Virus World

A recent NIH-funded study shows potential for long-term HIV remission in children without medication, marking a significant advance in treatment. Announced at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, Colorado, a groundbreaking study funded by the National Institutes of Health has unveiled that four children born with HIV were able to live for more than a year without detectable levels of the virus after their HIV medication was paused. This finding from the P1115 study hints at the potential for achieving long-term remission in children born with HIV, a significant stride in the ongoing battle against the virus.

Early Intervention: A Ray of Hope

The P1115 study focused on the impact of early intensive antiretroviral therapy (ART) in infants infected with HIV before birth. HIV, a virus that attacks the immune system, can hide within the body, making it challenging to eradicate. However, these children's ability to live more than a year without medication and with no detectable virus brings new optimism to scientists and medical professionals. It suggests that early, aggressive treatment may limit HIV reservoirs, potentially enabling periods of remission in pediatric patients.

The Mississippi Baby: Pioneering Early Treatment

Inspired by the case of the "Mississippi Baby," who was born with HIV and received intensive ART hours after birth and was seemingly cured for a few years, researchers have been motivated to explore the possibility of long-term remission in children. Although the "Mississippi Baby" eventually tested positive for HIV again at age 4, the case provided invaluable insights into the potential benefits of early and aggressive treatment. The NIH has since invested in global research studies, like P1115, to further investigate these possibilities.

Implications for Future Treatment

While all children in the P1115 study eventually saw their HIV return, the period during which some of them had no detectable HIV without taking medication marks a significant discovery. According to Adeodata Kekitiinwa, MBChB, MMed, the study's investigator of record, this trial moves us closer to a paradigm shift in HIV treatment. It raises the possibility that antiretroviral therapy could be used effectively for a "season of life," rather than being a lifelong necessity. This potential shift could dramatically change the approach to treating children born with HIV, offering them a chance at a healthier life without the constant burden of medication. The study's findings not only fuel hope for achieving long-term remission among children born with HIV but also underscore the importance of continuous research and innovation in the field. As scientists work towards unlocking the secrets of HIV remission, these children's stories stand as beacons of possibility, pointing towards a future where HIV can be managed more effectively, and perhaps, eventually overcome.

In new research, scientists have linked increased CT scan exposure to an increased risk of blood cancer in younger people. A team of researchers at Barcelona Institute for Global Health found that childhood exposure to CT scan radiation is linked to an increased risk of blood cancer in the years that follow. The study is published today (9 November) in the scientific journal, Nature Medicine.  "We must keep studying how we can limit radiation exposure in those seeking diagnoses, as this could help prevent cases of blood cancer, potentially saving lives"

Background

Growing evidence suggests that adult COVID-19 patients are at an increased risk of stroke, which is attributed to various factors such as hypercoagulability, immune-mediated thrombosis, changes in the renin-angiotensin system, cardioembolism, and other COVID-19 mediated changes to the cardiac and nervous systems. The ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to use the angiotensin-converting enzyme-2 (ACE-2) receptors to enter host cells is also linked to neurotropism and the effect of the virus on multiple organ systems. However, there is a scarcity of information on whether children with COVID-19 are at a higher risk of stroke. While studies have found no increase in the risk of ischemic stroke in pediatric COVID-19 patients during the early pandemic, neurological complications, and some forms of vasculopathy have been observed in a quarter of the MIS-C patients. Furthermore, while thromboembolism and stroke have been considered rare complications of MIS-C, the causal relationships are not well understood.

About the study

In the present study, the researchers conducted retrospective analyses on two population-based cohorts of children under 18. The first cohort included children diagnosed with intracranial hemorrhage, cerebral infarction, ischemic stroke, or cerebrovascular accident between March 2020 and June 2021. The second comprised children hospitalized with stroke between March 2015 and February 2020 at the Primary Children's Hospital in Utah, United States. Data on demographic characteristics such as gender, age, socioeconomic status, insurance coverage, and race or ethnicity were obtained from electronic records. Additional information such as medical histories, COVID-19 polymerase chain reaction (PCR) test results, COVID-19 vaccination data, hospital, and intensive care unit admission dates and duration, the time elapsed between COVID-19 symptom onset and stroke, National Institute of Health Stroke Scale (NIHSS) upon presentation of stroke, stroke characteristics, treatment administered, and stroke outcomes were evaluated.

Results

The results reported 16 cases of pediatric ischemic strokes in patients between the ages of eight months and 17 years. The incidence of ischemic stroke was correlated with an increase in COVID-19 infections in children but was not associated with an increased occurrence of MIS-C. One-third of the patients who had a stroke had previous SARS-CoV-2 infections, had been diagnosed with MIS-C, were not vaccinated, or had antibodies against SARS-CoV-2 when they suffered the stroke. Since other viral infections during the time had decreased, COVID-19 is thought to be a trigger for stroke. Contrary to previous studies that reported increased focal cerebral arteriopathy associated with COVID-19, the present study found large-vessel occlusive stroke more prevalent in the pandemic and pre-pandemic cohorts. While three of the patients had been diagnosed with MIS-C at the stroke time, three other patients with mild or asymptomatic previous SARS-CoV-2 infections and no diagnosed MIS-C patients also suffered strokes. Only a quarter of the pandemic cohort patients were administered tissue plasminogen activator or a thrombectomy since the diagnosis of stroke in most patients in the pandemic, and pre-pandemic cohorts were delayed. Furthermore, acute SARS-CoV-2 infections were not found to be associated with stroke, suggesting that stroke could be associated with the hyperinflammatory state observed in COVID-19 patients in the two to six weeks after recovery. Additionally, the prothrombotic state and hypercoagulability that results from the activation of clotting cascades and endothelial damage due to the viral infection have also been implicated in the occurrence of strokes in pediatric patients. The study suggested that stroke could occur a month after the COVID-19 infection, possibly due to the hypercoagulability and prothrombotic state resulting from the weeks following SARS-CoV-2 infections. Furthermore, since the incidence of stroke in the pediatric population is rare, and the presentations of stroke symptoms in children are vague, it is often misdiagnosed or diagnosed late, delaying intervention.

Conclusions

To summarize, the study investigated the association between stroke, COVID-19 infections, and multisystem inflammatory syndrome in children using a retrospective analysis on two cohorts of pediatric stroke patients, one spanning the COVID-19 pandemic and one pre-pandemic. The results indicated that stroke is a delayed complication of previous SARS-CoV-2 infections but is not associated with acute infections or MIS-C. Furthermore, stroke is often diagnosed late in pediatric patients due to vague symptoms, delaying treatments and interventions.

Study published in Pediatric Neurology (Nov. 19, 2022):

https://doi.org/10.1016/j.pediatrneurol.2022.10.003

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 

Kid-size doses of Pfizer’s COVID-19 vaccine appear safe and nearly 91% effective at preventing symptomatic infections in 5- to 11-year-olds, according to study details released Friday as the U.S. considers opening vaccinations to that age group. The shots could begin in early November, with the first children in line fully protected by Christmas, if regulators give the go-ahead. That would represent a major expansion of the nation’s vaccine drive, encompassing roughly 28 million elementary school-age youngsters. Details of Pfizer’s study were posted online. The Food and Drug Administration was expected to post its own review of the company’s safety and effectiveness data later in the day. Advisers to the FDA will publicly debate the evidence next week. If the agency itself authorizes the shots, the Centers for Disease Control and Prevention will make the final decision on who should receive them. Full-strength Pfizer shots already are authorized for anyone 12 or older, but pediatricians and many parents are anxiously awaiting protection for younger children to stem rising infections and record hospitalizations among them from the extra-contagious delta variant and to help keep kids in school. The Biden administration has purchased enough kid-size doses — in special orange-capped vials to distinguish them from adult vaccine — for the nation’s 5- to 11-year-olds. If the vaccine is cleared, millions of doses will be promptly shipped around the country, along with kid-size needles. More than 25,000 pediatricians and primary care providers already have signed up to get the shots into little arms.

The Pfizer study tracked 2,268 children in the 5-to-11 group who got two shots three weeks apart of either a placebo or the low-dose vaccine. Each dose was one-third the amount given to teens and adults. Researchers calculated the low-dose vaccine was nearly 91% effective, based on 16 COVID-19 cases in youngsters given dummy shots versus three cases among vaccinated children. There were no severe illnesses reported among any of the youngsters, but the vaccinated ones had much milder symptoms than their unvaccinated counterparts. Most of the study data was collected in the U.S. during August and September, when the delta variant had become the dominant COVID-19 strain. In addition, young children given the low-dose shots developed coronavirus-fighting antibody levels just as strong as teens and young adults who got regular-strength vaccinations. In another piece of encouraging news, the CDC reported earlier this week that even as the delta variant surged over the summer, Pfizer vaccinations were 93% effective at preventing hospitalizations among 12- to 18-year-olds. Pfizer’s study of younger children found the low-dose shots proved safe, with similar or fewer temporary side effects such as sore arms, fever or achiness that teens experience. The study isn’t large enough to detect any extremely rare side effects, such as the heart inflammation that occasionally occurs after the second dose, mostly in young men. While children run a lower risk of severe illness or death than older people, COVID-19 has killed more than 630 Americans 18 and under, according to the CDC. Nearly 6.2 million children have been infected with the coronavirus, more than 1.1 million in the last six weeks as the delta variant surged, the American Academy of Pediatrics says. Moderna also is studying its COVID-19 shots in elementary school-age youngsters. Pfizer and Moderna are studying even younger children as well, down to 6-month-olds. Results are expected later in the year.

Results of the Study available in the FDA site:

https://www.fda.gov/media/153409/download 

The Zika virus could shrink tumors in a childhood cancer that makes up one in seven cancer deaths, a study from researchers at Nemours Children's Health in Florida suggests. Scientists are hoping to turn a deadly African virus into a therapy for a deadly childhood cancer. The Zika virus is a mosquito-borne infection that reduces levels of a protein which forms in excess levels in patients with certain cancers. A team of researchers in Florida has shown that, in mice at least, it can can wipe out  tumors known as neuroblastomas, which make up one in seven childhood cancer deaths and form in the nerve cells as children develop.

This fall, parents and pediatricians will have a new option to protect babies from a lung-attacking virus that is the leading cause of hospitalization in infants under a year old in the United States every year. The US Food and Drug Administration approved nirsevimab to protect newborns from respiratory syncytial virus, or RSV, on Monday. Nirsevimab, which will be sold under the brand name Beyfortus, is not a vaccine. Vaccines prompt the body to make antibodies to defend against pathogens. Instead, nirsevimab is a form of passive immunity. It’s a ready-made antibody that can bind to the virus and block it from infecting healthy cells. The immune system doesn’t have to make anything. It’s given as a single injection to an infant before RSV season, which usually peaks in the fall and winter months. The FDA approval also allows a second injection for infants up to 24 months of age who remain vulnerable through their second RSV season. “RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” said Dr. John Farley, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families and the health care system,” Farley said in a news release.

The group of experts who advise the US Centers for Disease Control and Prevention on its vaccine recommendations will next weigh in. The Advisory Committee on Immunization Practices, or ACIP, has issued draft recommendations and clinical considerations for nirsevimab’s use, but the group is expected to formalize those with a vote at its next meeting. After the CDC signs off, nirsevimab will become the second antibody available to protect young children against RSV. The other, called palivizumab or Synagis, has been used only to protect the most vulnerable babies: those born prematurely who are younger than 6 months. It lasts only a short time in the body, so doctors give it once a month, starting just before RSV season, until the risk has passed. It has been a help, but it’s only partially effective. It keeps vulnerable babies out of the hospital about 50% of the time. The antibody in nirsevimab has been stabilized so it lasts longer in the body — four to six months — and it seems to be more potent. It’s approved for use in all infants, even healthy infants born full-term. “This virus can affect all babies, so not just babies with certain health conditions but even healthy babies. So as a pediatrician, I’m very excited about the idea of having an immunization to prevent serious illness from RSV,” said Dr. Rachel Dawkins, medical director of the pediatric and adolescent medical clinics at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida.

Nirsevimab may not be the only option for preventing the infection this fall. The FDA is weighing whether to approve Pfizer’s vaccine for pregnant women that would also protect babies. In that case, the mom makes the antibodies, which cross the placenta to safeguard the fetus and are expected to last through an infant’s first few months of life. That vaccine would protect babies from the moment they are born, a benefit if the infection shows up out of season. Vaccines also prompt the mom’s body to make more than one kind of antibody, which would provide broader-spectrum protection. “I would say any strategy that we can use to help prevent RSV and infants is a great one,” Dawkins said. “So if moms are able to be vaccinated to hopefully protect their newborns, that’s great. Or if the babies are able to be given this antibody, also great, and I think there is some evidence that they work together.” In a presentation at their June meeting, the ACIP committee thinking through the potential use of the antibody said that it may make sense to give both types of protection in certain circumstances but that most healthy babies will need only one or the other. “Obviously, they need to consider how both of those preventive products for RSV infection will coexist,“ said Dr. Michael Greenberg, a pediatrician who is North American medical head of vaccines for Sanofi, the company that is marketing the antibody. “Nirsevimab is really the first that’s going to be able to offer the protection for all infants, sort of irrespective of when they’re born, because there’s the flexibility in the timing of the administration,” Greenberg told CNN. In the clinical trials that led to its approval, nirsevimab was about 70% effective at cutting the risk that a baby would need a doctor’s visit for RSV, and it was about 78% effective at preventing hospitalizations due to RSV compared with a placebo, according to an FDA analysis.

That means nirsevimab would prevent 1 RSV hospitalization for every 56 infants treated. So even though antibodies like this tend one to be pricey, doctors say that if it keeps babies out of the hospital, that will probably make it worth the cost. In studies, the therapy was generally safe and well-tolerated. A few infants — less than 1% — had skin reactions after their shots, but these went away with treatment. “We run this gauntlet every year — RSV season,” said Dr. Frank Esper, a pediatric infectious disease specialist at the Cleveland Clinic in Ohio. “We see a lot of these infants. They come in; they can’t breathe. That’s the problem. That’s what RSV does. It causes so much swelling and secretions in their breathing tubes, called the bronchioles, that they just can’t get enough oxygen.” RSV is the leading cause of hospitalization in infants up to 1 year old. Most babies with RSV need extra oxygen; doctors help support their breathing for two or three days, and then they get better. “Babies are small, and because babies are small, their airways are small, and so it takes just a little amount of inflammation to clog them all up, and that’s what RSV does,” Esper said. In rare cases, RSV can be deadly. According to the CDC, it kills between 100 and 300 infants each year. And it’s not just a threat to young children; RSV sickens and kills elderly adults each year, too. Vaccines geared toward seniors have just been approved. “So anything that we have that can fight that problem, then the better,” Esper said. Eight years ago, Cheryl Meany enrolled in an early study testing nirsevimab when she was pregnant with twin girls. The babies were born a little early, at 33 weeks, as twins often are, and their early arrival meant they were more vulnerable to infections. She said she felt cautious about enrolling in the study, but her doctor told her he would absolutely do it if they were his own kids. Her newborns were given injections shortly after birth, but she didn’t find out that they’d gotten the active antibodies until almost five years later. “I kind of had an inkling,” Meany said. “They were born in December, and we live in upstate New York, where cold and flu season is rampant around here. And I’m a teacher, and my husband at the time was working in the hospital as a respiratory therapist, our older daughter was in school, so … just germs everywhere.” She says her twins were in day care at the time, “and they never got sick.” “This was just the best start for them and being preemies and all of the things that could have happened,” Meany said. “I really do believe that this kept them healthy in order to grow and thrive.”

FDA press release (July 17, 2023):

https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-prevent-rsv-babies-and-toddlers 

This report describes the investigation into the first young infant with confirmed monkeypox in Florida. In August 2022, the Florida  Department of Health (FDOH) was notified of a suspected case of monkeypox in an infant aged <2 months who was admitted to a Florida hospital with a rash and cellulitis. This case report highlights findings from the related epidemiologic investigation and describes the public health actions taken. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* This is the youngest patient with confirmed monkeypox infection in Florida to date. The infant was initially evaluated in an emergency department (ED) for a raised erythematous rash on the arms, legs, and trunk which had been present for 5 days. A rash swab was collected for bacterial culture and yielded a negative test result. Varicella, herpes simplex virus, and HIV testing were also negative. The patient returned to the ED 2 days later, at which time the rash had progressed to include numerous, diffusely scattered papulovesicular lesions over the body, many with central umbilication. The infant was admitted to the hospital with a diagnosis of molluscum contagiosum and started on intravenous antibiotics for secondary bacterial cellulitis associated with having scratched a lesion on the arm. The lesions subsequently spread to the back, soles of feet, face, and eyelid and became pustular over the first few days of admission. Swabs from forehead and back lesions tested positive for Orthopoxvirus DNA and Clade II Monkeypox virus DNA by polymerase chain reaction 10 days after rash onset (Figure). Results were confirmed by the Florida public health laboratory and CDC.† FDOH and hospital clinicians consulted with CDC regarding treatment options.

The infant was treated with oral tecovirimat and Vaccinia Immune Globulin Intravenous (1). Prophylactic trifluridine§ drops were administered to prevent ophthalmic complications from the eyelid lesion. The infant remained afebrile and stable throughout the course of illness, tolerated the treatments well, and fully recovered. The infant had no history of travel, no history of acute infections in the 3 weeks preceding rash onset, no known immunocompromising conditions, did not attend a child care facility, and had no caregivers outside the home. Within the home, the infant was cared for by four caregivers. Caregiver A acted as the main guardian throughout the infant’s hospital stay and had prolonged exposure with skin-to-skin contact. Caregiver B reported activities that placed him at high risk for monkeypox exposure during the 2 months preceding the infant’s illness (2). Caregiver B reported hematuria and fever, followed by a rash within the 3 weeks before the infant’s symptom onset. One day before the infant became symptomatic, caregiver B moved to another state and sought medical care for his symptoms. He received a positive Orthopoxvirus DNA test result 2 days after the infant’s positive test result, after which, he was lost to follow-up. The infant had daily close contact with caregiver B in the home for 6 weeks before rash onset. Possible routes of transmission included shared bed linens and skin-to-skin contact through holding and daily care activities.

Background: There has been a rapid surge of SARS-CoV-2 Omicron hospitalisations globally. However, the intrinsic severity of Omicron BA.2 is unknown, which could be determined by studying Hong Kong (HK) children who were both uninfected and unvaccinated before the Omicron wave.

Methods: This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes of the Omicron BA.2-dominant fifth wave (5 to 28 February 2022, n=1147), prior SARS-CoV-2 variants (1 January 2020 to 1 November 2021, n=737), and influenza and parainfluenza (1 January 2015 to 31 December 2019, n=32212 and n=16423, respectively) in children 0-11 years old. Outcomes included fatalities, paediatric intensive care unit (PICU) admissions and neurological and respiratory complications.

Findings: Four deaths (0.35%) occurred during the Omicron wave, resulting in a higher in-hospital case fatality rate than other SARS-CoV-2 variants (0%), influenza (0.05%) and parainfluenza (0.04%). PICU admission was higher for Omicron than other SARS-CoV-2 variants (OR=18.50, 95% CI 2.42-140.70, p=0.005) and influenza (OR=2.32, 95% CI 1.48-3.64, p<0.001). The proportion with neurological complications was 14.91% (171 out of 1,147) for Omicron, which was higher than influenza and parainfluenza (OR=1.75 95% CI 1.48-2.08 and OR=2.06 95% CI 1.74-2.46, p<0.001 for both, respectively). Croup occurred for Omicron more than other SARS-CoV-2 variants (OR=11.47, 95% CI 2.77-47.46 p = 0.001) and influenza (OR= 2.08, 95% CI 1.58-2.74 p<0.001) but not parainfluenza.

Interpretation: The intrinsic severity of Omicron BA.2 is not mild as evident by the fatality and severe complications of the uninfected and unvaccinated children.

Preprint available  (March 21, 2022) The Lancet:

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4063036 

Arkansas health officials reported COVID-19 case data during IDWeek that demonstrate the severe toll the delta variant has had on the state’s children.During a July peak, although the number of pediatric COVID-19 cases was lower than the last peak in January, hospitalizations and other indications of severe disease increased significantly, according to Michael Cima, PhD, MPH,state epidemiologist for the Arkansas Department of Health, and colleagues.  Cima conducted the research with Infectious Diseases in Children Editorial Board Member José R. Romero, MD, the state’s secretary of health, and Donald E. Warden, MPH, another epidemiologist in the department. During a presentation, Cima noted that the delta variant became the dominant circulating SARS-CoV-2 virus in Arkansas in June and early July.  “Growing evidence suggests that the delta variant is not only far more infectious than the next most infectious variant of concern, but it's also potentially more virulent, so naturally the question has been asked, How does the delta variant impact the pediatric population? Is a more severe disease being observed?” Cima said.

The researchers examined pediatric records for the 3 months they called “key inflection points” for the COVID-19 pandemic in Arkansas: July 2020, January 2021 and July 2021. They reviewed rates of hospitalization and ICU use, use of mechanical ventilation and, “to a lesser extent,” multisystem inflammatory syndrome in children (MIS-C), Cima said. Data showed that pediatric COVID-19 cases numbered 3,268 in July 2020, 11,735 in January 2021 and 8,031 in July 2021. Despite nearly 32% fewer cases occurring in July 2021 compared with January, there were around 42% more hospitalizations (105 vs. 74), 69% more ICU admissions (18 vs. 11) and a 300% increase in the use of mechanical ventilation, Cima and colleagues reported. Cima said PICU bed availability reached single digits in the entire state. He also noted that the state observed fewer MIS-C cases over the summer but that it was possible that cases would increase because there is usually a delay between infection and the appearance of MIS-C symptoms.