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Saturday, October 2, 2021

Clinical Chem: Noninvasive Blood or Saliva Tests for Cancer, COVID-19 Promising

 Noninvasive tests for colorectal cancer, prostate cancer and COVID-19 were among the highlights of the American Association for Clinical Chemistry (AACC) meeting September 26-30.

One of the most exciting of the tests may be a blood test to diagnose colorectal cancer (CRC), simply because it could compete with colonoscopies. Researchers from the Medical Research Institute, Alexandria, Egypt, described a multiplexed panel of serum biomarkers to profile inflammatory mediators that have carcinogenic roles.

The researchers found that serum eotaxin-1, macrophage-inflammatory protein-1 beta (MIP-1 beta), granulocyte colony-stimulating factor (G-CSF), and vascular endothelial growth factor A (VEGF-A) are significantly elevated in patients with CRC compared to patients in the non-malignant group.

“Also, there was a statistically significant increase in serum level of G-CSF and VEGF-A among CRC patients compared to those with precancerous colon polyp,” the authors wrote in the e-poster.

The study involved 87 colonoscopy patients, 35 of which had CRC and 52 were non-malignant. Those without malignancies were segmented into those with colon polyps (9), inflamed mucosa (24) and normal mucosa (19.)  

Lead author Mona Eldeeb and colleagues devised the diagnostic panel to overcome the challenges posed by the poor performance of other non-invasive tests for colorectal cancer and the patient non-compliance associated with invasive tests.

Based on these results, they said this assay panel was more discriminating than stool occult blood tests and, therefore, could reduce false positive rates and unneeded colonoscopies. Consequently, they suggested it could be a promising screening and diagnostic tool for CRC.

On Wednesday, another team presented a non-invasive diagnostic panel to diagnosis prostate cancer early and to distinguish it from benign prostatic hyperplasia. It uses miRNAs and saliva. 

As Jamal Amri and Mona Alaee of Tehran University of Medical Sciences explained in an e-poster, this panel could be a solution to the current problem of distinguishing between malignant prostate cancer and benign prostatic hyperplasia in healthy men.  

“Increased salivary PSA, MiR-193a-5P, MiR-323, MiR-744, MiR-182, and MiR-199, and decreased salivary MiR-101, MiR-203, and MiR-573 levels can be used as a new non-invasive diagnostic panel for early and accurate diagnosis of prostate cancer and benign prostatic hyperplasia, (and) also differentiate BPH from healthy men,” they wrote.

Prostate-specific antigen levels and biopsies “are not sufficient for an accurate, early diagnosis, and (are) associated with the suffering of patients,” they pointed out. “The advantage of our study is the use of several microRNAs, which have been reported to be detectable in the blood much earlier than the progression of cancer, which makes for a better diagnosis, as well as the use of saliva as a noninvasive biological sample that causes little pain to patients,” Amri said in a statement.

Amri and Alaee two assayed 180 men between ages 45 and 50, of which one-third recently had been diagnosed with prostate cancer, one-third were newly diagnosed with benign prostatic hyperplasia, and one-third were healthy. Saliva and serum samples were taken from each.

When saliva tests are used to detect or manage COVID-19, however, their results are mixed when compared to nasal swabs, several researchers reported in their poster presentations.

For example, a team from Luxor Scientific, led by L. Contella, tested 308 samples and found that 29 samples were positive and 5 were inconclusive for the presence of the SARS-CoV-2 virus. Then they compared results from analyzing saliva samples and nasal swab samples.

They found that the saliva test detected 85% of known COVID-19 cases versus the 94% identified by nasal swab, but that saliva detected two individuals that nasal swabs failed to identify. That bumped the saliva test’s success rate to 97.7%.  Thus, they concluded that saliva tests could alleviate bottlenecks when supplies are scarce, and also could eliminate the need for direct patient contact for healthcare workers.

Researchers J.D. Silva and Danielle Alves Gomes Zauli of Grupo Pardini in Brazil also championed saliva tests for COVID-19 diagnosis as a way to make testing more accurate and more comfortable for patients.

Silva and Zauli compared 101 nasal swabs on which performed RT-qPCR had been performed with results obtained by saliva samples from the same patients. Targets were the ORF1ab, N, and S genes. Results showed the sensitivity for the saliva samples was 90% and specificity of 100%, when compared to results from the nasal swab samples. Low viral load affected sensitivity, but “the test obtained an optimal efficiency of reaction,” they reported, that could make this saliva test an important option for COVID-19 diagnostic testing.

For clinical management of COVID-19, however, saliva-based tests may be less useful, according to another research team from Grupo Pardini. Led by Fernando. K. Marques, it compared the results of paired saliva and nasopharyngeal swabs specimens that were collected from 29 COVID-19 patients on the same day.

“Using nasopharyngeal swab RT-qPCR as the reference standard, the sensitivity and specificity of (the) Covid Ag Oral Detect Kit were 66.7% and 100%, respectively,” the team reported. Consequently, they conceded, “The usefulness of saliva specimens for diagnosing COVID-19 remains controversial because the reported diagnostic sensitivity varies widely between studies.”

Although saliva may be an alternative specimen for COVID-19 diagnosis, the low sensitivity of the test would require increasing the sample size to enable more accurate evaluations.

https://www.biospace.com/article/aacc-buzz-noninvasive-blood-or-saliva-tests-for-cancer-and-covid-19-are-promising/

Could a New Vaccine Help Slow the Opioid Epidemic?

 According to the Centers for Disease Control and Prevention (CDC), nearly 500,000 Americans perished due to an overdose of either prescription or illicit opioids between 1999 and 2019, and they stood out as the leading cause of drug deaths in 2020. Now, scientists are making progress toward a vaccine that could help protect against these deadly overdoses.  

At least three different research groups across the U.S. are developing such vaccines. The furthest along is being tested for safety and efficacy in humans in a clinical trial run by Sandra Comer, a professor of neurobiology in the department of psychiatry at Columbia University, and Marco Pravetoni, of the University of Minnesota Medical School.

Following the same basic principle as vaccines against COVID-19 and influenza, the Columbia vaccine aims to make antibodies that will target and destroy a specific invader – in this case, a type of narcotic called oxycodone, an opioid used in painkillers such as the oft-abused OxyContin.

“So to speak, the vaccine-induced antibodies work like an antidote or like a sponge soaking up the circulating drug target so that the drug cannot exert its effects/actions,” Pravetoni, who designed the vaccine, told The Washington Times.

Comer told NBC News that while the vaccine would not prevent cravings for the drug, but instead be used in conjunction with medications that do – it could serve as an added layer of protection for people at high risk. The theory is that if addicted individuals use oxycodone, the antibodies would bind to it and prevent it from reaching the brain – where opioids slow a person’s breathing to potentially fatal levels.

While the concept is being called “inventive” by addiction specialists such as Sharon Walsh, director of the Center on Drug and Alcohol Research at the University of Kentucky, and may still be years away, it is now much less theoretical. With the sixth trial participant receiving the shot on Sept 28, it seems realistic that there could soon be a new weapon in the arsenal against opioid overdoses.

The trial is aiming to enroll 45 people between 18 and 59 who are in active opioid addiction, as Comer said that they wouldn’t want to give the vaccine to somebody who is currently stable because it might trigger a relapse. The study has so far enrolled 7 patients, but two have dropped out. The participants will receive either an injection of the vaccine or a placebo once a month for three to four months.

While drugs currently on the market such as naltrexone, methadone and buprenorphine are highly effective, Comer said these are not enough to slow the crisis as relapse rates hover around 50% after six months of treatment.

“We’re hoping that the addition of a vaccine will serve as a ‘safety net’ against overdose if a patient does discontinue their treatment medication and relapses to opioid use. It also may provide us with a window of time to reengage patients in treatment if/when they relapse,” she said.

News of this latest effort to combat the opioid epidemic comes the same week as another settlement pertaining to the crisis was announced. Generics giant Teva Pharmaceuticals reached a $15 million agreement with the state of Louisiana to settle claims against the company over its marketing of opioid products. In September, a U.S. Bankruptcy Court approved Purdue Pharmaceuticals' reorganization plan, in effect releasing the Sackler family, the company’s owners, from future liability. 

https://www.biospace.com/article/could-a-new-vaccine-help-slow-the-opioid-epidemic-/

How sepsis need not be fatal

 Sepsis, the body’s life-threatening response to infection affecting about 1.7 million adults in  the United States each year, can lead to multisystem organ failure with a high mortality rate. 

No targeted therapeutics against this condition have been developed in the last decades. Now, however, a team led by biomedical scientists at the University of California, Riverside, offers some hope for future treatment during sepsis awareness month.

The researchers, led by Meera Nair and Adam Godzik in the School of Medicine, identified molecular biomarkers, pathways and immune cell dynamics associated with sepsis that could be therapeutically targeted to prevent the condition from leading to death. These blood cell biomarkers — the protein CD52 in lymphocytes; and the protein S100A9 involved in inflammatory processes — are present in all blood cells but highly expressed in people with sepsis. How these biomarkers change early in sepsis — specifically, within the first six hours — could determine whether the patient survives or dies. 

“These biomarkers were found to uniquely change within six hours in the blood of patients with sepsis and affected specific cellular pathways in specific immune cells,” said Nair, an associate professor of biomedical sciences, who co-led the study published in the Journal of Leukocyte Biology. “Changes in CD52 expression were associated with good outcomes, which means promoting the activation of protective immune cells. S100A9, on the other hand, acted as a molecular driver of fatal sepsis. We appear to have found a molecular driver and a molecular protector of sepsis.”

According to Nair, the team also found the molecular pathways for fatal sepsis and COVID-19 converge. 

“Severe COVID appears to trigger molecular pathways identical to sepsis,” she said. “Further analysis of these pathways can help us diagnose and treat both diseases.”

In particular, the research team also found that in people with sepsis, blood platelets — cell types involved in normal blood flow and coagulation — lost their function, as they do in COVID patients. The researchers argue that if the platelets’ function could be restored by targeting the main regulators of this process, it could promote survival in both sepsis and COVID. 

Nair explained that when a patient is diagnosed with sepsis and admitted to the intensive care unit, physicians use clinical scoring systems, such as the APACHE-2 and SOFA scores, to help predict severity of illness and probability of mortality.

“Clinicians still cannot predict whether the patient is going to survive or die and what specific treatment to give that may improve their survival chances,” she said. “There is no way, unfortunately, of triaging the patients to figure out if they would benefit from one treatment versus another. We wanted to address this by finding molecular biomarkers that are better predictors of whether a patient survives or dies. We appear to have found some candidates.”

The study, done in partnership with clinicians at the Riverside University Health System, or RUHS, involved sampling the blood of five patients with sepsis. Dr. Walter Klein, the paper’s co-author and a pulmonologist at RUHS, noted clinical scoring systems do not provide specific therapeutic targets for patients. 

“From a clinical perspective, the treatment of sepsis largely focuses on early recognition, early systemic antibiotics/source control of the infection, and support of failing organ systems,” he said. “What is missing in the clinical arena are specific therapies that reverse the patient’s dysregulated immune response to infection. The importance of basic science research like this is to hopefully find individualized treatments one day where we can rapidly reverse the patient’s multi-organ failure and prevent mortality.”

Unlike other studies that analyzed blood samples from patients with sepsis at time zero, when patients are first diagnosed with the disease, the research team analyzed blood samples of sepsis patients at time zero and six hours later — two different time points from differing outcomes in sepsis.

“We have snapshots in two time-steps that show us how the biomarkers are evolving,” said Godzik, the Bruce D. and Nancy B. Varner Presidential Endowed Chair in Cancer Research at UCR and a professor of biomedical sciences, who co-led the study. “We can enhance this evolution in the right direction, toward survival. If the patient is heading in the wrong direction, toward fatality, we can intervene to change the trajectory of the disease. With this work, we have gone beyond the static snapshot and moved into a more dynamic process.”

Blood samples obtained from RUHS were processed at a single-cell sequencer at UCR, allowing the researchers to understand the behavior of each cell rather than an average of all cells. 

“We found that many cell types behaved differently in sepsis,” said Xinru Qiu, the co-first author of the paper and a graduate student in Godzik’s lab. “Using single cell sequencing, we could separately track the trajectory of different cell types. Single-cell resolution is like having a street-level view of an area versus a satellite view of it, and an understanding of what each cell contributes were key in helping us find our results.”

According to Godzik, when news reports note someone has died of complications from an infection, it generally means the person died of sepsis. 

“Thirty percent of all deaths in hospitals are caused by sepsis,” he said. “Sepsis is an unmet need with no treatment. Our work offers a path to treatment because we have extended the view from single molecules to processes in cells. After all, it is the molecular pathways involved that can be interrupted. Oftentimes, people think if a gene is a biomarker of a disease, a drug should target it. Well, not necessarily. If the bumper of your car — the tag or marker — is destroyed in a car accident, you may have need to fix the brakes — the pathway.”

Nair stressed that the study was possible only through a multidisciplinary approach. 

“As an immunologist, I teamed up with Adam, who is a computational biologist, and with RUHS clinicians,” she said.  “It’s only through such collaborative work that we can start to unravel the complexity of fatal sepsis, offering insight into new treatments that could change the trajectory of sepsis patients who may face a fatal outcome.”

Next, the researchers plan to focus on similarities between sepsis and COVID-19 and have already begun research funded by the Center for Health Disparities Research at UCR. 

“We are doing a molecular analysis of the long-term effects of COVID-19 on immune homeostasis,” Nair said. “We would like to see if our sepsis research findings could apply also to COVID-19.”

###

Nair, Godzik, Qiu, and Klein were joined in the research by Jiang Li, the co-first author of the research paper, and Lukasz Jaroszewski at UCR; and Drs. Jeff Bonenfant and Aarti Mittal at RUHS. 

The research was supported by the UCR School of Medicine, a School of Medicine Dean’s innovation grant to Bonenfant, and the National Institutes of Health. Bonenfant completed his medical residency at the UCR School of Medicine in 2018.

The research paper is titled “Dynamic changes in human single cell transcriptional signatures during fatal sepsis.”

https://www.eurekalert.org/news-releases/930020

Primary care needs of Covid survivors with diabetes huge, growing

 The huge and growing burden of treatment needed for survivors of COVID-19 with diabetes in primary care is the subject of a special session on the infection at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD), given by Professor Kamlesh Khunti of the Diabetes Research Centre, University of Leicester, UK.

He will discuss how, among the risk factors for COVID-19 mortality, type 2 diabetes has emerged as an important and common risk factor for COVID-19 related hospital admissions and mortality. Studies have also shown that hyperglycaemia abnormally high blood sugar) in people with type 2 diabetes is associated with worse outcomes.

“A public health crisis such as the COVID-19 pandemic poses both direct and indirect risks to people with chronic diseases due to disruptions in care,” explains Prof Khunti. “These include reductions in routine care, access to emergencies, poor adherence to treatments and psychological impact. Globally, diabetes has also been shown to be the most disrupted chronic condition during the pandemic. The pandemic has led to reductions in face-to-face consultations and reductions in routine screening of risk factors. This is likely to have increased the disproportionate impact of COVID-19 pandemic in socioeconomically deprived and ethnic minority populations.”

He will say it is imperative that people with diabetes now get the routine care they need, including risk factor assessment and management and self-management education programmes including referral for psychological support where appropriate. “COVID-19 is also likely to have long term impact on people with diabetes and these patients need to be closely monitored in the short and medium term,” he adds. “The risks of complications and mortality are high in people with diabetes admitted with COVID-19 following discharge and these patients will require a more intensive follow-up. Finally, it will be important to encourage COVID-19 vaccinations for all those with diabetes.”

How infection by SARS-CoV-2 can lead to kidney disorders

 A review article published in the journal Frontiers in Physiology by researchers affiliated with the Federal University of São Paulo (UNIFESP) in Brazil discusses the mechanisms whereby SARS-CoV-2 damages the kidneys, potentially serving as a basis for further research in pursuit of treatments to prevent severe renal problems and even chronic kidney disease in COVID-19 patients.

The study shows that interaction with angiotensin-converting enzyme 2 (ACE2) not only enables the virus to infect and replicate in human cells but can cause a significant imbalance in the renin-angiotensin system, which regulates arterial blood pressure, and the kallikrein-kinin system, which is involved in inflammation, control of blood pressure, and other processes. 

Impairment of ACE2's biological functions can lead to a drop in renal blood flow and a reduced glomerular filtration rate (GFR), altering the capacity of the kidneys to eliminate substances (metabolites) that are toxic in excessive quantities. It can also increase vasoconstriction in the kidneys, leading to renal function deterioration.

"Studies and systematic reviews have confirmed 20%-40% incidence of acute renal injury in COVID-19 patients. Data now being published shows that recovery is slower in some cases and complications requiring dialysis occur in others," said Nayara Azinheira Nobrega Cruz, first author of the article.

Another part of the study, analyzing data on infection by SARS-CoV-2 in  and the role of ACE2 in placenta, was also published recently in Clinical Science. It showed that pregnant women infected by the virus run a greater risk of developing pre-eclampsia, a disorder characterized by persistent high blood pressure that can cause serious harm to mother and baby. 

The prospect of a rise in the number of cases of severe  injury due to the COVID-19 pandemic is a grave concern, according to Professor Dulce Elena Casarini, co-principal investigator for the study alongside José Medina Pestana, who heads EPM-UNIFESP's Kidney Hospital (HRIM) and is a member of the São Paulo State Government's Coronavirus Contingency Center.

"If demand for dialysis is rising now, we may see a rise in demand for kidney transplants before long," Casarini told.

The number of kidney transplants performed in Brazil averaged a little over 5,900 per year between 2017 and 2019, according to data from the Ministry of Health, but the waiting list grew from 28,351 to 29,554 in the period.

Research by an international group of scientists published on September 1, 2021, in the Journal of the American Society of Nephrology, using data from the United States showed that seven out of every 10,000 mild or moderate COVID-19 patients required dialysis or a kidney transplant in the period March 2020 to March 2021. Among non-hospitalized patients, the risk of acute renal injury within six months of infection was 23% higher than among non-infected subjects.

Multiple functions

According to Lilian Caroline Gonçalves de Oliveira, head of UNIFESP's Kidney and Hormone Laboratory and a co-author of the article, one of the points analyzed was the role of ACE2 in the pathogenesis of COVID-19. "The importance of the ACE2 receptor to cell invasion by SARS-CoV-2 has been known for some time. The interaction between the virus and the receptor prevents ACE2 from performing its protective functions," Oliveira said.

The article on the study notes that the mechanism of renal involvement in COVID-19 is unknown and may be multifactorial, adding that infection by the virus may indirectly injure the kidneys via systemic inflammation, hypoxemia (low blood oxygen), shock, hypotension, and renin-angiotensin system imbalance.

The renin-angiotensin system comprises a series of reactions that help regulate blood pressure. When blood pressure falls, for example, the kidneys release the enzyme renin into the bloodstream, where it produces angiotensin 1, which is converted by ACE into angiotensin 2, an active hormone that induces vasoconstriction by acting on the wall muscles of the small arteries. Under normal conditions, a harmonious balance between ACE and ACE2 maintains renin-angiotensin system homeostasis.

Furthermore, the virus can infect kidney cells, causing damage directly, compromising the intra-renal renin-angiotensin system, and contributing to acute and long-term diseases. "Our review is a compilation that can serve as a basis for future research and shows the importance of the impact of COVID-19 on other organs besides the respiratory system," Cruz said.

More information: Nayara Azinheira Nobrega Cruz et al, Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients, Frontiers in Physiology (2021). DOI: 10.3389/fphys.2021.700220

https://medicalxpress.com/news/2021-09-infection-sars-cov-kidney-disorders.html

Nasal microbiota holds clues to who will develop symptoms from SARS-CoV-2

 The microbiota in the nose and upper throat likely contains biomarkers for assessing how sick an individual infected with SARS-CoV-2 may get and for developing new treatment strategies to improve their outcome, researchers say.

This nasopharyngeal microbiota is generally considered a frontline protection against viruses, bacteria and other pathogens that enter these natural passageways, says Dr. Sadanand Fulzele, geriatric researcher in the Department of Medicine at the Medical College of Georgia at Augusta University.

Distinct patterns emerged when the researchers examined the microbiota of 27 individuals age 49 to 78 who were negative for the , 30 who were positive but had no symptoms, and 27 who were positive with moderate symptoms that did not require hospitalization, they report in the journal Diagnostics.

"Millions of people get infected and relatively few of them become symptomatic. This might be one of the reasons," says Dr. Ravindra Kolhe, director of MCG's Georgia Esoteric and Molecular Laboratory, or GEM Lab. which has performed more than 100,000 COVID tests.

The most significant changes were in those who were symptomatic, including about half those patients not having a sufficient amount of microbiota to even sequence, says corresponding author Fulzele.

They were surprised to find these "low reads" of bacteria in the nasopharyngeal cavity of symptomatic individuals versus only two and four individuals in the negative and positive with no symptoms groups, respectively. The vast majority of the positive individuals with no symptoms still had sufficient microbiota, notes first author Kolhe.

"We don't know which came first, the disease or the wipeout of the microbiota," Fulzele says. Runny noses and sneezing might account for the loss, an already significantly lower number of bacterial inhabitants might have increased the individuals' risk for developing these kinds of symptoms, or the virus may have changed the landscape, says Fulzele, who suspects it's the latter.

Based on experience with microbiota in the gastrointestinal tract, Kolhe thinks the different microbiota content and size is another good bet and they both would like a definitive answer. "We don't have sufficient data at this moment," Kolhe says.

They found differences in the type of bacteria as well, although the researchers note that the function of some of the bacteria they found are not well understood.

As the virus' name and nearly two years of experience with it indicate, a major method for transmitting severe acute respiratory syndrome coronavirus 2, or SARS-Cov-2, is when someone coughs, sneezes or even talks, and droplets called aerosols carrying the virus move through the air and into another person's nose or mouth.

Those age 65 and older and/or with underlying  like hypertension and diabetes, are considered at increased risk for hospitalization and death from the infection, so they decided to look at the microbiota in the upper part of the respiratory system called the nasopharynx of older individuals.

The moist, mucus-producing lining of this area works like a natural barrier to invaders and there also is a significant complement of immune cells present, Fulzele says, and their response to respiratory viruses is key.

The area also is abundant with ACE-2 receptors, to which the spiky virus binds, and Kolhe says it's a major landing spot for this virus.

Their new findings indicate that the altered microbiota in the symptomatic patients impacted their immune response to the virus, Kolhe and Fulzele say.

The symptomatic individuals had significantly higher levels of two bacterial species, including Cutibacterium, generally found on the skin and associated with acne but also with heart infection and shoulder infections following surgery. Conversely there was a significantly lower presence of a handful of other, not well-studied bacterium.

The microbiota of both infected groups, symptomatic and asymptomatic, had high levels of bacterium like Cyanobacteria, also called blue green algae, that can be found in contaminated water but is a usual inhabitant of the microbiome in humans which appears to have a role in regulating the immune response. These bacterium typically enter the body through mucosal surfaces, like those in the nose, and are known to cause pneumonia and liver damage. Those who were symptomatic had twice as much of this bacterium as their asymptomatic counterparts.

Fulzele notes that between the asymptomatic and symptomatic there was no significant change in microbiota diversity—just those big differences in volume—but they did see a lot of individual bacterium moving up and down in numbers.

For example, their graph of the number of another water-loving bacterium Amylibacter, looked like stair steps as it moved from negative to positive with symptoms individuals, while there was a downward trend in a handful of other bacterium.

While the relationship between the nasopharyngeal microbiota and the severity of COVID-19 remains unknown, their study indicates a "strong association" between the nasal microbiota, SARS-CoV-2 infection and severity, they write.

Their analysis was done before the current virus variants began to surface, but the researchers say the differences in the microbiota likely will hold for these as well and they have already begun that analysis.

Larger studies are needed to ensure that the clear patterns they found hold, the researchers say. They are putting together a grant application that will enable a larger study and looking for other testing sites who want to be partners. Using the same nasopharyngeal swab used for many COVID tests would enable a microbiota analysis to be done at the same time as testing, they say.

They note the striking contrast that has emerged over nearly two years of experience with the virus, with the majority of those infected being asymptomatic or experiencing mild symptoms like they would with a cold, while others get severe viral pneumonia, require hospitalization and die.

A handful of recent studies have now been published suggesting that the bacterial composition of the nasal canal can have a "drastic" influence on the development of respiratory infections and the severity of symptoms, they write. Some studies have indicated that the nasal microbiota can influence the viral load, immune response and symptoms of a rhinovirus infection, which is responsible for somewhere between 10-40% of common colds.

A myriad of other conditions like inflammatory bowel syndrome, peptic ulcers and viral diseases have been linked to significant changes in the microbiota of the gut, nasal and oral cavity, they write.

Diversity of bacterium in the  is generally a good thing, and it's something that naturally decreases with age, says Fulzele, and also can be harmed by habits like smoking and improved by those like eating a diverse diet.


Explore further

Common factors within the gut associated with depression and bipolar disorder

More information: Ravindra Kolhe et al, Alteration in Nasopharyngeal Microbiota Profile in Aged Patients with COVID-19, Diagnostics (2021). DOI: 10.3390/diagnostics11091622
https://medicalxpress.com/news/2021-09-nasal-microbiota-clues-symptoms-sars-cov-.html

COVID-19 may trigger hyperglycemia and worsen disease by harming fat cells

 COVID-19 may bring high risks of severe disease and death in many patients by disrupting key metabolic signals and thereby triggering hyperglycemia, according to a new study from researchers at Weill Cornell Medicine and NewYork-Presbyterian.

In the study, reported Sept. 15 in Cell Metabolism, the researchers found that hyperglycemia—having high blood sugar levels—is common in hospitalized COVID-19 patients and is strongly associated with worse outcomes. The researchers also found evidence suggesting that SARS-CoV-2, the coronavirus that causes COVID-19, can induce hyperglycemia by disrupting fat cells' production of adiponectin, a hormone that helps regulate blood sugar levels. 

"We normally don't think that fat cells are very active, but in fact they synthesize many protective proteins for your body—and it appears that SARS-CoV-2 may disable that protection in many patients," said Dr. James Lo, an associate professor of  in the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center. 

Hyperglycemia, the core feature of diabetes, is associated with inflammation and weakened immunity against infections, and was recognized as a significant risk factor for severe COVID-19 early in the pandemic. However, doctors later began finding evidence that COVID-19 is associated with hyperglycemia in patients who have no history of diabetes. 

To better understand this important but mysterious aspect of COVID-19, Dr. Lo and colleagues analyzed the records of 3,854 patients who were hospitalized with COVID-19 at NewYork-Presbyterian /Weill Cornell Medical Center, NewYork-Presbyterian Queens and NewYork-Presbyterian Lower Manhattan Hospital. in the first few months of the pandemic in the United States. 

They found that a remarkably high proportion (49.7 percent) of these patients presented with hyperglycemia or developed it during their hospital stays. 

Hyperglycemia in these COVID-19 patients was also strikingly associated with worse outcomes. Compared to patients with normal blood sugar levels, the patients with hyperglycemia were 9 times more likely to develop severe lung dysfunction (acute respiratory distress syndrome, or ARDS), 15 times more likely to be given mechanical ventilation, and 3 times more likely to die. 

Surprisingly, the researchers found that hyperglycemia and the dire risks it brings also occur in other, non-COVID-19 forms of severe lung dysfunction. They found it in the same proportion in ARDS cases associated with COVID-19 and in ARDS cases from non-COVID-19 causes such as severe influenza or bacterial pneumonia. However, hyperglycemia in the latter cases appeared to be caused mostly by the death or dysfunction of beta cells that produce insulin, the principal hormone that regulates blood sugar levels. "In contrast, hyperglycemia in COVID-19 patients is mainly caused by , in which insulin is present but the tissues it normally acts upon are no longer sensitive to it," said first author Dr. Moritz Reiterer, a postdoctoral fellow in Dr. Lo's laboratory. 

Further tests revealed that the COVID-19 ARDS patients had severe declines in blood levels of adiponectin, a hormone produced by fat cells which normally has a protective effect against diabetes by enhancing insulin sensitivity. 

How SARS-CoV-2 disrupts fat cells' production of adiponectin isn't yet clear. It may do so indirectly, by raising the general level of inflammation, which in turn disrupts fat cells. But the researchers demonstrated that SARS-CoV-2 can infect human and mouse fat cells, hinting at the possibility that the virus disrupts adiponectin production in this direct way in COVID-19 patients. 

The results open up a novel perspective on COVID-19, offering, among other things, a new explanation for why some people have worse COVID-19 outcomes. 

"Patients with obesity, for example, may be more vulnerable to COVID-19 because they may already have some degree of insulin resistance and fat cell dysfunction, and possibly their fat cells are more susceptible to infection," Dr. Lo said. 

The findings also suggest that a class of diabetes drugs called thiazolidinediones, which boost adiponectin production, may be useful in treating COVID-19 when it includes hyperglycemia. Further research is needed before this becomes clinically actionable. 

Dr. Lo is now investigating whether COVID-19-induced  persists and develops into diabetes even after the recovery from COVID-19. 


Explore further

Improving glycemic control may also aid COVID-19 outcomes

More information: Moritz Reiterer et al, Hyperglycemia in Acute COVID-19 is Characterized by Insulin Resistance and Adipose Tissue Infectivity by SARS-CoV-2, Cell Metabolism (2021). DOI: 10.1016/j.cmet.2021.09.009
https://medicalxpress.com/news/2021-10-covid-trigger-hyperglycemia-worsen-disease.html