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15 result(s) for "Dada, Ashraf"
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The effect of novel vitamin D3 compounds on saliva samples from COVID-19 patients: a lab study
Vitamin D has shown antimicrobial effects. This study aimed to explore the antiviral effects of vitamin D3 on saliva samples collected from patients with coronavirus disease-19 (COVID-19) and compare saliva and swab results to aid in policy development. Saliva and swab samples were collected from adult patients with a positive test for COVID-19 at the King Faisal Specialist Hospital and Research Centre, Jeddah. Patients who were immunocompromised and pregnant and aged < 18 years were excluded. Vitamin D3 compound (100, 300, 800, and 1,200 IU) was added to the first saliva sample in the laboratory (n = 20); the rest of the swab specimens were compared with the saliva samples via real-time polymerase chain reaction. Of the 257 patients, 236 (94.8%) had positive saliva sample test results, 7 (2.8%) had errors, and 6 (2.4%) had negative results. Of the 236 positive tests, 235 (99.6%) had a cycle threshold (Ct) indicating strong positive reactions, and only one (Ct = 28.86) was weak. Among the 236 positive results, 235 (99.6%) exhibited robust positive reactions, indicating a substantial positive sample size. Thus, saliva might be a dependable alternative testing tool when obtaining swab samples from patients is inconvenient or challenging.
An open-source, automated, and cost-effective platform for COVID-19 diagnosis and rapid portable genomic surveillance using nanopore sequencing
The COVID-19 pandemic, caused by SARS-CoV-2, has emphasized the necessity for scalable diagnostic workflows using locally produced reagents and basic laboratory equipment with minimal dependence on global supply chains. We introduce an open-source automated platform for high-throughput RNA extraction and pathogen diagnosis, which uses reagents almost entirely produced in-house. This platform integrates our methods for self-manufacturing magnetic nanoparticles and qRT-PCR reagents-both of which have received regulatory approval for clinical use–with an in-house, open-source robotic extraction protocol. It also incorporates our \"Nanopore Sequencing of Isothermal Rapid Viral Amplification for Near Real-time Analysis\" (NIRVANA) technology, designed for tracking SARS-CoV-2 mutations and variants. The platform exhibits high reproducibility and consistency without cross-contamination, and its limit of detection, sensitivity, and specificity are comparable to commercial assays. Automated NIRVANA effectively identifies circulating SARS-CoV-2 variants. Our in-house, cost-effective reagents, automated diagnostic workflows, and portable genomic surveillance strategies provide a scalable and rapid solution for COVID-19 diagnosis and variant tracking, essential for current and future pandemic responses.
Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans, Saudi Arabia
Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.
SpyDirect: A Novel Biofunctionalization Method for High Stability and Longevity of Electronic Biosensors
Electronic immunosensors are indispensable tools for diagnostics, particularly in scenarios demanding immediate results. Conventionally, these sensors rely on the chemical immobilization of antibodies onto electrodes. However, globular proteins tend to adsorb and unfold on these surfaces. Therefore, self‐assembled monolayers (SAMs) of thiolated alkyl molecules are commonly used for indirect gold–antibody coupling. Here, a limitation associated with SAMs is revealed, wherein they curtail the longevity of protein sensors, particularly when integrated into the state‐of‐the‐art transducer of organic bioelectronics—the organic electrochemical transistor. The SpyDirect method is introduced, generating an ultrahigh‐density array of oriented nanobody receptors stably linked to the gold electrode without any SAMs. It is accomplished by directly coupling cysteine‐terminated and orientation‐optimized spyTag peptides, onto which nanobody‐spyCatcher fusion proteins are autocatalytically attached, yielding a dense and uniform biorecognition layer. The structure‐guided design optimizes the conformation and packing of flexibly tethered nanobodies. This biolayer enhances shelf‐life and reduces background noise in various complex media. SpyDirect functionalization is faster and easier than SAM‐based methods and does not necessitate organic solvents, rendering the sensors eco‐friendly, accessible, and amenable to scalability. SpyDirect represents a broadly applicable biofunctionalization method for enhancing the cost‐effectiveness, sustainability, and longevity of electronic biosensors, all without compromising sensitivity. SpyDirect creates high‐density, fully oriented nanobody layers on gold gate electrodes of organic electrochemical transistors in a simple water‐based two‐step functionalization process. SpyDirect enhances sensor lifespan and reduces background noise, improving cost‐effectiveness, sustainability, and scalability.
SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors
Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19. HLA antibodies have been identified as the main cause for transfusion-related acute lung injury (TRALI), a well-documented life-threatening complication of transfusions. The TRALI risk could be high in COVID-19 patients who need convalescent plasma, as such patients usually have already an impaired respiratory system affected by the SARS-CoV-2 infection. In this study, we screened 34 convalescent plasma donors on the presence of antibodies against HLA class I and II antigens. All included donors have no any history of sensitization events such as blood transfusions, pregnancy, or previous transplants. We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors. This finding might have the potential to reduce the risk of TRALI and mortality rate in COVID-19 patients by implementing HLA diagnostic strategies before the administration of convalescent plasma.
Molecular Epidemiology of SARS-CoV-2 and Clinical Manifestations among Organ Transplant Recipients with COVID-19
RNA viruses, including SARS-CoV-2, rely on genetic mutation as a major evolutionary mechanism, leading to the emergence of variants. Organ transplant recipients (OTRs) may be particularly vulnerable to such mutations, making it crucial to monitor the spread and evolution of SARS-CoV-2 in this population. This cohort study investigated the molecular epidemiology of SARS-CoV-2 by comparing the SARS-CoV-2 whole genome, demographic characteristics, clinical conditions, and outcomes of COVID-19 illness among OTRs (n = 19) and non-OTRs with (n = 38) or without (n = 30) comorbid conditions. Most patients without comorbidities were female, whereas most OTRs were male. Age varied significantly among the three groups: patients with comorbidities were the oldest, and patients without comorbidities were the youngest. Whole-genome sequencing revealed that OTRs with mild disease had higher numbers of unusual mutations than patients in the other two groups. Additionally, OTRs who died had similar spike monoclonal antibody resistance mutations and 3CLpro mutations, which may confer resistance to nirmatrelvir, ensitrelvir, and GC37 therapy. The presence of those unusual mutations may impact the severity of COVID-19 illness in OTRs by affecting the virus’s ability to evade the immune system or respond to treatment. The higher mutation rate in OTRs may also increase the risk of the emergence of new virus variants. These findings highlight the importance of monitoring the genetic makeup of SARS-CoV-2 in all immunocompromised populations and patients with comorbidity.
A COVID-19 family cluster with retinitis pigmentosa and hypogammaglobulinemia
Hypogammaglobulinemia is a heterogeneous group of innate and acquired antibody deficiency with variable disease severity, recurrent pneumonia, and bronchiectasis. The outcome of COVID in patients with hypogammaglobulinemia is variable depending on age, comorbidities, type of immunodeficiency, and use of immunoglobulins. We report the favorable outcome of two family members diagnosed with DNAJC17-related retinitis pigmentosa and hypogammaglobulinemia syndrome and infected with SARS-CoV-2 following contact with their mother who had COVID-19. We describe the different immune dysfunction in these patients and their impact on the course and management of SARS-CoV-2 infection.
Outcome of Transplant Recipients Infected with Omicron BA.1 and BA.2: A Single-Center Retrospective Study in Saudi Arabia
The outcome of transplant recipients is variable depending on the study population, vaccination status and COVID-19 variants. Our aim was to study the impact of Omicron subvariants on the mortality of transplant recipients. We reviewed the results of SARS-CoV-2 whole genome sequence of random isolates collected from 29 December 2021 until 17 May 2022 in King Faisal Specialist Hospital and Research center, Jeddah (KFSHRC-J), Saudi Arabia performed as hospital genomic surveillance program for COVID-19 variants. We included 25 transplant patients infected with confirmed Omicron variants.17 (68%) and 8 (32%) patients had Omicron BA.1 and BA.2, respectively. 12 (68%) patients had renal transplants. Only 36% of patients received three doses of COVID-19 vaccines. 23 (92%) patients required hospitalization. 20 (80%) patients survived and 6 (25%) required intensive care unit (ICU) admission. Among ICU patients, 66.7% were more than 50 years, 50% had two to three comorbidities and 5 out of 6 (83%) died. The mortality of transplant patients infected with Omicron variants in our cohort was higher than other centers as a limited number of patients received booster vaccines. Optimizing booster vaccination is the most efficient method to improve the mortality of COVID-19 in transplant recipients recognizing the inefficacy of monoclonal antibodies in the presence of SARS-CoV-2 emerging variants. We did not show a difference in mortality in transplant patients infected with Omicron BA.1 and BA.2 knowing the limitation of our sample size.
Resolution of Extensive Xanthomas Associated With Severe Hypertriglyceridemia via Modified Therapeutic Plasma Exchange
Abstract Severe hypertriglyceridemia can be manifested by xanthomas. Therapeutic plasma exchange (TPE) is an invasive medical procedure that has been documented as a viable approach for severe hypertriglyceridemia when cases would be refractory to conventional therapies. TPE is mainly an optional therapeutic modality for cases of severe acute pancreatitis or preventing the recurrence of pancreatitis. Beyond this clinical application, data are scarce on TPE utilization in managing cutaneous lesions associated with hypertriglyceridemia. We present a case of severe hypertriglyceridemia accompanied by extensive xanthomas of various types and a history of recurrent pancreatitis. After conventional therapy failed, a modified plasmapheresis regimen was used and was able to achieve a fast and marked reduction in the patient’s serum triglyceride levels with complete resolution of the extensive cutaneous lesions, providing him a newfound comfort he had not experienced in some time and suggesting the regimen potentially could be considered in the treatment of refractory severe hypertriglyceridemia with debilitating cutaneous complications.
Time‐Multiplexed Organic Electrochemical Transistor for Saliva‐Based Rapid Detection of Viral Proteins
Timely and accurate diagnosis of respiratory infections is complicated by the symptomatic overlap between highly transmissible pathogens such as respiratory syncytial virus (RSV), influenza A (IAV), and influenza B (IBV), highlighting the need for rapid and reliable diagnostics. Here, we report a time‐multiplexed nanobody‐functionalized organic electrochemical transistor (OECT) biosensor for the sensitive detection of RSV, IAV, and IBV directly from unprocessed saliva samples. The platform integrates arrays of nanobody‐functionalized gate electrodes that are exposed in parallel to a single sample and sequentially addressed through a shared transistor channel. We characterize nine previously reported nanobodies and immobilize the best‐performing ones using an oriented SpyDirect self‐assembly strategy. The nanobody‐functionalized gate electrodes are paired with a high‐performance p‐type organic mixed ionic‐electronic conductor channel, enabling efficient signal transduction. The sensor achieves a limit of detection of ca. 1 f m and identifies viral targets within 15 min, without sample preprocessing. In a clinical validation using 17 samples, the platform demonstrated 100% specificity, 86.7% sensitivity, and 88.2% overall accuracy. By combining highly specific nanobodies, a high‐gain transducer, customized surface pre‐treatment, and a time‐multiplexed multi‐gate architecture, this approach provides a scalable and user‐friendly platform for point‐of‐care virus detection.