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1.
Medicina (Kaunas) ; 59(3)2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36984508

RESUMEN

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Infección Irruptiva , Anticuerpos Antivirales
2.
Neurosciences (Riyadh) ; 28(2): 136-142, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37045456

RESUMEN

OBJECTIVES: To report cases of cerebral phaeohyphomycosis at a tertiary hospital in Riyadh, Saudi Arabia. Phaeohyphomycetes are a widely distributed group of fungi whose cell walls contain 1,8 dihydroxynaphthalene-melanin. Cerebral infections caused by these fungi are uncommon and primarily associated with neurotrophic phaeohyphomycetes. METHODS: In January of 2020 we looked back to identify cases of culture-positive cerebral phaeohyphomycosis from our medical records at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia. Data on demographics, potential risk factors, clinical presentation, treatment, and outcomes were analyzed. RESULTS: Twelve cases of cerebral phaeohyphomycosis were identified, of which 4 were caused by Rhinocladiella mackenziei and the other 8 were caused by various phaeohyphomycetes. There were 2 cases caused by Neoscytalidium dimidiatum, and one case each caused by the following: Acrophialophora fusispora, Chaetomium atrobrunneum, Exophiala dermatitidis, Exerohilum rostratum, Fonsecaea pedrosoi, and Cladophialophora bantiana. Most patients (10 of 12) had underlying immunosuppression. R. mackenziei caused a brain-only infection manifesting as abscess formation. Four patients survived for more than a year after therapy. Surgical evacuation and triazole therapy with posaconazole or itraconazole, alone or in combination with other antifungal agents, were associated with success. CONCLUSION: Cerebral phaeohyphomycosis is an uncommon fungal infection that primarily affects immunocompromised patients and is associated with poor prognosis. R. mackenziei is the most prevalent fungus in our facility and has been linked to a universal mortality.


Asunto(s)
Feohifomicosis Cerebral , Micosis , Humanos , Arabia Saudita/epidemiología , Feohifomicosis Cerebral/tratamiento farmacológico , Centros de Atención Terciaria , Atención Terciaria de Salud , Micosis/tratamiento farmacológico , Micosis/microbiología , Antifúngicos/uso terapéutico
3.
BMC Infect Dis ; 22(1): 542, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35698046

RESUMEN

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.


Asunto(s)
Bacteriemia , Infecciones por Enterobacteriaceae , Neumonía Asociada a la Atención Médica , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/epidemiología , Escherichia coli , Femenino , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Estudios Prospectivos , Arabia Saudita/epidemiología
4.
J Clin Microbiol ; 59(5)2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33674285

RESUMEN

Combating the ongoing coronavirus disease 2019 (COVID-19) pandemic demands accurate, rapid, and point-of-care testing with fast results to triage cases for isolation and treatment. The current testing relies on reverse transcriptase PCR (RT-PCR), which is routinely performed in well-equipped laboratories by trained professionals at specific locations. However, during busy periods, high numbers of samples queued for testing can delay the test results, impacting efforts to reduce the infection risk. Besides, the absence of well-established laboratories at remote sites and low-resourced environments can contribute to a silent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These reasons compel the need to accommodate point-of-care testing for COVID-19 that meets the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable). This study assessed the agreement and accuracy of the portable Biomeme SARS-CoV-2 system against the gold standard tests. Nasopharyngeal and nasal swabs were used. Of the 192 samples tested using the Biomeme SARS-CoV-2 system, the results from 189 samples (98.4%) were in agreement with the reference standard-of-care RT-PCR testing for SARS-CoV-2. The portable system generated simultaneous results for nine samples in 80 min with high positive and negative percent agreements of 99.0% and 97.8%, respectively. We performed separate testing in a sealed glove box, offering complete biosafety containment. Thus, the Biomeme SARS-CoV-2 system can help decentralize COVID-19 testing and offer rapid test results for patients in remote and low-resourced settings.


Asunto(s)
Prueba de Ácido Nucleico para COVID-19/instrumentación , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/instrumentación , Humanos , SARS-CoV-2 , Sensibilidad y Especificidad
5.
Transpl Infect Dis ; 23(2): e13473, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32978858

RESUMEN

BACKGROUND: Tuberculosis (TB) is a major complication following transplantation. The likelihood of TB may be increased in transplant patients living in TB-endemic areas such as Saudi Arabia. In areas where TB is less common, guidelines recommend isoniazid (INH) for TB prophylaxis depending on patient and donor screening results. However, in TB-endemic regions, studies have supported its use in all transplant patients regardless of TB screening results. This study aimed to compare the safety and effectiveness of administering INH prophylaxis therapy based on the TB screening results of lung transplant (LT) recipients. METHODS: We conducted a single-center retrospective cohort study on LT recipients. The outcomes were compared between patients who were administered screening-based prophylaxis (SBP) with INH based on their tuberculin skin tests (TSTs) or QuantiFERON results and those who were administered empirical prophylaxis (EP) with INH regardless of TB screening results. The primary endpoint was the incidence of TB infection, and the secondary endpoints were INH-induced hepatotoxicity and INH resistance. RESULTS: A total of 50 patients received SBP and 30 received EP. TB incidences were 8% and 0%, respectively (P = .0487). One of these patients had INH resistance, and one patient experienced INH-induced hepatotoxicity (P = .1591); both were in the SBP group. CONCLUSION: The low rates of TB infection, INH-induced hepatotoxicity, and INH resistance in the EP group suggest that INH prophylaxis appears to prevent TB and can be safely used in all LT recipients. However, prospective studies using large sample sizes are required to confirm these findings.


Asunto(s)
Isoniazida/uso terapéutico , Tuberculosis , Adulto , Antituberculosos/uso terapéutico , Femenino , Humanos , Pulmón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Arabia Saudita , Receptores de Trasplantes , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control , Adulto Joven
6.
Mycoses ; 63(5): 452-460, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32072717

RESUMEN

BACKGROUND: Candida auris is a difficult-to-diagnose multidrug-resistant yeast that can cause invasive infections with high mortality. Since emerging in 2009, this pathogen has been associated with numerous outbreaks around the world. Whole genome sequencing (WGS) is instrumental for understanding the emergence and local transmission of this pathogen. OBJECTIVES: To describe the clinical, molecular characteristics of Candida auris infection and clinical outcome in our centre. PATIENTS AND METHODS: Patients with positive cultures for Candida auris were identified in a microbiology database. Clinical characteristics and antifungal susceptibility were obtained. Isolates were sent to the US CDC for whole genome sequencing. RESULTS: Seven unique patients with eight different isolates were identified. Seven isolates were sent to the US CDC for whole genome sequencing. None of the patients had bloodstream infection. Thirty-day mortality was higher in infected patients compared with those who were colonised. Seven of the eight isolates were resistant to both fluconazole, and five were resistant to amphotericin B. WGS analysis demonstrated that the seven isolates belonged to the South Asian clade but formed two distinct subclades suggesting two independent introductions and ongoing transmission within the facility. CONCLUSIONS: Candida auris is associated with a high mortality rate in infected patients. Strict infection control measures and surveillance for asymptomatic cases are warranted to halt ongoing transmission.


Asunto(s)
Candida/genética , Candidiasis/microbiología , Candidiasis/transmisión , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Infecciones Asintomáticas , Candida/patogenicidad , Candidiasis/mortalidad , Brotes de Enfermedades , Farmacorresistencia Fúngica Múltiple , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Arabia Saudita , Resultado del Tratamiento , Secuenciación Completa del Genoma
8.
Sci Rep ; 14(1): 14459, 2024 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914597

RESUMEN

Stenotrophomonas maltophilia is a nonfermenting gram-negative bacterium associated with multiple nosocomial outbreaks. Antibiotic resistance increases healthcare costs, disease severity, and mortality. Multidrug-resistant infections (such as S. maltophilia infection) are difficult to treat with conventional antimicrobials. This study aimed to investigate the isolation rates, and resistance trends of S. maltophilia infections over the past 19 years, and provide future projections until 2030. In total, 4466 patients with S. maltophilia infection were identified. The adult and main surgical intensive care unit (ICU) had the highest numbers of patients (32.2%), followed by the cardiology department (29.8%), and the paediatric ICU (10%). The prevalence of S. maltophilia isolation increased from 7% [95% confidence interval (CI) 6.3-7.7%] in 2004-2007 to 15% [95% CI 10.7-19.9%] in 2020-2022. Most S. maltophilia isolates were resistant to ceftazidime (72.5%), levofloxacin (56%), and trimethoprim-sulfamethoxazole (14.05%), according to our study. A consistent and significant difference was found between S. maltophilia-positive ICU patients and non-ICU patients (P = 0.0017) during the three-year pandemic of COVID-19 (2019-2021). The prevalence of S. maltophilia isolates is expected to reach 15.08% [95% CI 12.58-17.59%] by 2030. Swift global action is needed to address this growing issue; healthcare authorities must set priorities and monitor infection escalations and treatment shortages.


Asunto(s)
Antibacterianos , Infecciones por Bacterias Gramnegativas , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/efectos de los fármacos , Stenotrophomonas maltophilia/aislamiento & purificación , Humanos , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Estudios Retrospectivos , Prevalencia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Masculino , Femenino , Adulto , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Farmacorresistencia Bacteriana Múltiple , Unidades de Cuidados Intensivos/estadística & datos numéricos , COVID-19/epidemiología , Niño , Farmacorresistencia Bacteriana , Anciano , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/tratamiento farmacológico
9.
Diagnostics (Basel) ; 14(2)2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38248079

RESUMEN

Human cytomegalovirus (HCMV) infection may be asymptomatic in healthy individuals but can cause severe complications in immunocompromised patients, including transplant recipients. Breakthrough and drug-resistant HCMV infections in such patients are major concerns. Clinicians are first challenged to accurately diagnose HCMV infection and then to identify the most effective antiviral drug and determine when to initiate therapy, alter drug dosage, or switch medication. This review critically examines HCMV diagnostics approaches, particularly for immunocompromised patients, and the development of genotypic techniques to rapidly diagnose drug resistance mutations. The current standard method to identify prevalent and well-known resistance mutations involves polymerase chain reaction amplification of UL97, UL54, and UL56 gene regions, followed by Sanger sequencing. This method can confirm clinical suspicion of drug resistance as well as determine the level of drug resistance and range of cross-resistance with other drugs. Despite the effectiveness of this approach, there remains an urgent need for more rapid and point-of-care HCMV diagnosis, allowing for timely lifesaving intervention.

10.
Int J Infect Dis ; 143: 107015, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38521447

RESUMEN

An mpox outbreak was declared in July 2022 by the world health organization (WHO). It causes a mild self-limiting disease however; in immunosuppressed hosts, it tends to cause severe disseminated infection. Most cases of mpox in sold organ transplant (SOT) recipients reported in the literature were treated with tecovirimat. Here we report two cases of severe disseminated mpox infection in renal transplant recipients that were successfully treated with brincidofovir. Both patients were discharged from the hospital with no immediate significant side effects from brincidofovir reported until the submission of this report.


Asunto(s)
Antivirales , Citosina , Citosina/análogos & derivados , Huésped Inmunocomprometido , Trasplante de Riñón , Organofosfonatos , Humanos , Trasplante de Riñón/efectos adversos , Antivirales/uso terapéutico , Citosina/uso terapéutico , Masculino , Organofosfonatos/uso terapéutico , Adulto , Receptores de Trasplantes , Resultado del Tratamiento , Persona de Mediana Edad
11.
J Infect Public Health ; 17(7): 102452, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38820895

RESUMEN

BACKGROUND: Amidst the persistent global health threat posed by the evolving SARS-CoV-2 virus throughout the four-year-long COVID-19 pandemic, the focus has now turned to the Omicron variant and its subvariant, JN.1, which has rapidly disseminated worldwide. This study reports on the characteristics and clinical manifestations of patients during the surge of the JN.1 variant in Saudi Arabia; it also investigates the evolution of SARS-CoV-2 variants in organ transplant patients and identifies patient risk factors. METHODS: A total of 151 nasopharyngeal samples from patients with PCR-confirmed SARS-CoV-2 infection were collected between September 2023 and January 2024. Demographic and clinical data of the patients were obtained from electronic health records. All confirmed positive samples underwent sequencing using Ion GeneStudio and the Ion AmpliSeq™ SARS-CoV-2 panel. RESULTS: During the surge of the JN.1 variant, the average age of the patients was 40 years, ranging from 3 to 93 years, and nearly 50% of the patients were male. Our investigation revealed that the J.N variant predominantly infected patients with comorbidities or organ transplant recipients (57.6%). Moreover, patients with comorbidities or organ transplants exhibited a higher number of mutations. In our organ transplant cohort, an increased total number of spike mutations was associated with a lower risk of developing severe disease (OR = 0.96, 95% CI: 0.93-0.98). CONCLUSIONS: Although JN.1 may not prove to be particularly harmful, it is crucial to recognize the persistent emergence of concerning variants, which create new pathways for the virus to evolve. The ongoing evolution of SARS-CoV-2 is evident in the continuous divergence of these variants from the original strain that marked the onset of the pandemic nearly four years ago.


Asunto(s)
COVID-19 , Trasplante de Órganos , SARS-CoV-2 , Receptores de Trasplantes , Humanos , Arabia Saudita/epidemiología , COVID-19/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , SARS-CoV-2/genética , Adolescente , Adulto Joven , Niño , Preescolar , Anciano de 80 o más Años , Receptores de Trasplantes/estadística & datos numéricos , Trasplante de Órganos/efectos adversos , Factores de Riesgo
12.
J Infect Public Health ; 17(2): 299-307, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38154433

RESUMEN

BACKGROUND: Pseudomonas aeruginosa is an opportunistic bacterium that causes serious hospital-acquired infections. To assess the risk of clinically isolated P. aeruginosa to human health, we analyzed the resistance and virulence mechanisms of a collection of clinical isolates. METHODS: This was a retrospective study in which P. aeruginosa isolates collected from January 1, 2018 to August 31, 2019 were analyzed using phenotypic and whole-genome sequencing (WGS) methods. The analysis included 48 clinical samples. Median patient age was 54.0 (29.5) years, and 58.3% of patients were women. Data from the microbiology laboratory database were reviewed to identify P. aeruginosa isolates. All unique isolates available for further testing were included, and related clinical data were collected. Infections were defined as hospital acquired if the index culture was obtained at least 48 h after hospitalization. RESULTS: High-risk P. aeruginosa clones, including sequence types (STs) ST235 and ST111, were identified, in addition to 12 new STs. The isolates showed varying degrees of biofilm formation ability when evaluated at room temperature, along with reduced metabolic activity, as measured by metabolic staining, suggesting their ability to evade antimicrobial therapy. Most isolates (77.1%) were multidrug resistant (MDR), with the highest resistance and susceptibility rates to beta-lactams and colistimethate sodium, respectively. CONCLUSIONS: The MDR phenotypes of the examined isolates can be explained by the high prevalence of efflux-mediated resistance- and hydrolytic enzyme-encoding genes. These isolates had high cytotoxic potential, as indicated by the detection of toxin production-related genes.


Asunto(s)
Antibacterianos , Infecciones por Pseudomonas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Virulencia/genética , Pseudomonas aeruginosa , Estudios Retrospectivos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Secuenciación Completa del Genoma , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/genética
13.
Microorganisms ; 12(3)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38543518

RESUMEN

The genome of severe acute respiratory coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has undergone a rapid evolution, resulting in the emergence of multiple SARS-CoV-2 variants with amino acid changes. This study aimed to sequence the whole genome of SARS-CoV-2 and detect the variants present in specimens from Saudi Arabia. Furthermore, we sought to analyze and characterize the amino acid changes in the various proteins of the identified SARS-CoV-2 variants. A total of 1161 samples from patients diagnosed with COVID-19 in Saudi Arabia, between 1 April 2021 and 31 July 2023, were analyzed. Whole genome sequencing was employed for variant identification and mutation analysis. The statistical analysis was performed using the Statistical Analytical Software SAS, version 9.4, and GraphPad, version 9.0. This study identified twenty-three variants and subvariants of SARS-CoV-2 within the population, with the Omicron BA.1 (21K) variant (37.0%) and the Delta (21J) variant (12%) being the most frequently detected. Notably, the Omicron subvariants exhibited a higher mean mutation rate. Amino acid mutations were observed in twelve proteins. Among these, the spike (S), ORF1a, nucleocapsid (N), and ORF1b proteins showed a higher frequency of amino acid mutations compared to other the viral proteins. The S protein exhibited the highest incidence of amino acid mutations (47.6%). Conversely, the ORF3a, ORF8, ORF7a, ORF6, and ORF7b proteins appeared more conserved, demonstrating the lowest percentage and frequency of amino acid mutations. The investigation of structural protein regions revealed the N-terminal S1 subunit of the S protein to frequently harbor mutations, while the N-terminal domain of the envelope (E) protein displayed the lowest mutation frequency. This study provides insights into the variants and genetic diversity of SARS-CoV-2, underscoring the need for further research to comprehend its genome evolution and the occurrence of mutations. These findings are pertinent to the development of testing approaches, therapeutics, and vaccine strategies.

14.
Cureus ; 15(8): e44356, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37779746

RESUMEN

Invasive fungal infection (IFI) is a significant global healthcare concern among critically ill and immunocompromised patients. In Middle Eastern countries, IFI has been steadily increasing among hospitalized patients in the past two decades. Diagnosis of IFI at an early stage is crucial for efficient management. Invasive fungal infection management is complex and requires the involvement of physicians from different specialties. There are several challenges associated with IFI management in the countries in the Middle East. This review aims to understand the key challenges associated with IFI management in the Middle East, encompassing epidemiology, diagnosis, therapeutic options, and optimizing a multidisciplinary approach. In addition, this review aims to incorporate expert opinions from multidisciplinary fields for optimizing IFI management in different Middle Eastern countries by addressing key decision points throughout the patient's journey. Lack of epidemiological data on fungal infections, slow and poorly sensitive conventional culture-based diagnostic tests, limited availability of biomarker testing, lack of awareness of clinical symptoms of the disease, limited knowledge on fungal infections, lack of local practice guidelines, and complicated disease management are the major challenges associated with IFI diagnosis and management in the Middle Eastern countries. Implementation of a multidisciplinary approach, antifungal stewardship, improved knowledge of fungal infections, the use of rapid diagnostic tests, and enhanced epidemiological research are warranted to lower the IFI burden in the Middle East.

15.
Viruses ; 16(1)2023 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-38257726

RESUMEN

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.


Asunto(s)
COVID-19 , Trasplante de Órganos , Humanos , Femenino , Masculino , SARS-CoV-2/genética , COVID-19/epidemiología , Epidemiología Molecular , Estudios de Cohortes , Trasplante de Órganos/efectos adversos
16.
Microorganisms ; 11(5)2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37317262

RESUMEN

SARS-CoV-2 genomic mutations outside the spike protein that may increase transmissibility and disease severity have not been well characterized. This study identified mutations in the nucleocapsid protein and their possible association with patient characteristics. We analyzed 695 samples from patients with confirmed COVID-19 in Saudi Arabia between 1 April 2021, and 30 April 2022. Nucleocapsid protein mutations were identified through whole genome sequencing. 𝜒2 tests and t tests assessed associations between mutations and patient characteristics. Logistic regression estimated the risk of intensive care unit (ICU) admission or death. Of the 60 mutations identified, R203K was the most common, followed by G204R, P13L, E31del, R32del, and S33del. These mutations were associated with reduced risk of ICU admission. P13L, E31del, R32del, and S33del were also associated with reduced risk of death. By contrast, D63G, R203M, and D377Y were associated with increased risk of ICU admission. Most mutations were detected in the SR-rich region, which was associated with low risk of death. The C-tail and central linker regions were associated with increased risk of ICU admission, whereas the N-arm region was associated with reduced ICU admission risk. Consequently, mutations in the N protein must be observed, as they may exacerbate viral infection and disease severity. Additional research is needed to validate the mutations' associations with clinical outcomes.

17.
Biotechniques ; 74(2): 69-75, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36794696

RESUMEN

The global demand for rapid identification of circulating SARS-CoV-2 variants of concern has led to a shortage of commercial kits. Therefore, this study aimed to develop and validate a rapid, cost-efficient genome sequencing protocol to identify circulating SARS-CoV-2 (variants of concern). Sets of primers flanking the SARS-CoV-2 spike gene were designed, verified and then validated using 282 nasopharyngeal positive samples for SARS-CoV-2. Protocol specificity was confirmed by comparing these results with SARS-CoV-2 whole-genome sequencing of the same samples. Out of 282 samples, 123 contained the alpha variant, 78 beta and 13 delta, which were indicted using in-house primers and next-generation sequencing; the numbers of variants found were 100% identical to the reference genome. This protocol is easily adaptable for detection of emerging variants during the pandemic.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2/genética , Cartilla de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación
18.
Healthcare (Basel) ; 11(4)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36833136

RESUMEN

BACKGROUND: In response to the global Mpox outbreaks, this survey aimed to assess the knowledge, perceptions, and advocacy of Mpox vaccines among solid organ transplant healthcare workers (HCWs) in Saudi Arabia. METHODS: A cross-sectional survey was conducted among solid organ transplant HCWs in Saudi Arabia from 15 August to 5 September 2022. A total of 199 responses were received from participants primarily working in the kidney (54.8%) and liver (14.6%) transplant units. RESULTS: The survey found that most participants were aware of the 2022 Mpox outbreak, but the majority were more concerned about COVID-19 than Mpox. While the majority of participants thought laboratory personnel and HCWs in direct contact with Mpox patients should receive the vaccine, less than 60% believed that all HCWs should be vaccinated. Additionally, over half of the participants lacked knowledge of animal-human transmission of the virus. CONCLUSION: The results highlight the need for increased education on Mpox among transplant HCWs in Saudi Arabia, particularly regarding the virus's transmission dynamics and vaccines. This education is crucial to improve HCWs' understanding of this emerging disease, especially given their vulnerability during the COVID-19 pandemic.

19.
Antibiotics (Basel) ; 12(3)2023 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-36978475

RESUMEN

Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.

20.
J Infect Public Health ; 16(11): 1837-1847, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37769584

RESUMEN

Infectious diseases present a global challenge, requiring accurate diagnosis, effective treatments, and preventive measures. Artificial intelligence (AI) has emerged as a promising tool for analysing complex molecular data and improving the diagnosis, treatment, and prevention of infectious diseases. Computer-aided detection (CAD) using convolutional neural networks (CNN) has gained prominence for diagnosing tuberculosis (TB) and other infectious diseases such as COVID-19, HIV, and viral pneumonia. The review discusses the challenges and limitations associated with AI in this field and explores various machine-learning models and AI-based approaches. Artificial neural networks (ANN), recurrent neural networks (RNN), support vector machines (SVM), multilayer neural networks (MLNN), CNN, long short-term memory (LSTM), and random forests (RF) are among the models discussed. The review emphasizes the potential of AI to enhance the accuracy and efficiency of diagnosis, treatment, and prevention of infectious diseases, highlighting the need for further research and development in this area.

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