Virus World

Common diabetes drug lowers SARS-CoV-2 levels, clinical trial finds Stephanie Soucheray, MA COVID-19 Thinglass/iStock Share Today, researchers from the University of Minnesota published evidence that the common diabetes drug metformin decreases the amount of SARS-CoV-2 in the body and helps reduce the risk of rebound symptoms if given early in the course of non-severe illness. The study, published in Clinical Infectious Diseases, suggests metformin may also help prevent long COVID. The researchers tested metformin against a placebo in 999 adults infected with COVID-19. More than 50% of the study enrollees were vaccinated, and treatment took place when the Omicron variant was the most dominant strain in the United States.

Study included those at standard-risk. Moreover, according to Carolyn Bramante, MD, principal investigator of the study and an assistant professor at the University of Minnesota, the study participants represented a standard- risk population, a group that currently lacks effective treatment options for the novel coronavirus. "This is not a high-risk population," Bramante told CIDRAP News. Instead, participants were 30 years or older, had a body mass index of 25 or higher (overweight), and did not require hospitalization for their COVID-19 infection. In several trials, Paxlovid has been shown to prevent deaths and hospitalization in high-risk, unvaccinated people, but standard-risk populations have not shown improvement in either time to resolution of symptoms or the incidence of hospitalization or death. Bramante said that these patient population demographics suggest metformin may be a clinical tool in outpatient medication that could be widely used. "The data support that someone would be justified if they prescribed it for outpatient treatment," she said.

Four-fold reduction in viral load by day 10. 

Participants were given a 14-day course of metformin, and participants collected nasal swabs on days 1, 5, and 10. Bramante said early treatment was key: Participants were enrolled within 3 days of a positive test, and if symptomatic, reported having symptoms for 7 or fewer days. The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo by day 10, the authors found, and those who received metformin were less likely to have a detectable viral load than placebo at days 5 or 10 (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55 to 0.94). Metformin reduced the odds of hospitalization or death through 28 days by 58%; emergency department visits, hospitalizations, and death through 14 days by 42%; and long COVID through 10 months by 42%. Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, 0.36 to 1.29). While the mechanism of action is not known, Bramante said metformin likely lowers inflammation and inhibits translation of the virus. In a commentary on the study, the authors write, "This study makes a strong case for a potential effect of metformin on COVID-19 virologic decay and prompts reevaluation of existing data in support of its use.

Research cited published (May 1, 2024) in Clin. Infect. Dis.:

https://doi.org/10.1093/cid/ciae159 

Research adds to growing evidence that pandemic may be contributing to rapid rise in people with diabetes. The research adds to mounting evidence the pandemic may be contributing to a rapidly escalating diabetes crisis, with individuals who have experienced more severe Covid at greatest risk. However, lifestyle factors such as being overweight or obese continue to be the main driver for the increase, with 4.3 million officially diagnosed cases in the UK alone. Although previous research has hinted that Sars-CoV-2 infection may increase the risk of developing diabetes – possibly by damaging insulin-producing cells in the pancreas – these studies were either relatively small or limited to specific groups of individuals, such as US military veterans, who may not represent the general population.

Emerging evidence suggests that coronavirus disease-2019 (COVID-19) may lead to a wide range of post-acute sequelae outcomes, including new onset of diabetes. The aim of this meta-analysis was to estimate the incidence of newly diagnosed diabetes in survivors of COVID-19. We searched MEDLINE, Scopus, Cochrane Central Register of Controlled Trials and the World Health Organization Global Literature on Coronavirus Disease and clinical trial registries for studies reporting the association of COVID-19 and diabetes. Search dates were December 2019–October 16, 2022. Two investigators independently assessed studies for inclusion. Risk of bias was assessed using the Newcastle–Ottawa Scale. We estimated the effect of COVID-19 on incident diabetes by random-effects meta-analyses using the generic inverse variance method.

We identified 8 eligible studies consisting of 4,270,747 COVID-19 patients and 43,203,759 controls. Median age was 43 years (interquartile range, IQR 35–49), and 50% were female. COVID-19 was associated with a 66% higher risk of incident diabetes (risk ratio, 1.66; 95% CI 1.38; 2.00). The risk was not modified by age, sex, or study quality. The median risk of bias assessment was 7. In this systematic review and meta-analysis, COVID-19 was associated with higher risk for developing new onset diabetes among survivors. Active monitoring of glucose dysregulation after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is warranted.

Published in Scientific Reports (Nov.23, 2022):

https://doi.org/10.1038/s41598-022-24185-7 

Children who contracted COVID-19 are at increased risk of being diagnosed with Type 1 diabetes. Researchers found a 72% increase in new Type 1 diabetes cases in those under 18 who contracted COVID-19. In a study published today in the journal JAMA Network Open, researchers at the Case Western Reserve University School of Medicine report that children and adolescents who contracted COVID-19 were more prone to developing T1D in the six months following their COVID diagnosis.  The findings showed a 72% increase in new diagnoses of T1D in COVID-19 patients 18 years old and younger—although the research emphasized that it is unclear whether COVID-19 triggers new onset of T1D. About 187,000 children and adolescents younger than 20 live with T1D nationally, according to the Centers for Disease Control and Prevention (CDC).  “Type 1 diabetes is considered an autoimmune disease,” said Pamela Davis, Distinguished University Professor and The Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine, a study corresponding author.

“It occurs mostly because the body’s immune defenses attack the cells that produce insulin, thereby stopping insulin production and causing the disease. COVID has been suggested to increase autoimmune responses, and our present finding reinforces that suggestion.” The team analyzed the de-identified electronic health records of nearly 1.1 million patients age 18 years and younger in the United States and 13 other countries diagnosed with the SARS-CoV-2 infection between March 2020 and December 2021 and also those diagnosed with a non-COVID-related respiratory infection during that same period. The study population was further divided into two groups: patients up to age 9 years and those age 10–18 years. After careful statistical matching to account for age, demographics and family history of diabetes, there were 285,628 in each group for a total of 571,256 patients.

Study findings

The research team found that among the more than 571,000 pediatric patients: 

• Within six months of SARS-CoV2 infection, 123 patients (0.043%) had received a new diagnosis of T1D, compared to 72 patients (0.025%) who received a new diagnosis following a non-COVID respiratory infection, an increase of 72% in new diagnoses.
• At one, three and six months following infection, the risk of diagnosis of T1D was substantially greater for those infected with SARS-CoV2 compared to those with non-COVID respiratory infections. Similar results were reported with patients in the infant-9-year-old and 10- to 18-year-old age groups.

“Families with high risk of type 1 diabetes in their children should be especially alert for symptoms of diabetes following COVID, and pediatricians should be alert for an influx of new cases of type 1 diabetes, especially since the Omicron variant of COVID spreads so rapidly among children,” Davis said.  “We may see a substantial increase in this disease in the coming months to years. Type 1 diabetes is a lifelong challenge for those who have it, and increased incidence represents substantial numbers of children afflicted.”  Rong Xu, also a corresponding author, professor of Biomedical Informatics at the School of Medicine and director of the Center for Artificial Intelligence in Drug Discovery, said further research is needed to examine if the increased risk of new onset T1D following SARS-CoV2 infection in pediatric patients will persist, who are vulnerable, and how to treat COVID-19 associated T1D in children. “We are also investigating possible changes in development of type 2 diabetes in children following SARS-CoV2 infection,” Xu said. T1D is most common in children while type 2 diabetes (T2D) is known as “adult-onset diabetes” and develops over time, often as the patient becomes resistant to the effects of insulin and later, as the pancreas stops making enough insulin, according to the CDC. The Case Western Reserve research team also included David Kaelber, professor of Internal Medicine, Pediatrics and Population and Quantitative Health Sciences, and medical students Ellen Kendall and Veronica Olaker. Previous COVID-related studies led by the CWRU team have found that the risk factor for Alzheimer’s disease increases by 50–80% in older adults who caught COVID and that people with dementia are twice as likely to contract COVID.

Research cited published in Jama Network (Sept. 23, 2022):

https://doi.org/10.1001/jamanetworkopen.2022.33014 

Emerging evidence points towards an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While pre-existing diabetes is associated with severe COVID-19, it is unclear if COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2 and cause β-cell depletion. We found that the SARS-CoV-2 receptor, ACE2 and related entry factors (TMPRSS2, NRP1, TRFC) are expressed in β-cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β-cells in patients who succumbed to COVID-19 and selectively infects human islet β-cells in vitro. We demonstrated SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion, and induces β-cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β-cell signaling, similar to that observed in Type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β-cell killing.

Published in Cell Metabolism (May 18, 2021):

https://doi.org/10.1016/j.cmet.2021.05.013 

Evidence from tissue studies and some people with COVID-19 shows that the virus damages insulin-producing cells. 

In mid-April, Finn Gnadt, an 18-year-old student from Kiel, Germany, learnt that he had been infected with the SARS-CoV-2 coronavirus despite feeling well. Gnadt’s parents had fallen ill after a river cruise in Austria, so his family was tested for virus antibodies, which are produced in response to infection. Gnadt thought he had endured the infection unscathed, but days later, he started to feel worn out and exceedingly thirsty. In early May, he was diagnosed with type 1 diabetes, and his physician, Tim Hollstein at the University Hospital Schleswig-Holstein in Kiel, suggested that the sudden onset might be linked to the viral infection.

In most people with type 1 diabetes, the body’s immune cells start destroying β-cells — which are responsible for producing the hormone insulin — in the pancreas, often suddenly. In Gnadt’s case, Hollstein suspected that the virus had destroyed his β-cells, because his blood didn’t contain the types of immune cells that typically damage the pancreatic islets where the β-cells live. Diabetes is already known to be a key risk factor for developing severe COVID-191 and people with the condition are more likely to die2. “Diabetes is dynamite if you get COVID-19,” says Paul Zimmet, who studies the metabolic disease at Monash University in Melbourne, Australia. Now Zimmet is among a growing number of researchers who think that diabetes doesn’t just make people more vulnerable to the coronavirus, but that the virus might also trigger diabetes in some3. “Diabetes itself is a pandemic just like the COVID-19 pandemic. The two pandemics could be clashing,” he says....

See also the NEJM letter (June 12, 2020):

https://doi.org/10.1056/NEJMc2018688

Investigators in the Smidt Heart Institute at Cedars-Sinai have confirmed that people who have had COVID-19 have an increased risk for new-onset diabetes—the most significant contributor to cardiovascular disease. "Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the omicron era," said Alan Kwan, MD, first and corresponding author of the study and a cardiovascular physician in the Smidt Heart Institute at Cedars-Sinai. The trend, Kwan says, is concerning because most people in the United States will eventually experience a COVID-19 infection. "This research study helps us understand—and better prepare for—the post-COVID-19 era of cardiovascular risk," Kwan said. The findings, published today in the journal JAMA Network Open, also suggest that the risk of type 2 diabetes appears lower in individuals who were already vaccinated against COVID-19 by the time they were infected. To determine the rising rates of diabetes, investigators evaluated medical records from 23,709 adult patients who had at least one documented COVID-19 infection and were treated within the Cedars-Sinai Health System in Los Angeles from 2020–2022. The average patient was 47 years old, and 54% of subjects were female.

Within the study time frame:

• The combined risk of type 2 diabetes after COVID-19 exposure—accounting for both vaccinated and unvaccinated patients—was 2.1%, with 70% occurring after COVID-19 infection versus 30% happening prior to COVID-19 exposure.
• The risk of type 2 diabetes after COVID-19 exposure for unvaccinated patients was 2.7%, with 74% occurring after COVID-19 infection versus 26% happening prior to COVID-19 exposure.
• The risk of type 2 diabetes after COVID-19 exposure for vaccinated patients was 1.0%, with 51% occurring after COVID-19 infection versus 49% happening prior to COVID-19 exposure.

"These results suggest that COVID-19 vaccination prior to infection may provide a protective effect against diabetes risk," said Kwan. "Although further studies are needed to validate this hypothesis, we remain steadfast in our belief that COVID-19 vaccination remains an important tool in protecting against COVID-19 and the still-uncertain risks that people may experience during the post-infection period." Susan Cheng, MD, MPH, senior author of the study, professor of Cardiology, and director for Cardiovascular Population Sciences in the Smidt Heart Institute, says these findings broaden the medical field's understanding of the effects of COVID-19 on the body, while simultaneously unearthing yet-to-be-answered questions. "Although we don't yet know for certain, the trends and patterns that we see in the data suggest that COVID-19 infection could be acting in certain settings like a disease accelerator, amplifying risk for a diagnosis that individuals might have otherwise received later in life," said Cheng, the Erika J. Glazer Chair in Women's Cardiovascular Health and Population Science.

"So, it could be that instead of being diagnosed with diabetes by age 65, a person with preexisting risk for diabetes might—after a COVID-19 infection—be more likely to develop diabetes by age 45 or 55." Diabetes disrupts normal metabolism and metabolic processes, preventing the pancreas from producing enough insulin, a hormone that helps regulate blood levels of glucose and amino acids. Because diabetes can damage vital organs and blood vessels, people with diabetes are at higher risk for heart attack and stroke. The disease affects an estimated 26 million people in the United States. This research, Kwan says, is one piece of the puzzle that will help researchers understand how to prevent metabolic as well as cardiovascular disease risk in the future. "As we learn how to live with COVID-19, we also have to be prepared to recognize and treat the various conditions linked to its aftereffects," said Kwan. "Our ultimate goal—with every research study we conduct—is to find ways to keep people healthy and able to engage in their everyday activities and lives."

Research cited published in JAMA (Feb.14, 2023):

https://doi.org/10.1001/jamanetworkopen.2022.55965 

As emerging clinical analyses suggest an increased risk of new-onset diabetes following COVID-19, a causal link and underlying mechanisms are yet to be established. Persistence of hyperglycaemia after disease regression and the potential infection of non-pancreatic tissue are adding another layer of complexity to the relationship between COVID-19 and diabetes mellitus. Clinical and epidemiological evidenceClinical and epidemiological evidenceAfter initial reports of new-onset hyperglycaemia coinciding with infection in the early phases of the pandemic, several large cohort studies now suggest an overall increased risk of new-onset diabetes mellitus (DM) for both type 1 diabetes (T1D)1,2 and type 2 diabetes (T2D)3,4,5,6 following COVID-19 infection. For T1D, however, epidemiological data are controversial — German2 and Scottish1 registries noted an increase in T1D diagnosis in children and adolescent shortly after a peak in SARS-CoV-2 infection numbers, whereas a larger population-based, repeated, cross-sectional study from Canada7 did not. Delayed diagnoses of naturally occurring T1D as an indirect result of the pandemic are likely confounding these results, while the challenge to verify past COVID-19 infection in children with new-onset diabetes further complicates association studies.

At the same time, evidence for a connection of COVID-19 with new-onset T2D appears more robust. Surveys of electronic patient records suggest an overall increased risk of new-onset DM up to 12 weeks post infection3, an increased likelihood of being prescribed insulin within 91 days of COVID-19 diagnosis3 and an excess burden of incident diabetes and hyperglycaemia (where > 77% were stratified as T2D) at 12-month follow up4. If and when glycaemic control is re-established after recovery from COVID-19 in those patients remains unclear. In some cohorts, glucose control had improved in 63–79% of patients 6 months after recovery5,8 and improved in 41–79% of patients 10 months after recovery5,6. Up to 56% of patients remained hyperglycaemic6. A separate cohort of hospitalized COVID-19 patients with dysglycaemia during acute infection displayed reversion to physiological glycaemic control in the post-acute phase in a 7 month follow-up9. Despite uncertainties regarding prevalence and persistence, dysglycaemia may thus represent a potential aspect of post-acute sequelae of SARS-CoV-2 (PASC), also commonly referred to as ‘long COVID’ (or ‘LC’).

However, these findings also do not necessarily imply a direct diabetogenic effect of SARS-CoV-2 infection, as hyperglycaemia is also observed after non-COVID acute respiratory distress syndrome, possibly as a result of systemic inflammation10. Nonetheless, occurrence of new-onset T2D3,4,5,6 and insulin resistance8 post-COVID suggests that SARS-CoV-2 infection may promote β-cell exhaustion in at-risk cohorts. Notably, breakthrough infection after vaccination was not associated with a significantly lower incidence of DM in the context of PASC, when compared to infections of unvaccinated individuals. However, a decreased risk of insulin use suggests ameloration of the severity of metabolic dysregulation by pre-exisiting immunity11. Furthermore, a recent preprint suggests an accumulating risk of new-onset DM with multiple re-infections12. Due to ethical reasons, correlative time-resolved data on insulin and glucose levels with degree of β-cell infection in humans will be invariably lacking, which will restrict our experimental knowledge to animal models, including non-human primates. Overall, the long-term risk for and burden of new-onset DM of any type following COVID-19, especially in light of newly emerging, immune-evasive variants and multiple subsequent infections, can only be clarified by population-level studies providing long term follow-up data and comprehensive data sets in the coming years.

Published in NatureMetabolism (Nov. 11, 2022):

https://doi.org/10.1038/s42255-022-00691-w 

Even mild SARS-CoV-2 infections can amplify a person’s chance of developing diabetes, especially for those already susceptible to the disease.  People who get COVID-19 have a greater risk of developing diabetes up to a year later, even after a mild SARS-CoV-2 infection, compared with those who never had the disease, a massive study1 of almost 200,000 people shows. The research, published in The Lancet Diabetes & Endocrinology earlier this month, is one of a growing number of studies2 showing that COVID-19 can increase a person’s risk of diabetes, months after infection. “When this whole pandemic recedes, we’re going to be left with the legacy of this pandemic — a legacy of chronic disease” for which health-care systems are unprepared, says study co-author Ziyad Al-Aly, chief researcher for the Veterans Affairs (VA) St Louis Healthcare System in Missouri.

Risks amplified

Al-Aly and Yan Xie, an epidemiologist also at the VA St Louis Healthcare System, looked at the medical records of more than 180,000 people who had survived for longer than a month after catching COVID-19. They compared these with records from two groups, each of which comprised around four million people without SARS-CoV-2 infection who had used the VA health-care system, either before or during the pandemic. The pair previously used a similar method to show that COVID-19 increases the risk of kidney disease3, heart failure and stroke4. The latest analysis found that people who had had COVID-19 were about 40% more likely to develop diabetes up to a year later than were veterans in the control groups. That meant that for every 1,000 people studied in each group, roughly 13 more individuals in the COVID-19 group were diagnosed with diabetes. Almost all cases detected were type 2 diabetes, in which the body becomes resistant to or doesn’t produce enough insulin. The chance of developing diabetes rose with increasing severity of COVID-19. People who were hospitalized or admitted to intensive care had roughly triple the risk compared with control individuals who did not have COVID-19. Even people who had mild infections and no previous risk factors for diabetes had increased odds of developing the chronic condition, says Al-Aly. Of the people with COVID-19 who avoided hospitalization, an extra 8 people out of every 1,000 studied had developed diabetes a year later compared with people who were not infected. People with a high body-mass index, a measure of obesity — and a considerable risk factor for type 2 diabetes — had more than double the risk of developing diabetes after a SARS-CoV-2 infection.

Global burden

Given the extraordinary number of COVID-19 cases globally — 480 million confirmed cases and counting — the modest increase in diabetes risk could correspond to a drastic rise in the number of people diagnosed with the disease worldwide, if the observed trends hold true, says Jonathan Shaw, an epidemiologist at the Baker Heart and Diabetes Institute in Melbourne, Australia. But the findings might not translate to other groups of people. The US veterans in the study were mostly older, white men, many of whom had elevated blood pressure and were overweight, putting them at high risk of developing diabetes, says Gideon Meyerowitz-Katz, an epidemiologist studying diabetes at the University of Wollongong in Australia. But that risk is much lower in younger people, he says, and higher in some other ethnic groups. And it’s possible that some people in the control group had undetected mild or asymptomatic COVID-19 but were never tested, potentially skewing the data, Al-Aly adds. Other factors might also be contributing to the apparent rise in diabetes among people who recovered from COVID-19, says Shaw. Existing cases of diabetes might have gone undetected until people sought medical care for COVID-19.

Elusive causes

Early in the pandemic, researchers raised concerns based on anecdotal reports in young people and children that SARS-CoV-2, like other viruses, might damage cells in the pancreas that produce insulin, triggering type 1 diabetes. But data on a link between SARS-CoV-2 infection and newly diagnosed cases of type 1 diabetes remain mixed. Several studies5–7 have found no evidence that the disease is causing the uptick in cases of type 1 diabetes in younger adults or children. And a laboratory study published in February also challenged the idea that SARS-COV-2 destroys insulin-producing pancreatic cells8. A lingering question is whether the metabolic changes observed in people who had COVID-19 persist after one year. More research is needed to clarify long-term trends in new-onset diabetes at a population level and to tease apart what might be causing them, says Shaw.

Research cited published in The Lancet Diabetes and Endocrinology (March 21, 2022):

https://doi.org/10.1016/S2213-8587(22)00044-4

COVID-19 isn’t just deadlier for people with diabetes, it’s also triggering the metabolic disease in many who didn’t previously have it, study shows.  When Ziyad Al-Aly’s research team told him how often diabetes appeared to strike COVID-19 survivors, he thought the data must be wrong, so he asked his five colleagues to crunch the numbers again. Weeks later, they returned the same findings after sifting through millions of patient records. By then Al-Aly had also gone digging into the scientific literature and was starting to come to terms with an alarming reality: COVID-19 isn’t just deadlier for people with diabetes, it’s also triggering the metabolic disease in many who didn’t previously have it.  “It took a while to convince me,” said Al-Aly, who directs the clinical epidemiology center at the Veterans Affairs St. Louis Health Care System in Missouri. “It was hard to believe that COVID could be doing this.” Among COVID-19′s many ripple effects, the worsening of the global diabetes burden could carry a heavy public health toll. The underlying mechanisms stoking new-onset diabetes aren’t clear, though some doctors suspect the SARS-CoV-2 virus may damage the pancreas, the gland that makes insulin that is needed to convert blood-sugar into energy. Sedentary lifestyles brought on by lockdowns could also be playing a role, as might late diagnoses after people avoided doctors’ offices. Even some children’s mild coronavirus cases can be followed by the swift onset of diabetes, scientists found.

New results from The Environmental Determinants of Diabetes in the Young study show an association between prolonged enterovirus infection and the development of autoimmunity to the insulin-producing pancreatic beta-cells that precedes type 1 diabetes. Notably, researchers also found that early adenovirus C infection seemed to confer protection from autoimmunity. The full findings were published Dec. 2 in Nature Medicine. 

Viruses have long been suspected to be involved in the development of T1D, an autoimmune condition, although past evidence has not been consistent enough to prove a connection. Investigators from theUniversity of South Florida Health (USF Health) Morsani College of Medicine, Baylor College of Medicine, and other institutions studied samples available through the TEDDY study, the largest prospective observational cohort study of newborns with increased genetic risk for T1D, to address this knowledge gap. TEDDY studies young children in the U.S. (Colorado, Georgia/Florida, and Washington State) and in Europe (Finland, Germany, and Sweden). "T1D occurs when the immune system destroys its own insulin-producing beta cells in the pancreas. Insulin is a hormone that regulates blood sugar in the body. Without it, the body cannot keep normal blood sugar levels causing serious medical complications," said coauthor Richard Lloyd, PhD, professor of molecular virology and microbiology at Baylor College of Medicine.  

In the current study, Vehik and her colleagues studied the virome, that is, all the viruses in the body. They analyzed thousands of stool samples collected from hundreds of children followed from birth in the TEDDY study, looking to identify a connection between the viruses and the development of autoimmunity against insulin-producing beta cells. The enterovirus Coxsackievirus has been implicated in T1D before, but the current results provide a completely new way to make the connection, by identifying specific viruses shed in the stool. The investigators were surprised to find that a prolonged infection of more than 30 days, rather than a short infection, was associated with autoimmunity. "This is important because enteroviruses are a very common type of virus, sometimes causing fever, sore throat, rash or nausea. A lot of children get them, but not everybody that gets the virus will get T1D," Vehik said. "Only a small subset of children who get enterovirus will go on to develop beta cell autoimmunity. Those whose infection lasts a month or longer will be at higher risk." A prolonged enterovirus infection might be an indicator that autoimmunity could develop. 

Beta cells of the pancreas express a cell surface protein that helps them talk to neighboring cells. This protein has been adopted by the virus as a receptor molecule to allow the virus to attach to the cell surface. The investigators discovered that children who carry a particular genetic variant in this virus receptor have a higher risk of developing beta cell autoimmunity. "This is the first time it has been shown that a variant in this virus receptor is tied to an increased risk for beta cell autoimmunity," Vehik said. Ultimately, this process leads to the onset of T1D, a life-threatening disease that requires life-long insulin injections to treat. Another discovery was that the presence in early life of adenovirus C, a virus that can cause respiratory infections, was associated with a lower risk of developing autoimmunity. It remains to be investigated whether having adenovirus C in early life would protect from developing beta cell autoimmunity. Adenoviruses use the same beta cell surface receptor as Coxsackievirus B, which may offer one clue to explain this connection, although further research is needed to fully understand the details....

Published in Nature Medicine (December 2, 2019):

https://doi.org/10.1038/s41591-019-0667-0