Browsing by Subject "SARS-CoV-2"
Now showing 1 - 10 of 217
Results Per Page
Sort Options
Item 1137. What Do We Know? Teaching Medical Students to Deal with Uncertainty as a Pandemic Unfolds(Oxford, 2020-10) Bauer, Margaret E.; Trujillo, Daniel; Brown, Cameron; Gomez, Martiza; Davidson, Darrell; Relich, Ryan F.; Allen, Bradley L.; Microbiology and Immunology, School of MedicineBackground The global COVID-19 pandemic has had a major impact on medical student education. As the pandemic spread nationwide, numerous universities shut down with only days’ notice, and medical students were removed from all patient care settings and restricted from campuses. Yet, the need and curiosity of these future physicians to understand this new disease was great, including how to interpret and integrate rapidly evolving information on the underlying viral and immune mechanisms, pathophysiology, and epidemiology. Time students spent away from patient care settings presented an opportunity to rapidly develop and deliver new curriculum covering SARS-CoV-2 and COVID-19. Methods A team of students and faculty at Indiana University developed a Fundamentals of COVID-19 course that included up-to-date information on the virology, immunology, and pathophysiology of COVID-19. The course was delivered online, with both synchronous and asynchronous activities. Virology and immunology of the coronavirus family, including current knowledge to-date of SARS-CoV-2, were delivered using a series of readings and brief videos, followed by a small group exercise that required students to choose and present to their peers a paper from the scientific literature on COVID-19. A similar approach was used to deliver content about the pathophysiology of COVID-19. To place the COVID-19 experience in context of other pandemics, students researched and educated their small group cohort on another historical pandemic. Results To measure course effectiveness, we administered a pre-course survey gauging students’ self-confidence in their knowledge of these topics; the same survey was administered after completion of the course. Surveys from 645 (89% of enrolled) 3rd and 4th year medical students who completed both surveys were analyzed. Results showed that the course elicited a 57% increase (p< 0.001) in students’ confidence in their knowledge of COVID-19 virology and immunology and a 64% increase (p< 0.001) in knowledge of the pathophysiology. Conclusion Data showed that the asynchronous content and group activities were successful in engaging and educating the students on foundational knowledge of COVID-19 and were an effective approach to rapidly evolving information when faced with a novel disease.Item 2020 Year in Review: Pharmacologic Treatments for COVID-19(2021-04) Saunders, Jessica L.; Davis, Michael D.; Pediatrics, School of MedicineCOVID-19, caused by SARS-CoV-2 infection, has led to a pandemic of acute respiratory illness. Pharmacologic treatments for COVID-19 have included treatments targeting infection prevention, prevention of viral replication, reducing inflammation and managing symptoms of respiratory failure caused by the disease. This is a review of key pharmacologic treatments for COVID-19 based on peer-reviewed articles from 2020.Item 241: Malignant Catatonia Possibly Precipitated by SARS-CoV-2 Infection(Wolters Kluwer, 2021) Johnson, Sean; Kapoor, Rajat; Kim, Yo Sup; Medicine, School of MedicineItem 3058 – Sars-Cov-2 Binding in Hematopoietic Stem and Progenitor Cells Under Low Oxygen Conditions(Elsevier, 2021) Dausinas, Paige; Hartman, Melissa; Allman, Lauren; O'Leary, Heather; Anatomy, Cell Biology and Physiology, School of MedicineThe SARS-CoV-2 pandemic highlighted a need for in-depth understanding of interaction/identification of receptors and mechanisms/functional consequences of viral binding/entry. SARS-CoV-2 spike protein (SBP) facilitates viral entry via ACE2 and/or NRP1 binding, with DPP4 as a potential co-receptor. These binding partners are expressed on various cell types including hematopoietic stem and progenitor (HSC/HSPC) cells [1-3]. HSC/HSPCs generate blood cells and reside in the low oxygen (lowO2, 1-4%) bone marrow niches that provide critical signals for maintenance, self-renewal, and differentiation. To investigate aspects of SARS-CoV-2 interactions with HSC/HSPC such as endogenous receptor expression, SPB binding and subsequent functional alterations in native low O2, we performed transcriptional and phenotypic/functional analysis. In lowO2, we identified increased surface expression of ACE2, DPP4 and NRP1, and enhanced binding of SBP to HSC/HSPC populations which amplified proliferation of SBP bound in lowO2. ACE2 and DPP4 surface expression were ∼2-fold higher in HSPCs (p=0.017, p=0.001) and HSCs (p=0.010, p=0.03), and NRP1 was ∼1.5-fold (p=0.002) higher in HSPCs in lowO2 compared to air. Interestingly, in lowO2, overall SBP binding was enhanced in HSPC (2.2-fold, p<.001) and HSC (2.6-fold, p=.018). Although not all cells expressing ACE2/DPP4/NRP1 bind SBP (∼50%), all cells exhibiting SBP binding in HSC/HSPC populations are triple positive for ACE2, NRP1, and DPP4. Additionally, we observed greater than a 2-fold increase in proliferation of SBP bound vs unbound cells in replating assays in lowO2 (p<.001). These data impart compelling evidence that SBP binding/functional outcomes are unique in low O2, providing a foundation that may have potential clinical implications for COVID19 treatment and expanding our baseline understanding of SARS-CoV-2 viral binding implications.Item A Cohort Study of Seroprevalence of Antibodies Against SARS-CoV-2 Infection Among Healthcare Workers at a Tertiary Hospital in Saudi Arabia(Dove Press, 2022-08-10) Mushcab, Hayat; Al-Tawfiq, Jaffar A.; Ghamdi, Mohammed; Babgi, Amani; Amir, Abdulrazack; Sheikh, Salwa S.; Darwisheh, Adel; Alobaid, Abrar; Jebakumar, Arulanantham Zechariah; Qahtani, Saeed; Al Sagheir, Ahmed; Medicine, School of MedicineBackground: The nature of the healthcare workers’ jobs standing at the frontline against the coronavirus disease 2019 (COVID-19) puts them at a higher risk of unknowingly contracting the disease and potentially contributing to the spread. This study aims to assess the overall positive seroconversion prevalence of SARS-CoV-2. Methods: This is a longitudinal cohort study of healthcare workers at Johns Hopkins Aramco Healthcare (JHAH). JHAH is a tertiary hospital located in Dhahran serving patients in several districts in the Eastern Province of Saudi Arabia. Participants were recruited between June and December 2020. Each participant had a serology blood test and completed the World Health Organization’s risk factor assessment questionnaire. Results: This study included 682 participants working in JHAH, representing 15.7% of our population. Out of the 682 participants, 15.2% had a positive SARS-CoV-2 rt-PCR before taking part in the study. However, only 87 tested positive for SARS-CoV-2 antibodies, a prevalence of 12.7% of all participants. Out of the 87 positives for SARS-CoV-2 antibodies, 17 participants never tested positive for COVID-19 rt-PCR, a prevalence of 2.9%. Moreover, not properly using alcohol-based hand rub or soap and water after the risk of body fluid exposure and wearing personal protective equipment when indicated were found to be statistically significant to having a positive SARS-CoV-2 IgG assay. Conclusion: Positive seroconversion rate was considerably low during the first wave of COVID-19 amongst JHAH’s healthcare workers and similar to other healthcare organizations in Saudi Arabia. Seropositivity correlated significantly with following infection prevention and control recommendations.Item A framework for reinitiating global academic exchange in the context of the COVID-19 pandemic(IJME, 2022-09-09) Kelly, Caitrin M.; Some, Fatma; Guiles, Daniel A.; Turissini, Matthew; Gardner, Adrian; Litzelman, Debra K.; Medicine, School of MedicineItem A Novel Regioselective Approach to Cyclize Phage-Displayed Peptides in Combination with Epitope-Directed Selection to Identify a Potent Neutralizing Macrocyclic Peptide for SARS-CoV-2(American Chemical Society, 2022) Hampton, J. Trae; Lalonde, Tyler J.; Tharp, Jeffery M.; Kurra, Yadagiri; Alugubelli, Yugendar R.; Roundy, Christopher M.; Hamer, Gabriel L.; Xu, Shiqing; Liu, Wenshe Ray; Biochemistry and Molecular Biology, School of MedicineUsing the regioselective cyanobenzothiazole condensation reaction with an N-terminal cysteine and the chloroacetamide reaction with an internal cysteine, a phage-displayed macrocyclic 12-mer peptide library was constructed and subsequently validated. Using this library in combination with iterative selections against two epitopes from the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein, macrocyclic peptides that strongly inhibit the interaction between the Spike RBD and ACE2, the human host receptor of SARS-CoV-2, were identified. The two epitopes were used instead of the Spike RBD to avoid selection of nonproductive macrocyclic peptides that bind RBD but do not directly inhibit its interactions with ACE2. Antiviral tests against SARS-CoV-2 showed that one macrocyclic peptide is highly potent against viral reproduction in Vero E6 cells with an EC50 value of 3.1 μM. The AlphaLISA-detected IC50 value for this macrocyclic peptide was 0.3 μM. The current study demonstrates that two kinetically-controlled reactions toward N-terminal and internal cysteines, respectively, are highly effective in the construction of phage-displayed macrocyclic peptides, and the selection based on the SARS-CoV-2 Spike epitopes is a promising methodology in the identification of peptidyl antivirals.Item A Putative long-range RNA-RNA interaction between ORF8 and Spike of SARS-CoV-2(Public Library of Science, 2022-09-01) Omoru, Okiemute Beatrice; Pereira, Filipe; Janga, Sarath Chandra; Manzourolajdad, Amirhossein; BioHealth Informatics, School of Informatics and ComputingSARS-CoV-2 has affected people worldwide as the causative agent of COVID-19. The virus is related to the highly lethal SARS-CoV-1 responsible for the 2002-2003 SARS outbreak in Asia. Research is ongoing to understand why both viruses have different spreading capacities and mortality rates. Like other beta coronaviruses, RNA-RNA interactions occur between different parts of the viral genomic RNA, resulting in discontinuous transcription and production of various sub-genomic RNAs. These sub-genomic RNAs are then translated into other viral proteins. In this work, we performed a comparative analysis for novel long-range RNA-RNA interactions that may involve the Spike region. Comparing in-silico fragment-based predictions between reference sequences of SARS-CoV-1 and SARS-CoV-2 revealed several predictions amongst which a thermodynamically stable long-range RNA-RNA interaction between (23660-23703 Spike) and (28025-28060 ORF8) unique to SARS-CoV-2 was observed. The patterns of sequence variation using data gathered worldwide further supported the predicted stability of the sub-interacting region (23679-23690 Spike) and (28031-28042 ORF8). Such RNA-RNA interactions can potentially impact viral life cycle including sub-genomic RNA production rates.Item A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2(Springer Nature, 2023) Yin, Qian; Luo, Wei; Mallajosyula, Vamsee; Bo, Yang; Guo, Jing; Xie, Jinghang; Sun, Meng; Verma, Rohit; Li, Chunfeng; Constantz, Christian M.; Wagar, Lisa E.; Li, Jing; Sola, Elsa; Gupta, Neha; Wang, Chunlin; Kask, Oliver; Chen, Xin; Yuan, Xue; Wu, Nicholas C.; Rao, Jianghong; Chien, Yueh-hsiu; Cheng, Jianjun; Pulendran, Bali; Davis, Mark M.; Microbiology and Immunology, School of MedicineThe ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.Item Acute Biventricular Heart Failure After COVID-19 Infection in an Orthotropic Heart Transplant Patient: A Case Report(Elsevier, 2021-05) Berg, Nicholas; Ilonze, Onyedika; Bajpai, Vatsal; Guglin, Maya; Rao, Roopa; Medicine, School of MedicineThe cardiac effects of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include myocarditis, takotsubo cardiomyopathy, pericardial effusion, and cardioembolic events in the general population. The effects of SARS-CoV-2 in heart transplant patients are unclear. We describe a case of myocarditis in the transplanted heart that responded to methylprednisolone.