4 results on '"Megan Culler Freeman"'
Search Results
2. #13: Respiratory and Intestinal Epithelial Cells Exhibit Differential Susceptibility and Innate Immune Responses to Contemporary EV-D68 Isolates
- Author
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Megan Culler Freeman, Alexandra I Wells, Jessica Ciomperlik-Patton, Michael M Myerburg, Jennifer Anstadt, and Carolyn B Coyne
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Infectious Diseases ,Pediatrics, Perinatology and Child Health ,General Medicine - Abstract
Background Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and associated with acute flaccid myelitis (AFM), a disease which causes paralysis in previously healthy patients, mostly children. AFM peaked in even numbered years, at least 2014–2018. While 2020 was expected to be a peak AFM year, few cases were seen, likely due to non-specific social distancing measures due to SARS-CoV-2. EV-D68 is primarily described as a respiratory pathogen, in contrast to ‘classic’ enteroviruses that are spread via the fecal-oral route. However, similar to other enteroviruses, EV-D68 has been detected in wastewater, suggesting it might also have an enteric route of transmission. Methods We used a panel of EV-D68 isolates, including a historic isolate from 2009 and multiple contemporary isolates from AFM peak years to define dynamics of viral replication and host response to infection. We performed comparative studies in primary human bronchial epithelial cells grown at an air-liquid interface and in primary human stem-cell derived intestinal enteroids. These human primary cell-based models more accurately reflect the cells targeted by EV-D68 in vivo. We defined growth characteristics, temperature sensitivity, infection polarity, and acid sensitivity in these parallel models. We used unbiased Luminex-based multianalyte profiling and bulk RNA-sequencing to define the innate immune response in each model. Results Conclusions Our findings suggest that a subset of contemporary isolates of EV-D68 have the potential to target both the human airway and gastrointestinal tracts as a potential route of infection, identifying a previously unrecognized potential route of infection as well as defining, for the first time, the innate immune response to infection in multiple relevant primary epithelial models. These findings are highly significant and are the first to characterize the viral replication and host innate immune response to a diverse panel of historic and contemporary EV-D68 isolates in both the respiratory and intestinal tracts.
- Published
- 2021
3. Immunocompromised Seroprevalence and Course of Illness of SARS-CoV-2 in One Pediatric Quaternary Care Center
- Author
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Megan Culler Freeman, Glenn J Rapsinski, Megan L Zilla, and Sarah E Wheeler
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0301 basic medicine ,Male ,medicine.medical_specialty ,Adolescent ,Prevalence ,serology ,Antibodies, Viral ,Inflammatory bowel disease ,Asymptomatic ,Serology ,03 medical and health sciences ,Immunocompromised Host ,0302 clinical medicine ,Seroepidemiologic Studies ,Internal medicine ,Medicine ,Seroprevalence ,Humans ,Pediatrics, Perinatology, and Child Health ,Child ,business.industry ,SARS-CoV-2 ,COVID-19 ,Infant ,General Medicine ,Pennsylvania ,medicine.disease ,Hospitals, Pediatric ,immunocompromised ,030104 developmental biology ,Infectious Diseases ,AcademicSubjects/MED00290 ,pediatric ,030220 oncology & carcinogenesis ,COVID-19 Nucleic Acid Testing ,Child, Preschool ,Immunoglobulin G ,Pediatrics, Perinatology and Child Health ,Spike Glycoprotein, Coronavirus ,Primary immunodeficiency ,Female ,Original Article ,Immunocompetence ,medicine.symptom ,business ,AcademicSubjects/MED00670 - Abstract
Background The burden of coronavirus disease 2019 (COVID-19) is poorly understood in pediatric patients due to frequent asymptomatic and mild presentations. Additionally, the disease prevalence in pediatric immunocompromised patients remains unknown. Methods This cross-sectional study tested convenience samples from pediatric patients who had clinically indicated lab work collected and an immunocompromising condition, including oncologic diagnoses, solid organ transplant (SOT), bone marrow transplant, primary immunodeficiency, and rheumatologic conditions or inflammatory bowel disease on systemic immunosuppression, for the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results We tested sera from 485 children and observed SARS-CoV-2 seroprevalence of 1.0% (Confidence Interval [CI] 95%: 0.3%–2.4%). Two patients were positive by nasopharyngeal (NP) swab Reverse transcriptase polymerase chain reaction (RT-PCR), but only 1 seroconverted. Patients with oncologic diagnoses or SOT were most likely to be tested for COVID-19 when presenting with respiratory illness as compared with other groups. Conclusions Seroprevalence of antibodies to SARS-CoV-2 in immunocompromised children was similar to that of an immunocompetent pediatric population (0.6%, CI 95%: 0.3%–1.1%), suggesting an adequate antibody response. However, none of the patients who tested positive for antibodies or via NP RT-PCR had more than a mild illness course and 2 patients did not have any reported illness, suggesting that SARS-CoV-2 may not cause a worse clinical outcome in immunosuppressed children, in contrast to immunocompromised adults., Seroprevalence of antibodies to SARS-CoV-2 in immunocompromised children was similar to immunocompetent children; however, all of the immunocompromised patients had only mild illness. Immunosuppressed children may not have a more severe infection with SARS-CoV-2 than immunocompetent counterparts, unlike in adults.
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- 2020
4. Neonatal Toxic Shock Syndrome–Like Exanthematous Disease in North America
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John V. Williams, John Ibrahim, Stephanie L. Mitchell, and Megan Culler Freeman
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Staphylococcus aureus ,medicine.medical_specialty ,Fever ,Erythema ,Disease ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Intensive Care Units, Neonatal ,030225 pediatrics ,medicine ,Humans ,Disease process ,0303 health sciences ,biology ,030306 microbiology ,business.industry ,C-reactive protein ,Infant, Newborn ,Toxic shock syndrome ,Toxic shock syndrome toxin ,General Medicine ,Exanthema ,Staphylococcal Infections ,medicine.disease ,Shock, Septic ,Rash ,Dermatology ,Infectious Diseases ,Pediatrics, Perinatology and Child Health ,biology.protein ,medicine.symptom ,business - Abstract
Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is a syndrome first reported in Japan. Neonates develop systemic exanthema, thrombocytopenia, and fever usually during the first week of life. The disease is distinguished from frank TSS because affected infants are not severely ill and do not meet TSS criteria. Most infants are confirmed to be colonized with TSST-1 producing strains of S. aureus. Suggested diagnostic criteria for NTED include a skin rash with generalized macular erythema and one of the following symptoms: fever >38.0°C, thrombocytopenia
- Published
- 2019
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