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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.

sick boy in bed

Clinical features of COVID-19 versus influenza

sick boy in bed

In a cohort retrospective study comparing clinical features of COVID-19 and seasonal flu, researchers found surprisingly little difference in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups.

As the fall approaches, pediatric hospitals will start seeing children with seasonal influenza A and B. At the same time, COVID-19 will be co-circulating in communities with the flu and other respiratory viruses, making it more difficult to identify and prevent the novel coronavirus.

With little published data directly comparing the clinical features of children with COVID-19 to those with seasonal flu, researchers at Children’s National Hospital decided to conduct a retrospective cohort study of patients in the two groups. Their findings — published September 8 in JAMA Network Open — surprised them.

The study — detailed in the article “Comparison of Clinical Features of US Children With COVID-19 vs Seasonal Influenza A and B” — showed no statistically significant differences in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups.

The other unexpected finding was that more patients with COVID-19 than those with seasonal influenza reported fever, cough, diarrhea or vomiting, headache, body ache or chest pain at the time of diagnosis, says Xiaoyan Song, Ph.D., M.Sc., M.B., the study’s principal investigator.

“I didn’t see this coming when I was thinking about doing the study,” says Dr. Song, director of Infection Control and Epidemiology at Children’s National since 2007 and a professor of pediatrics at the George Washington University School of Medicine and Health Sciences. “It took several rounds of thinking and combing through the data to convince myself that this was the conclusion.”

Given that much remains unknown about COVID-19, the researchers’ discovery that children with the disease present with more symptoms at the time of diagnosis is a valuable one.

“It’s a good cue from a prevention and planning perspective,” says Dr. Song. “We always emphasize early recognition and early isolation with COVID. Having a clinical picture in mind will assist clinicians as they diagnose patients with symptoms of the coronavirus.”

The study included 315 children who were diagnosed with a laboratory-confirmed COVID-19 between March 25, 2020, and May 15, 2020, and 1,402 children who were diagnosed with a laboratory-confirmed seasonal influenza between Oct. 1, 2019, and June 6, 2020, at Children’s National. Asymptomatic patients who tested positive for COVID-19 during pre-admission or pre-procedural screening were excluded from the study.

Of the 315 patients who tested positive for COVID-19, 52% were male, with a median age of 8.4 years. Of these patients, 54 (17.1 %) were hospitalized, including 18 (5.7%) who were admitted to the intensive care unit (ICU) and 10 (3.2%) who received mechanical ventilator treatment.

Among the 1,402 patients who tested positive for influenza A or B, 52% were male, with a median age of 3.9 years, and 291 (21.2%) were hospitalized, including 143 for influenza A and 148 for influenza B. Ninety-eight patients (7.0%) were admitted to the ICU, and 27 (1.9%) received mechanical ventilator support.

The study showed a slight difference in the age of children hospitalized with COVID-19 compared to those hospitalized with seasonal influenza. Patients hospitalized with COVID-19 had a median age of 9.7 years vs. those hospitalized with seasonal influenza who had a median age of 4.2 years.

In both groups, fever was the most often reported symptom at the time of diagnosis followed by cough. A greater proportion of patients hospitalized with COVID-19 than those hospitalized with seasonal influenza reported fever (76% vs. 55%), cough (48% vs. 31%), diarrhea or vomiting (26% vs. 12%), headache (11% vs. 3%), body ache/myalgia (22% vs. 7%), and chest pain (11% vs. 3%).

More patients hospitalized with COVID-19 than those with seasonal influenza reported sore throat or congestion (22% vs. 20%) and shortness of breath (30% vs. 20%), but the differences were not statistically significant.

During the study period, the researchers noticed an abrupt decline of influenza cases at Children’s National after local schools closed in mid-March and stay-at-home orders were implemented about two weeks later to combat the community spread of COVID-19. Dr. Song says the impact of school closures on the spread of COVID-19 among children is the next area of study for her research team.

“We want to assess the quantitative impact of school closures so we can determine at what point the cost of closing schools and staying at home outweighs the benefit of reducing transmission of COVID-19 and burdens on the health care system,” she says.

Dr. Song urges members of the community “first and foremost to stay calm and be strong. We’re learning new and valuable things about this virus each day, which in turn improves care. The collision of the flu and COVID-19 this fall could mean an increase in pediatric hospitalizations. That’s why it’s important to get your flu shot, because it can help take at least one respiratory virus out of circulation.”

Other researchers who contributed to this study include Meghan Delaney, D.O.; Rahul K. Shah, M.D.; Joseph M. Campos, Ph.D.; David L. Wessel, M.D.; and Roberta L. DeBiasi, M.D.

young boy and teddy bear in face masks

Study provides important insight into spread of COVID-19 in children

young boy and teddy bear in face masks

New research suggests that children can shed SARS-CoV-2, the virus that causes COVID-19, even if they never develop symptoms or for long after symptoms have cleared. But many questions remain about the significance of the pediatric population as vectors for this sometimes deadly disease.

New research suggests that children can shed SARS-CoV-2, the virus that causes COVID-19, even if they never develop symptoms or for long after symptoms have cleared. But many questions remain about the significance of the pediatric population as vectors for this sometimes deadly disease, according to an invited commentary by Children’s National Hospital doctors that accompanies this new study published online Aug. 28, 2020 in JAMA Pediatrics. The commissioned editorial, written by Roberta L. DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases, and Meghan Delaney, D.O., M.P.H., chief of the Division of Pathology and Lab Medicine, provides important insight on the role children might play in the spread of COVID-19 as communities continue to develop public health strategies to reign in this disease.

The study that sparked this commentary focused on 91 pediatric patients followed at 22 hospitals throughout South Korea. “Unlike in the American health system, those who test positive for COVID-19 in South Korea stay at the hospital until they clear their infections even if they aren’t symptomatic,” explains Dr. DeBiasi.

The patients here were identified for testing through contact tracing or developing symptoms. About 22% never developed symptoms, 20% were initially asymptomatic but developed symptoms later, and 58% were symptomatic at their initial test. Over the course of the study, the hospitals where these children stayed continued to test them every three days on average, providing a picture of how long viral shedding continues over time.

The study’s findings show that the duration of symptoms varied widely, from three days to nearly three weeks. There was also a significant spread in how long children continued to shed virus and could be potentially infectious. While the virus was detectable for an average of about two-and-a-half weeks in the entire group, a significant portion of the children — about a fifth of the asymptomatic patients and about half of the symptomatic ones — were still shedding virus at the three week mark.

Drs. DeBiasi and Delaney write in their commentary that the study makes several important points that add to the knowledge base about COVID-19 in children. One of these is the large number of asymptomatic patients — about a fifth of the group followed in this study. Another is that children, a group widely thought to develop mostly mild disease that quickly passes, can retain symptoms for weeks. A third and important point, they say, is the duration of viral shedding. Even asymptomatic children continued to shed virus for a long time after initial testing, making them potential key vectors.

However, the commentary authors say, despite these important findings, the study raises several questions. One concerns the link between testing and transmission. A qualitative “positive” or “negative” on testing platforms may not necessarily reflect infectivity, with some positives reflecting bits of genetic material that may not be able to make someone sick or negatives reflecting low levels of virus that may still be infectious.

Testing reliability may be further limited by the testers themselves, with sampling along different portions of the respiratory tract or even by different staff members leading to different laboratory results. It’s also unknown whether asymptomatic individuals are shedding different quantities of virus than those with symptoms, a drawback of the qualitative testing performed by most labs. Further, testing only for active virus instead of antibodies ignores the vast number of individuals who may have had and cleared an asymptomatic or mild infection, an important factor for understanding herd immunity.

Lastly, Drs. DeBiasi and Delaney point out, the study only tested for viral shedding from the respiratory tract even though multiple studies have detected the virus in other bodily fluids, including stool. It’s unknown what role these other sources might play in the spread of this disease.

Drs. DeBiasi and Delaney note that each of these findings and additional questions could affect public health efforts continually being developed and refined to bring COVID-19 under control in the U.S. and around the world. Children’s National has added their own research to these efforts, with ongoing studies to assess how SARS-CoV-2 infections proceed in children, including how antibodies develop both at the individual and population level.

“Each of these pieces of information that we, our collaborators and other scientists around the world are working to gather,” says Dr. DeBiasi, “is critical for developing policies that will slow the rate of viral transmission in our community.”

coronavirus

Higher COVID-19 rates seen in minority socioeconomically disadvantaged children

coronavirus

Minority and socioeconomically disadvantaged children have significantly higher rates of COVID-19 infection, a new study led by Children’s National Hospital researchers shows.

Minority and socioeconomically disadvantaged children have significantly higher rates of COVID-19 infection, a new study led by Children’s National Hospital researchers shows. These findings, reported online August 5 in Pediatrics, parallel similar health disparities for the novel coronavirus that have been found in adults, the authors state.

COVID-19, an infection caused by the novel coronavirus SARS-CoV-2 that emerged in late 2019, has infected more than 4.5 million Americans, including tens of thousands of children. Early in the pandemic, studies highlighted significant disparities in the rates of infection in the U.S., with minorities and socioeconomically disadvantaged adults bearing much higher burdens of infection. However, says Monika Goyal, M.D., M.S.C.E, a pediatric emergency medicine specialist and associate division chief in the Division of Emergency Medicine at Children’s National whose research focuses on health disparities, it’s been unclear whether these disproportionate rates of infection also extend to youth.

To investigate this question, she and her colleagues looked to data collected between March 21, 2020, and April 28, 2020, from a drive-through/walk-up COVID-19 testing site affiliated with Children’s National — one of the first exclusively pediatric testing sites for the virus in the U.S. To access this free testing site, funded by philanthropic support, patients between the ages of 0 and 22 years needed to meet specific criteria: mild symptoms and either known exposure, high-risk status, family member with high-risk status or required testing for work. Physicians referred patients through an online portal that collected basic demographic information, reported symptoms and the reason for referral.

When Dr. Goyal and her colleagues analyzed the data from the first 1,000 patients tested at this site, they found that infection rates differed dramatically among different racial and ethnic groups. While about 7% of non-Hispanic white children were positive for COVID-19, about 30% of non-Hispanic Black and 46% of Hispanic children were positive.

“You’re going from about one in 10 non-Hispanic white children to one in three non-Hispanic Black children and one in two Hispanic children. It’s striking,” says Dr. Goyal.

Using data from the American Families Survey, which uses five-year census estimates derived from home address to estimate median family income, the researchers separated the group of 1,000 patients into estimated family income quartiles. They found marked disparities in COVID-19 positivity rates by income levels: while those in the highest quartile had infection rates of about 9%, about 38% of those in the lowest quartile were infected.

There were additional disparities in exposure status, Dr. Goyal adds. Of the 10% of patients who reported known exposure to COVID-19, about 11% of these were non-Hispanic white. However, non-Hispanic Black children were triple this number.

Although these numbers show clear disparities in COVID-19 infection rates, the authors are now trying to understand why these disparities occur and how they can be mitigated.

“Some possible reasons may be socioeconomic factors that increase exposure, differences in access to health care and resources, as well as structural racism,” says Dr. Goyal.

She adds that Children’s National is working to address those factors that might increase risk for COVID-19 infection and poor outcomes by helping to identify unmet needs — such as food and/or housing insecurity — and steer patients toward resources when patients receive their test results.

“As clinicians and researchers at Children’s National, we pride ourselves on not only being a top-tier research institution that provides cutting-edge care to children, but by being a hospital that cares about the community we serve,” says Denice Cora-Bramble, M.D., M.B.A., chief medical officer of Ambulatory and Community Health Services at Children’s National and the research study’s senior author. “There’s still so much work to be done to achieve health equity for children.”

Other Children’s National researchers who contributed to this study include Joelle N. Simpson, M.D.; Meleah D. Boyle, M.P.H, Gia M. Badolato, M.P.H; Meghan Delaney, D.O,. M.P.H.; and Robert McCarter Jr., Sc.D.

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Study finds children can become seriously ill with COVID-19

coronavirus

Despite early reports suggesting COVID-19 does not seriously impact children, a new study shows that children who contract COVID-19 can become very ill.

In contrast to the prevailing view that the novel coronavirus known as COVID-19 does not seriously impact children, a new study finds that children who contract the virus can become very ill—many of them critically so, according to physician researchers at Children’s National Hospital. Their results, published in the Journal of Pediatrics and among the first reports from a U.S. institution caring for children and young adults, shows differences in the characteristics of children who recovered at home, were hospitalized, or who required life support measures. These findings highlight the spectrum of illness in children, and could help doctors and parents better predict which pediatric patients are more likely to become severely ill as a consequence of the virus.

In late 2019, researchers identified a new coronavirus, known as SARS-CoV-2, which causes COVID-19. As the disease spread around the world, the vast majority of reports suggested that elderly patients bear the vast majority of the disease burden and that children are at less risk for either infection or severe disease. However, study leader Roberta DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases at Children’s National, states that she and her colleagues began noticing an influx of children coming to the hospital for evaluation of a range of symptoms starting in mid-March 2020, who were tested and determined to be infected with COVID-19. One quarter of these children required hospitalization or life support.

“It was very apparent to us within the first several weeks of the epidemic that this was a very different situation than our colleagues on the West Coast of the US had described as their experience just weeks before,” DeBiasi says. “Right away, we knew that it was important for us to not only care for these sick children, but to examine the factors causing severe disease, and warn others who provide medical care to children.”

To better understand this phenomenon, she and her colleagues examined the medical records of symptomatic children and young adults who sought treatment at Children’s National for COVID-19 between March 15 and April 30, 2020. Each of these 177 children tested positive using a rapid assay to detect SARS-CoV-2 performed at the hospital. The researchers gathered data on each patient, including demographic details such as age and sex; their symptoms; whether they had any underlying medical conditions; and whether these patients were non-hospitalized, hospitalized, or required critical care.

The results of their analysis show that there was about an even split of male and female patients who tested positive for COVID-19 at Children’s National during this time period. About 25% of these patients required hospitalization. Of those hospitalized, about 75% weren’t considered critically ill and about 25% required life support measures. These included supplemental oxygen delivered by intubation and mechanical ventilation, BiPAP, or high-flow nasal cannula – all treatments that support breathing – as well as other support measures such as dialysis, blood pressure support and medications to treat infection as well as inflammation.

Although patients who were hospitalized spanned the entire age range, more than half of them were either under a year old or more than 15 years old. The children and young adults over 15 years of age, Dr. DeBiasi explains, were more likely to require critical care.

About 39% of all COVID-19 patients had underlying medical conditions, including asthma, which has been highlighted as a risk factor for worse outcomes with this infection. However, DeBiasi says, although underlying conditions were more common as a whole in hospitalized patients – present in about two thirds of hospitalized and 80% of critically ill – asthma didn’t increase the risk of hospitalization or critical illness. On the other hand, children with underlying neurological conditions, such as cerebral palsy, microcephaly, or global developmental delay, as well as those with underlying cardiac, hematologic, or oncologic conditions were significantly more likely to require hospitalization.

In addition, although early reports of COVID-19 suggested that fever and respiratory symptoms are hallmarks of this infection, Dr. DeBiasi and her colleagues found that fewer than half of patients had both concurrently. Those with mild, upper respiratory symptoms, such as runny nose, congestion, and cough were less likely to end up hospitalized than those with more severe respiratory symptoms, such as shortness of breath. The frequency of other symptoms including diarrhea, chest pain and loss of sense of smell or taste was similar among hospitalized and non-hospitalized patients.

Dr. DeBiasi notes that although other East Coast hospitals are anecdotally reporting similar upticks in pediatric COVID-19 patients who become seriously ill, it’s currently unclear what factors might account for differences from the less frequent and milder pediatric illness on the West Coast. Some factors might include a higher East Coast population density, differences between the genetic, racial and ethnic makeup of the two populations, or differences between the viral strains circulating in both regions (an Asian strain on the West Coast, and a European strain on the East Coast).

Regardless, she says, the good news is that the more researchers learn about this viral illness, the better prepared parents, medical personnel and hospitals will be to deal with this ongoing threat.

Other researchers from Children’s National who participated in this study include Xiaoyan Song, Ph.D., M.Sc.Meghan Delaney, D.O., M.P.H.Michael Bell, M.D. Karen Smith, M.D.Jay Pershad, M.D., Emily Ansusinha, Andrea Hahn, M.D., M.S., Rana Hamdy, M.D., M.P.H., MSCE, Nada Harik, M.D.Benjamin Hanisch, M.D.Barbara Jantausch, M.D.Adeline Koay, MBBS, MS.c., Robin Steinhorn, Kurt Newman, M.D. and David Wessel, M.D.