- Dean, B. V. (x)
- COVID-19 Research (x)
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Show moreIdentifying emergent patterns of coronavirus disease 2019 (COVID-19) at the local level presents a geographic challenge. The need is not only to integrate multiple data streams from different sources, scales, and cadences, but to also identify meaningful spatial patterns in these data, especially in vulnerable settings where even small numbers and low rates are important to pinpoint for early intervention. This paper identifies a gap in current analytical approaches and presents a near-real time assessment of emergent disease that can be used to guide a local intervention strategy: Geographic Monitoring for Early Disease Detection (GeoMEDD). Through integration of a spatial database and two types of clustering algorithms, GeoMEDD uses incoming test data to provide multiple spatial and temporal perspectives on an ever changing disease landscape by connecting cases using different spatial and temporal thresholds. GeoMEDD has proven effective in revealing these different types of clusters, as well as the influencers and accelerators that give insight as to why a cluster exists where it does, and why it evolves, leading to the saving of lives through more timely and geographically targeted intervention.
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Show moreObjective: The 2019 novel coronavirus (COVID-19) is disproportionately impacting older individuals and healthcare workers. Otolaryngologists are especially susceptible with the elevated risk of aerosolization and corresponding high viral loads. This study utilizes a geospatial analysis to illustrate the comparative risks of older otolaryngologists across the United States during the COVID-19 pandemic. Methods and materials: Demographic and state population data were extracted from the State Physician Workforce Reports published by the AAMC for the year 2018. A geospatial heat map of the United States was then constructed to illustrate the location of COVID-19 confirmed case counts and the distributions of ENTs over 60 years for each state. Results: In 2018, out of a total of 9578 practicing U.S. ENT surgeons, 3081 were older than 60 years (32.2%). The states with the highest proportion of ENTs over 60 were Maine, Delaware, Hawaii, and Louisiana. The states with the highest ratios of confirmed COVID-19 cases to the number of total ENTs over 60 were New York, New Jersey, Massachusetts, and Michigan. Results: In 2018, out of a total of 9578 practicing U.S. ENT surgeons, 3081 were older than 60 years (32.2%). The states with the highest proportion of ENTs over 60 were Maine, Delaware, Hawaii, and Louisiana. The states with the highest ratios of confirmed COVID-19 cases to the number of total ENTs over 60 were New York, New Jersey, Massachusetts, and Michigan. Results: In 2018, out of a total of 9578 practicing U.S. ENT surgeons, 3081 were older than 60 years (32.2%). The states with the highest proportion of ENTs over 60 were Maine, Delaware, Hawaii, and Louisiana. The states with the highest ratios of confirmed COVID-19 cases to the number of total ENTs over 60 were New York, New Jersey, Massachusetts, and Michigan. Results: In 2018, out of a total of 9578 practicing U.S. ENT surgeons, 3081 were older than 60 years (32.2%). The states with the highest proportion of ENTs over 60 were Maine, Delaware, Hawaii, and Louisiana. The states with the highest ratios of confirmed COVID-19 cases to the number of total ENTs over 60 were New York, New Jersey, Massachusetts, and Michigan. Conclusions: Based on our models, New York, New Jersey, Massachusetts, and Michigan represent states where older ENTs may be the most susceptible to developing severe complications from nosocomial transmission of COVID-19 due to a combination of high COVID-19 case volumes and a high proportion of ENTs over 60 years. Conclusions: Based on our models, New York, New Jersey, Massachusetts, and Michigan represent states where older ENTs may be the most susceptible to developing severe complications from nosocomial transmission of COVID-19 due to a combination of high COVID-19 case volumes and a high proportion of ENTs over 60 years. Keywords: Age; COVID-19; Nosocomial transmission; Novel coronavirus 2019; Otolaryngology. Keywords: Age; COVID-19; Nosocomial transmission; Novel coronavirus 2019; Otolaryngology.
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Show moreWith the arrival of the coronavirus disease (SARS-CoV-2) in the United States, care practice paradigms have drastically changed. Data from China suggest that the new virus poses additional risks as case fatality of patients with cancer was higher at 5.6% compared to 2.3% of the general population. There are three proposed major strategies to address care for patients with cancer in this SARS-CoV-2 pandemic with postponing treatment for those with stable cancer, increasing personal protection provisions for patients with cancer, and increasing monitoring if a patient becomes infected with SARS-CoV-2. In this present commentary, we discuss the unique mental health challenges and burdens of patients with head and neck cancer in the times of the SARS-CoV-2 pandemic and approaches to mitigate these stressors through telemedicine to reduce future burdens to the patient and the health care system. Keywords: corona; covid; head and neck cancer; survival; virus.
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Show moreSARS-CoV2 is a novel coronavirus, responsible for the COVID-19 pandemic declared by the World Health Organization. Thanks to the latest advancements in the field of molecular and computational techniques and information and communication technologies (ICTs), artificial intelligence (AI) and Big Data can help in handling the huge, unprecedented amount of data derived from public health surveillance, real-time epidemic outbreaks monitoring, trend now-casting/forecasting, regular situation briefing and updating from governmental institutions and organisms, and health facility utilization information. The present review is aimed at overviewing the potential applications of AI and Big Data in the global effort to manage the pandemic. Keywords: Big Data; artificial intelligence; epidemiology; public health; viral outbreak.
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Show moreBACKGROUND: Coronaviruses infect numerous animal species causing a variety of illnesses including respiratory, neurologic and enteric disease. Human coronaviruses (HCoV) are mainly associated with respiratory tract disease but have been implicated in enteric disease. OBJECTIVES: To investigate the frequency of coronaviruses in stool samples from children and adults with gastrointestinal illness by RT-PCR. STUDY DESIGN: Clinical samples submitted for infectious diarrhea testing were collected from December 2007 through March 2008. RNA extraction and RT-PCR was performed for stools negative for Clostridium difficile using primer sets against HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. Clinical data from samples positive for coronaviruses were reviewed and recorded. RESULTS: Samples from 479 patients were collected including 151 pediatric (<= 18yrs), and 328 adults (> 18yrs). Of these samples, 4 patients (1.3%, 2 adult; 2 pediatric) screened positive for the presence of a coronavirus. All detected coronaviruses were identified as HCoV-HKU1. No stools screened positive for either HCoV-229E, HCoV-NL63 or HCoV-OC43. All HCoV-HKU1 positive samples occurred between mid January to mid February. Clinical manifestations from HCoV-HKU1 positive patients included diarrhea, emesis and respiratory complaints. Three (75%) patients were admitted to the hospital with a median length of stay of 6 days. CONCLUSIONS: Coronaviruses as a group are not commonly identified in stool samples of patients presenting with gastrointestinal illness. HCoV-HKU1 can be identified in stool samples from children and adults with gastrointestinal disease, with most individuals having respiratory findings as well. No stool samples screened positive for HCoV-NL63, HCoV-229E, or HCoV-OC43.
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Show moreThe 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death. While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis. Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death. Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis. At present, the pathophysiology underlying the hypercoagulable state is poorly understood. However, a growing body of data suggests that the initial events occur in the lung. A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy. This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis. Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies. Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.
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Show moreSevere acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. Virus entry into cells is mediated through interactions between spike (S) glycoprotein and angiotensin-converting enzyme 2 (ACE2). Alanine scanning mutagenesis analysis was performed to identify determinants on ACE2 critical for SARS-CoV infection. Results indicated that charged amino acids between residues 22 and 57 were important, K26 and D30, in particular. Peptides representing various regions of ACE2 critical for virus infection were chemically synthesized and evaluated for antiviral activity. Two peptides (a.a. 22–44 and 22–57) exhibited a modest antiviral activity with IC(50) of about 50 μM and 6 μM, respectively. One peptide comprised of two discontinuous segments of ACE2 (a.a. 22–44 and 351–357) artificially linked together by glycine, exhibited a potent antiviral activity with IC(50) of about 0.1 μM. This novel peptide is a promising candidate as a therapeutic agent against this deadly emerging pathogen.
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Show moreBackground: There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. Objective: Develop evidence-based rapid guidelines intended to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19. Methods: IDSA formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results: The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. Conclusions: The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.
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Show moreRNA viruses are major threats to global society and mass outbreaks can cause long-lasting damage to international economies. RNA and related retro viruses represent a large and diverse family that contribute to the onset of human diseases such as AIDS; certain cancers like T cell lymphoma; severe acute respiratory illnesses as seen with COVID-19; and others. The hallmark of this viral family is the storage of genetic material in the form of RNA, and upon infecting host cells, their RNA genomes reprogram the cellular environment to favor productive viral replication. RNA is a multifunctional biomolecule that not only stores and transmits heritable information, but it also has the capacity to catalyze complex biochemical reactions. It is therefore no surprise that RNA viruses use this functional diversity to their advantage to sustain chronic or lifelong infections. Efforts to subvert RNA viruses therefore requires a deep understanding of the mechanisms by which these pathogens usurp cellular machinery. Here, we briefly summarize several experimental techniques that individually inform on key physicochemical features of viral RNA genomes and their interactions with proteins. Each of these techniques provide important vantage points to understand the complexities of virus-host interactions, but we attempt to make the case that by integrating these and similar methods, more vivid descriptions of how viruses reprogram the cellular environment emerges. These vivid descriptions should expedite the identification of novel therapeutic targets.
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Show moreObjective: To investigate a cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in employees working on 1 floor of a hospital administration building. Methods: Contact tracing was performed to identify potential exposures and all employees were tested for SARS-CoV-2. Whole-genome sequencing was performed to determine the relatedness of SARS-CoV-2 samples from infected personnel and from control cases in the health-care system with coronavirus disease 2019 (COVID-19) during the same period. Carbon dioxide levels were measured during a workday to assess adequacy of ventilation; readings >800 parts per million (ppm) were considered an indication of suboptimal ventilation. To assess the potential for airborne transmission, DNA-barcoded aerosols were released, and real-time polymerase chain reaction was used to quantify particles recovered from air samples in multiple locations. Results: Between December 22, 2020, and January 8, 2021, 17 coworkers tested positive for SARS-CoV-2, including 13 symptomatic and 4 asymptomatic individuals. Of the 5 cluster SARS-CoV-2 samples sequenced, 3 were genetically related, but these employees denied higher-risk contacts with one another. None of the sequences from the cluster were genetically related to the 17 control sequences of SARS-CoV-2. Carbon dioxide levels increased during a workday but never exceeded 800 ppm. DNA-barcoded aerosol particles were dispersed from the sites of release to locations throughout the floor; 20% of air samples had >1 log10 particles. Conclusions: In a hospital administration building outbreak, sequencing of SARS-CoV-2 confirmed transmission among coworkers. Transmission occurred despite the absence of higher-risk exposures and in a setting with adequate ventilation based on monitoring of carbon dioxide levels.
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Show moreThe current worldwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that causes coronavirus disease 2019 (COVID-19) has brought some medical systems to the brink of collapse. This crisis is also negatively impacting the care of patients with non-COVID-19 conditions, including those with cerebellar ataxia (CA). Older patients with CA and those with immune-mediated ataxias on immunosuppressive medication are potentially at high risk of developing serious complications of the infection, although it is also possible that immunosuppressive agents may provide a defense against cytokine storm. This has implications for even greater attention to preventing contracting the disease through physical distancing and/or isolation. The CA patient population is also at higher risk because of the neurological complexities of their underlying disorder and the comorbid medical illnesses that often accompany the genetic ataxias. As the disruption of social patterns and healthcare delivery in response to the crisis continues, interruption of rehabilitation, speech and language therapy, and face-to-face consultations threatens to have a negative impact on the course and well-being of CA patients. Mental and physical health is also potentially at greater risk because the prevailing uncertainty and anxiety may be superimposed upon cerebellum-specific neuropsychological challenges. We identify and review some of the short- and long-term consequences of this global pandemic for the community of ataxia patients and their families and for the clinical and academic neurologists/ataxiologists caring for these patients. This includes the recognition that telemedicine has emerged as a principle means of caregiver-patient contact and that neurological manifestations of COVID-19 including those specific to cerebellar neurobiology are increasingly recognized and will require close surveillance and monitoring. This COVID-19 Cerebellum Task Force consensus provides some guidance on how we may approach this uncertain time and consider preparing for the new realities we face in CA patient care once this acute crisis has passed. Keywords: COVID-19; Cerebellar ataxia; Cerebellum; SARS-CoV-2.
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Show moreIn this review, we summarize the current status of nucleic acid and antigen testing required for diagnosing SARS-CoV-2 infection and COVID-19 disease. Nucleic acid amplification (NAAT) and antigen-detection (Ag) tests occupy a critically important frontline of defense against SARS-CoV-2 in clinical and public health settings. In early stages of this outbreak, we observed that identifying the causative agent of a new illness of unknown origin was greatly accelerated by characterizing the nucleic acid signature of the novel coronavirus. Results from nucleic acid sequencing led to the development of highly sensitive RT-PCR testing for use in clinical settings and to informing best practices for patient care, and in public health settings to the development of strategies for protecting populations. As the current COVID-19 pandemic has evolved, we have seen how NAAT performance has been used to guide and optimize specimen collection, inform patient triage decisions, reveal unexpected clinical symptoms, clarify risks of transmission within patient care facilities, and guide appropriate treatment strategies. For public health settings during the earliest stages of the pandemic, NAATs served as the only tool available for studying the epidemiology of this new disease by identifying infected individuals, studying transmission patterns, modeling population impacts, and enabling disease control organizations and governments to make challenging disease mitigation recommendations to protect the expanding breadth of populations at risk. With time, the nucleic acid signature has provided the information necessary to understand SARS-CoV-2 protein expression for further development of antigen-based point-of-care (POC) diagnostic tests. The advent of massive parallel sequencing (ie, next generation sequencing) has afforded the characterization of this novel pathogen, informed the sequences best adapted for RT-PCR assays, guided vaccine production, and is currently used for tracking and monitoring SARS-CoV-2 variants.
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Show moreHuman coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV-host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the "Complementary Exposure" pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2. Keywords: Bioinformatics; Comparative genomics; Proteomic analysis.
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Show moreIn light of concerns over the potential detrimental effects of declining care continuity, and the need for connection between patients and health care providers, our multidisciplinary group considered the possible ways that relationships might be developed in different kinds of health care encounters.We were surprised to discover many avenues to invest in relationships, even in non-continuity consultations, and how meaningful human connections might be developed even in telehealth visits. Opportunities range from the quality of attention or the structure of the time during the visit, to supporting relationship development in how care is organized at the local or system level and in the use of digital encounters. These ways of investing in relationships can exhibit different manifestations and emphases during different kinds of visits, but most are available during all kinds of encounters.Recognizing and supporting the many ways of investing in relationships has great potential to create a positive sea change in a health care system that currently feels fragmented and depersonalized to both patients and health care clinicians.The current COVID-19 pandemic is full of opportunity to use remote communication to develop healing human relationships. What we need in a pandemic is not social distancing, but physical distancing with social connectedness. Keywords: COVID-19; clinician-patient communication/relationship; continuity of care; investing in relationship; primary care issues; relationship-centered care; telehealth; telemedicine.
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Show moreBackground: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. Methods: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. Results: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. Conclusion: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic. Keywords: COVID-19; Lung cancer; Non-small cell lung cancer; Pandemic; Radiotherapy; Small cell lung cancer.
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