Virus World

A study found that the floor and walls around the toilet could still get contaminated with viruses from the toilet bowl even when the lid is down during flushing. Will shutting the toilet lid when you flush really keep nasty microbes from leaving the bowl and spraying all over the place? Well, it’s not exactly an open and shut case, according to a new study published in the American Journal of Infection Control. The study found that the floor and walls around the toilet could still go quite viral, so to speak, even when the lid stays down during the flush. Yes, even the walls around the toilet ended up getting contaminated with viruses from the toilet bowl. For the study, a team of researchers from the University of Arizona (Madison P. Goforth, BS Stephanie A. Boone, PhD Justin Clark, MS Priscilla B. Valenzuela, MS, FRSPH, and Charles P. Gerba, PhD) and Reckitt Benckiser, LLC, the makers of Lysol (Julie McKinney, PhD, and M. Khalid Ijaz, DVM, PhD) dumped some bacteriophage MS2 into two different types of toilets...

The report distinguished two patterns of liver involvement after COVID-19: acute liver failure that required transplantation and acute hepatitis with injury to the bile system.  On June 7, 2022, the World Health Organization (WHO) and the World Hepatitis Alliance, at their World Hepatitis Summit 2022, released a joint news statement in which they also briefly addressed the current cases of unexplained acute hepatitis (liver inflammation) among young children. There have been some 700 such cases in the last five months, spanning 34 countries, coinciding with the Omicron phase of the pandemic. The United Kingdom and the United States lead in the number of cases, each with more than 200.  The clinical signs of the disease come on suddenly, with a high proportion of children developing liver failure and around six percent needing a liver transplant. Nine have died. The most common symptoms are vomiting and jaundice, the yellowing of the skin and the sclera of the eyes.  Many in the scientific community speculated that the disease fell into the spectrum of the multisystem inflammatory syndrome-children (MIS-C) arising from a previous COVID infection, which can afflict a minority of children and adolescents after the acute phase of COVID has passed and their infections have already cleared, meaning that once acute hepatitis manifests, their COVID tests are negative. Many have also not had antibody tests conducted to confirm previous COVID infections.  Speaking with New Scientist, Dr. Deepti Gurdasani of Queen Mary University of London said, “I think we have seen hepatitis as part of MIS-C before, but not in the numbers that are being seen now.” She explained that the rise could be because Omicron has infected millions of children in a few short months. Many public health officials, including the US Centers for Disease Control and Prevention (CDC) and the WHO, have placed undue emphasis on adenovirus infections, which commonly cause colds and flu-like symptoms in the population. However, they almost never cause liver failure among previously healthy children, or even the immuncocompromised, for that matter. 

Despite experience with adenoviruses and ample expertise on viral infections and liver injury that have been amply documented in the literature, this didn’t stop the CDC from writing on May 6, 2022, “This cluster [in Kentucky], along with recently identified possible cases in Europe, suggest that adenovirus should be considered in the differential diagnosis of acute hepatitis of unknown etiology among children.”  But in their report they clearly stated that on liver biopsies no [adenovirus] viral infections were ever observed. Even with the use of the electron microscope, no viral particles were evident. In the very rare instances where adenoviruses have caused liver failure among immunocompromised children, in 100 percent of cases the adenovirus was detected in liver cells. On May 22 the WHO provided a more nuanced perspective, writing, “While adenovirus is a plausible hypothesis as part of the pathogenesis mechanism [the manner of development of disease], further investigations are ongoing for the causative agent; adenovirus infection (which generally causes mild self-limiting gastrointestinal or respiratory infections in young children) does not fully explain the more severe clinical picture observed with these cases.” Dr. Farid Jalali, a gastroenterologist, has emphatically denounced the claim that these recent unexplained pediatric acute liver failures are associated with the detection of adenovirus in the patients, especially in the context of the COVID-19 pandemic and recent massive waves of Omicron infections.

Adenoviruses are common and can colonize the areas of the respiratory and intestinal tracts. Finding them doesn’t necessarily indicate they were the cause of the disease. He emphasized that public health institutions are doing a disservice to the children and families of the afflicted by suggesting such an association and are only minimizing the dangers posed by the current policies that allow SARS-CoV-2 to persist in human communities.  The debate in the scientific community has been ongoing. However, a recent study from Tel Aviv University has provided new evidence that COVID is indeed responsible for these acute liver failure cases. Lead author Dr. Shiri Cooper and colleagues submitted a report last Friday to the Journal of Pediatric Gastroenterology and Nutrition on five pediatric cases that had recovered from asymptomatic or mild COVID and later suffered acute liver injury. They distinguished two patterns of liver involvement after COVID-19: acute liver failure that required transplantation and acute hepatitis with injury to the bile system. Interestingly, the two patients with liver failure were aged only three and five months, and those older, aged eight to 13, developed a disease pattern similar to their adult counterparts.  In adults, post-COVID liver injury has been described in the medical literature but usually as a late complication of severe COVID and hospitalization that leads to progressive liver failure.  Cooper and colleagues in the current study from Tel Aviv University wrote, “The clinical manifestation of the pediatric patients suggests that the pathogenesis is not related to the severity of acute [COVID] disease” as it is in adults. The disease among children frequently presents several months after the diagnosis of COVID-19. In their study, the mean time from COVID to liver failure was 75 days, which explains why so many of these cases were missed as Long-COVID complications, because children are routinely missed in diagnosing the milder form of acute disease. 

Many of the findings in the children with liver failure have also been seen in adults, such as the swelling and enlargement of the liver. The walls of the gallbladders were thickened, and the bile ducts were dilated. Biopsies of the liver showed extensive inflammation. In other words, the disease process that has been attributed to adults after their COVID infection has distinct parallels with these children and their acute liver inflammation. Because of the claimed association with adenovirus, the authors of the Israeli study also attempted to investigate this hypothesis.  First, they commented on published results by the European CDC on 14 cases. None showed adenovirus in any residual liver cells, called hepatocytes: “One case underwent adenovirus PCR of liver tissue which was negative.” In another case series of six patients, none of the liver biopsies showed the presence of any adenovirus particles. But as already noted, in rare cases of adenovirus-induced liver failure, liver biopsies in all the cases showed viral particles were present.  In the five patients in Israel, “The adenovirus stain was negative in all, and the histologic features [under the microscope] were not suggestive of adenovirus hepatitis. Three patients had adenovirus PCR performed from whole blood, and in one, it was positive. However, as the liver histology was not suggestive of adenovirus infection, we did not consider it as the culprit for the hepatitis.” As to the mechanism of injury, the authors suggested that damage to the immune system from COVID is likely the cause, and considerable effort is needed to understand these complex processes. It is all the more necessary that public health authorities stop being obstructionists, heed the weight of the evidence that has already been presented, and acknowledge the dangers posed by COVID and the reckless “herd immunity” policy that exposes children to unnecessary harm.  Dr. Lisa Iannattone stated bluntly on Twitter, “Anyone putting forth the hypothesis that there are two novel pediatric liver failure outbreaks caused by two different viruses happening at the same time is not someone to be taken seriously. I don’t care what ‘very serious institution’ they work for. This is absurd. It’s COVID.”

Research Cited available in the Journal of Pediatric Gastroenterology and Nutrition (June 10, 2022):

https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx 

Recently, the Centers for Diseases and Control released a nationwide health alert about an increase in hepatitis cases of unknown origin in children, raising concern about potential sequelae of COVID-19 infection. In this study, we test whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children. We performed a retrospective cohort study on a nation-wide database of patient electronic health records (EHRs) in the US. The study population comprise 796,369 children between the ages of 1-10 years including 245,675 who had contracted COVID-19 during March 11, 2020 - March 11, 2022 and 550,694 who contracted non-COVID other respiratory infection (ORI) during the same timeframe. Compared to children infected with other respiratory infections, children infected with COVID- 19 infection were at significantly increased risk for elevated AST or ALT (hazard ratio or HR: 2.52, 95% confidence interval or CI: 2.03-3.12) and total bilirubin (HR: 3.35, 95% CI: 2.16- 5.18). These results suggest acute and long-term hepatic sequelae of COVID-19 in pediatric patients. Further investigation is needed to clarify if post-COVID-19 related hepatic injury described in this study is related to the current increase in pediatric hepatitis cases of unknown origin.

Preprint iin medRxiv (May 14, 2022):

https://doi.org/10.1101/2022.05.10.22274866 

Health officials in the UK have released new details in their ongoing investigation of an unusual series of hepatitis cases in children. The new report helps explain why they have zeroed in on a possible link to the adenovirus family, the UK Health Security Agency announced Monday.  Since the beginning of the year, at least 111 children have been identified in the UK with acute liver inflammation that does not appear to be caused by the group of hepatitis viruses that would've been a more likely culprit. Many more cases have been announced in the US and other countries around the world. Roughly three-quarters of the 53 children who were tested for adenovirus in the UK came back positive. The virus that causes Covid-19, on the other hand, was found in only a sixth of children who were tested — in line with the levels of community transmission in the UK. 

People in Hong Kong are falling ill from a hepatitis virus found in rats -- but nobody knows how they're being infected. In 2018, infectious disease experts at the University of Hong Kong came across an unusual patient. The 56-year-old man, who had undergone a liver transplant, was showing abnormal liver functions with no obvious cause. Tests found that his immune system was responding to hepatitis E -- but they couldn't actually find the human strain of the hepatitis E virus (HEV) in his blood.

Hepatitis E is a liver disease that can also cause fever, jaundice and an enlarged liver. The virus comes in four species, which circulate in different animals; at the time, only one of these four was known to infect humans. With tests for that human strain of HEV negative, the researchers redesigned the diagnostic test, ran it again -- and found, for the first time in history, rat hepatitis E in a human. "Suddenly, we have a virus that can jump from street rats to humans," said Dr. Siddharth Sridhar, a microbiologist and one of the HKU researchers who made the discovery. It was such an unusual and unprecedented infection that the team wondered if it was a "one-off incident, one patient who was in the wrong place at the wrong time." But then it happened again. And again. 

Since that first study, 10 more Hong Kong residents have tested positive with rat hepatitis E, also known as rat HEV. The most recent case came a week ago; a 61-year-old man with abnormal liver function tested positive on April 30. And there might be hundreds more infected undiagnosed people out there, said Sridhar. The housing estate where the 56-year-old rat hepatitis E patient lived in Hong Kong. Signs of a rat infestation were found here after he was confirmed infected in 2018. The human strain of hepatitis E is typically transmitted through fecal contamination of drinking water, according to the World Health Organization.....

UC San Diego researchers linked a gut bacteria toxin to worse clinical outcomes in patients with alcoholic liver disease, and discovered that treatment with bacteriophages clears the bacteria and eliminates the disease in mice. 

Bacteriophages (phages) are viruses that specifically destroy bacteria. In the early 20th century, researchers experimented with phages as a potential method for treating bacterial infections. But then antibiotics emerged and phages fell out of favor. With the rise of antibiotic-resistant infections, however, researchers have renewed their interest in phage therapy. In limited cases, patients with life-threatening multidrug-resistant bacterial infections have been successfully treated with experimental phage therapy after all other alternatives were exhausted. Researchers at University of California San Diego School of Medicine and their collaborators have now for the first time successfully applied phage therapy in mice for a condition that’s not considered a classic bacterial infection: alcoholic liver disease. The study publishes November 13, 2019 in Nature.

“We not only linked a specific bacterial toxin to worse clinical outcomes in patients with alcoholic liver disease, we found a way to break that link by precisely editing gut microbiota with phages,” said senior author Bernd Schnabl, MD, professor of medicine and gastroenterology at UC San Diego School of Medicine and director of the National Institutes of Health-funded San Diego Digestive Diseases Research Center. Up to 75 percent of patients with severe alcoholic hepatitis, the most serious form of alcohol-related liver disease, die within 90 days of diagnosis. The condition is most commonly treated with corticosteroids, but they aren’t highly effective. Early liver transplantation is the only cure, but is only offered at select medical centers to a limited number of patients. In fact, there are only approximately 8,000 liver transplants for all reasons in the United States each year, according to the American Liver Foundation, with a waiting list of roughly 14,000 people.  

Alcohol itself can directly damage liver cells. But Schnabl and team had previously discovered that alcohol is also harmful to the liver for a second reason: It diminishes natural gut antibiotics, leaving mice more prone to bacterial growth in the liver and exacerbating alcohol-induced liver disease. In the current study, Schnabl’s team — including many collaborators around the world — addressed two primary questions: How do gut bacteria contribute to liver damage? And can phages be used to reduce the bacteria and thus alleviate alcoholic liver disease?  The researchers discovered that liver cells are injured by cytolysin, a toxin secreted by Enterococcus faecalis, a type of bacteria typically found in low numbers in the healthy human gut. They also found that people with alcoholic hepatitis have more cytolysin-producing E. faecalis in their guts than healthy people. The more E. faecalis present, the more severe their liver disease. For people with alcoholic liver disease, more than five percent of their fecal bacteria were Enterococcus, compared to almost none in healthy people or people with alcoholic use disorder. Approximately 80 percent of alcoholic hepatitis patients have E. faecalis living in their feces, and 30 percent are positive for cytolysin. Moreover, the researchers found that nearly 90 percent of cytolysin-positive patients with alcoholic hepatitis died within 180 days of hospital admission, compared to approximately 4 percent of cytolysin-negative patients.

Next, the team transferred feces from cytolysin-positive and cytolysin-negative people with alcoholic hepatitis to mice. Mice with cytolysin-positive humanized gut microbiomes developed more severe alcohol-induced liver disease and survived less than mice without cytolysin. To investigate the potential for phage therapy, the researchers isolated from sewage water four different phages that specifically target cytolysin-producing E. faecalis. When they treated the mice with the targeting phages, the bacteria were eradicated and alcohol-induced liver disease was abolished. Control phages that target other bacteria or non-cytolytic E. faecalis had no effect. “This phage therapy has only so far been tested in mice, and a clinical trial will be required to test the safety of this approach, and validate our findings in patients with alcoholic hepatitis,” Schnabl said.

Published in Nature (November 13, 2019):

https://doi.org/10.1038/s41586-019-1742-x

Infection with multiple common viruses may be responsible for the cases that puzzled doctors last year. Last year, reports of severe, unexplained hepatitis in previously healthy children puzzled health experts around the world. Now, a small new study of American children adds to the evidence that the cases, which remained extremely rare, may have been caused by a simultaneous infection with multiple common viruses, including one known as adeno-associated virus type 2, or AAV2. AAV2 is not typically associated with disease, and it requires a second “helper” virus in order to replicate. Many of the children with unexplained hepatitis, or liver inflammation, were infected with multiple helper viruses, the researchers found. Although the idea remains speculative, the timing of the outbreak may have been related to the loosening of pandemic precautions, leaving large numbers of young children exposed to common viruses they had not previously encountered. “It may have resulted in a population that was highly vulnerable to getting infected with multiple viral infections,” said Dr. Charles Chiu, an infectious disease specialist and microbiologist at the University of California, San Francisco, and an author of the new study. The research appeared Thursday in the journal Nature, alongside two British studies that also implicated AAV2 in the hepatitis cases. Preliminary versions of the British studies were posted online last summer. The consistent findings are “quite striking,” said Dr. Frank Tacke, head of the gastroenterology and hepatology department at the Charité University Medical Center in Berlin, who was not involved in the research but wrote an accompanying commentary. “The fact that three independent groups found this from different areas of the world actually makes it really convincing.” Still, the findings are not definitive, and many uncertainties remain, including how these infections might trigger hepatitis and whether AAV2 plays a causal role or is “just a bystander,” Dr. Tacke said. (There has also been some debate about whether the cases truly became more commonlast year or whether they were part of a previously unrecognized phenomenon.) The cases date back to the fall of 2021 but seemed to peak last spring and summer before tapering off, experts said. By last July, more than 1,000 probable cases had been reported in 35 countries, including the United States, according to the World Health Organization. Roughly 5 percent of children required liver transplants, and 2 percent died. In several early studies, scientists found that many of the affected children were infected with adenoviruses, particularly adenovirus 41, which typically causes gastrointestinal symptoms. Adenoviruses are not typically known to cause hepatitis in otherwise healthy children, but they are common helper viruses for AAV2.

Finding a probable culprit can sometimes happen fairly quickly when something new pops up in the infectious diseases sphere. But that doesn't mean the end of the mystery. I n early April, when word began to circulate that hospitals in the United Kingdom were seeing unexplained hepatitis cases in very young children, some physicians and researchers on this side of the Atlantic experienced a moment of déjà vu. Kevin Messacar and colleagues at Children’s Hospital Colorado found themselves remarking on how reminiscent the unfolding investigation was of a medical mystery they’ve been enmeshed in for the past eight years — acute flaccid myelitis, or AFM, a polio-like condition in children. Meanwhile, Carlos Pardo, the co-principal investigator of a National Institutes of Health study into the natural history of AFM, started fielding queries from hepatologists at Johns Hopkins Medicine, where he teaches, about what kinds of samples they should be collecting from suspected hepatitis cases.  “There are many parallels between this initial investigation of these cases of hepatitis of unknown origin and our initial investigations of AFM cases,” Messacar, a pediatric infectious disease physician and an associate professor at the University of Colorado, told STAT. As public health agencies race to figure out what is behind the unusual hepatitis cases, Messacar, Pardo, and others believe there are lessons to be learned from the ongoing efforts to solve the mysteries of AFM.

Chief among them is that getting to satisfactory answers is likely going to take time. There may be an answer to the fundamental question of what is causing these illnesses. But the whys and the how — Why now? Why only some children? Why these children? How is the damage being done? — may take considerably longer to resolve. “I think it could be a very difficult nut to crack,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy. Finding a probable culprit can sometimes happen fairly quickly when something new pops up in the infectious diseases sphere, said Thomas Clark, deputy director of the division of viral diseases at the Centers for Disease Control and Prevention. Clark was the CDC’s incident manager for the AFM investigation in 2018-2019. Such was the case when scientists started investigating AFM, which first pinged on the medical world’s radar in 2012, after California reported a few cases of unexplained paralysis among children. Suspicion soon focused on EV-D68, a member of the enterovirus family that is now generally assumed to be the primary cause of AFM. (Another enterovirus, A71, is also thought to trigger the condition in some cases.)  AFM cases occur in very low numbers year round, but have been seen to cluster in every-other-year surges that occurred in 2014, 2016, and 2018. Where in an odd year there may be two or three dozen cases, there were 153 cases and 239 cases in 2016 and 2018, respectively. (Like many other viral illnesses, AFM has been driven to very low levels during the first two years of the Covid-19 pandemic, with an expected spike of cases failing to materialize in 2020.)

Settling on a suspect seems to have happened even faster with the unexplained cases of pediatric hepatitis, with many researchers hypothesizing that an adenovirus might be to blame. In the cases, previously healthy children, many under the age of 5, develop severe liver inflammation. Some — about 14% of the cases reported so far in the United States and 10% of those reported in the U.K. — have required liver transplants and a few children have died. The first observed cases occurred last October in Alabama, where five of the state’s eventual nine cases tested positive for an adenovirus. Like enteroviruses, the adenovirus family is large, encompassing about 50 types that infect people. Most cause cold-like illnesses, but a couple are known to infect the gastrointestinal tract. The one spotted by the Alabama physicians was one of the latter, type 41. A substantial portion — though not all — of the roughly 450 cases reported worldwide at this point have tested positive for adenovirus, and in the U.K., more in-depth testing has revealed at least some of those were adenovirus type 41.  It remains unclear if this is an incidental finding unrelated to the hepatitis, or if the virus is causing the condition. Investigators are also exploring the question of whether there is some other contributing factor, such as the possibility that two years of pandemic-induced masking and social distancing may have left children’s immune systems inexperienced in fighting off an infection like this one. Another theory is that current or prior Covid-19 infection is amplifying the illness induced by adenovirus infection. As of yet, testing of liver biopsies taken from a number of the suspected cases and from failed livers that were removed from the children who needed transplants has not shown signs of adenovirus infection. Fingering a culprit, though, is only the first step in getting to the bottom of why a small but unusual number of very young children are ending up in hospital with their livers under attack. “It is often true, I guess, that the most commonly implicated virus or the one that’s putatively identified ends up explaining the illness,” said the CDC’s Clark. “But the mechanisms and the why are the challenge to figure out.” Scientists are still working to explain why EV-D68 causes paralysis as well as why it only does so in a tiny fraction of the children it infects.....

Researchers suspect an adenovirus may be involved, but are still searching for the cause of illness.   Puzzled scientists are searching for the cause of a strange and alarming outbreak of severe hepatitis in young children, with 74 cases documented in the United Kingdom and three in Spain. Clinicians in Denmark and the Netherlands are also reporting similar cases. And in the United States, the Centers for Disease Control and Prevention (CDC) said late yesterday it is investigating nine cases in Alabama. Viruses can cause hepatitis, an inflammation of the liver, but otherwise-healthy children rarely become seriously ill. As of 12 April, none of the U.K. or Spanish children have died, but some are very sick: All have been admitted to hospitals and seven required liver transplants, six of them in the United Kingdom, according to a World Health Organization (WHO) statement issued today. Two of the nine affected children in Alabama have required liver transplants, the state’s Department of Public Health announced this afternoon. The leading theory is that an adenovirus, a family of viruses that more typically cause colds, is the culprit—up to half of the sickened children in the United Kingdom tested positive for such a virus, as did all the children in Alabama. But so far, the evidence is too thin to resolve the mystery, researchers and physicians say. “This is a severe phenomenon,” says Deirdre Kelly, a pediatric hepatologist at Birmingham Children’s Hospital in the United Kingdom. “These [were] perfectly healthy children … up to a week ago.” Not all the news is bad, however. “Most of [the children] recover on their own,” Kelly notes. “This should be taken seriously,” WHO’s Regional Office for Europe wrote in an emailed statement.

“The increase is unexpected and the usual causes have been excluded.” Scottish investigators first identified the outbreak on 31 March, when they alerted Public Health Scotland to a cluster of 3- to 5-year-olds admitted to the Royal Hospital for Children in Glasgow in the first 3 weeks of March. Each was diagnosed with severe hepatitis of unknown cause. Typically, Scotland sees fewer than four such cases annually, the investigators wrote in a paper published yesterday. But there have been 13 cases in Scottish children as of 12 April, all but one in March and April.  Kelly, who works at one of England’s three centers for pediatric liver disease and transplantation, says that since the start of this year, her unit has seen 40 cases of childhood hepatitis of uncertain cause. Over the same January to April period in 2018, her unit saw only seven such children. Most of the U.K. children are 2 to 5 years old, according to a statement issued on 8 April by the UK Health Security Agency. The European Centre for Disease Prevention and Control issued a public alert on 12 April about the U.K. outbreak, noting that vomiting and jaundice—yellowing of the skin and the whites of the eyes—are common symptoms. Early hypotheses about what might be making the children sick included a toxic exposure from food, drinks, or toys, but suspicion now centers on a virus. None of the U.K. or Spanish kids had the hepatitis A, B, C, or E viruses, typical infectious causes of the disease. But a handful of children tested positive for SARS-CoV-2 infection shortly before or upon hospital admission; none had received a COVID-19 vaccine. In addition, as many as half had adenovirus, a common virus passed by respiratory droplets and from touching infected people or virus on surfaces. It can cause vomiting, diarrhea, conjunctivitis, and cold symptoms but rarely causes hepatitis. “The leading hypotheses center around adenovirus—either a new variant with a distinct clinical syndrome or a routinely circulating variant that is more severely impacting younger children who are immunologically naïve,” the Scottish investigators wrote.

Isolation of the youngest children during the pandemic lockdown may have left them immunologically vulnerable because they haven’t been exposed to the multiplicity of viruses, including adenoviruses, that typically attend toddlerhood. “We are seeing a surge in typical childhood viral infections as children come out of lockdown, [as well as] a surge in adenovirus infections”—but can’t be sure that one is causing the other, says Will Irving, a clinical virologist at the University of Nottingham. Researchers continue to study other possibilities. For example, the immunological effects of a prior episode of COVID-19 might have left children more vulnerable to infection or the illness could be a long-term complication of COVID-19 itself. An unidentified toxin has also not been ruled out. All the cases might not have a single cause, cautions Jim McMenamin, an epidemiologist who heads the infection service of Public Health Scotland. “It’s awfully important that we ensure we are looking for everything, that we are not confining ourselves to saying this is simply one viral cause.”

In the United States, CDC is helping the Alabama Department of Public Health investigate nine cases of hepatitis in children ranging in age from 1 to 6 years old and who also tested positive for adenovirus. The cases have occurred since October 2021, Kristen Nordlund, a CDC spokesperson, wrote in the statement emailed to ScienceInsider last night.  “CDC is working with state health departments to see if there are additional U.S. cases, and what may be causing these cases,” she wrote. “Adenovirus may be the cause for these, but investigators are still learning more—including ruling out the more common causes of hepatitis.” Wes Stubblefield, a district medical officer with the Alabama Department of Public Health, said in an interview today that the most recent case in Alabama occurred in February, and that five of the nine children tested positive for adenovirus-41, a strain that commonly causes gastroenteritis.

Meanwhile, in Spain, the government of the Madrid region announced on 13 April that three regions—Madrid, Aragón, and Castilla-La Mancha—had each reported a case of severe hepatitis of unknown origin in young children. One child has received a liver transplant. Physicians at major pediatric liver centers in the Netherlands and Denmark told ScienceInsider yesterday they are seeing similar trends. “There are children that are very sick and have been referred for transplantation,” says Ruben de Kleine, a pediatric liver transplant surgeon at University Medical Center Groningen. “We have assessed a similar number of kids for transplantation within the first 4 months of 2022 [to what we] normally do in a whole year.” At Copenhagen University Hospital, too, “we have more cases with [acute liver failure] than we normally have,” says pediatric hepatologist Marianne Hørby Jørgensen. No children there have needed transplants. Hørby Jørgensen and de Kleine both stress that parents should not panic. To date, clinicians have identified small numbers of cases in their countries where, combined, more than 230,000 infants are born each year.

Spring Bank Pharmaceuticals is stopping work on an experimental treatment for hepatitis B virus after serious side effects, including one patient death, were reported in a mid-stage study. The Spring Bank (NASDAQ: SBPH) drug, inarigivir soproxil, was the company’s lead therapeutic candidate. No details were released about the side effects observed in the clinical trial. Hopkinton, MA-based Spring Bank said Wednesday that it will work with outside experts and clinical trial investigators to care for the patients in the Phase 2b study, and to better understand what happened. Going forward, the company plans to focus on its immuno-oncology and inflammation research. Spring Bank’s stock price slid more than 23 percent to $1.30 per share after the news was announced Wednesday morning.

Inarigivir was designed to selectively activate a protein in liver cells called retinoic acid-inducible gene 1. This approach was hoped to block replication of the hepatitis B virus and kick off the interferon signaling pathways that are part of the body’s antiviral defense. The company also hoped that this dual mechanism would make it attractive as part of a combination treatment with other hepatitis B therapies. Spring Bank had tested inarigivir in partnership with Gilead Sciences (NASDAQ: GILD). Separate Phase 2 studies evaluated a 200 mg dose of that drug in combination with Gilead’s tenofovir disoproxil fumarate (Viread) and tenofovir alafenamide (Vemlidy). Spring Bank says the patient death occurred in a Phase 2 study that tested a 400 mg dose of inarigivir by itself after patients stopped treatment with other antiviral therapies. With its lead hepatitis B drug now sidelined, Spring Bank will turn its attention to cancer and inflammatory drugs developed with its stimulator of interferon genes (STING) agonist platform. The most advanced of those drug candidates, SB 11285, is currently in a Phase 1a/1b study testing it in cancer. In a prepared statement, Spring Bank president and CEO Martin Driscoll said that he hopes to have enough data by the end of this year to support advancing that drug to Phase 2...