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1.
International Journal of Public Health Science ; 12(2):568-575, 2023.
Article in English | Scopus | ID: covidwho-2285585

ABSTRACT

This study explored if significant improvements in knowledge, attitude, and practices among college students will be observed post E-health education program on COVID-19 prevention. The study reports a pre-post quantitative research on 178 college students. The participants received nine sessions of e-health education developed using the Communicable Disease Control Health Education Curriculum Analysis Tool (HECAT) through Zoom. The adapted and modified questionnaire was developed from previously published literature regarding viral epidemics related to MERS-CoV disease, infection prevention, and control measures for COVID-19 by World Health Organization and the Communicable Disease Control and Prevention guidelines. The first phase gathers the relevant profile and background of the participants, and the last phase comprises post-evaluation. The data were analyzed using SPSS version 27. The results indicate above-average means for knowledge on COVID-19 prevention in the pretest (17.75±2.27) and the posttest (17.60±2.95). Moreover, the participants were aware of the importance of vaccination, social distancing measures, following health protocols, and the essentiality of compliance with government agencies' guidelines. However, the participants were not practicing some of these health measures, as evidenced by the low means in the pretest (1.75±0.97) and posttest (1.66±1.08). All tests for significant differences of pretest and posttest means of knowledge (p=0.46), attitude (p=0.12), and practices (p=0.41) on COVID-19 prevention were all insignificant. Our study provides evidence that the online health education program improved college students' knowledge and attitude toward COVID-19 prevention. Still, they did not adhere to or practice some of the health measures to prevent its transmission. © 2023, Intelektual Pustaka Media Utama. All rights reserved.

2.
Sleep Med X ; 5: 100067, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-2262665

ABSTRACT

Objective/Background: Healthcare workers have experienced high rates of psychiatric symptom burden and occupational attrition during the COVID-19 pandemic. Identifying contributory factors can inform prevention and mitigation measures. Here, we explore the potential contributions of occupational stressors vs COVID-19 infection to insomnia symptoms in US healthcare workers.Patients/Methods: An online self-report survey was collected between September 2020 and July 2022 from N = 594 US healthcare workers, with longitudinal follow-up up to 9 months. Assessments included the Insomnia Severity Index (ISI), the PTSD Checklist for DSM-5 (PCL-5), and a 13-item scale assessing COVID-19 related occupational stressors. Results: Insomnia was common (45% of participants reported at least moderate and 9.2% reported severe symptoms at one or more timepoint) and significantly associated with difficulty completing work-related tasks, increased likelihood of occupational attrition, and thoughts of suicide or self-harm (all p<.0001). In multivariable regression with age, gender, and family COVID-19 history as covariates, past two-week COVID-related occupational stressors, peak COVID-related occupational stressors, and personal history of COVID-19 infection were all significantly related to past two-week ISI scores (ß = 1.7 ± 0.14SE, ß = 0.08 ± 0.03, and ß = 0.69 ± 0.22 respectively). Although similar results were found for the PCL-5, when ISI and PCL-5 items were separated by factor, COVID-19 infection was significantly related only to the factor consisting of sleep-related items. Conclusions: Both recent occupational stress and personal history of COVID-19 infection were significantly associated with insomnia in healthcare workers. These results suggest that both addressing occupational stressors and reducing rate of COVID-19 infection are important to protect healthcare workers and the healthcare workforce.

4.
22nd International Conference on Electronic Business, ICEB 2022 ; 22:212-225, 2022.
Article in English | Scopus | ID: covidwho-2207907

ABSTRACT

This paper questions the prevalent approach in assessing the value of e-learning through the information system model. A recall is made of the evolution of DeLone and McCain model and other theory at the basis of such assessment, namely TAM derived models and performance models. In these years of covid which imposed e-learning on schools, without adequate preparation this examination is more than ever important since it changes the logic of the assessment. The covid19 caused an unvoluntary use of e-learning that questions the validity of prevalent models. An integrated model, which take this aspect into consideration, is proposed in this article, to be validated empirically in a soon future. © 2022 International Consortium for Electronic Business. All rights reserved.

5.
Front Immunol ; 13: 1070424, 2022.
Article in English | MEDLINE | ID: covidwho-2215284

ABSTRACT

Acinetobacter baumannii is a nosocomic opportunistic Gram-negative bacteria known for its extensive drug-resistant phenotype. A. baumannii hospital-acquired infections are major contributors to increased costs and mortality observed during the COVID-19 pandemic. With few effective antimicrobials available for treatment of this pathogen, immune-based therapy becomes an attractive strategy to combat multi-drug resistant Acinetobacter infection. Immunotherapeutics is a field of growing interest with advances in vaccines and monoclonal antibodies providing insight into the protective immune response required to successfully combat this pathogen. This review focuses on current knowledge describing the adaptive immune response to A. baumannii, the importance of antibody-mediated protection, developments in cell-mediated protection, and their respective therapeutic application going forward. With A. baumannii's increasing resistance to most current antimicrobials, elucidating an effective host adaptive immune response is paramount in the guidance of future immunotherapeutic development.


Subject(s)
Acinetobacter baumannii , COVID-19 Drug Treatment , Cross Infection , Humans , Pandemics , Antibodies, Monoclonal
6.
J Psychiatr Res ; 158: 202-208, 2023 02.
Article in English | MEDLINE | ID: covidwho-2165628

ABSTRACT

The COVID-19 pandemic has increased healthcare workers' (HCWs) risk for posttraumatic stress disorder (PTSD). Although subthreshold PTSD symptoms (PTSS) are common and increase vulnerability for health impairments, they have received little attention. We examined the prevalence of subthreshold PTSS and their relationship to physical health symptoms and sleep problems among HCWs during the pandemic's second wave (01/21-02/21). Participants (N = 852; 63.1% male; Mage = 38.34) completed the Short-Form PTSD Checklist (SF-PCL), the Cohen-Hoberman Inventory of Physical Symptoms, and the PROMIS Sleep-Related Impairment-Short-Form 4a. We created three groups with the SF-PCL: scores ≥11 = probable PTSD (5.5%); scores between 1 and 10 = subthreshold PTSS (55.3%); scores of 0 = no PTSS (39.2%). After controlling for demographics, occupational characteristics, and COVID-19 status, HCWs with subthreshold PTSS experienced greater physical health symptoms and sleep problems than HCWs with no PTSS. While HCWs with PTSD reported the greatest health impairment, HCWs with subthreshold PTSS reported 88% more physical health symptoms and 36% more sleep problems than HCWs with no PTSS. Subthreshold PTSS are common and increase risk for health impairment. Interventions addressing HCWs' mental health in response to the COVID-19 pandemic must include subthreshold PTSS to ensure their effectiveness.


Subject(s)
COVID-19 , Sleep Wake Disorders , Stress Disorders, Post-Traumatic , Adult , Female , Humans , Male , COVID-19/epidemiology , Cross-Sectional Studies , Health Personnel/psychology , Pandemics , Prevalence , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/complications , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/etiology
7.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2147356

ABSTRACT

Acinetobacter baumannii is a nosocomic opportunistic Gram-negative bacteria known for its extensive drug-resistant phenotype. A. baumannii hospital-acquired infections are major contributors to increased costs and mortality observed during the COVID-19 pandemic. With few effective antimicrobials available for treatment of this pathogen, immune-based therapy becomes an attractive strategy to combat multi-drug resistant Acinetobacter infection. Immunotherapeutics is a field of growing interest with advances in vaccines and monoclonal antibodies providing insight into the protective immune response required to successfully combat this pathogen. This review focuses on current knowledge describing the adaptive immune response to A. baumannii, the importance of antibody-mediated protection, developments in cell-mediated protection, and their respective therapeutic application going forward. With A. baumannii’s increasing resistance to most current antimicrobials, elucidating an effective host adaptive immune response is paramount in the guidance of future immunotherapeutic development.

8.
J Am Coll Emerg Physicians Open ; 3(6): e12830, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2127690

ABSTRACT

Objective: Understanding variables associated with coronavirus disease 2019 (COVID-19) vaccine confidence and hesitancy may inform strategies to improve vaccine uptake in clinical settings such as the emergency department (ED). We aim to identify factors contributing to COVID-19 vaccine acceptance and to assess patient attitudes surrounding offering COVID-19 vaccines in the ED. Methods: We conducted a survey of a convenience sample of patients and patient visitors over the age 18 years, who were native English or Spanish speakers. The survey was conducted from March through August 2021 at 3 EDs in New York City. The survey was administered via an electronic format, and participants provided verbal consent. Results: Our sample size was 377. Individuals with post-graduate degrees viewed vaccines positively (Prevalence Ratio [PR], 1.63; 95% Confidence Interval [CI], 1.07-2.47).  Of the various high-risk medical conditions associated with adverse COVID-19 infection outcomes, diabetes was the only condition associated with more positive views of vaccines (PR, 1.37; CI, 1.17-1.59). Of all participants, 71.21% stated that they believed offering a COVID-19 vaccine in the ED was a good idea. Of unvaccinated participants, 21.80% stated they would get vaccinated if it were offered to them in the ED. Conclusion: EDs can serve as a safety net for vulnerable populations and can act as an access point for vaccination.

9.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.27.22281582

ABSTRACT

Abstract Objective/Background: Healthcare workers have experienced high rates of psychiatric symptom burden and occupational attrition during the COVID-19 pandemic. Identifying contributory factors can inform prevention and mitigation measures. Here, we explore the potential contributions of occupational stressors vs COVID-19 infection to insomnia symptoms in US healthcare workers. Patients/Methods: An online self-report survey was collected between September 2020 and July 2022 from N=594 US healthcare workers, with longitudinal follow-up up to 9 months. Assessments included the Insomnia Severity Index (ISI), the PTSD Checklist for DSM-5 (PCL-5), and a 13-item scale assessing COVID-19 related occupational stressors. Results: Insomnia was common (45% of participants reported at least moderate and 9.2% reported severe symptoms at one or more timepoint) and significantly associated with difficulty completing work-related tasks, increased likelihood of occupational attrition, and thoughts of suicide or self-harm (all p<.0001). In multivariable regression with age, gender, and family COVID-19 history as covariates, past two-week COVID-related occupational stressors, peak COVID-related occupational stressors, and personal history of COVID-19 infection were all significantly related to past two-week ISI scores (Beta=1.7+/-0.14SE, Beta=0.08+/-0.03, and Beta=0.69+/-0.22 respectively). Although similar results were found for the PCL-5, when ISI and PCL-5 items were separated by factor, COVID-19 infection was significantly related only to the factor consisting of sleep-related items. Conclusions: Both recent occupational stress and personal history of COVID-19 infection were significantly associated with insomnia in healthcare workers. These results suggest that both addressing occupational stressors and reducing rate of COVID-19 infection are important to protect healthcare workers and the healthcare workforce.


Subject(s)
Occupational Diseases , Tooth Attrition , Sleep Initiation and Maintenance Disorders , Mental Disorders , Stress Disorders, Post-Traumatic , COVID-19
10.
Journal of Health Sciences ; 12(1):74-82, 2022.
Article in English | Scopus | ID: covidwho-1847882

ABSTRACT

Introduction: The global COVID-19 pandemic has aggravated challenges involving college students’ mental health and well-being. Some literature suggested developing online programs to address the pandemic’s impact on college students’ mental health and well-being. Thus, this study assessed if significant improvement in well-being among college students can be observed after introducing an online well-being program. Methods: The study utilized a quantitative methodology, mainly using a two-group pretest-posttest design on 178 college students in a private college and state university. The experimental group received 3 months of the well-being program while the control resumed their activities of daily living (ADL). The modified positive emotion, engagement, relationship, meaning, and accomplishment (PERMA) profiler questionnaire was the primary evaluation instrument that measured the participants’ well-being. The first phase gathered the participants’ relevant profile and background, and the last phase concluded with the evaluation of the program. Data were analyzed using SPSS v.21. Results: Based on the post-evaluation PERMA scores, the experimental participants (M = 7.21, SD 1.70) did not differ much from the control (M = 7.07, SD = 1.55) according to a t-test t(176) = -1.07, p = 0.57 as computed using a two-sample independent t-test at a significance level of a = 0.05. The overall PERMA score description is normal functioning. The Pearson correlation of the experimental group’s pre-test and post-test scores (r(91) = 0.01, p = 0.904) and the control (r(83) = 0.04, p = 0.732) group did not indicate an evidence of a significant relationship. Conclusion: The results do not provide evidence of a significant difference and relationship between the experimental participants’ pre-test and post-test PERMA scores after the online well-being program. © 2022. Villarino, et al.;. All Rights Reserved.

11.
J Am Coll Emerg Physicians Open ; 3(3): e12728, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1819356

ABSTRACT

Background: The COVID-19 pandemic has resulted in over 6 million deaths worldwide as of March 2022. Adverse psychological effects on patients and the general public linked to the pandemic have been well documented. Methods: We conducted a retrospective analysis of adult emergency department (ED) encounters with diagnoses of anxiety, depression, and suicidal ideation using International Classification of Diseases, Tenth Revision (ICD-10) codes at a tertiary care hospital in New York City from March 15 through July 31, 2020 and compared it with ED encounters during the same time period in the previous 3 years (2017-2019). The relative risk (RR) of these diagnoses was calculated comparing a prepandemic sample to a pandemic sample, accounting for total volume of ED visits. Results: A total of 2816 patient encounters met the inclusion criteria. The study period in 2020 had 31.5% lower overall ED volume seen during the same time period in the previous 3 years (27,874 vs average 40,716 ED encounters). The risk of presenting with anxiety during the study period in 2020 compared to prior 3 years was 1.40 (95% confidence interval [CI] 1.21-1.63), for depression was 1.47 (95% CI 1.28-1.69), and for suicidal ideation was 1.05 (95% CI 0.90-1.23). There was an increase in admissions for depression during the pandemic period (15.2% increase, 95% CI 4.6%-25.7%). Conclusion: There was a relative increase in patients presenting to the ED with complaints of anxiety and depression during the height of the COVID-19 pandemic, while absolute numbers remained stable. Our results highlight the importance of acute care-based mental health resources and interventions to support patients during this pandemic.

12.
Exp Biol Med (Maywood) ; 247(12): 1055-1060, 2022 06.
Article in English | MEDLINE | ID: covidwho-1775258

ABSTRACT

Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.


Subject(s)
COVID-19 , Immunity, Humoral , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , COVID-19 Serotherapy
14.
European Journal of Obstetrics & Gynecology & Reproductive Biology ; 270:N.PAG-N.PAG, 2022.
Article in English | Academic Search Complete | ID: covidwho-1748054
15.
West J Emerg Med ; 23(2): 246-250, 2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1737294

ABSTRACT

INTRODUCTION: The 2019 novel coronavirus pandemic has caused significant disruptions in the clinical operations of hospitals as well as clinical education, training, and research at academic centers. New York State was among the first and largest epicenters of the pandemic, resulting in significant disruptions across its 29 emergency medicine (EM) residency programs. We conducted a cross-sectional observational study of EM residency programs in New York State to assess the impact of the pandemic on resident education and training programs. METHODS: We surveyed a cross-sectional sample of residency programs throughout New York State in June 2020, in the timeframe immediately after the state's first "wave" of the pandemic. The survey was distributed to program leadership and elicited information on pandemic-prompted curricular modifications and other educational changes. The survey covered topics related to disruptions in medical education and sought details on solutions to educational issues encountered by programs. RESULTS: Of the 29 accredited EM residency programs in New York State, leadership from 22 (76%) responded. Of these participating programs, 11 (50%) experienced high pandemic impact on clinical services, 21 (95%) canceled their own trainees' off-service rotations, 22 (100%) canceled or postponed visiting medical student rotations, 22 (100%) adopted virtual conference formats (most within the first week of the pandemic wave), and 11 (50%) stopped all prospective research (excluding COVID-19 research), while most programs continued retrospective research. CONCLUSION: This study highlights the profound educational impact of the pandemic on residency programs in one of the hardest- and earliest-hit regions in the United States. Specifically, it highlights the ubiquity of virtual conferencing, the significant impact on research, and the concerns about canceled rotations and missed training opportunities for residents, as well as prehospital and non-physician practitioner trainees. This data should be used to prompt discussion regarding the necessity of alternate educational modalities for pandemic times and the sequelae of implementing these plans.


Subject(s)
COVID-19 , Emergency Medicine , Internship and Residency , COVID-19/epidemiology , Cross-Sectional Studies , Emergency Medicine/education , Humans , New York/epidemiology , Prospective Studies , Retrospective Studies , United States/epidemiology
16.
JAMA Netw Open ; 5(1): e2143167, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1689491
17.
J Am Coll Emerg Physicians Open ; 2(6): e12546, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1595157

ABSTRACT

OBJECTIVE: Professional satisfaction is associated with career longevity, individual well-being, and patient care and safety. Lack of physician engagement promotes the opposite. This study sought to identify important facets contributing to decreased career satisfaction using a large national data set of practicing emergency physicians. METHODS: We performed a secondary analysis of the national Longitudinal Study of Emergency Physicians survey conducted by the American Board of Emergency Medicine. The survey was composed of 57 variables including career satisfaction as well as occupational and psychological variables potentially associated with career satisfaction. Factor analysis was used to determine the important latent variables. Ordinal logistic regression was performed to determine statistical significance among the latent variables with overall career satisfaction. RESULTS: A total of 863 participants were recorded. The overall mean career satisfaction rate was 3.9 on a 5-point Likert scale with 1 and 5 indicating "least satisfied" and "most satisfied," respectively. Our analysis revealed 9 factors related to job satisfaction. Two latent factors, exhaustion/stress and administration/respect, were statistically significant. When comparing satisfaction scores between sex, there was a statistically significant difference with men reporting a higher satisfaction rate (P = 0.0092). Age was also statistically significant with overall satisfaction lower for younger physicians than older physicians. CONCLUSION: Our study found that emergency physicians are overall satisfied with emergency medicine, although with variability depending on sex and age. In addition, we characterized job satisfaction into 9 factors that significantly contribute to job satisfaction. Future work exploring these factors may help elucidate the development of targeted interventions to improve professional well-being in the emergency medicine workforce.

18.
J Emerg Manag ; 18(7): 45-48, 2021.
Article in English | MEDLINE | ID: covidwho-1497659

ABSTRACT

STUDY OBJECTIVES: Prior to COVID-19, telemedicine and its applications to the emergency department (ED) had made significant inroads toward remote evaluation and care. During the local peak of the COVID-19 pandemic in New York City (NYC), there was a dramatic increase in telemedicine based patient encounters for suspected COVID-19 symptoms. In response, pathways were developed to promote a standardized telemedicine approach to remote evaluation and assessment of suspected COVID-19 patients. METHODS: A pathway was developed and implemented at two academic EDs in NYC, which collectively had approximately 8,300 telemedicine visits for suspected COVID-19 from March 2020 to June 2020. A protocol was developed by an expert consensus panel of four board-certified emergency physicians and two pediatric emergency physicians, all with telemedicine training/administrative roles. RESULTS: The pathway was initiated for any telehealth patient with suspected COVID-19 symptoms (cough, fever, shortness of breath, and bodyaches). A standardized history solicited known or suspected risk factors for worse prognosis, including age > 50, cardiovascular or lung disease, obesity, immunosuppression, and living alone, as well as a focused assessment of symptom severity and exercise tolerance. An exam at rest included visual counting of breaths along with instruction on palpation of radial pulse. Saturation was included if pulse oximetry was available. If exam at rest was reassuring, providers were instructed to repeat the respiratory assessment on exertion by having the patient walk in place briskly for 1 minute. Patients with severe illness defined by resting or exertional respiratory rate greater than 30 and/or oxygen saturation less than 90 percent were instructed to go to the ED. Patients with moderate illness defined by exertional metrics of respiratory rate less than 22, oxygen saturation greater than 94 percent, and heart rate less than 125 were discharged from the virtual urgent care visit with a repeat telehealth follow-up call at either 12 or 24 hours depending on the number of risk factors. Patients without risk factors and with reassuring respiratory assessment were discharged from the telemedicine encounter with reassurance and standard discharge precautions for escalation of care. CONCLUSION: Designing and disseminating a standardized pathway helped to provide a framework to approach patients suspected of COVID-19 over telemedicine. Future work focusing on patient outcome data will help guide and refine any standardized telehealth approach to the COVID-19-suspected patient.


Subject(s)
COVID-19 , Telemedicine , Child , Humans , Pandemics , Patient Discharge , SARS-CoV-2
19.
J Occup Environ Med ; 63(10): 852-856, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1447666

ABSTRACT

OBJECTIVE: Vaccine hesitancy limits population protection from SARS-CoV (coronavirus disease [COVID-19]). Vaccine hesitancy among healthcare workers (HCW) could put patients and coworkers at risk. METHODS: We surveyed 475 emergency department and emergency medical service workers from January to February 2021 to determine vaccine intent/uptake, perceived COVID-19 vulnerability, and factors associated with vaccine intent/uptake. RESULTS: Although 79% of HCWs received or had plans to receive the COVID-19 vaccine, 21% had no intent/were unvaccinated; intent/uptake was lower among females (odds ratio [OR] = 0.34) and those with a history of COVID-19 infection (OR = 0.55), and higher among those with advanced degrees (OR = 3.53) and high perceived COVID-19 vulnerability (OR = 1.99). CONCLUSIONS: This study provides a timely assessment of vaccination status among frontline HCWs and highlights subgroups who may be at high risk of exposure and transmission.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Cross-Sectional Studies , Emergency Service, Hospital , Female , Health Personnel , Humans , SARS-CoV-2 , Vaccination
20.
Antimicrob Agents Chemother ; 65(9): e0060221, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1434879

ABSTRACT

Remdesivir (RDV; GS-5734, Veklury), the first FDA-approved antiviral to treat COVID-19, is a single-diastereomer monophosphoramidate prodrug of an adenosine analogue. RDV is taken up in the target cells and metabolized in multiple steps to form the active nucleoside triphosphate (TP) (GS-443902), which, in turn, acts as a potent and selective inhibitor of multiple viral RNA polymerases. In this report, we profiled the key enzymes involved in the RDV metabolic pathway with multiple parallel approaches: (i) bioinformatic analysis of nucleoside/nucleotide metabolic enzyme mRNA expression using public human tissue and lung single-cell bulk mRNA sequence (RNA-seq) data sets, (ii) protein and mRNA quantification of enzymes in human lung tissue and primary lung cells, (iii) biochemical studies on the catalytic rate of key enzymes, (iv) effects of specific enzyme inhibitors on the GS-443902 formation, and (v) the effects of these inhibitors on RDV antiviral activity against SARS-CoV-2 in cell culture. Our data collectively demonstrated that carboxylesterase 1 (CES1) and cathepsin A (CatA) are enzymes involved in hydrolyzing RDV to its alanine intermediate MetX, which is further hydrolyzed to the monophosphate form by histidine triad nucleotide-binding protein 1 (HINT1). The monophosphate is then consecutively phosphorylated to diphosphate and triphosphate by cellular phosphotransferases. Our data support the hypothesis that the unique properties of RDV prodrug not only allow lung-specific accumulation critical for the treatment of respiratory viral infection such as COVID-19 but also enable efficient intracellular metabolism of RDV and its MetX to monophosphate and successive phosphorylation to form the active TP in disease-relevant cells.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Humans , Lung , Nerve Tissue Proteins
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