Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant (preprint)

This study investigated the effectiveness of natural infection in preventing reinfection with the JN.1 variant during a large JN.1 wave in Qatar, using a test-negative case-control study design. The overall effectiveness of previous infection in preventing reinfection with JN.1 was estimated at only 1.8% (95% CI: -9.3-12.6%). This effectiveness demonstrated a rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9-94.7%) within 3 to less than 6 months after the previous infection to 50.9% (95% CI: -11.8-78.7%) in the subsequent 3 months, and further dropping to 18.3% (95% CI: -34.6-56.3%) in the subsequent 3 months. Ultimately, it reached a negligible level after one year. The findings show that the protection of natural infection against reinfection with JN.1 is strong only among those who were infected within the last 6 months, with variants such as XBB*. However, this protection wanes rapidly and is entirely lost one year after the previous infection. The findings support considerable immune evasion by JN.1.

Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication.

The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due to PLpro's restricted substrate binding pocket. In this report, we screened a 115 000-compound library for PLpro inhibitors and identified a new pharmacophore, based on a mercapto-pyrimidine fragment that is a reversible covalent inhibitor (RCI) of PLpro and inhibits viral replication in cells. Compound 5 had an IC50 of 5.1 µM for PLpro inhibition and hit optimization yielded a derivative with increased potency (IC50 0.85 µM, 6-fold higher). Activity based profiling of compound 5 demonstrated that it reacts with PLpro cysteines. We show here that compound 5 represents a new class of RCIs, which undergo an addition elimination reaction with cysteines in their target proteins. We further show that their reversibility is catalyzed by exogenous thiols and is dependent on the size of the incoming thiol. In contrast, traditional RCIs are all based upon the Michael addition reaction mechanism and their reversibility is base-catalyzed. We identify a new class of RCIs that introduces a more reactive warhead with a pronounced selectivity profile based on thiol ligand size. This could allow the expansion of RCI modality use towards a larger group of proteins important for human disease.

A turning point in COVID-19 severity and fatality during the pandemic: A national cohort study in Qatar (preprint)

Background: This study assessed the evolution of COVID-19 severity and fatality by utilizing rigorous and standardized criteria that were consistently applied throughout the pandemic in Qatar. Methods: A national cohort study was conducted on Qataris, using data on COVID-19 acute-care and ICU hospitalizations, as well as severe, critical, and fatal COVID-19 cases classified according to the World Health Organization criteria. Results: The cumulative incidence of severe, critical, or fatal COVID-19 after 3.14 years of follow-up was 0.45% (95% CI: 0.43-0.47%). The incidence rate for severe, critical, or fatal COVID-19 throughout the pandemic was 1.43 (95% CI: 1.35-1.50) per 1,000 person-years. In the pre-omicron phase, first omicron wave, and combined phases, it was 2.01 (95% CI: 1.90-2.13), 3.70 (95% CI: 3.25-4.22), and 2.18 (95% CI: 2.07-2.30) per 1,000 person-years, respectively. The post-first omicron phase saw a drastic drop to 0.10 (95% CI: 0.08-0.14) per 1,000 person-years, a 95.4% reduction. Among all severe, critical, and fatal cases, 99.5% occurred during the primary infection. The cumulative incidence of fatal COVID-19 was 0.042% (95% CI: 0.036-0.050%), with an incidence rate of 0.13 (95% CI: 0.11-0.16) per 1,000 person-years. In the post-first omicron phase, the incidence rate of fatal COVID-19 decreased by 90.0% compared to earlier stages. Both severity and fatality exhibited an exponential increase with age and a linear increase with the number of coexisting conditions. Conclusions: The conclusion of the first omicron wave was a turning point in the severity of the pandemic. While vaccination and enhanced case management reduced severity gradually, the rapid accumulation of natural immunity during the initial omicron wave appears to have played the crucial role in driving this shift in severity.

Effects of SARS-CoV-2 Alpha, Beta, and Delta variants, age, vaccination, and prior infection on infectiousness of SARS-CoV-2 infections.

In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness in small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination.

Synthesis, spectroscopic, crystallographic, quantum and molecular docking investigations of cis-4,5-diphenylimidazolidine-2-thione

We present the synthesis and characterization of stereoselective thione. The synthetic procedure includes readily available starting materials and minimum side products. The reaction of meso‑stilbenediamine with carbon disulphide in the presence of strong base gave cis-4,5-diphenylimidazolidine-2-thione (DPIT) in an excellent yield. The thione compound was characterized via FT-IR and mass spectroscopy. In addition, the crystal structure of it was determined by single crystal X-rays diffraction analysis which inferred that the molecular configuration was stabilized by intramolecular π⋯π stacking interaction. The crystal packing was mainly stabilized by N-H⋯S bonding. Hirshfeld surface analysis was performed for the exploration of the intermolecular interactions. Void analysis was carried out to predict the mechanical stability. Interaction energy between the molecular pairs is calculated which showed that the dispersion energy played a dominant role in the stabilization of the crystal packing. Moreover, the quantum computational methods were used to study the molecular structure and electronic properties of entitled compound. The molecular geometries were optimized for possible thione and thiole tautomeric structures. A comparison of total energy of molecular tautomers indicates that thione tautomer possesses lower total energy which is about 20.18 Kcal/mol lower than thiole tautomer. The electronic properties of thione derivative were studied including 3-D wavefunction delocalization of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals and their orbital energy gap. The HOMO-LUMO energy gap for DPIT was found to be 4.874 eV. The delocalization of wavefunction indicates the probable presence of HOMO and HOMO-1 are mainly localized over C-S bond owing to the presence of lone pair of electrons in the sulfur atom. Additionally, the molecular docking study was also carried out for main protease (Mpro) of SARS-CoV-2. The binding energy calculation and investigation of intermolecular interactions highlighted the probable inhibition tendency of DPIT for SARS-CoV-2. The present experimental and computational studies indicate a significant potential of entitled molecule for electronic and biological perspectives.

Media dependency, uses, and gratifications, and knowledge gap in online learning during the COVID-19 pandemic: The case of Afghanistan and Turkey

This study aims to address how dependency on media for learning purposes increased dramatically during COVID-19 by assessing the effects of online learning on students' academic performance during the COVID-19 pandemic with a specific focus on Afghanistan and Turkey. Through the theoretical framework of the uses and gratifications theory, the study tries to explain the uses of devices to use the internet for learning purposes to gratify the needs of students during the pandemic. Furthermore, the study tries to address how the knowledge gap between students of different countries affects students' academic performance during online learning and their uses and gratifications of media during COVID-19. The study followed the quantitative research method where primary data was collected from 400 participants (200 Afghan and 200 Turkish students) through a close-ended survey questionnaire.The study found that Turkish students were more satisfied with the online learning process during the COVID-19 pandemic than Afghan students. Furthermore, there is a considerable difference in attitude, perceived impact, and satisfaction with online learning during the COVID-19 pandemic among Afghan and Turkish students. Due to the knowledge gap, Turkish students had a better attitude toward online learning during the pandemic as compared to Afghan students. The study also found that Turkish students perceived a more significant impact of online learning on their academic performance during the COVID-19 pandemic in contrast to Afghan students. Limited access to different media and technological resources for Afghan students shaped their learning outcomes by lowering their academic performance.

A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication.

Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro, and had an IC50 of 18 µM for PLpro inhibition. Compound 1 also had low non-specific reactivity with thiols and reacted with glutathione 1-2 orders of magnitude slower than other commonly used electrophilic warheads. Finally, compound 1 had low toxicity in cells and mice and has a molecular weight of only 247 daltons and consequently has great potential for further optimization. Collectively, these results demonstrate that compound 1 is a promising lead fragment for future PLpro drug discovery campaigns.

Machine Learning Models Towards Prediction of COVID and Non-COVID 19 Patients in the Hospital's Intensive Care Units (ICU)

The global proliferation of COVID-19 prompted research towards the virus's detection and eventual eradication. One important area of research is the use of machine learning (ML) to realize and battle COVID-19. The goal of this study is to use machine learning to monitor COVID and non-COVID-19 patients and decide whether or not to transfer them to the intensive care unit (ICU). The precise disease diagnosis was essential due to the lack of oxygen supplementation in the majority of hospitals around the world. It will improve the effectiveness of the ICU facilities and lessen the load on the medical personnel and the ICU facilities by accurately forecasting how patients will be treated. If stable patients are recognized among all patients, home treatment could be established for stable patients. In this research, three machine learning algorithms were chosen as the method used, which are K-Nearest Neighbor (KNN), Support Vector Machine (SVM), and Extra Tree Classifier. These algorithms were chosen for their simplicity and robustness and based on the conducted literature review. A dataset containing 100 ICU and 131 stable patients of Covid and non-Covid samples from 24th Moscow City State Hospital was used. By using SMOTE technique with 10-fold cross-validation and feature selection on the dataset, KNN achieved an accuracy of 94.65%, SVM with an accuracy of 94.65%, and an accuracy of 96.18% for the Extra Tree Classifier. The outcomes of this research on the selected dataset prove how accurate these algorithms were able to predict the classes © 2022, Mathematical Modelling of Engineering Problems.All Rights Reserved.

Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study.

BACKGROUND: Long-term effectiveness of COVID-19 mRNA boosters in populations with different previous infection histories and clinical vulnerability profiles is inadequately understood. We aimed to investigate the effectiveness of a booster (third dose) vaccination against SARS-CoV-2 infection and against severe, critical, or fatal COVID-19, relative to that of primary-series (two-dose) vaccination over a follow-up duration of 1 year. METHODS: This observational, matched, retrospective, cohort study was done on the population of Qatar in people with different immune histories and different clinical vulnerability to infection. The source of data are Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation, and death. Associations were estimated using inverse-probability-weighted Cox proportional-hazards regression models. The primary outcome of the study is the effectiveness of COVID-19 mRNA boosters against infection and against severe COVID-19. FINDINGS: Data were obtained for 2 228 686 people who had received at least two vaccine doses starting from Jan 5, 2021, of whom 658 947 (29·6%) went on to receive a third dose before data cutoff on Oct 12, 2022. There were 20 528 incident infections in the three-dose cohort and 30 771 infections in the two-dose cohort. Booster effectiveness relative to primary series was 26·2% (95% CI 23·6-28·6) against infection and 75·1% (40·2-89·6) against severe, critical, or fatal COVID-19, during 1-year follow-up after the booster. Among people clinically vulnerable to severe COVID-19, effectiveness was 34·2% (27·0-40·6) against infection and 76·6% (34·5-91·7) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 61·4% (60·2-62·6) in the first month after the booster but waned thereafter and was modest at only 15·5% (8·3-22·2) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2·75* subvariant incidence, effectiveness was progressively negative albeit with wide CIs. Similar patterns of protection were observed irrespective of previous infection status, clinical vulnerability, or type of vaccine (BNT162b2 vs mRNA-1273). INTERPRETATION: Protection against omicron infection waned after the booster, and eventually suggested a possibility for negative immune imprinting. However, boosters substantially reduced infection and severe COVID-19, particularly among individuals who were clinically vulnerable, affirming the public health value of booster vaccination. FUNDING: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core (both at Weill Cornell Medicine-Qatar), Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, and Qatar University Biomedical Research Center.

Jordanian nursing students' engagement and satisfaction with e-learning during COVID-19 pandemic.

BACKGROUND: Nursing education was affected by the COVID-19 pandemic as most institutions shifted to e-learning. The aim of the current study was to examine students' engagement and satisfaction levels with e-learning during the COVID-19 pandemic. METHODS: A descriptive correlation design was used to guide this study. A voluntary response sampling method was used to recruit undergraduate nursing programs in Jordan. Data were collected using an electronic link to a self-reported questionnaire. RESULTS: A total of 1,562 undergraduate nursing students responded to the questionnaire. The study showed that most students have high engagement in the emotional, skills, and performance subscales and low engagement in the participation subscale. Further, they were moderately satisfied with e-learning during the COVID-19 pandemic. CONCLUSIONS: Students identified several issues regarding their e-learning, which must be considered to improve their engagement and satisfaction. Further, the study revealed several shortcomings in preparing students to attend e-learning classes.

Molecular interactions of Zyesami with the SARS-CoV-2 nsp10/nsp16 protein complex.

Background SARS-CoV-2 emerged in late 2019, causes COVID-19. Patients treated with Zyesami were found to be 3-fold decrease in respiratory failure and improvement in clinical outcome. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins that essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that required nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis. Objective We aimed the in silico determination of inhibitory consequences of Zyesami on the SARS-CoV-2 nsp10/nsp16 complex. Targeting SARS-CoV-2 nsp10/ nsp16 protein complex may be used for the development of drug against the COVID-19. Methods I-TASSER was used for secondary structure prediction of Zyesami. CABS-dock was used for modelling of Zyesami with SARS-CoV-2 nsp16 interaction. The docked complex was visualized using PyMol. The quality of the docking model was checked by using ProQdock. Results The 3D structure of SARS-CoV 2, nsp10/nsp16 showed that essential interactions exist between nsp10 and nsp16. Significant contact areas of Zyesami exist across amino acid residues of nsp10; Asn40-Thr47, Val57-Pro59, Gly69-Ser72, Cys77-Pro84, Lys93-Tyr96. In addition, polar contacts between nsp16 and Zyesami are Asn299-Ser440, Val297-Asn443, Gly149-Tyr437, Gln159-Lys430, Asn178-Arg429, Ser146-Arg429, Ser146-Arg429, Lys147-Arg429, Asr221-Thr422, Lys183-Asp423, Lys183-Asp423, and Gln219-Asp423 the residues are shown of nsp16 and Zyesami respectively. Conclusion The structural bioinformatics analyses have indicated the potential binding specificity of Zyesami and nsp16. Data predict how the initial binding of Zyesami with nsp10 and nsp16 may occur. Moreover, this binding could significantly inhibit the 2 -O-MTase activity of the SARS-CoV nsp10/16 complex.

Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: An observational study (preprint)

Background: Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population. Methods: We estimated these population immunities in Qatar population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies. Findings: Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped immediately after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November of 2021. Effectiveness declined linearly by ~1 percentage point every 5 days. After Omicron emergence, effectiveness dropped suddenly from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped immediately after Omicron emergence from 83.0% (95% CI: 65.6 -91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration. Interpretation: High population immunity may not be sustained beyond a year. This creates fertile grounds for repeated waves of infection to occur, but these waves may increasingly exhibit a benign pattern of infection. Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

On the Sensitivity and Affinity of Gold, Silver, and Platinum Surfaces against the SARS-CoV-2 Virus: A Comparative Computational Study.

The novel coronavirus disease and its complications have motivated the design of new sensors with the highest sensitivity, and affinity for the detection of the SARS-CoV-2 virus is considered in many research studies. In this research article, we employ full atomistic molecular dynamics (MD) models to study the interactions between the receptor binding domain (RBD) and spike protein of the coronavirus and different metals such as gold (Au), platinum (Pt), and silver (Ag) to analyze their sensitivity against this virus. The comparison between the RBD interactions with ACE2 (angiotensin-converting enzyme 2) and different metals indicates that metals have remarkable effects on the structural features and dynamical properties of the RBD. The binding site of the RBD has more affinity to the surfaces of gold, platinum, and silver than to the other parts of the protein. Moreover, the initial configuration of the RBD relative to the metal surface plays an important role in the stability of metal complexes with the RBD. The binding face of the protein to the metal surface has been changed in the presence of different metals. In other words, the residues of the RBD that participate in RBD interactions with the metals are different irrespective of the initial configurations in which the [Asn, Thr, Tyr], [Ser, Thr, Tyr], and [Asn, Asp, Tyr] residues of the protein have a greater affinity to Ag, Au, and Pt, respectively. The corresponding metals have a considerable affinity to the RBD, which due to strong interactions with the protein can change the secondary structure and structural features. Based on the obtained results during the complexation process between the protein and metals, the helical structure of the protein changes to the bend and antiparallel ß-sheets. The calculated binding energies for the RBD complexes with silver, gold, and platinum are -95.03, -138.03, and -133.96 kcal·mol-1, respectively. The adsorption process of the spike protein on the surfaces of different metals represents similar results and indicates that the entire spike protein of the coronavirus forms a more stable complex with the gold surface compared with other metals. Moreover, the RBD of the spike protein has more interactions with the surfaces than with the other parts of the protein. Therefore, it is possible to predict the properties of the coronavirus on the metal surface based on the dynamical behavior of the RBD. Overall, our computational results confirm that the gold surface can be considered as an outstanding substrate for developing new sensors with the highest sensitivity against SARS-CoV-2.

Impact of the COVID-19 pandemic on the management and outcomes of emergency surgical patients: A retrospective cohort study.

INTRODUCTION: The COVID-19 pandemic has led to drastic measures being implemented for the management of surgical patients across all health services worldwide, including the National Health Service in the United Kingdom. It is suspected that the virus has had a detrimental effect on perioperative morbidity and mortality. Therefore, the aim of this study was to assess the impact of the COVID-19 pandemic on these outcomes in emergency general surgical patients. METHODS: Emergency general surgical admissions were included in this retrospective cohort study in one of the COVID-19 hotspots in the South East of England. The primary outcome was the 30-day mortality rate. Secondary outcomes included the length of stay in hospital, complication rate and severity grade and admission rates to the ITU. RESULTS: Of 123 patients, COVID-19 was detected in 12.2%. Testing was not carried out in 26%. When comparing COVID-positive to COVID-negative patients, the mean age was 71.8 + 8.8 vs. 50.7 + 5.7, respectively, and female patients accounted for 40.0 vs. 52.6%. The 30-day mortality rate was 26.7 vs. 3.9 (OR 6.49, p = 0.02), respectively. The length of stay in hospital was 20.5 + 22.2 vs. 7.7 + 9.8 (p < 0.01), the rate of complications was 80.0 vs. 23.7 (OR 12.9, p < 0.01), and the rate of admission to the ITU was 33.3 vs. 7.9% (OR 5.83, p = 0.01). CONCLUSION: This study demonstrates the detrimental effect of COVID-19 on emergency general surgery, with significantly worsened surgical outcomes.

Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.

SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it with available clinical data and use it to simulate the effectiveness of vaccines against viral variants with lower antigenicity, increased virulence, or enhanced cell binding for various vaccine platforms. The analysis includes the omicron variant as well as hypothetical future variants with even greater immune evasion of vaccine-induced antibodies and addresses the potential benefits of the new bivalent vaccines. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts ongoing booster requirements for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model suggests possible strategies for future vaccinations and suggests tailored strategies for high-risk groups.

Trends in the Rates of Extended-Spectrum-ß-Lactamase-Producing Enterobacterales Isolated from Urine Cultures during the COVID-19 Pandemic in Ontario, Canada.

Worldwide, extended-spectrum ß-lactamase (ESBL) rates are increasing at an alarming level with increasing rates of health care exposures, international travel, and antibiotic usage. In this study, we investigated whether enhanced social isolation, travel restrictions, and the reduced use of antibiotics in Ontario, Canada during coronavirus disease 2019 (COVID-19) pandemic had an impact on ESBL rates in urine cultures collected from the community and long-term-care (LTC) facilities across the province. Data from a total of 8.6 million urine cultures performed at LifeLabs Ontario from 2016 to 2021 were utilized for analysis. ESBL-producing Escherichia coli (ESBL Escherichia coli) and ESBL Klebsiella pneumoniae were identified using standard operating procedures. Data trends were estimated by interrupted time series (ITS) regression analysis. Among 2.3 million positive urine cultures, 48.9% and 7.2% grew E. coli and K. pneumoniae, of which 5.8% and 3.3% produced ESBLs, respectively. While the overall rate of ESBL isolation was higher in the pandemic period than in the prepandemic period, by ITS regression analysis of the monthly rates of ESBL isolation, decreasing trends were noted for ESBL E. coli in both the community and LTC facilities and for ESBL K. pneumoniae in the community. The ESBL K. pneumoniae rates in LTC facilities continued to increase throughout the COVID-19 period. By subgroup analysis for different genders, age groups, and local health integration network (LHIN) units, similar trends were seen in most cases (P < 0.05), except for a few densely populated LHINs where rate changes were not statistically significant. IMPORTANCE Community-onset urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales, particularly E. coli and K. pneumoniae, are a major public health concern. In this study, we assessed the impact of COVID-19 on ESBL rates in urine cultures in Ontario, Canada. Our results show the recent epidemiology of ESBL-producing Enterobacterales in urine cultures from both the community and LTC facilities in Ontario, Canada, and the impact of COVID-19 restrictions on ESBL trends for the entire province as well as different subgroups of the population based on demographic and geographic characteristics. Our results may have important public health implications in the context of the gradual easing of COVID-19 restrictions.

An International, Multicenter Evaluation of Pharmacist Medication Management in Icu Recovery Centers

INTRODUCTION: Post Intensive Care Syndrome (PICS) is a new or worsening impairment in physical, cognitive, or mental health following critical illness. Similar to PICS, survivors of critical illness due to COVID-19 may develop Post Acute Sequelae of SARS-CoV-2 Infection (PASC) or Long COVID. ICU recovery centers (ICU-RC) are suggested as an interprofessional approach to treat patients with PICS or PASC. Currently, over 40 different ICU-RC worldwide report having a clinical pharmacist. The purpose of this study was to describe the role of pharmacists in identifying and treating medication-related problems in survivors of critical illness. METHOD(S): This prospective, observational study was conducted in 12 ICU-RC between September 2019 and July 2021. A full medication review comprising of medication reconciliation, a patient interview, and counseling session was conducted by a clinical pharmacist on patients seen at the ICU-RC. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Data are reported using descriptive statistics. RESULT(S): A total of 507 patients were referred to an ICU-RC, of which 474 attended and 472 had a full medication review performed by a pharmacist. 237 (47%) of referred patients had a diagnosis of COVID-19. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (IQR 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. There was no difference in median total number of medications prescribed at the start and end of the patient visit (10, IQR = 5, 15). The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%) patients, respectively. Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients and ADEs were identified in 69 (15%) patients. Drug interactions were identified in 30 (6%) patients. CONCLUSION(S): Pharmacists play an integral role in ICURC resulting in identification, prevention, and treatment of numerous medication-related problems. This paper should serve as a call to action on the importance of including a pharmacist on the interprofessional team in ICU-RC.