Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs.

OBJECTIVES: During the COVID-19 pandemic in Qatar, many patients who were severely ill were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Here, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drug resistance. METHODS: Whole genomes of 76 clinical C. auris isolates, including 65 from patients with COVID-19 collected from March 2020 to June 2021, from nine major hospitals were sequenced on Illumina NextSeq. Single nucleotide polymorphisms were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data were compared with those published prior to the COVID-19 pandemic from 2018 to 2020 in Qatar. RESULTS: Genomic analysis revealed low genetic variability among the isolates from patients with and without COVID-19, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, more than 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions: Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison with pre-COVID-19 pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. DISCUSSION: Candida auris isolates from patients with COVID-19 and from most patient samples without COVID-19 in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins, and amphotericin B. Understanding the epidemiology and drug resistance will inform the infection control strategy and drug therapy.

Characteristics and comparisons of acute stroke in "recovered" to "active COVID-19 and "pre-pandemic" in Qatar database.

Understanding the relationship of COVID-19 to stroke is important. We compare characteristics of pre-pandemic stroke (PPS), cases in acute COVID infection (CS) and in patients who have recovered from COVID-19 infection (RCS). We interrogated the Qatar stroke database for all stroke admissions between Jan 2020 and Feb 2021 (PPS) to CS and RCS to determine how COVID-19 affected ischemic stroke sub-types, clinical course, and outcomes prior to, during and post-pandemic peak. There were 3264 cases admitted (pre-pandemic: 3111, stroke in COVID-19: 60 and recovered COVID-19 stroke: 93). Patients with CS were significantly younger, had more severe symptoms, fever on presentation, more ICU admissions and poor stroke recovery at discharge when compared to PPS and RCS. Large vessel disease and cardioembolic disease was significantly higher in CS compared to PPS or RCS. There was a significant decline in stroke mimics in CS. Stroke in RCS has characteristics similar to PPS with no evidence of lasting effects of the virus on the short-term. However, CS is a more serious disease and tends to be more severe and have a poor prognosis.

Challenges in the diagnosis of pulmonary mucormycosis in a diabetic with a review of literature.

Diabetes Mellitus appears to be the most common underlying condition associated with mucormycosis; a rare opportunistic fungal infection associated with high morbidity and mortality. Pulmonary mucormycosis may mimic pneumonia and thus pose challenges in achieving a timely diagnosis critical to successful outcomes. We present a case of a 65-year-old diabetic who presented with fever and haemoptysis that was managed as pneumonia. A bronchial alveolar lavage grew Rhizopus mould that was thought to be a contaminant as he responded well to antibiotics. He required another admission in 4 weeks due to worsening symptoms. Failure to respond to antibiotics and ongoing clinical and radiological deterioration led to a lobectomy that confirmed a diagnosis of pulmonary mucormycosis. He responded well to surgical resection and antifungal therapy with a complete recovery. Elusive clinical presentation and insensitive conventional diagnostic techniques may make the diagnosis of mucormycosis challenging. Our case reports highlight the issues involved in the diagnosis and management of pulmonary Mucormycosis mimicking as pneumonia.

SARS-CoV-2 and guttate psoriasis: A case report and review of literature.

Guttate psoriasis is a rare dermatological presentation of SARS-CoV-2 infection and is seen mainly in patients with an underlying disease psoriasis.

Genomic Epidemiology of Candida auris in Qatar Reveals Hospital Transmission Dynamics and a South Asian Origin.

Candida auris is an emerging, multidrug-resistant fungal pathogen that has become a public health threat with an increasing incidence of infections worldwide. Candida auris spreads easily among patients within and between hospitals. Infections and outbreaks caused by C. auris have been reported in the Middle East region including Oman, Kuwait, Saudi Arabia, and Qatar; however, the origin of these isolates is largely unknown. Pathogen whole genome sequencing (WGS) was used to determine the epidemiology and drug resistance mutations of C. auris in Qatar. Forty-four samples isolated from patients in three hospitals and the hospital environment were sequenced by Illumina NextSeq. Core genome single nucleotide polymorphisms (SNPs) revealed that all isolates belonged to the South Asian lineage with genetic heterogeneity that suggests previous acquisition from foreign healthcare. The genetic variability among the outbreak isolates in the two hospitals (A and B) was low. Four environmental isolates clustered with the related clinical isolates, and epidemiologically linked isolates clustered together, suggesting that the ongoing transmission of C. auris could be linked to infected/colonized patients and the hospital environment. Prominent mutations Y132F and K143R in ERG11 linked to increased fluconazole resistance were detected.

Paragonimus infection: Rare manifestation with pericardial effusion: A Case report and Literature review.

BACKGROUND: Paragonimus, is a globally distributed trematode, with human disease limited to endemic regions. It can be transmitted to humans through ingestion of intermediate hosts that are crustaceans. Most symptomatic infections consist of pulmonary disease, and in aberrant migration of immature flukes, extrapulmonary manifestations may occur. These presentations are relatively uncommon and may affect various organs with atypical Clinico-radiological pathologies that are often challenging to diagnose. Pericardial involvement has scarcely been reported before. Furthermore, the management, clinical outcomes and potential complications of this involvement remain unclear. CASE REPORT: Our patient is a 31-year-old Nepalese male who presented with abdominal distension and lower limb oedema. Initial work up revealed pericardial effusion, and analysis was suggestive of exudative lymphocytic effusion. Supported by positive QuantiFERON result along with his demographic data, the patient was treated presumptively as a case of tuberculous pericarditis, despite the negative initial Mycobacterial Tuberculosis work up. During follow up, the patient lacked clinical response and repeated echocardiography showed signs of tamponade with concomitant pleural effusion. subsequently video-assisted-thoracoscopy pericardial window along with pericardial and pleural biopsy were performed. Histopathological examination of the biopsied tissue revealed non-necrotizing granulomas containing a parasitic egg suggestive of Paragonimus. Fortunately, the patient received treatment with praziquantel and subsequently made good clinical recovery. CONCLUSION: Diagnosis of extrapulmonary Paragonimus infection can be challenging given its rarity and clinical picture mimicking other infectious aetiologies. Pericardial involvement is seldom reported in the literature and clinical suspicion should be raised particularly when dealing with atypical presentations and relevant demographic data.

Prevalence of elevated anxiety symptoms among children in quarantine with COVID-19 infection in the State of Qatar: A cross-sectional study.

BACKGROUND: Children are particularly vulnerable to the psychological effects of the COVID-19 pandemic. The disruption in daily life has impacted children significantly. Moreover, the increased worrying associated with the probability of getting infected or becoming seriously unwell due to infection can potentially precipitate anxiety disorders among children. OBJECTIVE: This study aimed to determine rates of elevated anxiety symptoms in children with COVID-19 infection. It also explored whether there were any differences in terms of age, gender, and residency status. METHOD: A cross-sectional, questionnaire-based study with 88 participants (children aged 7-13 years, 54.5% males, 45.5% females) from two institutional quarantine centers. The Spence Children's Anxiety Scale and its validated Arabic version (self-reported questionnaires) were used to measure anxiety symptoms. RESULTS: 36.3% children reported elevated anxiety symptoms. A lower rate of 32.8% was reported in younger children (7-11 years) compared to 45.8% in older children (12 and 13 years). 70.4% and 57.9% children reported physical injury fears and separation anxiety respectively. A higher prevalence of overall anxiety was reported in children from expatriate families (40.6%) compared to native children (25%). The difference in the mean scores between the expatriate and native group of children was found statistically significant for obsessive-compulsive symptoms. CONCLUSIONS: The prevalence of elevated anxiety symptoms among children in quarantine with COVID-19 infection can be much higher than that reported in the general population. Older children can have elevated anxiety symptoms more commonly than their younger counterparts can. Expatriate children are likely to be more vulnerable to the psychological impact of the pandemic compared to children from local families. Our results suggest the crucial need of focusing on the psychological impact of COVID-19 pandemic on children. The prioritization and effective management of the mental health needs of children should be a vital component of the overall, global response to the pandemic.

Impact of Direct Acting Antiviral Agent Therapy upon Extrahepatic Manifestations of Hepatitis C Virus Infection.

PURPOSE OF REVIEW: Direct acting antiviral agents (DAAs) have emerged as simple, short, safe, and effective treatments for chronic hepatitis C (CHC) infection. CHC is a systemic disease with frequent and multiple extrahepatic manifestations. The beneficial effects of DAA treatment regimens extend beyond improvement in liver-related outcomes to amelioration of extra hepatic manifestations and are likely to have economic implications. The purpose of this review is to evaluate the effect of DAAs on extra hepatic manifestations of CHC virus infection. RECENT FINDINGS: Recent studies indicate that DAAs are associated with reduction in all-cause mortality, even in patients without significant hepatic fibrosis. They are also associated with reduction in incident cardiovascular disease and diabetes. DAAs are the mainstay of treatment in HCV-associated cryoglobulinemia and lymphoma. Successful HCV therapy with DAAs also improves patient-related outcomes such as health-related quality of life. DAAs improve extrahepatic manifestations of CHC virus infection. Future studies are needed to evaluate the long-term durability of treatment response and for accounting amelioration of extrahepatic manifestations into the cost effectiveness of DAA regimens.

Early events in herpes simplex virus lifecycle with implications for an infection of lifetime.

Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral "surfing" along filopodia. Viral glycoproteins then bind to one or more of several cell surface receptors, such as herpesvirus entry mediator (HVEM), nectin-1, 3-O sulfated heparan sulfate (3-OS HS), paired immunoglobulin-like receptor α, and non-muscle myosin-IIA. At least five viral envelope glycoproteins participate in entry and these include gB, gC, gD and gH-gL. Post-entry, these glycoproteins may also facilitate cell-to-cell spread of the virus, which helps in the evasion of physical barriers as well as several components of the innate and adaptive immune responses. The spread may be facilitated by membrane fusion, movement across tight junctions, transfer across neuronal synapses, or the recruitment of actin-containing structures. This review summarizes some of the recent advances in our understanding of HSV entry and cell-to-cell spread.

The septic shock-associated IL-10 -1082 A > G polymorphism mediates allele-specific transcription via poly(ADP-Ribose) polymerase 1 in macrophages engulfing apoptotic cells.

The biallelic IL-10 single nucleotide polymorphism at -1082 of the promoter region linked to individual variation in cytokine inducibility has been strongly implicated in several pathological conditions including the development of, and outcomes in, septic shock during pneumococcal infection, acute respiratory distress syndrome, and cardiac dysfunction. However, the molecular basis of the single nucleotide polymorphism-mediated variable IL-10 production levels has not been explored. In this study, we report that the -1082G > A alleles in the promoter region of the human IL-10 gene physically interact with a nuclear protein in an allele-specific manner that results in different levels of IL-10 transcription. This protein has been identified as poly(ADP-ribose) polymerase 1 (PARP-1). We show that PARP-1 acts as a transcription repressor, and its DNA-binding activity is strongly regulated in macrophages that engulf apoptotic cells but not stimulated with LPS. These findings unveil a novel role of PARP-1 in the regulation of IL-10 production in an allele-dependent way, which determines individual susceptibility to sepsis-induced inflammatory pathology and the immunological sequelae in a physiological process in which clearance of infection-induced apoptotic cells by professional phagocytes triggers the cytokine synthesis.

Development of a transmucosal technique for erythromycin delivery to treat gastroparesis.

Gastroparesis is a serious condition that limits meal or medication emptying from the stomach, resulting in a variety of symptoms, altered nutrition, and inconsistent medication delivery. Our aim was to develop a transmucosal system to deliver erythromycin (EM), a gastric prokinetic agent, to bypass intestinal absorption. Humans and Sprague-Dawley rats were given EM by injection, gavage, or transmucosal gel with or without permeation enhancers. Pharmacokinetics were compared between subjects and across different delivery modalities. Drug concentrations in blood were measured using a bioassay. Design of Experiment techniques were used to optimize transmucosal antibiotic delivery in the Sprague-Dawley Model. Finally, we examined the scale-up of transmucosal delivery to human patients. Transmucosal delivery of EM increased with addition of ursodeoxycholate. While EM release from gels with ursodeoxycholate was significant, it was less than by injection. Scale-up to a human model indicated that delivery of EM using this transmucosal delivery system is insufficient for clinical need. The transport of EM seems limited by its solubility in water and thickness of the epithelial cell layers. Providing successful transmucosal delivery of EM and similar molecules to humans will require more aggressive techniques to disrupt the cellular layer, or pro-drug strategies to increase lipid solubility.