COVID Concerns, Vaccine, Safe Schools, Solid Tumors, Sepsis, Asthma

 

By Jillian Rose Lim and Nancy McCann

This week in the news, our researchers at Children’s Hospital of Philadelphia continue their coverage of COVID-19 from a number of angles, as psychologists study mental resilience during the pandemic, vaccine expert Paul Offit, MD, weighs in on the progress-to-date of a vaccine, allergy researchers look at the impact of stay-at-home orders on asthma events, and PolicyLab Director David Rubin, MD, MSCE, comments on safe school re-opening. On top of that, read about a promising new treatment for high-risk solid tumors, and learn which of our innovative sepsis research projects found its way on the National Institutes of Health (NIH) Director’s blog.

New Study Finds Signs of Altruism in Individuals’ COVID-19 Concerns

People appear to be more worried about the well-being of others than themselves when it comes to COVID-19 related concerns, new findings published by the Lifespan Brain Institute (LiBI) suggest. A collaborative effort between CHOP and the University of Pennsylvania, LiBi researchers embarked on a study about stress and resilience during the coronavirus pandemic using an online survey, covid19resilience.org. The study involves 3,042 participants from the United States and Israel. Because it looks at potential sources of stress during the pandemic (such as contracting the virus, having a family member contract the virus, experiencing financial burdens, and other factors), the survey’s data offers a unique window into the pandemic’s effect on mental health and how strengthening resilience may help individuals cope.

Survey respondents’ concerns about contracting the virus appear to be outweighed by worries over whether family members might contract the virus and whether they are unknowingly spreading the virus themselves, according to the most recent set of findings published in Translational Psychiatry. Furthermore, respondents with higher resilience scores reported lower COVID-19-related worries and reduced anxiety and depression.

“The opportunity to study mental resilience during this pandemic is unprecedented,” said Ran Barzilay, MD, PhD, lead author of the paper and a child and adolescent psychiatrist at CHOP. “Our frontline healthcare workers are acutely aware of the mental health challenges facing everyone right now, so there is an urgent need to quantify the effects of resilience and determine how future studies might guide us toward improving mental health under these changing circumstances.”

Read the full press release, and learn more about the covid19resilience.org research project on Cornerstone.

Policylab Joins Good Morning America to Discuss Safe School Reopening

Our own David Rubin, MD, MSCE, appeared on Good Morning America (GMA) Aug. 20 to comment on the latest COVID-19 metrics from PolicyLab’s model, and how the data can guide communities in reopening schools safely. Dr. Rubin, who is director of PolicyLab, leads an interdisciplinary team from CHOP and Penn in developing an innovative model to track and project the COVID-19 epidemic across the U.S. The model observes how social distancing, population density, and daily temperatures affect the number and spread of infections over time across 747 counties, accounting for test positivity rates and population characteristics. The team also recently published new guidance on school reopening that emphasizes two key metrics, county-level case counts and test positivity rates.

Check out Dr. Rubin’s appearance on GMA here.

Vaccine Expert Gives Update on COVID-19 Vaccine Development for JAMA

Paul Offit, MD, director of the Vaccine Educator Center at CHOP and an internationally recognized virology and immunology expert, once again joined Howard Bauchner, MD, editor in chief of the Journal of the American Medical Association (JAMA), to discuss updates on a coronavirus vaccine in a JAMA Network live stream video. Dr. Offit, who has a lengthy experience in vaccine development and research, offered his perspective on where we stand in vaccine development and commented on some of the vaccines currently in the works from a number of pharmaceutical companies around the world.

“We’re waiting right now for critical data, and those critical data are going to come from Phase 3 trials,” said Dr. Offit in the live stream. “Right now, we’re looking at Phase 1 data, minimal Phase 2 data, and we don’t really have any idea what the safety portfolios are going to look like in larger numbers of people or whether these vaccines are going to be effective; so right now we’re just waiting to see.”

In our June 5 edition of In the News, we featured Dr. Offit’s previous appearance on the JAMA Network, where he spoke about the key components needed for a successful COVID-19 vaccine. Dr. Offit is co-inventor of RotaTeq®, the rotavirus vaccine recommended for use in infants by the Centers for Disease Control, and he is currently a member of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) group.

Watch Dr. Offit's comments in the full JAMA video on YouTube.

CHOP Researchers Evaluate Promising Coronavirus Vaccine

SARS-CoV-2 mRNA-based vaccines are among the most promising vaccine candidates against COVID-19. Benefits include the possibility of a stronger safety profile than virus-based vaccine platforms, mRNA vaccine antigens can be rapidly designed and produced, and nucleoside-modified mRNA-LNP vaccines have been demonstrated to induce extremely potent and protective immune responses against other viruses after administration of a single dose in animal models.

In a study published in Immunity, researchers, including co-authors Michael Hogan, a postdoctoral fellow, and Annie Toulmin, a graduate student, in the Eisenlohr Lab, evaluate two nucleoside-modified mRNA vaccine candidates working with mouse models and demonstrate that they induce potent T and B cell immune responses and high levels of neutralizing antibodies after administration of a single vaccine dose.

The researchers provided a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein, or the spike receptor-binding domain. They demonstrated that a single dose of these vaccines induced strong type 1 CD4+ and CD8+ T cell responses, and long-lived plasma and memory B cell responses. They detected robust and sustained neutralizing antibody responses, and the antibodies elicited by nucleoside-modified mRNA vaccines did not show antibody-dependent enhancement of infection in vitro. T cell responses were particularly strong in the lungs of immunized mouse models, suggesting that T cells may be able to protect against COVID-19 pneumonia. Their findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

“If reproducible in humans, this one-time immunization feature of the vaccine platform would be particularly important in a pandemic or epidemic setting, by inducing immune protection after a single point-of-care visit,” the authors noted.

CHOP Sepsis Research Featured in NIH Director’s Blog

Francis Collins, MD, NIH Director, shared his take on exciting new sepsis work by our hematology researchers in his NIH Director’s Blog post, published Aug. 18. With much creativity and enthusiasm, Dr. Collins wrote about a study from Kandace Gollomp, MD, and Mortimer Poncz, MD, that describes a promising new approach to treat sepsis. Sepsis is the body’s overwhelming inflammatory response to an infection, such as pneumonia.

Drs. Gollomp and Poncz’s method seeks to “flip the script,” in Dr. Collins’ own words, on previous approaches to treatment by making neutrophil extracellular traps (NETs) “even stickier to catch more bacteria,” thereby lowering the bacteria count and helping patients recover. Described by Dr. Collins as “sticky, spider-like webs made of DNA and antibacterial proteins,” NETS are made by human immune cells called neutrophils. When activated, NETS trap sepsis-causing bacteria. In their study published in Blood, Drs. Gollomp and Poncz describe how adding a protein, platelet factor.4, to NETS may enhance how they capture bacteria.

Learn more about this innovative work in Dr. Collins’ full blog post about our scientists’ sepsis research.

Fewer Serious Asthma Events After COVID-19 Stay-At-Home Orders

Since Philadelphia and surrounding areas issued “stay-at-home” orders March 17, CHOP observed a 60 percent decrease in healthcare visits for both outpatient and hospitalized asthma patients. Now, in a new study published in the Journal of Allergy and Clinical Immunology, CHOP and Penn researchers suggest fewer rhinovirus infections due to masking, social distancing, and hygiene measures may be the cause. Pollution levels, which can worsen asthma symptoms, were not significantly lower compared to previous years and did not appear to contribute to fewer asthma events.

“This paper demonstrates that social distancing is an effective tool in reducing transmission of any virus, whether it’s a coronavirus or an asthma-exacerbating rhinovirus,” said David Hill, MD, PhD, senior author and attending physician with the Division of Allergy and Immunology, in a press release.

When analyzing visits made by asthma patients after March 17, Dr. Hill and his colleagues also found that telehealth video visits were the most utilized way patients saw their doctor, and the study team observed a decrease in outpatient steroid prescription.

“These findings can help inform how we care for asthma patients, not only during this pandemic, but also after we return to a new normal,” Dr. Hill said. “Asthma is one of the most common chronic childhood diseases, affecting one out of every 12 school-aged children in the United States. We should explore whether enhanced infection-prevention measures have utility in children with asthma, irrespective of COVID-19.”

Learn more in the press release.

Novel Treatment Shows Success in Treating High-Risk Solid Tumors

Cancers that involve high-risk solid tumors such as neuroblastoma and Ewing sarcoma can be challenging to cure because the tumors often develop resistance to therapies. Now, researchers in our Cancer Center at CHOP have engineered a novel treatment that appears to overcome common drug resistance and may potentially elicit fewer toxicities than most cancer treatments. In a breakthrough study published in Cancer Research, the team showed that their treatment leads to long-term remissions in 80 percent to 100 percent of animal models with drug-resistant or high-risk solid tumors.

“The results of our studies show that the cancer therapeutic we developed is highly effective in treating at least three different types of high-risk pediatric solid tumors with intrinsic or acquired drug resistance,” said Garrett M. Brodeur, MD, director of the Cancer Predisposition Program at CHOP and co-senior author of the study, alongside Michael Chorny, PhD, and Ivan Alferiev, PhD. “Given that this treatment is also likely to be much less toxic than most cancer therapies for these types of tumors, in addition to showing remarkable therapeutic effects against aggressive disease, we think these results warrant further exploration of the agent in clinical trials.”

The research team had engineered a prodrug, which is a medication that is inert until converted by the body into a pharmacologically active drug, in such a way that it overcomes the issues of poor efficacy and high toxicity often seen in previous prodrug use. By attaching four residues of a pharmacologically enhanced drug, SN22, through a breakable bond to a four-arm polyethylene glycol scaffold, the team extended the drug’s circulation time, allowing 50 to 100 times as much drug to be taken up by the tumor. SN22’s modified structure also protected it from cell transports that could push the drug out of tumor cells. Thanks to these modifications, the resulting high drug levels in the tumor tissue were sustained for hours and days.

“Taken together, the superior efficacy and improved biocompatibility of our prodrug, which we demonstrated in several clinically relevant models of high-risk cancer, make it a highly promising new therapeutic capable of addressing the considerable limitations of current treatments,” Dr. Chorny said.

Learn more in the press release.

ICYMI

Catch up on our headlines from our Aug. 14 In the News:

• Tami Benton Receives 2020 Humanitarian Award
• Language Assessment Performance Linked to Psychosis in 22q11.2 Deletion Syndrome
• Clinician Intervention Reduced Antibiotic Prescribing for Pediatric Respiratory Infections
• Youth Involved in Continuous Glucose Monitoring Decisions More Likely to Use It
• New Algorithm Helps Identify Sites of DNA Methylation

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