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1.
Biomolecules ; 11(6)2021 05 23.
Article in English | MEDLINE | ID: covidwho-1243950

ABSTRACT

COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 12 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 160 million (>20% located in United States) and killed more than 3.3 million people around the world (>20% deaths in USA). As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors-S/Ace2, Tmprss2, Cathepsins L and K, and Mpro-to prevent binding, membrane fusion and replication of the virus, respectively. All together, we generated an ensemble of structural conformations that increase high-quality docking outcomes to screen over >6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional >30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high-value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Binding Sites , COVID-19/pathology , COVID-19/virology , Drug Discovery , Drug Repositioning , Humans , Machine Learning , Molecular Docking Simulation , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Serine Endopeptidases/chemistry , Serine Endopeptidases/metabolism , Viral Envelope Proteins/antagonists & inhibitors , Viral Envelope Proteins/metabolism , Virus Replication/drug effects
2.
J Am Assoc Nurse Pract ; 33(12): 1120-1124, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1075656

ABSTRACT

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has required swift implementation of innovative practices in health care across the globe. We describe a nurse practitioner (NP) and physician assistant (PA)-led initiative to implement telemonitoring (TM) of noncritical patients with COVID-19 by critical care NPs and PAs (C19TM) for early detection of decompensation and early transfer to the intensive care unit (ICU). Every hospitalized patient with suspected or confirmed COVID-19 received an initial telemedicine consult with a critical care NP or PA. Patients were subsequently monitored via electronic health record once every 12-hour shift for the following indicators: oxygen modality and flow, increase in oxygen requirements, sustained tachypnea, and hemodynamic instability. If signs of decompensation were noted, the NP/PA would remotely reassess the patient, provide recommendations to the hospital internal medicine team, and transfer the patient to the ICU. The primary goal was to avoid cardiopulmonary deterioration requiring aerosol-generating procedures outside of the ICU. Over 65 days, 113 patients (86 suspected and 27 confirmed) were enrolled in C19TM. As a result, there were 13 transfers to the ICU, none of which required an aerosol-generating procedure outside of the ICU.


Subject(s)
COVID-19 , Nurse Practitioners , Physician Assistants , Critical Illness , Humans , SARS-CoV-2
3.
Neurol Neurochir Pol ; 54(4): 312-322, 2020.
Article in English | MEDLINE | ID: covidwho-1067910

ABSTRACT

AIM: To evaluate five illustrative cases and perform a literature review to identify and describe a working approach to adult-onset white matter diseases (WMD). STATE OF THE ART: Inherited WMD are a group of disorders often seen in childhood. In adulthood, progressive WMDs are rare, apart from the common nonspecific causes of hypertension and other cerebrovascular diseases. The pattern of WMDs on neuroimaging can be an important clue to the final diagnosis. Due to the adoption of a combined clinical-imaging-laboratory approach, WMD is becoming better recognised, in addition to the rapidly evolving field of genomics in this area. CLINICAL IMPLICATIONS: While paediatric WMDs have a well-defined and literature-based clinical-laboratory approach to diagnosis, adult-onset WMDs remain an important, pathologically diverse, radiographic phenotype, with different and distinct neuropathologies among the various subtypes of WMD. Adult-onset WMDs comprise a wide collection of both acquired and inherited aetiologies. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neurological complications are emerging, we are as yet unaware of it causing WMD outside of post-anoxic changes. It is important to recognise WMD as a potentially undefined acquired or genetic syndrome, even when extensive full genome testing reveals variants of unknown significance. FUTURE DIRECTIONS: We propose a combined clinical-imaging-laboratory approach to WMD and continued exploration of acquired and genetic factors. Adult-onset WMD, even given this approach, can be challenging because hypertension is often comorbid. Therefore, we propose that undiagnosed patients with WMD be entered into multicentre National Organisation for Rare Diseases registries to help researchers worldwide make new discoveries that will hopefully translate into future cures.


Subject(s)
Leukoencephalopathies/diagnosis , Leukoencephalopathies/etiology , Adult , Betacoronavirus , COVID-19 , Coronavirus Infections , Humans , Pandemics , Pneumonia, Viral , SARS-CoV-2 , White Matter/pathology
4.
Mayo Clin Proc Innov Qual Outcomes ; 4(6): 736-744, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-978359

ABSTRACT

OBJECTIVE: To describe telemedicine utilization in neurosurgery at a single tertiary institution to provide outpatient care during the coronavirus disease 2019 (COVID-19) pandemic, with 315 telemedicine visits performed by the neurosurgery department. PATIENTS AND METHODS: In response to the COVID-19 pandemic national stay-at-home orders and postponed elective surgeries, we converted upcoming clinic visits into telemedicine visits and rescheduled other patients thought not to be markedly affected by surgical postponement. We reviewed the charts of all patients who had telehealth visits from April 1 through April 30, 2020, and collected demographic information, diagnosis, type of visit, and whether they received surgery; a satisfaction questionnaire was also administered. RESULTS: In March 2020, 94% (644 of 685) of the neurosurgery clinic visits were face-to-face, whereas in April 2020, 55% (315 of 573) of the visits were telemedicine (P<.001). In April, of the 315 telemedicine visits, 172 (55%) were phone consults and 143 (45%) video consults; 101 (32%) were new consults, 195 (62%) return visits, and 18 (6%) postoperative follow-up. New consults were more likely to be video with audio than return visits and postoperative follow-up (P<.001). Only 39 patients (12%) required surgery. Ninety-one percent of the questionnaire respondents were very likely to recommend telemedicine. CONCLUSION: Rapid implementation of telemedicine to evaluate neurosurgery patients became an effective tool for preoperative consultation, postoperative and follow-up visits during the COVID-19 pandemic, and decreased risks of exposure to severe acute respiratory syndrome coronavirus 2 to patients and health care staff. Future larger studies should investigate the cost-effectiveness of telemedicine used to triage surgical from nonsurgical patients, potential cost-savings from reducing travel burdens and lost work time, improved access, reduced wait times, and impact on patient satisfaction.

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