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Children have more COVID-19 antibodies than previously thought, study finds

coronavirus

Seroprevalence of antibodies to SARS-CoV-2 in healthy children and children with chronic diseases is higher than researchers previously believed, according to a new study published in The Pediatric Infectious Diseases Journal. The study, which included 385 children in the Washington metropolitan area, found a 9.46% SARS-CoV-2 seroprevalence among this group. Researchers from Children’s National Hospital also identified predictive factors such as specific symptoms, race and ethnicity, that are associated with the antibodies’ presence in the blood, also known as seropositivity.

The 9.46% seroprevalence in healthy children and children with chronic diseases is higher than previously reported. However, this rate remains below the theoretical herd immunity threshold, estimated between 50% and 67% for the general population in the absence of any interventions — like vaccination — and assuming possible lasting immunity.

“We believe our estimate is a close approximation of seroprevalence for the diverse pediatric population in our region,” said the study authors, including Burak Bahar, M.D., lead author and director of Laboratory Informatics at Children’s National.

Since most symptomatic individuals are adults and they have been the main focus for seroprevalence studies, there is still a lack of information about SARS-CoV-2 seroprevalence for pediatric patients and healthy kids. With this study, researchers wanted to shed light on the knowledge gap in COVID-19 pediatric research.

“Parents are key allies who can help scientists better understand the virus’ behavior in children,” said Dr. Bahar.

Until now, it was also unknown if children with chronic diseases had less evidence of antibodies due to underlying conditions, particularly illnesses that cause weakened immune systems. The study showed no notable difference in the association with seropositivity among chronic illness groups, including immunocompromised children.

“Our findings offer important information as all children, with chronic illness or not, could be considered for ‘back to school’ transitions, because they have the same levels of protection. This means they all can have access to social, emotional and behavioral development,” said the authors.

The researchers explored co-existing conditions, symptomatology and demographics as predictors of antibody presence. The analysis showed that children with chronic conditions like asthma, diabetes and cancer were not predictors. This means that these sick kids, when introduced to the virus, make antibodies at the same levels as kids without these diseases.

While most participants were asymptomatic, in those who tested positive for anti-SARS-CoV-2 antibodies, fever, headache and cough were the most common symptoms.

Among the demographics, Hispanic children had a higher seropositive rate than white children. However, median household income based on reported zip code and state of residency were not found to be associated with having antibodies or not.

To determine the impact of continued infections in the community, future studies are needed to identify possible changes in the seroprevalence over a more extended period and to assess seropositivity with vaccination implementation, as that may influence the current rate.

The study is a snapshot in time from July to October 2020. The sample size of 385 patients included both healthy children and those with chronic diseases (69.7%) ranging from 2 months to 22 years old. From the sample pool, 38 individuals were found to have antibodies against SARS-CoV-2. To assess demographic characteristics, symptoms and co-existing conditions associated with seropositivity the researchers used a survey.

A related SARS-CoV-2 antibody production study published on Sept. 3, 2020 in the Journal of Pediatrics, also led by Bahar et al., found that antibodies are detected 18 days after a positive COVID-19 test in children. The authors further noted that the virus and antibodies can co-exist in young patients, so even if seropositivity is detected, they may still transmit the virus.

antibodies attached to COVID

Study shows COVID-19 antibodies and virus can coexist

antibodies attached to COVID

Children’s National study shows that children can have COVID-19 antibodies and the virus in their system simultaneously.

With many questions remaining around how children spread COVID-19, Children’s National Hospital researchers set out to improve the understanding of how long it takes pediatric patients with the virus to clear it from their systems, and at what point they start to make antibodies that work against the coronavirus. The study, published Sept. 3 in the Journal of Pediatrics, finds that the virus and antibodies can coexist in young patients.

“With most viruses, when you start to detect antibodies, you won’t detect the virus anymore. But with COVID-19, we’re seeing both,” says Burak Bahar, M.D., lead author of the study and director of Laboratory Informatics at Children’s National. “This means children still have the potential to transmit the virus even if antibodies are detected.”

She adds that the next phase of research will be to test if the virus that is present alongside the antibodies can be transmitted to other people. It also remains unknown if antibodies correlate with immunity, and how long antibodies and potential protection from reinfection last.

The study also assessed the timing of viral clearance and immunologic response. It found the median time from viral positivity to negativity, when the virus can no longer be detected, was 25 days. The median time to seropositivity, or the presence of antibodies in the blood, was 18 days, while the median time to reach adequate levels of neutralizing antibodies was 36 days. Neutralizing antibodies are important in potentially protecting a person from re-infection of the same virus.

This study used a retrospective analysis of 6,369 children tested for SARS-CoV-2, the virus that causes COVID-19, and 215 patients who underwent antibody testing at Children’s National between March 13, 2020, and June 21, 2020. Out of the 215 patients, 33 had co-testing for both the virus and antibodies during their disease course. Nine of the 33 showed presence of antibodies in their blood while also later testing positive for the virus.

Also of note, researchers found patients 6 through 15 years old took a longer time to clear the virus (median of 32 days) compared to patients 16 through 22 years old (median of 18 days). Females in the 6-15 age group also took longer to clear the virus than males (median of 44 days for females compared to median of 25.5 days for males).

Although there is emerging data regarding this timing in adults with COVID-19, there is far less data when it comes to the pediatric population. The findings being gathered by Children’s National researchers and scientists around the world are critical to helping understand the unique impact on children and their role in viral transmission.

“The takeaway here is that we can’t let our guard down just because a child has antibodies or is no longer showing symptoms,” says Dr. Bahar. “The continued role of good hygiene and social distancing remains critical.”

Other researchers who contributed to this study include Cyril Jacquot, M.D.; Delores Y Mo,M.D.; Roberta L DeBiasi, M.D.; Joseph Campos, Ph.D.; and Meghan Delaney, D.O.

ID-KD vaccine induced T-cell cytotoxicity

Fighting lethal cancer with a one-two punch

The immune system is the ultimate yin and yang, explains Anthony D. Sandler, M.D., senior vice president and surgeon-in-chief of the Joseph E. Robert Jr. Center for Surgical Care at Children’s National in Washington, D.C. With an ineffective immune system, infections such as the flu or diarrheal illness can run unchecked, causing devastating destruction. But on the other hand, excess immune activity leads to autoimmune diseases, such as lupus or multiple sclerosis. Thus, the immune system has “checks and balances” to stay controlled.

Cancer takes advantage of “the checks and balances,” harnessing the natural brakes that the immune system puts in place to avoid overactivity. As the cancer advances, molecular signals from tumor cells themselves turn on these natural checkpoints, allowing cancers to evade immune attack.

Several years ago, a breakthrough in pharmaceutical science led to a new class of drugs called checkpoint inhibitors. These medicines take those proverbial brakes off the immune system, allowing it to vigorously attack malignancies. However, Dr. Sandler says, these drugs have not worked uniformly and in some cancers, they barely work at all against the cancer.

One of these non-responders is high risk neuroblastoma, a common solid tumor found outside the skull in children. About 800 U.S. children are diagnosed with this cancer every year. And kids who have the high-risk form of neuroblastoma have poor prognoses, regardless of which treatments doctors use.

However, new research could lead to promising ways to fight high-risk neuroblastoma by enabling the immune system to recognize these tumors and spark an immune response. Dr. Sandler and colleagues recently reported on these results in the Jan. 29, 2018, PLOS Medicine using an experimental model of the disease.

The researchers created this model by injecting the preclinical models with cancer cells from an experimental version of neuroblastoma. The researchers then waited several days for the tumors to grow. Samples of these tumors showed that they expressed a protein on their cell surfaces known as PD-L1, a protein that is also expressed in many other types of human cancers to evade immune system detection.

To thwart this protective feature, the researchers made a cancer vaccine by removing cells from the experimental model’s tumors and selectively turning off a gene known as Id2. Then, they irradiated them, a treatment that made these cells visible to the immune system but blocked the cells from dividing to avoid new tumors from developing.

They delivered these cells back to the experimental models, along with two different checkpoint inhibitor drugs – antibodies for proteins known as CLTA-4 and PD-L1 – over the course of three treatments, delivered every three days. Although most checkpoint inhibitors are administered over months to years, this treatment was short-term for the experimental models, Dr. Sandler explains. The preclinical models were completely finished with cancer treatment after just three doses.

Over the next few weeks, the researchers witnessed an astounding turnaround: While experimental models that hadn’t received any treatment uniformly died within 20 days, those that received the combined vaccine and checkpoint inhibitors were all cured of their disease. Furthermore, when the researchers challenged these preclinical models with new cancer cells six months later, no new tumors developed. In essence, Dr. Sandler says, the preclinical models had become immune to neuroblastoma.

Further studies on human patient tumors suggest that this could prove to be a promising treatment for children with high-risk neuroblastoma. The patient samples examined show that while tumors with a low risk profile are typically infiltrated with numerous immune cells, tumors that are high-risk are generally barren of immune cells. That means they’re unlikely to respond to checkpoint inhibiting drugs alone, which require a significant immune presence in the tumor microenvironment. However, Dr. Sandler says, activating an immune response with a custom-made vaccine from tumor cells could spur the immune response necessary to make these stubborn cancers respond to checkpoint inhibitors.

Dr. Sandler cautions that the exact vaccine treatment used in the study won’t be feasible for people. The protocol to make the tumor cells immunogenic is cumbersome and may not be applicable to gene targeting in human patients. However, he and his team are currently working on developing more feasible methods for crafting cancer vaccines for kids. They also have discovered a new immune checkpoint molecule that could make this approach even more effective.

“By letting immune cells do all the work we may eventually be able to provide hope for patients where there was little before,” Dr. Sandler says.

In addition to Dr. Sandler, study co-authors include Priya Srinivasan, Xiaofang Wu, Mousumi Basu and Christopher Rossi, all of the Joseph E. Robert Jr. Center for Surgical Care and The Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI), at Children’s National in Washington, D.C.

Financial support for research described in this post was provided by the EVAN Foundation, the Catherine Blair foundation, the Michael Sandler Research Fund and SZI.

ID-KD vaccine induced T-cell cytotoxicity

Mechanism of Id2kd Neuro2a vaccination combined with α-CTLA-4 and α-PD-L1 immunotherapy in a neuroblastoma model. During a vaccine priming phase, CTLA-4 blockade enhances activation and proliferation of T-cells that express programmed cell death 1 (PD1) and migrate to the tumor. Programmed cell death-ligand 1 (PD-L1) is up-regulated on the tumor cells, inducing adaptive resistance. Blocking PD-L1 allows for enhanced cytotoxic effector function of the CD8+ tumor-infiltrating lymphocytes. Artist: Olivia Abbate