they had received a positive COVID-19 test. 68% of those people stated that they had experienced either loss of smell or taste as part of their symptomology of the illness. All the participants in the survey reside in either the United States or the United Kingdom.
After contrasting the genetic differences between those who experienced loss of taste or smell as a symptom of COVID-19 and those who did not, the team discovered a region of the genome associated with a spot located near the UGT2A1 and UGT2A2 genes. These two genes are expressed within tissue in the nose and are involved in smell and the metabolization of odorants.
“It was this really beautiful example of science where, starting with a large body of activated research participants who have done this 23andMe test, we were able to quickly gain biological insights into this disease that would otherwise be very difficult to do,” said geneticist Adam Auton, PhD (above), Vice President, Human Genetics at 23andMe and lead author of the study, in the USA Today article. If found to be accurate, the findings could lead to clinically-useful clinical laboratory tests and to development of improved precision medicine therapies for patients who are predisposed to the condition. (Photo copyright: 23andMe.)
It’s unclear if or how UGT2A1 and UGT2A2 genes may be involved in the process that leads to loss of taste or smell, but the 23andMe researchers hypothesize the genes may play a role in the physiology of infected cells which leads to the impairments.
The team found that 72% of female respondents reported loss of taste or smell as a symptom of COVID-19, which was higher than the 61% of male respondents who reported the same symptoms. In addition, the respondents who reported loss of taste or smell were typically younger than those who did not report those symptoms and persons of East Asian or African American ancestry were significantly less likely to report those symptoms.
An earlier study, titled, “Growing Public Health Concerns of COVID-19 Chronic Olfactory Dysfunction,” which appeared in the journal JAMA Otolaryngology-Head and Neck Surgery, stated that six months after contracting COVID-19 as many as 1.6 million people in the US experienced either lingering changes to their ability to smell or a complete loss of that sense.
Helping Patients Understand Why They Were Affected
Experts believe 23andMe’s findings may help patients deal with loss of taste or smell after a COVID-19 infection and increase the chance of finding suitable treatments.
“It answers the question of ‘why me’ when it comes to taste and smell loss with COVID-19,” Danielle Reed, PhD, Associate Director, Monell Chemical Senses Center, told USA Today. “Some people have it and some do not. Inborn genetics may partially explain why.”
Earlier research suggested the loss of these senses was related to a failure to protect the sensory cells of the nose and tongue from the viral infection. But according to Reed, the 23andMe study findings suggest a different cause.
“The pathways that break down the chemicals that cause taste and smell in the first place might be over or underactive, reducing or distorting the ability to taste and smell,” she said.
The 23andMe researchers noted their study had a few limitations:
It was biased towards individuals of European ancestry and lacked a replication cohort.
It relied on self-reported cases and symptom status.
No distinction between the loss of taste or smell could be determined as they were combined in a single survey question, making it unclear whether their findings relate more strongly to one symptom or the other.
Currently, there is no clinical imperative to test people in advance to see if they have a genetic predisposition to loss of smell or taste after a COVID-19 infection.
Nevertheless, this new insight into the human genome demonstrates the ongoing pace at which researchers are teasing out useful knowledge about the functions of human DNA. That knowledge will be used to do two things: first, to develop relevant, clinically-useful clinical laboratory tests, and second, to develop therapies for treating people with these genetic predispositions should they experience negative health conditions due to those genetic sequences.
