Campos Archives

Novel SARS-CoV-2 spike variant found in a newborn in Washington, D.C.

February 24, 2021

coronavirus molecules with DNA

Researchers at Children’s National Hospital found a new SARS-CoV-2 spike variant in a neonatal patient, according to a study that genetically sequenced the virus in 27 pediatric patients. The newborn presented with a viral load of 50,000 times more particles than the average patient, which led to identifying the N679S spike protein variant — the earliest known sample of this coronavirus lineage in the U.S. mid-Atlantic region.

While the paper is posted to the preprint server medRxiv and has not been peer-reviewed, it represents an early step towards establishing better surveillance of the COVID-19 pandemic. The new variant helps understand the process of viral adaptation, potentially informing treatment development and vaccine design for any viral variants in the future.

All genomes change and evolve. Additional viral variants are expected to emerge as more patients are infected. The data analysis recognized eight other cases in Washington, D.C., with the N679S variant, pointing toward a European origin due to the genetic similarity between of SARS-CoV-2 strains in the U.S. and United Kingdom.

“We need to sequence more cases to identify variants and stay ahead of the virus,” said Drew Michael, Ph.D., molecular geneticist at Children’s National and senior author of the study. “The United States sequences a tiny fraction of all cases, and because we are not sequencing enough, we are not aware of the variants in SARS-CoV-2 that may be spreading in our community.”

“Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak,” was published on the preprint server medRxiv. Additional authors include Jonathan LoTempio, Erik Billings, Kyah Draper, Christal Ralph, Mahdi Moshgriz, Nhat Duong, Jennifer Dien Bard, Xiaowu Gai, David Wessel, M.D., Roberta L. DeBiasi, M.D., M.S., Joseph M. Campos, Ph.D., Eric Vilain, M.D., Ph.D. and Meghan Delaney, D.O., M.P.H.

You can read the full preprint on medRxiv.

Study shows COVID-19 antibodies and virus can coexist

October 27, 2020

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.

Clinical features of COVID-19 versus influenza

September 24, 2020

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.

Case report highlights importance of antibiotic stewardship

August 10, 2020

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well.

A recent meningitis case treated at Children’s National Hospital raises serious concerns about a rise in antibiotic resistance in the common bacterium that caused it, researchers from the hospital write in a case report. Their findings, published online August 3 in the Journal of the Pediatric Infectious Disease Society, could change laboratory and clinical practice across the U.S. and potentially around the globe.

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well, say case report authors Gillian Taormina, D.O., a third year fellow in Pediatric Infectious Diseases at Children’s National, who was on service for this recent case, and Joseph Campos, Ph.D., D(ABMM), FAAM, director of the Microbiology Laboratory and the Infectious Diseases Molecular Diagnostics Laboratory at Children’s National. As standard clinical practice in the U.S., they explain, patients who are thought to have this infection are typically treated first with the broad spectrum antibiotic ceftriaxone while they wait for a microbiology lab to identify the causative organism from blood or cerebrospinal fluid samples. Once the organism is identified as N. meningitidis, patients are typically treated with penicillin or ampicillin, antibiotics with a narrower spectrum of activity that’s less likely to lead to ceftriaxone resistance. Family members and other close contacts are often prophylactically treated with an antibiotic called ciprofloxacin.

Because N. meningitidis has historically been sensitive to these antibiotics, most laboratories do not perform tests to confirm drug susceptibility, Dr. Campos says. But the protocol at Children’s National is to screen these isolates for penicillin and ampicillin resistance with a rapid 5-minute test. The isolate from Dr. Taormina’s five-month-old patient – a previously healthy infant from Maryland who came to the Children’s National emergency room after six days of fever and congestion – yielded surprising results: N. meningitidis grown from the patient’s blood was positive for beta-lactamase, an enzyme that destroys the active component in the family of antibiotics that includes penicillin and ampicillin. This isolate was also found resistant to ciprofloxacin.

“The lab used a rapid test, and after just a few minutes, it was positive,” Dr. Campos says. “We did it again to make sure it was accurate, and the results were reproducible. That’s when we knew we needed to share this finding with the public health authorities.”

Dr. Campos, Dr. Taormina and their colleagues sent samples of the antibiotic-resistant bacteria first to the Washington, D.C. Public Health Laboratory and the Maryland Department of Health, and later to the Centers for Disease Control and Prevention (CDC). When the CDC asked other state laboratories to send their own N. meningitidis samples to be tested, 33 were positive for beta-lactamase. And like the bacterium isolated from Dr. Taormina’s patient, 11 of these were also resistant to ciprofloxacin.

“These bacteria wouldn’t have been susceptible to the common antibiotics that we would normally use for this infection,” Dr. Taormina says, “so it’s entirely possible that the infections caused by these bacteria could have been treated inappropriately if doctors used the standard protocol.”

Dr. Taormina says that her patient cleared his infection after staying on ceftriaxone, the original antibiotic he’d been prescribed, for the recommended seven days. His six family members and close contacts were prophylactically treated with rifampin instead of ciprofloxacin.

Although this case had a positive outcome, Dr. Campos says it raises the alarm for other N. meningitidis infections in the U.S., where antibiotic resistance is a growing concern. The danger is even higher in other countries, where the vaccine that children in the U.S. commonly receive for N. meningitidis at age 11 isn’t available.

In the meantime, Drs. Taormina and Campos say their case highlights the need for the appropriate use of antibiotics, known as antibiotic stewardship, which is only possible with close partnerships between infectious disease doctors and microbiology laboratories.

“Our lab and the infectious diseases service at Children’s National interact every day on cases like this to make sure we’re doing the best job we can in diagnosing and managing infections,” says Dr. Campos. “We’re a team.”

Other Children’s National authors who contributed to this case report include infectious disease specialist Benjamin Hanisch, M.D.

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