Browsing by Author "Shabestari, Seyed Ali Safizadeh"

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Analyzing single cell transcriptome data from severe COVID-19 patients
(2022) Nassir, Nasna; Tambi, Richa; Bankapur, Asma; Karuvantevida, Noushad; Zehra, Binte; Begum, Ghausia; Hameid, Reem Abdel; Ahmed, Awab; Shabestari, Seyed Ali Safizadeh; Hachim, Mahmood Yaseen; Alsheikh-Ali, Alawi; Berdiev, Bakhrom; Al Heialy, Saba; Uddin, Mohammed
SUMMARY: We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. We construct COVID-19 comorbid disease-associated gene list using multiple databases and literature resources. Next, we identify specific cell type where comorbid genes are upregulated. We further characterize the identified cell type using gene enrichment analysis. We detect upregulation of marker gene restricted to severe COVID-19 cell type and validate our findings using in silico, in vivo, and in vitro cellular models.
Diagnostic Accuracy of Cerebrospinal Fluid Multiplex Polymerase Chain Reaction Panel Testing in Patients With Suspected Central Nervous System Infections: A Multi-Center Study in the United Arab Emirates
(2024-01) Ghoweba, Yousra; Shabestari, Seyed Ali Safizadeh; Malik, Zainab A
Abstract: Background: Delays in diagnosis and treatment of central nervous system (CNS) infections can lead to significant morbidity and mortality among children and adults. Prior antibiotic treatment is a major hurdle to accurate diagnosis due to falsely negative cerebrospinal fluid (CSF) cultures in partially treated patients. Increasingly, molecular diagnostic methods using multiplex polymerase chain reaction (mPCR) testing on CSF samples are being utilized in clinical practice for timely and accurate diagnosis. However, there is no data regarding the diagnostic accuracy or clinical impact of CSF mPCR testing in the Middle East region. We sought to compare the diagnostic accuracy of an automated mPCR CSF panel with routine CSF culture, the current gold standard, in the United Arab Emirates (UAE). Methods This single-gated, multi-center, diagnostic accuracy study included patients from birth onwards who were admitted to any of the three participating hospitals with an initial diagnosis of meningitis or encephalitis, between January 2017 and March 2021, and had CSF samples collected for mPCR and culture. Sociodemographic, clinical, and molecular data were collected for all. Results A total of 353 CSF samples were collected from patients from 0-90 years old hospitalized for suspected CNS infection. Children constituted 51% of the study population, and males were slightly over-represented (55.2%). Pathogens were detected by mPCR in 78 (22%) CSF samples, of which 19 (24%) were bacteria and 59 (76%) were viruses. No fungal pathogens were detected. Enteroviruses were the most prevalent CNS pathogen among our cohort (40%), followed by herpes simplex virus type 2 (HSV-2) (12.5%). Children constituted 69% of positive samples for enterovirus, while HSV-2 was exclusively detected among adults. Using CSF culture as the diagnostic gold standard, the mPCR panel demonstrated high specificity (100%) and sensitivity (96.3%) in diagnosing CNS infection among all age groups. mPCR testing demonstrated a high overall percentage of agreement (OPA) with CSF culture (98.9%). Patients with bacterial meningitis had a significantly longer hospitalization (p=0.004) and duration of antibiotic therapy (p=0.001) compared to those with viral meningitis. Three CSF samples were negative on mPCR testing but positive on culture. These pathogens included: methicillin-sensitive Staphylococcus aureus(MSSA), Bacillus cereus, and Mycobacterium Tuberculosis (MTB). In addition, 13 patients had negative CSF cultures but tested positive on CSF mPCR. These pathogens included Streptococcus pneumoniae (seven patients), Haemophilus influenzae (three patients), Streptococcus agalactiae (two patients), and Escherichia coli (one patient). All discordant results were confirmed by reviewing the patient's clinical presentation, CSF analysis, clinical course, and final diagnosis. Conclusion CSF mPCR panel is a highly sensitive and specific diagnostic tool for the diagnosis of CNS infections among all age groups in the UAE. Routine use of CSF mPCR panels can decrease healthcare costs by reducing the length of stay and can also aid antibiotic stewardship efforts by reducing antibiotic overuse in patients with viral CSF infections. CSF culture and mPCR complement each other by identifying CNS pathogens in patients with prior antibiotic exposure who would otherwise be missed if relying on CSF culture alone. However, concomitant CSF culture samples should be sent to avoid missing unusual CNS pathogens.
Diagnostic accuracy of QuickVue® Dipstick Strep A test and its effect on antibiotic prescribing in children in the United Arab Emirates
(2019) Shabestari, Seyed Ali Safizadeh
Background: Unnecessary antibiotic prescription to patients with upper respiratory tract infections (URTIs) has led to the increase in antibiotics resistant bacteria rates. In this study, we evaluated the diagnostic accuracy of QuickVue® Dipstick Strep A test (QV-SAT) in children presenting with acute pharyngotonsillitis and its effect on antibiotic prescribing. Methods: A single-gated diagnostic accuracy study of children with fever, runny nose, and tonsillitis presenting to a paediatric clinic between March 2016 and September 2018. Paired throat swabs for QV-SAT and culture were collected. None of the children received antibiotics prior to sample collection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the test were calculated. Results: Two hundred four children were included in this study. 111 (54.4%) were boys and 146 (71.6%) were under the age of 5 years. QV-SAT was positive in 44 (21.6%) and throat cult ure was positive for Group A β- haemolytic Streptococcus (GAS) in 42 (20.6%) of the children. The results of QV-SAT were highly consistent with culture results: only 2 (0.9%) children with negative results had a positive throat culture. The sensitivity of the QV-SAT in the identification of GAS infection was 100% (95% CI 91.6%, 100%) and the NPV was 100% (95% CI 99.9%, 100%). Only 42 children ( 20.6%) were given antibiotics, while 162 (79.4%) were not. Conclusion: The QV-SAT is a quick and reliable test that can help dramatically reduce antibiotic prescriptions to children presenting with fever and acute pharyngotonsillitis.
Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19
(2021) Nassir, Nasna; Tambi, Richa; Bankapur, Asma; Al Heialy, Saba; Karuvantevida, Noushad; Zehra, Binte; Begum, Ghausia; Hameid, Reem Abdel; Ahmed, Awab; Shabestari, Seyed Ali Safizadeh; Kandasamy, Richard K; Loney, Tom; Tayoun, Ahmad Abou; Nowotny, Norbert; Hachim, Mahmood Yaseen; Berdiev, Bakhrom; Alsheikh-Ali, Alawi; Uddin, Mohammed
Summary: Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.