title: Global analysis of the COVID-19 pandemic using simple epidemiological models

text: Several analytical models have been used in this work to describe the evolution of death cases arising from coronavirus (COVID-19). The Death or `D' model is a simplified version of the SIR (susceptible-infected-recovered) model, which assumes no recovery over time, and allows for the transmission-dynamics equations to be solved analytically. The D-model can be extended to describe various focuses of infection, which may account for the original pandemic (D1), the lockdown (D2) and other effects (Dn). The evolution of the COVID-19 pandemic in several countries (China, Spain, Italy, France, UK, Iran, USA and Germany) shows a similar behavior in concord with the D-model trend, characterized by a rapid increase of death cases followed by a slow decline, which are affected by the earliness and efficiency of the lockdown effect. These results are in agreement with more accurate calculations using the extended SIR model with a parametrized solution and more sophisticated Monte Carlo grid simulations, which predict similar trends and indicate a common evolution of the pandemic with universal parameters.


title: Die SARS-CoV-2-Pandemie und ein Suizidversuch bei wahnhafter Störung./ [The SARS-CoV-2 Pandemic and an Attempted Suicide of a Patient with Delusional Disorder]

text: The SARS-CoV-2 pandemic triggered increasing symptoms of an undiagnosed delusional disorder at a mid-60-year-old woman resulting in an attempted suicide. Because of a pandemic with noticeable and visible social changes, it seems likely that people with previously subclinical psychotic illnesses are more often admitted to psychiatric care for the first time. Building a therapeutic relationship and integrating her into an outpatient clinic was possible despite her lack of insight into the illness and her rejection of medical treatment.


Practicing Good Laboratory Hygiene, Even in a Pandemic


Uropathologists During the COVID-19 Pandemic: What Can Be Learned in Terms of Social Interaction, Visibility, and Social Distance


title: Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection

text: Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10%. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 h after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.


title: Minimal Access Gardening: Laparoscopic Techniques during Coronavirus Disease Lockdown

text: OBJECTIVE: To demonstrate techniques of laparoscopic surgery while all elective procedures are suspended. DESIGN: Stepwise demonstration of key skills required when gardening with minimal access techniques. SETTING: Gynecologist residence in self-isolation, Manchester, United Kingdom. INTERVENTIONS: Owing to the coronavirus disease pandemic, elective operations are currently suspended in the United Kingdom. In addition, there have been concerns regarding the safety of laparoscopic surgery and risk of transmission of the coronavirus disease [1,2]. As a result, laparoscopic surgeons are at risk of skill deterioration, and it is uncertain whether this may have an impact on patient safety when lockdown measures are de-escalated. Combining gardening, one of the major pastimes during the lockdown period, and minimal access surgical skills, this video demonstrates the different ways minimal access surgery may be applied to horticulture. In the first described technique, what the author believes to be hedge bindweed (Calystegia sepium) was excised using a grasper and a tripolar cutting device (Fig. 1). For obvious reasons diathermy is not available within the home environment, but the retractable cutting blade was used to efficiently slice through the stems required for weed removal. The disadvantage of this technique is clearly that the unwanted species is likely to regrow in 12 months. In the second described technique, dandelions (genus Taraxacum) (Fig. 2), which are native to Eurasia and North America, were excised at the flowering stage, thereby effectively preventing asexual reproduction by apomixis. The technique similarly uses the retractable blade of the tripolar cutting device. The third technique demonstrates harvesting of an unknown species using a soil dissection technique. To facilitate complete removal of the plant and to reduce the risk of recurrence, the roots are carefully dissected out using blunt dissection. As with many techniques, patience is of paramount importance. Last, ensuring hydration of plants is crucial to their early stage of development. Laparoscopic watering techniques are usually simplified when an irrigation and suction device is employed. However, within a low-resource setting a slow process of "cup feeding" is required and requires meticulous dexterity (Fig. 3). Unfortunately, during this demonstration a common complication of a loss of instrument occurred, but the subject was luckily successfully hydrated. CONCLUSION: While a lockdown remains in place, many gynecologists are not able to maintain their laparoscopic surgical skills. It is important to combine activities of daily living with minimal access training to maintain our physical and mental well-being. More research is clearly needed in the area of minimal access horticulture to expand this new and exciting subspecialty.


title: NANDA-I, NOC, and NIC Linkages to SARS-Cov-2 (Covid-19): Part 1. Community Response

text: PURPOSE: We developed linkages using interoperable standardized nursing terminologies, NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC), to present initial guidance for the development of care plans focused on COVID-19 for nurses practicing in community or public health roles. METHODS: Seven nurse experts identified the linkages of NANDA-I, NOC and NIC for our work related to the COVID-19 pandemic. A model was developed to guide the project. The first step in creating linkages focused on the identification of nursing diagnoses. Then, for each nursing diagnosis, outcomes aligned with all components of the diagnosis were categorized and a list of nursing interventions was selected. The experts used their clinical judgment to make final decisions on the linkages selected in this study. FINDINGS: Two community level nursing diagnoses were identified as key problems appropriate for a pandemic related to COVID-19: Deficient Community Health and Ineffective Community Coping. For the nursing diagnosis Deficient Community Health, eight nursing outcomes and 12 nursing interventions were selected. In comparison for the nursing diagnosis, Ineffective Community Coping, nine nursing outcomes and 18 nursing interventions were identified. A total of40 concepts were identified for future development across the three classifications. CONCLUSIONS: The nursing diagnoses, outcomes and interventions selected during this linkage process provide knowledge to support the community challenged with responding to the COVID-19 pandemic, provide the opportunity to quantify the impact of nursing care, and enhance nursing practice by promoting the use of three standardized terminologies. IMPLICATIONS FOR NURSING PRACTICE: NANDA-I, NOC and NIC linkages identified in this manuscript provide resources to support clinical decisions and care plan development for nurses practicing in the community.


title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS

text: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.


title: How COVID may improve care: rethinking cervical cancer prevention

text: These past months of the COVID pandemic have given us ample opportunity to reflect on the US health care system. Despite overwhelming tragedy, it is an opportunity for us to learn and to change. As we postpone routine visits because of the pandemic, we worry about risks for patients who delay cancer screening. We use cervical cancer screening and prevention as an example of how we can use some "lessons learned" from the pandemic to prevent "collateral losses," such as an increase in cancers. COVID-related health system changes, like the more rapid evaluation of diagnostic tests and vaccines, the transition to compensated virtual care for most counseling and education visits, and broadened access to home services all offer potential benefits to the delivery of cervical cancer screening and prevention. While we detail the case for cervical cancer prevention, many of the issues discussed are generalizable to other preventative measures. It would be a tragedy if the morbidity and mortality of COVID is multiplied because of additional suffering caused by delayed or deferred cancer screening and diagnostic evaluation-but maybe with creativity and reflection, we can use this pandemic to improve care.


title: Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management

text: OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns. MATERIALS AND METHODS. This study included the first 51 patients with a diagnosis of COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). We reviewed the clinical information, CT images, and corresponding image reports of these 53 patients. The CT images included images from 99 chest CT examinations, including initial and follow-up CT studies. We compared the image reports of the initial CT study with the laboratory test results and identified CT patterns suggestive of viral infection. RESULTS. COVID-19 was misdiagnosed as a common infection at the initial CT study in two inpatients with underlying disease and COVID-19. Viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus. These patients were isolated and obtained treatment. Ground-glass opacities (GGOs) and consolidation with or without vascular enlargement, interlobular septal thickening, and air bronchogram sign are common CT features of COVID-19. The The "reversed halo" sign and pulmonary nodules with a halo sign are uncommon CT features. The CT findings of COVID-19 overlap with the CT findings of adenovirus infection. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. CONCLUSION. We found that chest CT had a low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients. However, CT is still limited for identifying specific viruses and distinguishing between viruses.


Reply to Comments on 'Co-infection of SARS-CoV-2 and HIV in a patient in Wuhan city, China'


title: Coronaviruses' sugar shields as vaccine candidates

text: A successful global healthcare response relies on versatile vaccines and production of broadly virus-neutralizing antibodies by the immune system to protect us from emerging infectious diseases The present 2019 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic highlights the urgent need for development of anti-viral biodefense Due to the genetic and proteomic diversities of viral pathogens, establishing versatile anti-viral vaccines or therapeutic agents is highly challenging Carbohydrate antigens represent an important class of immunological targets for vaccine development and immunotherapy against microbial infections In this mini review, some concepts and strategies for exploring the potential of immunogenic sugar moieties as CoV vaccine candidates are presented


Climate and clean air responses to COVID-19: a comment


COVID-19 and dengue virus coepidemics in Pakistan: A dangerous combination for an overburdened healthcare system


title: Coronavirus disease 2019-The principles of the curve, explained simply

text: In the setting of the coronavirus disease 2019 pandemic, the concept of the disease curve has become ubiquitous in medicine and across society. Nevertheless, even among medical specialists, there are common misconception about the curve and how it affects population outcomes. This article provides a simple review of the various population dynamics at play. Principles such as the area under the curve and the threshold of capacity are discussed and simply conceptualized. Understanding the fundamental characteristics of a problem can allow us to see it with more clarity. By the end of the article, the reader will gain an effortless a sense of insight on this topic.


Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis


How Dermatologists Can Learn and Contribute at the Leading Edge of the COVID-19 Global Pandemic


title: Editorial Perspective: Perils and promise for child and adolescent sleep and associated psychopathology during the COVID-19 pandemic

text: It is anticipated that the novel coronavirus disease 2019 (COVID-19) pandemic and associated societal response will have wide-ranging impacts on youth development and mental health. Sleep is crucial for child and adolescent health and well-being, and the potential for sleep problems to emerge or worsen during and following the pandemic is high. This may be particularly true for children and adolescents who are at heightened risk for the onset of sleep and mental health disturbances and for those whom developmental changes impacting sleep are rapidly occurring. Youth with preexisting psychopathologies (including anxiety and depression) and neurodevelopmental conditions (including attention-deficit/hyperactivity disorder and autism spectrum disorder) could be especially vulnerable to disturbed sleep during this period of change and uncertainty. It is thus imperative that sleep considerations be part of research and clinical initiatives aimed at understanding and mitigating the impact of the COVID-19 pandemic in children and adolescents. This article considers ways in which the pandemic may impact sleep, including research and clinical implications.


Actions required to assure continuous supply of anti-rheumatic medication during the SARS-CoV-2/COVID-19 pandemic. Response to: 'Treatment adherence behaviours in rheumatic diseases during pandemic COVID-19: a Latin American experience' by Pineda-Sic et al


title: Neurological diseases of cattle in the state of Goiás, Brazil (2010-2017)/ Doenças neurológicas de bovinos no estado de Goiás (2010-2017)

text: A retrospective study was conducted on neurological diseases of cattle in the state of Goiás, Brazil, from March 2010 to August 2017. Samples of three veterinary diagnostic laboratories were analyzed. Diagnosis was established in 170 out of 407 cattle with neurological signs. Epidemiological, clinical, and anatomic pathology features of each case were researched in the files. Main disorders included diseases caused by viruses (rabies 29.41%, meningoencephalitis by bovine herpesvirus 15.88%, and malignant catarrhal fever 1.76%), by bacteria (botulism 5.88%, suppurative meningitis 3.53%, encephalic abscesses 2.94%, listeriosis 1.76%, and thrombotic meningoencephalitis 1.76%), of metabolic origin (polioencephalomalacia 17.06%), of indefinite cause (lymphoplasmacytic meningoencephalitis 11.18%, traumatic hemorrhages 3.53%, and multifocal malacia with gliosis 1.18%), congenital (hydrocephaly 1.18% and multiple malformations 0.59%), toxic (urea poisoning 1.18% and insecticide poisoning 0.59%), and parasitic (meningoencephalitis associated with infection by Trypanosoma sp. 0.59%).(AU)


title: Necessity and feasibility of viral RNA detection in specialist ophthalmic institute during the COVID-19 epidemic/ 中华实验眼科杂志

text: The prevention and treatment of COVID-19 in China is now at a key stage. The tasks faced by the medical organs are fighting against the COVID-19 while providing the medical services orderly. As a Specialist medical institution nationwide, ophthalmic hospitals are resuming receiving patients and performing operations gradually, including precision interruption of the epidemic, prevention of the secondary virus transmission, and avoidance of nosocomial cross infection among health care providers are required. We explored a multifaceted management for the prevention and control of epidemic, with a special focus on the individual protection for patients and medical staffs. A preliminary positive effect can be observed as a result. The main measures taken cover two aspects. On the one hand, 2019-nCoV ribonucleic acid (RNA) detection and hematological indices inspection including C-reactive protein (CRP) and serum amyloid A (SAA) are listed as routine tests of preoperative screening for ocular surgical patients. These tests are required to be completed upon the admission to avoid the possibility of accepting any asymptomatic infected individual and to reduce the risk of nosocomial cross infection. On the other hand, the 2019-nCoV RNA detection is also provided to high-risk employees who visited affected area recently. This assists in obtaining guarantee in both safety and quality of medical services provided, but also helps in lessening the mental and spiritual stress for medical staffs. It is expected that these measures can contribute to the work of our peers of ophthalmology in the prevention and control of COVID-19 and to the safe environment where the medical services are provided, and provide a reference for other outbreak of virus-causing disease.


title: Spatiotemporal Characteristics of COVID-19 Epidemic in the United States

text: BACKGROUND: A range of near-real-time online/mobile mapping dashboards and applications have been used to track the COVID-19 pandemic worldwide. It remains unknown about small area-based spatiotemporal patterns of COVID-19 in the United States. METHODS: We obtained county-based counts of COVID-19 cases confirmed in the United States from January 22 to May 13, 2020 (N=1,386,050). We characterized the dynamics of COVID-19 epidemic through detecting weekly hotspots of newly confirmed cases using Spatial and Space-Time Scan Statistics and quantifying the trends of incidence of COVID-19 by county characteristics using the Joinpoint analysis. RESULTS: Along with the national plateau reached in early April, COVID-19 incidence significantly decreased in the Northeast (estimated weekly percentage changes [EWPC]: -16.6%), but remained increasing in the Midwest, South and West Regions (EWPCs: 13.2%, 5.6%, and 5.7%, respectively). Higher risks of clustering and incidence of COVID-19 were consistently observed in metropolitan vs rural counties, counties closest to core airports, most populous counties, and counties with highest proportion of racial/ethnic minority counties. However, geographic differences in the incidence have shrunk since early April, driven by a significant decrease in the incidence in these counties (EWPC range: -2.0% - -4.2%) and a consistent increase in other areas (EWPC range: 1.5% - 20.3%). CONCLUSIONS: To substantially decrease the nationwide incidence of COVID-19, strict social distancing measures should be continuously implemented, especially in geographic areas with increasing risks, including rural areas. Spatiotemporal characteristics and trends of COVID-19 should be considered in decision-making on the timeline of re-opening for states and localities.


title: Effect of throat washings on detection of 2019 novel coronavirus

text: The 2019 novel coronavirus was detected in the self-collected throat washings. Positive testing rate of throat washing was much higher than that of Nasopharyngeal swabs. Throat washing is a promising candidate for 2019-nCoV screening and monitoring due to its noninvasive and reliability.


First antibody against COVID-19 spike protein enters phase I


title: Coronavirus disease 2019 (COVID-19): an evidence map of medical literature

text: BACKGROUND: Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises. METHODS: In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps. RESULTS: The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4-16). CONCLUSIONS: Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.


A Brave New World: Lessons from the COVID-19 Pandemic for Transitioning to Sustainable Supply and Production


Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine


title: Readability of online patient education material for the novel coronavirus disease (COVID-19): a cross-sectional health literacy study

text: OBJECTIVES: The internet has become one of the most important resources for the general population when searching for healthcare information. However, the information available is not always suitable for all readers because of its difficult readability. We sought to assess the readability of online information regarding the novel coronavirus disease (COVID-19) and establish whether they follow the patient educational information reading level recommendations. STUDY DESIGN: This is a cross-sectional study. METHODS: We searched five key terms on Google and the first 30 results from each of the searches were considered for analysis. Five validated readability tests were utilized to establish the reading level for each article. RESULTS: Of the 150 gathered articles, 61 met the inclusion criteria and were evaluated. None (0%) of the articles met the recommended 5th to 6th grade reading level (of an 11-12-year-old). The mean readability scores were Flesch Reading Ease 44.14, Flesch-Kincaid Grade Level 12.04, Gunning-Fog Index 14.27, Simple Measure of Gobbledygook SMOG Index 10.71, and Coleman-Liau Index 12.69. CONCLUSIONS: Online educational articles on COVID-19 provide information too difficult to read for the general population. The readability of articles regarding COVID-19 and other diseases needs to improve so that the general population may understand health information better and may respond adequately to protect themselves and limit the spread of infection.


title: Learning Diagnosis of COVID-19 from a Single Radiological Image

text: Radiological image is currently adopted as the visual evidence for COVID-19 diagnosis in clinical. Using deep models to realize automated infection measurement and COVID-19 diagnosis is important for faster examination based on radiological imaging. Unfortunately, collecting large training data systematically in the early stage is difficult. To address this problem, we explore the feasibility of learning deep models for COVID-19 diagnosis from a single radiological image by resorting to synthesizing diverse radiological images. Specifically, we propose a novel conditional generative model, called CoSinGAN, which can be learned from a single radiological image with a given condition, i.e., the annotations of the lung and COVID-19 infection. Our CoSinGAN is able to capture the conditional distribution of visual finds of COVID-19 infection, and further synthesize diverse and high-resolution radiological images that match the input conditions precisely. Both deep classification and segmentation networks trained on synthesized samples from CoSinGAN achieve notable detection accuracy of COVID-19 infection. Such results are significantly better than the counterparts trained on the same extremely small number of real samples (1 or 2 real samples) by using strong data augmentation, and approximate to the counterparts trained on large dataset (2846 real images). It confirms our method can significantly reduce the performance gap between deep models trained on extremely small dataset and on large dataset, and thus has the potential to realize learning COVID-19 diagnosis from few radiological images in the early stage of COVID-19 pandemic. Our codes are made publicly available at https://github.com/PengyiZhang/CoSinGAN.


title: Porcine epidemic diarrhea virus deficient in RNA cap guanine-N-7 methylation is attenuated and induces higher type I and III interferon responses

text: The 5' cap methylation of viral RNA plays an important role in RNA stability, efficient translation, and immune evasion. Thus, RNA cap methylation is an attractive target for antiviral discovery and development of new live attenuated vaccines. For coronaviruses, RNA cap structure is first methylated at guanine N-7 (G-N-7) position by nonstructural protein 14 (nsp14), which facilitates and precedes the subsequent ribose 2'-O methylation by nsp16-nsp10 complex. Using porcine epidemic diarrhea virus (PEDV), an Alphacoronavirus, as a model, we showed that G-N-7 methyltransferase (G-N-7 MTase) of PEDV nsp14 methylated RNA substrates in a sequence-unspecific manner. PEDV nsp14 can efficiently methylate RNA substrates with various lengths in both neutral and alkaline pH environment, and can methylate cap analogs (GpppA and GpppG) and single nucleotide GTP but not ATP, CTP, or UTP. Mutations to the S-adenosyl-L-methionine (SAM) binding motif in the nsp14 abolished the G-N-7 MTase activity and were lethal to PEDV. However, recombinant rPEDV-D350A with a single mutation (D350A) in nsp14, which retained 29.0% of G-N-7 MTase activity, was viable. Recombinant rPEDV-D350A formed significantly smaller plaque and had significant defects in viral protein synthesis and viral replication in Vero CCL-81 cells and intestinal porcine epithelial cells (IPEC-DQ) cells. Notably, rPEDV-D350A induced significantly higher expression of both type I and III interferons in IPEC-DQ cells compared to the parental rPEDV. Collectively, our results demonstrate that G-N-7 MTase activity of PEDV modulates viral replication, gene expression, and innate immune responses.IMPORTANCE Coronaviruses (CoVs) include a wide range of important human and animal pathogens. Examples of human CoVs include severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and the most recently emerged SARS-CoV-2. Examples of pig CoVs include porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine enteric alphacoronavirus (SeACoV). There are no vaccines or antiviral drugs for most of these viruses. All known CoVs encode a bifunctional nsp14 protein which possesses ExoN and G-N-7 MTase activities, responsible for replication fidelity and RNA cap G-N-7 methylation, respectively. Here, we biochemically characterized G-N-7 MTase of PEDV nsp14 and found that G-N-7 MTase-deficient PEDV was defective in replication and induced higher type I and III interferons. These findings highlight that CoV G-N-7 MTase may be a novel target for rational design of live attenuated vaccines and antiviral drugs.


[Rapid investigation plan of clinical courses and key diagnosis and treatment equipment requirements for the patients of the 2019 Novel Coronavirus Pneumonia (COVID-19)]


title: Evaluación de la incidencia y perfil de riesgo de Covid-19 según comorbilidad previa en adultos ≥50 años del área de Tarragona./ [Evaluation of incidence and risk profile for suffering Covid-19 infection by underlying conditions among middle-aged and older adults in Tarragona.]

text: OBJECTIVE: Population-based data on the current Covid-19 pandemic is scarce. This study investigated incidence and risk to suffer Covid-19 by baseline underlying conditions in people ≥50 years in Tarragona region across march-april 2020. METHODS: Population-based retrospective cohort study involving 79,071 adults ≥50 years-old in Tarragona region (Southern Catalonia, Spain). Cohort characteristics (age, sex, residence, vaccinations history and comorbidities) were established at baseline, and Covid-19 cases occurring between 01/03/2020-30/04/2020 were registered. Cox regression analysis calculating Hazard ratios (HRs) adjusted by age, sex and comorbidities was used to estimate risk for Covid-19. RESULTS: Across study period, 1,547 cohort members were PCR tested (22.6% positive) and 367 were presumptive cases without PCR tested. Considering PCR-confirmed Covid-19, incidence (per 100,000 persons-period) was 441 overall (248, 141, 424, 1,303 and 3,135 in 50-59, 60-69, 70-79, 80-89 and ≥90 years-old, respectively; 380 in men and 497 in women; 259 in community-dwelling and 10,571 in nursing-home). By comorbidities, maximum incidence emerged among persons with neurological disease (2,723), atrial fibrillation (1,348), chronic renal failure (1,050), cardiac disease (856), respiratory disease (798) and diabetes (706). Lower incidence appeared in rheumatic diseases (230) and smokers (180). In multivariable analysis focused on community-dwelling individuals (N=77,671), only cardiac disease (HR: 1.47; 95% CI: 1.01-2.15; p=0.045) and respiratory disease (HR: 1.75; 95% CI: 1.00-3.02; p=0.051) were associated with an increased risk, whereas smoking (HR:0.43; 95% CI: 0.25-0.74; p=0.002) and influenza vaccinated (HR: 0.63; 95% CI: 0.43-0.92; p=0.015) appeared associated with a decreased risk. CONCLUSIONS: Apart of increasing age and nursing-home residence, chronic respiratory and cardiac disease appear at increased risk for suffering covid19. This study investigated population-based incidence of Covid-19 infection by underlying conditions among adults ≥50 years in Tarragona (Southern Catalonia, Spain) across two first months pandemic period.


Resúmenes al Español


title: Stopping Covid-19: A pandemic-management service value chain approach

text: A logical strategy to contain the Covid-19 pandemic is to completely isolate everyone for 2 weeks (the incubation period of the virus). However, such a strategy can have prohibitive economic and social costs and, therefore, will be difficult to implement. At the same time, the current situation is leading to an expanding humanitarian, health and economic crisis. Based on principles of the Theory of Constraints, we propose in this article the "Shutting-down Transmission Of Pandemic" (STOP Covid-19) plan that would reliably contain the pandemic, mitigate its economic consequences, and boost societal confidence. This plan requires the implementation of four strategies over 90 days: (a) stop all international, domestic passenger air and intercity bus/train travel; (b) create administrative zones of about 1 million people; (c) stop all non-emergency cross-zonal travel except for transportation of goods, and (d) deploy an information-driven service value chain to control the spread of the pandemic within a zone.


title: Ventilated Upper Airway Endoscopic Endonasal Procedure Mask: Surgical Safety in the COVID-19 Era

text: BACKGROUND: COVID-19 poses a risk to the endoscopic skull base surgeon. Significant efforts to improving safety have been employed, including the use of personal protective equipment, preoperative COVID-19 testing, and recently the use of a modified surgical mask barrier. OBJECTIVE: To reduce the risks of pathogen transmission during endoscopic skull base surgery. METHODS: This study was exempt from Institutional Review Board approval. Our study utilizes a 3-dimensional (3D)-printed mask with an anterior aperture fitted with a surgical glove with ports designed to allow for surgical instrumentation and side ports to accommodate suction ventilation and an endotracheal tube. As an alternative, a modified laparoscopic surgery trocar served as a port for instruments, and, on the contralateral side, rubber tubing was used over the endoscrub endosheath to create an airtight seal. Surgical freedom and aerosolization were tested in both modalities. RESULTS: The ventilated mask allowed for excellent surgical maneuverability and freedom. The trocar system was effective for posterior surgical procedures, allowing access to critical paramedian structures, and afforded a superior surgical seal, but was limited in terms of visualization and maneuverability during anterior approaches. Aerosolization was reduced using both the mask and nasal trocar. CONCLUSION: The ventilated upper airway endoscopic procedure mask allows for a sealed surgical barrier during endoscopic skull base surgery and may play a critical role in advancing skull base surgery in the COVID-19 era. The nasal trocar may be a useful alternative in instances where 3D printing is not available. Additional studies are needed to validate these preliminary findings.


England's health policy response to covid-19


title: COVID-19 pandemic: do we need systematic screening of patients with cardiovascular risk factors in Low and Middle-Income Countries (LMICs) for preventing death?

text: COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.


title: COVID-19 Clinical Diagnostics and Testing Technology

text: Given the global nature of the COVID-19 pandemic, the need for disease detection and expanding testing capacity remains a critical priority. This review discusses the technological advances in testing capability and methodology that are currently employed or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for SARS-CoV-2 testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID-19 diagnostics on the horizon. Antibody response against SARS-CoV-2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.


title: Transmission of airborne virus through sneezed and coughed droplets

text: The spread of COVID19 through droplets ejected by infected individuals in the air during sneezing and coughing has been considered as a matter of key concern. Therefore, a quantitative understanding of the propagation of droplets containing the virus assumes immense importance in formulating the preventive strategies. In the present work we rigorously investigate the evolution of droplets in space and time under varying external conditions of temperature, humidity, air flow by using laws of statistical mechanics. The effects of drag, diffusion and the gravity on the droplets of different sizes and ejection velocities have been taken into consideration during its motion in the air. In still air it is found that bigger droplets traverse larger distance but the smaller droplets remain suspended in the air for longer time. Therefore, in still air the horizontal distance that a healthy individual should maintain from an infected one is determined by the bigger droplets but the time interval to be maintained between the two is determined by the smaller droplets. Here we show that in places with flowing air the lighter droplets travel larger distance and have the ability to remain suspended in the air for longer time. Therefore, we conclude that both temporal as well as the geometric distance that a healthy individual should maintain from an infected one is determined by the smaller droplets if there is flowing air. The small droplets travel larger distance and remain suspended in the air for long time under the influence of flow making the use of mask mandatory to prevent the virus. The the maintenance of only stationary separation between healthy and infected individual is not substantiated. The quantitative results obtained here will be useful to devise strategies for preventing also the spread of other types of droplets containing microorganisms.


title: The Spectrum of Cardiac Manifestations in Coronavirus Disease 2019 (COVID-19) - a Systematic Echocardiographic Study

text: Background: Information regarding the cardiac manifestations of COVID-19 is scarce. We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection. Methods: 100 consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared to reference values. Echocardiographic studies included left ventricular (LV) systolic and diastolic function, valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound. A second exam was performed in case of clinical deterioration. Results: Thirty two patients (32%) had a normal echocardiogram at baseline. The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%). Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared to patients with normal troponin or better clinical condition, but had worse RV function. Clinical deterioration occurred in 20% of patients. In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients). Femoral vein thrombosis (DVT) was diagnosed in 5 of 12 patients with RV failure. Conclusions:In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic and RV function are impaired. Elevated troponin and poorer clinical grade are associated with worse RV function. In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without DVT, is more common, but acute LV systolic dysfunction was noted in ≈20%.


title: Quantitative Separation of Tremor and Ataxia in Essential Tremor

text: OBJECTIVE: This study addresses a very important problem in Neurology, distinguishing tremor and ataxia using quantitative methods. Specifically, we aimed to quantitatively separate dysmetria, a cardinal sign of ataxia, from tremor in Essential Tremor (ET). METHODS: In experiment 1, we compared nineteen participants diagnosed with ET undergoing thalamic deep brain stimulation (DBS; ETDBS ) to 19 healthy controls (HC). We quantified tremor during postural tasks using accelerometry and dysmetria with fast, reverse-at-target goal-directed movements. To ensure that endpoint accuracy was unaffected by tremor, we quantified dysmetria in selected trials manifesting a smooth trajectory to the endpoint. Finally, we manipulated tremor amplitude by switching DBS ON and OFF to examine its effect on dysmetria. In experiment 2, we compared 10 ET participants (ET) with 10 HC to determine if we could identify and distinguish dysmetria from tremor in non-DBS ET. RESULTS: Three findings suggest that we can quantify dysmetria independent of tremor in ET. First, ETDBS and ET exhibited greater dysmetria than HC and dysmetria did not correlate with tremor (R2 <0.01). Second, even for trials with tremor-free trajectories to the target, ET exhibited greater dysmetria than HC (p<0.01). Third, activating DBS reduced tremor (p<0.01) but had no effect on dysmetria (p>0.2). INTERPRETATION: We demonstrate that dysmetria can be quantified independent of tremor using fast, reverse at target goal-directed movements. These results have important implications for the understanding of ET and other cerebellar and tremor disorders. Future research should examine the neurophysiological mechanisms underlying each symptom and characterize their independent contribution to disability. This article is protected by copyright. All rights reserved.


Risk of Increased Physical Inactivity During COVID-19 Outbreak in Older People: A Call for Actions


title: Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant

text: BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.


title: Radiology Education Amid COVID-19 Pandemic and Possible Solutions

text: Along with the rest of the world, the United States is inundated by the COVID-19 pandemic. The medical services in the country have been severely affected. The pandemic poses extraordinary challenges to academic institutions including radiology residency and fellowship programs. Herein, we delineate major difficulties faced by our radiology training program and mitigating countermeasures. The primary objective is to discuss the changes in our radiology training programs due to COVID-19 to allow for continued radiology education.


title: Novel coronavirus (COVID-19) infection: What a doctor on the frontline needs to know

text: Coronavirus disease 2019 (COVID-19) is a zoonotic respiratory infection originating from Wuhan, China. Rapidly spreading from Wuhan to all inhabited continents of the world, the World Health Organisation declared COVID-19 a pandemic on March 11, 2019. Infected patients present with fever and cough; radiological features include bilateral infiltrates on chest x-ray and computed tomography scanning. Management is supportive with oxygen supplementation, broad-spectrum antibiotics as well as careful fluid balancing. A number of drugs, both new and old, are currently in clinical trials and being used on an experimental basis in clinical practice. The COVID-19 pandemic is the greatest worldwide public health crisis of a generation, and has led to seismic political, economic and social changes. This review provides an overview of COVID-19 for junior doctors who find themselves on a new frontline of healthcare.


title: Emergence of New Disease: How Can Artificial Intelligence Help?

text: Emergence of new disease remains a critical parameter in human health and society. Advances in artificial intelligence (AI) allow for rapid processing and analysis of massive and complex data. In this forum article, the recent applications across disease prediction and drug development in relation to the COVID-19 pandemic are reviewed.


title: Effectiveness and safety of available treatments for COVID-19 during pregnancy: a critical review

text: Background: COVID-19 is a pandemic disease caused by the SARS-CoV-2 and it spread globally in the last few months. The complete lack of specific treatment forced clinicians to use old drugs, chosen for their efficacy against similar viruses or their in vitro activity. Trials on patients are ongoing but the majority of information comes from small case series and single center reports. We aimed to provide a literature review on the putative effectiveness and safety of available treatments for COVID-19 in pregnant women.Methods: We reviewed all the available literature concerning the drugs that have been used in the treatment of COVID-19 during pregnancy and whose safe assumption during pregnancy had been demonstrated by clinical studies (i.e. including studies on other infectious diseases). Drugs contra-indicated during pregnancy or with unknown adverse effects were not included in our review.Results and conclusions: Clinical trials are not often conducted among pregnant patients for safety reasons and this means that drugs that may be effective in general population cannot be used for pregnant women due to the lack of knowledge of side effects in this category of people .The choice to use a specific drug for COVID-19 in pregnancy should take into account benefits and possible adverse events in each single case. In the current situation of uncertainty and poor knowledge about the management of COVID-19 during pregnancy, this present overview may provide useful information for physicians with practical implications.


title: Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model

text: OBJECTIVE: To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model. METHODS: Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5 µg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas. RESULTS: TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P<0.01) and in vitro (90% vs. 65% reduction in wound area, P<0.01). Moreover, topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4, HMGCoA, SPT, filaggrin, loricrin and involucrin (P<0.05 vs. vehicle-treated controls) on day 3 after wounding. Likewise, TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 (33.06±2.09 g/(m2·h) vs. 24.60±2.04 g/(m2·h), P<0.01). CONCLUSIONS: Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function, leading to acceleration of acute cutaneous WH. Topical products containing TASE could be used to manage acute cutaneous WH.


title: Epidemiology and clinical course of COVID-19 in Shanghai, China

text: Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.


title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK

text: BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a "lockdown" was implemented across the UK. We compared measured contact patterns during the "lockdown" to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37-0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22-0.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.


title: Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations

text: The novel coronavirus, COVID-19, caused by SARS-CoV-2, is a global health pandemic that started in December 2019. The effective drug target among coronaviruses is the main protease Mpro, because of its essential role in processing the polyproteins that are translated from the viral RNA. In this study, the bioactivity of some selected heterocyclic drugs named Favipiravir (1), Amodiaquine (2), 2'-Fluoro-2'-deoxycytidine (3), and Ribavirin (4) was evaluated as inhibitors and nucleotide analogues for COVID-19 using computational modeling strategies. The density functional theory (DFT) calculations were performed to estimate the thermal parameters, dipole moment, polarizability, and molecular electrostatic potential of the present drugs; additionally, Mulliken atomic charges of the drugs as well as the chemical reactivity descriptors were investigated. The nominated drugs were docked on SARS-CoV-2 main protease (PDB: 6LU7) to evaluate the binding affinity of these drugs. Besides, the computations data of DFT the docking simulation studies was predicted that the Amodiaquine (2) has the least binding energy (-7.77 Kcal/mol) and might serve as a good inhibitor to SARS-CoV-2 comparable with the approved medicines, hydroxychloroquine, and remdesivir which have binding affinity -6.06 and -4.96 Kcal/mol, respectively. The high binding affinity of 2 was attributed to the presence of three hydrogen bonds along with different hydrophobic interactions between the drug and the critical amino acids residues of the receptor. Finally, the estimated molecular electrostatic potential results by DFT were used to illustrate the molecular docking findings. The DFT calculations showed that drug 2 has the highest of lying HOMO, electrophilicity index, basicity, and dipole moment. All these parameters could share with different extent to significantly affect the binding affinity of these drugs with the active protein sites.


title: The SARS-CoV-2 epidemic in Zimbabwe: Quo vadis?

text: The trajectory, and impact of the SARS-CoV-2 pandemic in sub-Saharan Africa is unclear, but it is seemingly varied between different countries, with most reporting low numbers. We use the situation in Zimbabwe to build an argument that the epidemic is likely to be attenuated in some countries with similar socio-economic and cultural structures. However, even an attenuated epidemic may overwhelm weak health systems, emphasising the importance of prevention. These prevention strategies should be tailored to the unique social and cultural networks of individual countries which may facilitate the spread of SARS-CoV 2. It is also equally important to maintain services for the major infectious diseases in the region such as tuberculosis and malaria. A breakdown of treatment and prevention services for these conditions may even overshadow the projected morbidity and mortality from COVID-19.


Increase in animal abuse likely during lockdown


Screen mirroring, screen casting and screen sharing during COVID-19: what dermatologists should know


title: Estimaci\'on del n\'umero de reproducci\'on de la epidemia COVID-19 en Culiac\'an Sinaloa, M\'exico

text: Currently the COVID-19 epidemic is developing in the City of Culiac\'n Sinaloa, Mexico, where up to April 20 of this year there have been 35 deaths associated with this epidemic. The reproduction number $(R_0)$ of an epidemic represents the average number of people infected by an infected person during their period of infection. In this work we use the data published by the Secretary of Health of the State of Sinaloa on the number of new infected cases confirmed per day and we estimate that the value of $R_0$ is 1.562 with a 95% confidence interval given by (1.401,1.742). We also estimate the mortality rate among the confirmed cases, which turned out to be 16.8%. - - - - - Actualmente la epidemia COVID-19 se est\'a desarrollando en la Ciudad de Culiac\'an Sinaloa, M\'exico, donde hasta el 20 de abril del presente a\~no han ocurrido 35 decesos asociados con esta epidemia. El n\'umero de reproducci\'on $(R_0)$ de una epidemia representa el n\'umero promedio de personas contagiadas por una persona infectada durante su periodo de infecci\'on. En este trabajo usamos los datos publicados por la Secretaria de Salud del Estado de Sinaloa sobre el n\'umero de nuevos casos infectados confirmados por dia y estimamos que el valor de $R_0$ es de 1.562 con un intervalo del 95% de confianza dado por (1.401,1.742). Estimamos tambi\'en la tasa de mortalidad entre los casos confirmados, la cual result\'o ser de 16.8%.


title: Social distancing with the Optimal Steps Model

text: With the Covid-19 pandemic an urgent need to simulate social distancing arises. The Optimal Steps Model (OSM) is a pedestrian locomotion model that operationalizes an individual's need for personal space. We present new parameter values for personal space in the Optimal Steps Model to simulate social distancing in the pedestrian dynamics simulator Vadere. Our approach is pragmatic. We consider two use cases: in the first we demand that a set social distance must never be violated. In the second the social distance must be kept only on average. For each use case we conduct simulation studies in a typical bottleneck scenario and measure contact times, that is, violations of the social distance rule. We derive rules of thumb for suitable parameter choices in dependency of the desired social distance. We test the rules of thumb for the social distances 1.5m and 2.0m and observe that the new parameter values indeed lead to the desired social distancing. Thus, the rules of thumb will quickly enable Vadere users to conduct their own studies without understanding the intricacies of the OSM implementation and without extensive parameter adjustment.


Distance, diffusion and the role of social media in a time of COVID contagion


title: Medical Rehabilitation in Pandemics: Towards a New Perspective

text: Missing (Commentary).


title: The daily impact of COVID-19 in gastroenterology

text: A new strain of coronavirus, called SARS-CoV-2, emerged in Wuhan, China, in December 2019, probably originating from a wild-animal contamination. Since then, the situation rapidly evolved from a cluster of patients with pneumonia, to a regional epidemic and now to a pandemic called COrona VIrus Disease 2019 (COVID-19). This evolution is related to the peculiar modes of transmission of the disease and to the globalization and lifestyle of the 21st century that created the perfect scenario for virus spread. Even though research has not evidenced particular susceptibility of inflammatory bowel disease (IBD) patients to SARS-CoV-2 infection, immunosuppressive and immunomodulatory treatments were considered potential risk factors. In this context, initiating treatments with these agents should be cautiously weighted and regular ongoing treatments shall be continued, while the dose of corticosteroids should be reduced whenever possible. Due to the increased risk of contamination, elective endoscopic procedures and surgeries should be postponed and IBD online appointments shall be considered. IBD patients shall also follow the recommendations provided to the general population, such as minimization of contact with infected or suspected patients and to wash hands frequently. In the absence of effective treatments and vaccines, this pandemic can only be controlled through prevention of SARS-CoV-2 transmission with the main objectives of providing patients the best healthcare possible and reduce mortality.


title: History-Aware Question Answering in a Blocks World Dialogue System

text: It is essential for dialogue-based spatial reasoning systems to maintain memory of historical states of the world. In addition to conveying that the dialogue agent is mentally present and engaged with the task, referring to historical states may be crucial for enabling collaborative planning (e.g., for planning to return to a previous state, or diagnosing a past misstep). In this paper, we approach the problem of spatial memory in a multi-modal spoken dialogue system capable of answering questions about interaction history in a physical blocks world setting. This work builds upon a full spatial question-answering pipeline consisting of a vision system, speech input and output mediated by an animated avatar, a dialogue system that robustly interprets spatial queries, and a constraint solver that derives answers based on 3-D spatial modelling. The contributions of this work include a symbolic dialogue context registering knowledge about discourse history and changes in the world, as well as a natural language understanding module capable of interpreting free-form historical questions and querying the dialogue context to form an answer.


title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan

text: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.


title: Return of the Coronavirus: 2019-nCoV

text: The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.


COVID-19 pandemic and impact on hematopoietic stem cell transplantation


Workforce Survival: Tracking Potential COVID-19 Exposure Amid Socioeconomic Activities Using Automatic Log-Keeping Apps


Cutaneous manifestations in COVID-19: familial cluster of urticarial rash


title: Author Correction: COVID-19: the vasculature unleashed

text: An amendment to this paper has been published and can be accessed via a link at the top of the paper.


title: COVID-19 and Long-Term Care Policy for Older People in Hong Kong

text: Hong Kong is a major international travel hub and a densely populated city geographically adjacent to Mainland China. Despite these risk factors, it has managed to contain the COVID-19 epidemic without a total lockdown of the city. Three months on since the outbreak, the city reported slightly more than 1,000 infected people, only four deaths and no infection in residential care homes or adult day care centers. Public health intervention and population behavioral change were credited as reasons for this success. Hong Kong's public health intervention was developed from the lessons learned during the SARS epidemic in 2003 that killed 299 people, including 57 residential care residents. This perspective summarizes Hong Kong's responses to the COVID-19 virus, with a specific focus on how the long-term care system contained the spread of COVID-19 into residential care homes and home and community-based services.


Dietary management of food protein-induced enterocolitis syndrome during the coronavirus disease 2019 pandemic


title: Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019

text: OBJECTIVE: The Coronavirus disease 2019 (COVID-19) which outbroke in December 2019 is highly contagious with a low cure rate. In view of this, there is an urgent need to find a more appropriate therapeutic scheme against COVID-19. The study aimed to investigate whether lopinavir/ritonavir (LPV/r) in combination with other pneumonia-associated adjuvant drugs has a better therapeutic effect on COVID-19. PATIENTS AND METHODS: Totally 47 patients with COVID-19 infection who were admitted to Rui'an People's Hospital between January 22 and January 29, 2020 were collected. The patients were divided into the test group and the control group according to whether they had been treated with LPV/r or not during hospitalization. Patients in the test group were treated with LPV/r combined with adjuvant medicine, while those in the control group were just treated with adjuvant medicine. The changes of body temperature, blood routine and blood biochemistry between the two groups were observed and compared. RESULTS: Both groups achieved good therapeutic effect with the body temperature of patients decreased gradually from admission to the 10th day of treatment. But the body temperature of patients in the test group decreased faster than that of the control group. Blood routine indexes showed that compared with the control group, the abnormal proportion of white blood cells, lymphocytes and C-reactive protein of the test group could be reduced to some extent. Blood biochemical indexes exhibited that the proportion of patients with abnormal alanine aminotransferase and aspartate aminotransferase in the test group were lower than the control group. The number of days for nCoV-RNA turning negative after treatment was significantly decreased in the test group than that in the control group. CONCLUSIONS: Compared with the treatment of pneumonia-associated adjuvant drugs alone, the combination treatment with LPV/r and adjuvant drugs has a more evident therapeutic effect in lowering the body temperature and restoring normal physiological mechanisms with no evident toxic and side effects. In view of these conclusions, we suggested that the use of LPV/r combined with pneumonia-associated adjuvant drugs in the clinical treatment for patients with COVID-19 should be promoted.


title: How young patients with cancer perceive the COVID-19 (coronavirus) epidemic in Milan, Italy: Is there room for other fears?

text: The rapid spread of coronavirus disease 2019 epidemic in Italy, in particular in the Milan focal point, required drastic measures and led to panic in the population. While in our center we did not change our approach to the treatment of our young patients with cancer, we developed a qualitative survey to assess their perception of the risk and level of stress. The survey showed that a relatively large proportion of young patients felt personally at risk of severe complications. We believe that we need to adequately inform our patients, focusing on hygienic measures and personal protection and prompt reporting of any suspicious symptoms.


title: Aerosol-generating procedures in head and neck surgery - can we improve practice after COVID-19?

text: The COVID-19 pandemic has had a dramatic impact on international medicine practice. The propensity for head and neck surgery to generate aerosols needs special consideration over and above simply adopting personal protective equipment. This study sought to interrogate the literature and evaluate whether which additional measures might provide benefit if routinely adopted in minimising viral transmission.


title: Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak — United States, December 31, 2019–February 4, 2020 ;MMWR

text: CDC, multiple other federal agencies, state and local health departments, and other partners are implementing aggressive measures to slow transmission of 2019-nCoV in the United States, be ready if widespread transmission occurs, and work on medical countermeasures


title: Can the COVID-19 epidemic be controlled on the basis of daily test reports?

text: This paper studies if and to which extent COVID-19 epidemics can be controlled by authorities taking decisions on public health measures on the basis of daily reports of swab test results, active cases and total cases. A suitably simplified process model is derived to support the controllability analysis, highlighting the presence of very significant time delay; the model is validated with data from several outbreaks. The analysis shows that suppression strategies can be effective if strong enough and enacted early on. It also shows how mitigation strategies can fail because of the combination of delay, unstable dynamics, and uncertainty in the feedback loop; approximate conditions based on the theory of limitation of linear control are given for feedback control to be feasible.


title: Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

text: In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC's impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.


COVID-19 and dialysis: why we should be worried


title: COVID-19 reveals weak health systems by design: Why we must re-make global health in this historic moment

text: The COVID-19 pandemic demonstrates the critical need to reimagine and repair the broken systems of global health. Specifically, the pandemic demonstrates the hollowness of the global health rhetoric of equity, the weaknesses of a health security-driven global health agenda, and the negative health impacts of power differentials not only globally, but also regionally and locally. This article analyses the effects of these inequities and calls on governments, multilateral agencies, universities, and NGOs to engage in true collaboration and partnership in this historic moment. Before this pandemic spreads further - including in the Global South - with potentially extreme impact, we must work together to rectify the field and practice of global health.


New Coronavirus (SARS-CoV-2): advances to flatten the curve the prison population


title: Non-Elective Pediatric Cardiac Catheterization During COVID-19 Pandemic: A New York Center Experience

text: BACKGROUND: COVID-19 has led to major changes in hospital systems across the world. In an effort to reduce viral transmission, conserve resources, and in accordance with institutional and state mandates, all elective procedures and surgeries were postponed during the initial outbreak. Guidelines for case selection are limited and management for pediatric catheterization laboratories during this crisis is unprecedented. OBJECTIVES: To report the protocols and case selection of a high-volume pediatric cardiac catheterization laboratory in the epicenter of the novel coronavirus (COVID-19) pandemic. METHODS: All pediatric cardiac catheterization procedures from March 16, 2020 through May 10, 2020 were reviewed. Changes to case selection and periprocedural workflow are described. Data were collected on COVID-19 testing status and primary procedure type, and all procedures were classified by urgency. RESULTS: There were 52 catheterizations performed on 50 patients. Endomyocardial biopsies were the most common procedure (n = 27; 52%). Interventional and diagnostic procedures represented 27% (n = 14) and 21% (n = 11) of cases, respectively. Two emergent procedures (3.8%) were performed on patients with positive COVID-19 testing. Most cases were performed on patients with negative COVID-19 testing (n = 33; 94%). CONCLUSIONS: Adjusting to the COVID-19 pandemic in a high-volume pediatric cardiac catheterization laboratory can be safely and effectively managed by prioritizing emergent and urgent cases and modifying workflow operations. The experience of this center may assist other pediatric cardiac catheterization laboratories in adapting to similar practice changes as the pandemic continues to evolve.


Why we should not stop giving aspirin to pregnant women during the COVID-19 pandemic


Will the COVID-19 pandemic affect HCV disease burden?


title: Oxidative stress-mediated epidermal growth factor receptor activation regulates PM2.5-induced over-secretion of pro-inflammatory mediators from human bronchial epithelial cells

text: BACKGROUND: Exposure to PM2.5 has been associated with increased morbidity and mortality of lung diseases although the underlying mechanisms have not been fully uncovered. Airway inflammation is a critical event in the pathogenesis of lung diseases. This study aimed to examine the role of oxidative stress and epidermal growth factor receptor (EGFR) in PM2.5-induced pro-inflammatory response in a human bronchial epithelial cell line, BEAS-2B. METHODS: BEAS-2B cells were exposed to 0, 20, 50, 100 and 150 µg/ml of PM2.5. Secretion of pro-inflammatory mediators including interleukin-6 (IL-6), IL-8 and IL-1ß was determined using enzyme linked immunosorbent assay. Levels of intracellular reactive oxygen species (ROS) were determined using flow cytometry. Phosphorylation of the EGFR was examined with immunoblotting. RESULTS: PM2.5 exposure increased the secretion of IL-6, IL-8, and IL-1ß in a concentration-dependent fashion. Moreover, exposure to PM2.5 elevated intracellular levels of ROS, and phosphorylation of the EGFR (Y1068). Pretreatment of BEAS-2B cells with either an antioxidant or a specific EGFR inhibitor significantly reduced PM2.5-induced IL-6, IL-8 and IL-1ß secretion, implying that both oxidative stress and EGFR activation were involved in PM2.5-induced pro-inflammatory response. Furthermore, pre-treatment of BEAS-2B cells with an antioxidant significantly blunted PM2.5-induced EGFR activation, suggesting that oxidative stress was required for PM2.5-induced EGFR activation. CONCLUSION: PM2.5 exposure induces pro-inflammatory response in human bronchial epithelial cells through oxidative stress-mediated EGFR activation.


title: Systematic Review of Clinical Insights into Novel Coronavirus (CoVID-19) Pandemic: Persisting Challenges in U.S. Rural Population

text: (1) Introduction. A recent viral outbreak of novel coronavirus (CoVID-19) was declared as a pandemic by the World Health Organization (WHO) due to its global public health concern. There has been an aggressive growth in the number of emerging cases suggesting rapid spread of the virus. Since the first reported case of CoVID-19, there has been vast progress in understanding the dynamics of CoVID-19. However, there is an increasing evidence of epidemiological disparity in disease burden between urban and rural areas, with rural areas having minimal pandemic preparedness and their own healthcare challenges. Therefore, this review aims to provide insight on the pathogenesis and the transmission dynamics of CoVID-19 along with pharmacological and non-pharmacological intervention strategies to mitigate the clinical manifestation of this virus. This review also aims to assess existing challenges of the CoVID-19 pandemic in rural areas based on past pandemic experiences and the effect on rural population. (2) Methods. A literature review was conducted using databases such as PubMed, Science Direct, Academic Search Premier, ProQuest, and Google Scholar, along with information from governmental organizations such as Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO). (3) Results. The causative virus, with its likely zoonotic origin, has demonstrated high pathogenicity in humans through increasing human-to-human transmission leading to extensive mitigation strategies, including patient quarantine and mass "social distancing" measures. Although the clinical manifestation of symptoms is mild in majority of the virus-inflicted population, critical patients may present with pneumonia and acute respiratory distress syndrome, exacerbated by pre-existing comorbidities, eventually leading to death. While effective coronavirus disease (CoVID-19)-specific vaccines and drugs are under clinical trials, several pharmacological and non-pharmacological interventions have been adapted to manage symptoms and curtail the effect of the virus to prevent increasing morbidity and mortality. Several persisting challenges have been noted for mitigating CoVID-19 in rural areas, including the poor healthcare infrastructure, health literacy, pandemic preparedness along with the fact that majority of rural population are frail subjects with pre-existing comorbidities. (4) Discussion. The increasing rate of incidence of CoVID-19 presents its own challenges, burdening healthcare institutions and the global economy, and impacting the physical and mental health of people worldwide. Given the clinical insights into CoVID-19 and the challenges presented in this review for the U.S. rural population, mitigation strategies should be designed accordingly to minimize the morbidity and mortality of this contagion.


Who is most likely to be infected with SARS-CoV-2?


title: CHEST Reviews: Addressing reduced laboratory-based pulmonary function testing during a pandemic

text: To reduce the spread of SARS-CoV-2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. As these mitigation strategies may be necessary for the next 6-18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFTs, which include spirometry, lung volumes, and diffusion capacity measurement, are essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, as well as novel digital health tools such as smartphone microphone spirometers, and mobile health technologies along integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options come important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the COVID-19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.


Update on clinical outcomes of women with COVID-19 during pregnancy


title: Erratum to rapid advice guidelines for management of children with COVID-19

text: [This corrects the article DOI: 10.21037/atm-20-3754.].


title: #lockdown: network-enhanced emotional profiling at the times of COVID-19

text: The COVID-19 pandemic forced countries all over the world to take unprecedented measures like nationwide lockdowns. To adequately understand the emotional and social repercussions, a large-scale reconstruction of how people perceived these unexpected events is necessary but currently missing. We address this gap through social media by introducing MERCURIAL (Multi-layer Co-occurrence Networks for Emotional Profiling), a framework which exploits linguistic networks of words and hashtags to reconstruct social discourse describing real-world events. We use MERCURIAL to analyse 101,767 tweets from Italy, the first country to react to the COVID-19 threat with a nationwide lockdown. The data were collected between 11th and 17th March, immediately after the announcement of the Italian lockdown and the WHO declaring COVID-19 a pandemic. Our analysis provides unique insights into the psychological burden of this crisis, focussing on: (i) the Italian official campaign for self-quarantine (#iorestoacasa}), (ii) national lockdown (#italylockdown), and (iii) social denounce (#sciacalli). Our exploration unveils evidence for the emergence of complex emotional profiles, where anger and fear (towards political debates and socio-economic repercussions) coexisted with trust, solidarity, and hope (related to the institutions and local communities). We discuss our findings in relation to mental well-being issues and coping mechanisms, like instigation to violence, grieving, and solidarity. We argue that our framework represents an innovative thermometer of emotional status, a powerful tool for policy makers to quickly gauge feelings in massive audiences and devise appropriate responses based on cognitive data.


title: Severe COVID-19 and aging: are monocytes the key?

text: The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation-related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.


title: Digital lensless holographic microscopy: numerical simulation and reconstruction with ImageJ

text: The description and validation of an ImageJ open-source plugin to numerically simulate and reconstruct digital lensless holographic microscopy (DLHM) holograms are presented. Two modules compose the presented plugin: the simulation module implements a discrete version of the Rayleigh-Somerfield diffraction formula, which allows the user to directly build a simulated hologram from a known phase and/or amplitude object by just introducing the geometry parameters of the simulated setup; the plugin's reconstruction module implements a discrete version of the Kirchhoff-Helmholtz diffraction integral, thus allowing the user to reconstruct DLHM holograms by introducing the parameters of the acquisition setup and the desired reconstruction distance. The plugin offers the two said modules within the robust environment provided by a complete set of built-in tools for image processing available in ImageJ. While the simulation module has been validated through the evaluation of the forecasted lateral resolution of a DLHM setup in terms of the numerical aperture, the reconstruction module is tested by means of reconstructing experimental DLHM holograms of biological samples.


title: Early Insights into Immune Responses during COVID-19

text: Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.


title: Cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity

text: Cytosine base editors (CBEs) enable efficient, programmable reversion of Tâ¢A to Câ¢G point mutations in the human genome. Recently, cytosine base editors with rAPOBEC1 were reported to induce unguided cytosine deamination in genomic DNA and cellular RNA. Here we report eight next-generation CBEs (BE4 with either RrA3F [wt, F130L], AmAPOBEC1, SsAPOBEC3B [wt, R54Q], or PpAPOBEC1 [wt, H122A, R33A]) that display comparable DNA on-target editing frequencies, whilst eliciting a 12- to 69-fold reduction in C-to-U edits in the transcriptome, and up to a 45-fold overall reduction in unguided off-target DNA deamination relative to BE4 containing rAPOBEC1. Further, no enrichment of genome-wide Câ¢G to Tâ¢A edits are observed in mammalian cells following transfection of mRNA encoding five of these next-generation editors. Taken together, these next-generation CBEs represent a collection of base editing tools for applications in which minimized off-target and high on-target activity are required.


title: Factors Associated with Resilience Among Medical Staff in Radiology Departments During The Outbreak of 2019 Novel Coronavirus Disease (COVID-19): A Cross-Sectional Study

text: BACKGROUND A growing body of evidence suggests that in the face of life adversity, threats, or other major stressful events, resilience is more conducive to individual adaptation and growth. MATERIAL AND METHODS The Connor-Davidson Resilience Scale and the Chinese Perceived Stress Scale were used to evaluate the resilience and perceived stress of 600 medical staff members from the radiology departments in 32 public hospitals in Sichuan Province, China, respectively. Multiple linear regression was used to analyze factors related to resilience. RESULTS The total resilience score was 65.76±17.26, wherein the toughness dimension score was 33.61±9.52, the strength dimension score was 21.25±5.50, and the optimism dimension score was 10.91±3.15. There was a significant negative correlation between perceived stress and resilience (r=-0.635, P<0.001). According to multivariate analysis, the total perceived stress score (ß=-1.318, P<0.001), gender (ß=-4.738, P<0.001), knowledge of COVID-19 (ß=2.884, P=0.043), knowledge of COVID-19 protective measures (ß=3.260, P=0.042), and availability of adequate protective materials (ß=-1.268, P=0.039) were independent influencing factors for resilience. CONCLUSIONS The resilience level of the medical staff in the radiology departments during the outbreak of COVID-19 was generally low, particularly regarding toughness. More attention should be paid to resilience influence factors such as high perceived stress, female gender, lack of understanding of COVID-19 and protective measures, and lack of protective materials, and targeted interventions should be undertaken to improve the resilience level of the medical staff in the radiology departments during the outbreak of COVID-19.


title: Potential Drugs Targeting Early Innate Immune Evasion of SARS-Coronavirus 2 via 2'-O-Methylation of Viral RNA

text: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the COVID-19 respiratory disease pandemic utilizes unique 2'-O-methyltransferase (2'-O-MTase) capping machinery to camouflage its RNA from innate immune recognition. The nsp16 catalytic subunit of the 2'-O-MTase is unusual in its requirement for a stimulatory subunit (nsp10) to catalyze the ribose 2'-O-methylation of the viral RNA cap. Here we provide a computational basis for drug repositioning or de novo drug development based on three differential traits of the intermolecular interactions of the SARS-CoV-2-specific nsp16/nsp10 heterodimer, namely: (1) the S-adenosyl-l-methionine-binding pocket of nsp16, (2) the unique "activating surface" between nsp16 and nsp10, and (3) the RNA-binding groove of nsp16. We employed ≈9000 U.S. Food and Drug Administration (FDA)-approved investigational and experimental drugs from the DrugBank repository for docking virtual screening. After molecular dynamics calculations of the stability of the binding modes of high-scoring nsp16/nsp10-drug complexes, we considered their pharmacological overlapping with functional modules of the virus-host interactome that is relevant to the viral lifecycle, and to the clinical features of COVID-19. Some of the predicted drugs (e.g., tegobuvir, sonidegib, siramesine, antrafenine, bemcentinib, itacitinib, or phthalocyanine) might be suitable for repurposing to pharmacologically reactivate innate immune restriction and antagonism of SARS-CoV-2 RNAs lacking 2'-O-methylation.


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Stigma during the COVID-19 pandemic


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Comment on "Encephalopathy in patients with COVID-19: A review"


Hospitals as health factories and the coronavirus epidemic


title: Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products

text: Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.