Browsing by Author "Gillrie, Mark R."

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    Prolonged SARS-CoV-2 infection following rituximab treatment: clinical course and response to therapeutic interventions correlated with quantitative viral cultures and cycle threshold values
    (2022-02-05) Thornton, Christina S.; Huntley, Kevin; Berenger, Byron M.; Bristow, Michael; Evans, David H.; Fonseca, Kevin; Franko, Angela; Gillrie, Mark R.; Lin, Yi-Chan; Povitz, Marcus; Shafey, Mona; Conly, John M.; Tremblay, Alain
    Abstract Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is completed through reverse transcriptase-PCR (RT-PCR) from either oropharyngeal or nasopharyngeal swabs, critically important for diagnostics but also from an infection control lens. Recent studies have suggested that COVID-19 patients can demonstrate prolonged viral shedding with immunosuppression as a key risk factor. Case presentation We present a case of an immunocompromised patient with SARS-CoV-2 infection demonstrating prolonged infectious viral shedding for 189 days with virus cultivability and clinical relapse with an identical strain based on whole genome sequencing, requiring a multi-modal therapeutic approach. We correlated clinical parameters, PCR cycle thresholds and viral culture until eventual resolution. Conclusions We successfully demonstrate resolution of viral shedding, administration of COVID-19 vaccination and maintenance of viral clearance. This case highlights implications in the immunosuppressed patient towards infection prevention and control that should consider those with prolonged viral shedding and may require ancillary testing to fully elucidate viral activity. Furthermore, this case raises several stimulating questions around complex COVID-19 patients around the role of steroids, effect of antiviral therapies in absence of B-cells, role for vaccination and the requirement of a multi-modal approach to eventually have successful clearance of the virus.
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    Understanding the Roles of Hypoxia-Inducible Factor 1 Alpha in Early Host Responses Against Pneumococcal Pneumonia
    (2023-09-11) Kang, Hellen; Gillrie, Mark R.; Kelly, Margaret M.; Surewaard, B.
    Pneumococcal pneumonia, caused by the bacteria Streptococcus pneumoniae (SP), is the leading infectious cause of death in young children worldwide. Current 2D human and small animal models used to study SP infections do not account for complex organ microenvironments or species-specific immune pathways, respectively. To address this, we created a human vascularized lung on a chip (LoC) containing a ventilated epithelial lined air-liquid interface surrounded by human lung fibroblasts and a functional microvascular network. Single cell RNA sequencing of LoC treated with SP for 6 hours demonstrated early hypoxia inducible factor 1- alpha (HIF-1α) target gene activation. Therefore, we hypothesized that HIF-1α-dependent immune responses play an important role in pneumococcal pneumonia. LoC showed increased CD15+ neutrophil recruitment from perfused whole blood in microvessels to tissue and airway during SP infection, partially mediated by HIF-1α. CXCL family chemokines and IL-17C gene expression, and protein release of the latter, increased 6 hours post-infection in LoC; however, we did not observe vascular or airway dysfunction and microvascular damage until 24 hours post-infection. SP-induced HIF-1α activation may be driven by rapidly activated upstream signaling pathways and may require metabolically active bacteria. Altogether, we have characterized a number of functional roles of HIF-1α during early stages of SP infection and showed the utility of LoC as a pre-clinical human model that can identify key inflammatory and cell-cell interactions during pneumococcal pneumonia.