Publications by authors named "Ahmed Abdul Azim"

6 Publications

  • Page 1 of 1

Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19.

JAMA 2021 04;325(15):1535-1544

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Importance: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines.

Objective: To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses.

Design, Setting, And Participants: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S.

Interventions: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group).

Main Outcomes And Measures: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses.

Results: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced.

Conclusion And Relevance: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.

Trial Registration: ClinicalTrials.gov Identifier: NCT04436276.
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http://dx.doi.org/10.1001/jama.2021.3645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953339PMC
April 2021

Open Development and Clinical Validation of Multiple 3D-Printed Sample-Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck.

medRxiv 2020 Apr 17. Epub 2020 Apr 17.

The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck in the way of high-sensitivity virological testing for COVID-19. To address this crisis, we designed and executed an innovative, radically cooperative, rapid-response translational-research program that brought together healthcare workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a rigorous multi-step preclinical evaluation on 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital's drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (κ=0.85-0.89). Cycle-threshold (Ct) values were not significantly different between each prototype and the control, supporting the new swabs' non-inferiority (Mann-Whitney U [MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. The swabs are available to order (http://printedswabs.org). Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.
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http://dx.doi.org/10.1101/2020.04.14.20065094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273259PMC
April 2020

Open Development and Clinical Validation of Multiple 3D-Printed Nasopharyngeal Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck.

J Clin Microbiol 2020 07 23;58(8). Epub 2020 Jul 23.

Clinical Microbiology Laboratories, Division of Clinical Pathology, Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck blocking clinical laboratories' ability to perform high-sensitivity virological testing for SARS-CoV-2. To address this crisis, we designed and executed an innovative, cooperative, rapid-response translational-research program that brought together health care workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a multistep preclinical evaluation of 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and we shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital's drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse transcriptase PCR (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (κ = 0.85 to 0.89). Cycle threshold ( ) values were not significantly different between each prototype and the control, supporting the new swabs' noninferiority (Mann-Whitney U [MWU] test,  > 0.05). Study staff preferred one of the prototypes over the others and preferred the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.
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http://dx.doi.org/10.1128/JCM.00876-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383530PMC
July 2020

The impact of smoking on patient outcomes in severe sepsis and septic shock.

J Intensive Care 2018 28;6:42. Epub 2018 Jul 28.

1Department of Pulmonary and Critical Care Medicine, Lahey Hospital and Medical Center, Burlington, MA USA.

Background: To assess, in the setting of severe sepsis and septic shock, whether current smokers have worse outcomes compared to non-smokers.

Methods: This is a retrospective analysis of immunocompetent adult patients with severe sepsis and septic shock at a tertiary medical center. The primary outcome was the effect of active smoking on hospital mortality. Chi-square test and logistic regression were used to assess categorical outcomes. Wilcoxon rank-sum was utilized to test the differences in continuous outcomes among the varied smoking histories. Multivariable logistic regression was used to evaluate the association of smoking and mortality, need for vasopressors, mechanical ventilation, and ICU admission.

Results: Of the 1437 charts reviewed, 562 patients were included. Current smokers accounted for 19% (107/562) of patients, while 81% (455/562) were non-smokers. The median hospital length of stay in survivors was significantly longer in current smokers versus non-smokers (8 vs 7 days,  = 0.03). There was a trend towards a higher mortality among current smokers, but this failed to meet statistical significance (OR 1.81, 95% CI 0.92-3.54,  = 0.08). On multivariable analysis, current smoking was associated with the need for mechanical ventilation (OR 2.38, 95% CI 1.06-5.34,  = 0.04), but that association was not observed with the need for vasopressors (OR 2.10, 95% CI 1.01-4.36,  = 0.58) nor ICU admission (OR 0.93, 95% CI 0.41-2.13,  = 0.86).

Conclusions: In patients with severe sepsis or septic shock, current smoking was associated with a longer hospital stay, the need for mechanical ventilation, and trended towards a higher mortality. Larger multicenter prospective case-control studies are needed to confirm these findings.
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http://dx.doi.org/10.1186/s40560-018-0312-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064183PMC
July 2018

The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis.

J Allergy Clin Immunol 2016 Feb 18;137(2):436-443.e9. Epub 2015 Sep 18.

Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

Background: Colonization by Aspergillus fumigatus in patients with cystic fibrosis (CF) can cause A fumigatus sensitization and/or allergic bronchopulmonary aspergillosis (ABPA), which affects pulmonary function and clinical outcomes. Recent studies show that specific allergens upregulate the surface-expressed basophil marker CD203c in sensitized subjects, a response that can be readily measured by using flow cytometry.

Objective: We sought to identify A fumigatus sensitization in patients with CF by using the basophil activation test (BAT).

Methods: Patients with CF attending Beaumont Hospital were screened for study inclusion. BAT was used to identify A fumigatus sensitization. Serologic (total and A fumigatus-specific IgE), pulmonary function, and body mass index measurements were performed.

Results: The BAT discriminates A fumigatus-sensitized from nonsensitized patients with CF. Persistent isolation of A fumigatus in sputum is a significant risk factor for A fumigatus sensitization. Levels of the A fumigatus-stimulated basophil activation marker CD203c inversely correlated with pulmonary function and body mass index in A fumigatus-sensitized but not nonsensitized patients with CF. Total and A fumigatus-specific IgE, but not IgG, levels are increased in A fumigatus-sensitized patients with CF and ABPA when compared with those in A fumigatus-sensitized and nonsensitized patients with CF without ABPA. Itraconazole treatment did not affect A fumigatus sensitization.

Conclusion: Combining the BAT with routine serologic testing allows classification of patients with CF into 3 groups: nonsensitized, A fumigatus-sensitized, and ABPA. Accurate and prompt identification of A fumigatus-associated clinical status might allow early and targeted therapeutic intervention, potentially improving clinical outcomes.
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http://dx.doi.org/10.1016/j.jaci.2015.07.045DOI Listing
February 2016

The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway.

Am J Respir Crit Care Med 2015 Dec;192(11):1314-24

1 Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.

Rationale: Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune and inflammatory processes.

Objectives: To investigate the capacity of anaerobes to contribute to cystic fibrosis (CF) airway pathogenesis via SCFAs.

Methods: Samples of 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFA levels in anaerobic supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of two SCFA receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings and 16HBE14o(-) and CFBE41o(-) cells were evaluated using reverse transcription polymerase chain reaction, Western blot analysis, laser scanning cytometry, and confocal microscopy. SCFA-induced IL-8 secretion was monitored by ELISA.

Measurements And Main Results: Fifty-seven (52.3%) of 109 PWCF were anaerobe positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF younger (n = 24) and older (n = 85) than 6 years of age. All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic, and butyric acids. SCFA levels were higher in BAL samples of adults than in those of children. GPR41 levels were elevated in CFBE41o(-) versus 16HBE14o(-) cells; CF versus non-CF bronchial brushings; and 16HBE14o(-) cells after treatment with cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dose-dependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells, with a higher production of IL-8 in CFBE41o(-) than in 16HBE14o(-) cells.

Conclusions: This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via up-regulated GPR41.
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http://dx.doi.org/10.1164/rccm.201505-0943OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731701PMC
December 2015
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