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Temporal evolution, most influential studies and sleeping beauties of the coronavirus literature
Abstract
Following the outbreak of SARS-CoV-2 disease, within less than 8 months, the 50 years-old scholarly literature of coronaviruses grew to nearly three times larger than its size prior to 2020. Here, temporal evolution of the coronavirus literature over the last 30 years (N = 43,769) is analysed along with its subdomain of SARS-CoV-2 articles (N = 27,460) and the subdomain of reviews and meta-analytic studies (N = 1027). The analyses are conducted through the lenses of co-citation and bibliographic coupling of documents. (1) Of the N = 1204 review and meta-analytical articles of the coronavirus literature, nearly 88% have been published and indexed during the first 8 months of 2020, marking an unprecedented attention to reviews and meta-analyses in this domain, prompted by the SARS-CoV-2 pandemic. (2) The subset of 2020 SARS-CoV-2 articles is bibliographically distant from the rest of this literature published prior to 2020. Individual articles of the SARS-CoV-2 segment with a bridging role between the two bodies of articles (i.e., before and after 2020) are identifiable. (3) Furthermore, the degree of bibliographic coupling within the 2020 SARS-CoV-2 cluster is much poorer compared to the cluster of articles published prior to 2020. This could, in part, be explained by the higher diversity of topics that are studied in relation to SARS-CoV-2 compared to the literature of coronaviruses published prior to the SARS-CoV-2 disease. (4) The analyses on the subset of SARS-CoV-2 literature identified studies published prior to 2020 that have now proven highly instrumental in the development of various clusters of publications linked to SARS-CoV-2. In particular, the so-called "sleeping beauties" of the coronavirus literature with an awakening in 2020 were identified, i.e., previously published studies of this literature that had remained relatively unnoticed for several years but gained sudden traction in 2020 in the wake of the SARS-CoV-2 outbreak. This work documents the historical development of the literature on coronaviruses as an event-driven literature and as a domain that exhibited, arguably, the most exceptional case of publication burst in the history of science. It also demonstrates how scholarly efforts undertaken during peace time or prior to a disease outbreak could suddenly play a critical role in prevention and mitigation of health disasters caused by new diseases.
Supplementary information:
The online version contains supplementary material available at 10.1007/s11192-021-04036-4.
... Sleeping beauties have always been one of the most challenging phenomena in scientometrics (van Raan, 2021;Haghani & Varamini, 2021;Garfield, 1980). Their citation patterns characterized by their spooky delayed awakening have urged multiple scientists to study the reasons behind late citation bursts (van Raan, 2021;Haghani & Varamini, 2021;Garfield, 1980). ...
... Sleeping beauties have always been one of the most challenging phenomena in scientometrics (van Raan, 2021;Haghani & Varamini, 2021;Garfield, 1980). Their citation patterns characterized by their spooky delayed awakening have urged multiple scientists to study the reasons behind late citation bursts (van Raan, 2021;Haghani & Varamini, 2021;Garfield, 1980). Such factors include the bibliographic features of sleeping beauties such as keywords (Yang, et al., 2022) as well as altmetric data like social media interactions (Hou & Yang, 2020). ...
... During the COVID-19 pandemic, a notable number of sleeping beauties have been awakened due to the resurgence of several topics that were not active in the last years and that reappeared because of their close semantic links with coronavirus research (Zhang, Cai, Fry, Wu, & Wagner, 2021). Several papers have been aroused thanks to being cited by or co-cited with a recent highly cited paper about the outbreak (Song, Situ, Zhu, & Lei, 2018;Haghani & Varamini, 2021). Fifteen publications published between 2003 and 2015 have been identified by Haghani and Varamini (2021) 1 as sleeping beauties awakened by the COVID-19 pandemic (Haghani & Varamini, 2021). ...
In this research letter, we build upon recent studies about the sleeping beauties awakened by the COVID-19 pandemic. We prove that a peak of citations for sleeping beauties is associated with a sharp increase in the number of citations received by their references. This demonstrates the existence of a cascading activation of citation-based sleeping beauties.
... The spread of SARS-CoV-2, first detected in Wuhan, China, was characterized by rapid transmission between humans, severe courses of disease and high mortality rates [89]. The effort that was put into the study of SARS-CoV-2 by the international scientific community however was immense [90]. Publishing companies of scientific journals made all publications on the subject openly accessible. ...
... Preprint publications were getting extremely important for sharing study results immediately with a broad scientific and public community. While this enabled fast publications of findings of international importance, the lack of an orderly peer review process also led to preprint publications of questionable reliance and a magnitude of publications that was easily overwhelming [90]. Some publications that were originally published on preprint servers never reached regular publication. ...
In this work, binding interactions between biomolecules were analyzed by a technique that is based on electrically controllable DNA nanolevers. The technique was applied to virus-receptor interactions for the first time. As receptors, primarily peptides on DNA nanostructures and antibodies were utilized. The DNA nanostructures were integrated into the measurement technique and enabled the presentation of the peptides in a controllable geometrical order. The number of peptides could be varied to be compatible to the binding sites of the viral surface proteins. Influenza A virus served as a model system, on which the general measurability was demonstrated. Variations of the receptor peptide, the surface ligand density, the measurement temperature and the virus subtypes showed the sensitivity and applicability of the technology. Additionally, the immobilization of virus particles enabled the measurement of differences in oligovalent binding of DNA-peptide nanostructures to the viral proteins in their native environment. When the coronavirus pandemic broke out in 2020, work on binding interactions of a peptide from the hACE2 receptor and the spike protein of the SARS-CoV-2 virus revealed that oligovalent binding can be quantified in the switchSENSE technology. It could also be shown that small changes in the amino acid sequence of the spike protein resulted in complete loss of binding. Interactions of the peptide and inactivated virus material as well as pseudo virus particles could be measured. Additionally, the switchSENSE technology was utilized to rank six antibodies for their binding affinity towards the nucleocapsid protein of SARS-CoV-2 for the development of a rapid antigen test device. The technique was furthermore employed to show binding of a non-enveloped virus (adenovirus) and a virus-like particle (norovirus-like particle) to antibodies. Apart from binding interactions, the use of DNA origami levers with a length of around 50 nm enabled the switching of virus material. This proved that the technology is also able to size objects with a hydrodynamic diameter larger than 14 nm. A theoretical work on diffusion and reaction-limited binding interactions revealed that the technique and the chosen parameters enable the determination of binding rate constants in the reaction-limited regime. Overall, the applicability of the switchSENSE technique to virus-receptor binding interactions could be demonstrated on multiple examples. While there are challenges that remain, the setup enables the determination of affinities between viruses and receptors in their native environment. Especially the possibilities regarding the quantification of oligo- and multivalent binding interactions could be presented.
... However, there are few bibliometric analyses exploring the temporal aspect of the pandemic, based on keywords or other indicators in COVID-19 scientific publications (Cai et al. 2021;Ebadi et al. 2021;Haghani and Varamini 2021;Lauper et al. 2021), using a combination of indexed and preprints databases, using a process that is totally auditable and reproducible. This is relevant due to the differences observed in the pandemic during the past two years, such as waves in number of new cases, new COVID-19 variants, new public policies and interventions, new proposed treatments and so on. ...
... Table 2 presents the importance of indexed databases, PubMed and Scopus, to spread and disclose the scientific information related to COVID-19, corresponding to almost 91% of the documents contained in this dataset. The use of this kind of database is preferable since the publications were peer-reviewed and indexed by highly rigorous and responsible vehicles regarding the dissemination of quality information (Casado-Aranda et al. 2021; Grammes et al. 2020;Haghani and Varamini 2021). ...
The mapping and analysis of scientific knowledge makes it possible to identify the dynamics and/or growth of a particular field of research or to support strategic decisions related to different research entities, based on bibliometric and/or scientometric indicators. However, with the exponential growth of scientific production, a systematic and data-oriented approach to the analysis of this large set of productions becomes increasingly essential. Thus, in this work, a data-oriented methodology was proposed, combining Data Analysis, Machine Learning and Complex Network Analysis techniques, and Data Version Control (DVC) tool, for the extraction of implicit knowledge in scientific production bases. In addition, the approach was validated through a case study in a COVID-19 manuscripts dataset, which had 199,895 articles published on arXiv, bioRxiv, medRxiv, PubMed and Scopus databases. The results suggest the feasibility of the proposed methodology, indicating the most active countries and the most explored themes in each period of the pandemic. Therefore, this study has the potential to instrument and expand strategic decisions by the scientific community, aiming at extracting knowledge that supports the fight against the COVID-19 pandemic.
... [30] However, these articles merely crammed charts regardless of the inflection points (IP) related to the trend on time-series-based data. For example, too many Figures in an article (e.g., 15, 18, and 20 charts, respectively [31][32][33] ) make readers confused about the focus of the research results. Dashboard-type visualization is thus required for development, particularly on the topic of vaccination effects against FRs around the world. ...
Background:
The new coronavirus disease 2019 (COVID-19) pandemic is raging worldwide. The administered vaccination has become a significant vehicle against the virus. Three hypotheses were made and required for validation: the number of vaccines administered is related to the country gross domestic product (GDP), vaccines can reduce the fatality rate (FR), and dashboards can present more meaningful information than traditionally static visualizations. Research data were downloaded from the GitHub website. The aims of this study are to verify that the number of vaccination uptakes is related to the country GDP, that vaccines can reduce FR, and that dashboards can provide more meaningful information than traditionally static visualizations.
Methods:
The COVID-19 cumulative number of confirmed cases (CNCCs) and deaths were downloaded from the GitHub website for countries/regions on November 6, 2021. Four variables between January 1, 2021, and November 6, 2021, were collected, including CNCCs and deaths, GDP per capita, and vaccine doses administered per 100 people (VD100) in countries/regions. We applied the Kano model, forest plot, and choropleth map to demonstrate and verify the 3 hypotheses using correlation coefficients (CC) between vaccination and FRs. Dashboards used to display the vaccination effects were on Google Maps.
Results:
We observed that the higher the GDP, the more vaccines are administered (Association = 0.68, t = 13.14, P < .001) in countries, the FR can be reduced by administering vaccinations that are proven except for the 4 groups of Asia, Low income, Lower middle income, and South America, as well as the application (app) with dashboard-type choropleth map can be used to show the comparison of vaccination rates for countries/regions using line charts.
Conclusion:
This research uses the Kano map, forest plot, and choropleth map to verify the 3 hypotheses and provides insights into the vaccination effect against the FR for relevant epidemic studies in the future.
... Knowledge foundations are significant to facilitate knowledge discovery [14][15][16][17]. Besides, most literature-based discovery studies on the global Covid-19 dataset [11,13] do not dive into specific topics to discover targeted knowledge for people pursuing different interests, such as basic medical research, epidemiological models, and social impacts research, etc. ...
Covid-19 is an unprecedented challenge that disruptively reshapes societies and scientific research communities. Facing the knowledge flood brought by the overwhelming volume of research efforts, there still lacks a platform to link those to previous knowledge foundations and efficiently visualize and understand them. Aiming to fill this gap, we propose a research framework in this paper to assist scientists in identifying, retrieving, and visualizing the emerging Covid-19 knowledge. The proposed framework incorporates principal topic decomposition (PCD), text analytics-based knowledge model (KM), and the hierarchical topic
tree (HTT) method to profile the research landscape, retrieve knowledge of specific interest, and visualize the knowledge structures. Initially, our topic analysis of 127,971 research papers published during 2020-2021 identified 35 research hotspots. Furthermore, we built up a knowledge model on the topic of vaccination and retrieved 92,286 research papers from the entire PubMed database as the knowledge foundation of this topic. Lastly, the HTT results of the retrieved papers highlighted multiple relevant disciplines, from whose branches we identified four future research directions: Monoclonal antibody treatments, vaccination in diabetic patients, vaccination effectiveness in SARS-CoV-2 antigenic drift, and vaccination� related allergic sensitization.
... At present, a plethora of scientometric and bibliometric studies have been published aiming at gaining more insights on the landscape of publications related to COVID-19 (13,(22)(23)(24)(25)(26). However, only a small portion of bibliometric analyses have explored temporally the pandemic in terms of research output during the first months (27)(28)(29)(30), and additionally, the economic aspect driving scholarly productivity has not been systematically examined. ...
Coronavirus disease 2019 (COVID-19), one of the most serious public health crises in over a century, has led to an unprecedented surge of publications across all areas of knowledge. This study assessed the early research productivity on COVID-19 in terms of vaccination, diagnosis, treatment, symptoms, risk factors, nutrition, and economy. The Scopus database was searched between January 1, 2020 and December 31, 2020 to initially examine the research productivity on COVID-19, as measured by total publications by the 20 highest-ranked countries according to gross domestic product. The literature search was then refined, and research productivity was assessed across seven major research domains related to COVID-19: vaccination, diagnosis, treatment, symptoms, risk factors, nutrition, and economy. The initial literature search yielded 53,348 publications. Among these, 27,801 publications involved authorship from a single country and 22,119 publications involved authorship from multiple countries. Overall, the United States was the most productive country (n = 13,491), with one and a half times or more publications than any other country, on COVID-19 and the selected domains related to it. However, following adjustment for population size, gross domestic product, and expenditure for research and development, countries of emerging economies such as India along countries of lower population density such as Switzerland, Indonesia, and Turkey exhibited higher research productivity. The surge of COVID-19 publications in such a short period of time underlines the capacity of the scientific community to respond against a global health emergency; however where future research priorities and resource distribution should be placed on the respective thematic fields at an international level, warrants further investigation.
... This methodology explores patterns of groups of documents being jointly cited by same articles, i.e., co-citation patterns, in identifying streams/clusters of research activities. To include a temporal component into the analysis, this method derives a series of co-citation networks from a series of equal-length time interval slices (Haghani and Varamini, 2021). These networks are then visualised in a way that displays influential items with more visually salient features. ...
Along with the increase in the frequency of disastrous wildfires and bushfires around the world during the recent decades, scholarly research efforts have also intensified in this domain. This work investigates divisions and trends of the domain of wildfire/bushfire research. Results show that this research domain has been growing exponentially. It is estimated that the field, as of 2021, it has grown to larger than 13,000 research items, with an excess of 1,200 new articles appearing every year. It also exhibits distinct characteristics of a multidisciplinary research domain. Analyses of the underlying studies reveal that the field is made up of five major divisions. These divisions embody research activities around (i) forest ecology and climate, (ii) fire detection and mapping technologies, (iii) community risk mitigation and planning, (iv) soil and water ecology, and (v) atmospheric science. Research into the sub-topics of reciprocal effects between climate change and fire activities, fire risk modelling/mapping (including burned area modelling), wildfire impact on organic matter, biomass burning, and human health impacts currently constitute trending areas of this field. Amongst these, the climate cluster showed an explosion of activities in 2020 while the human health cluster is identified as the most recent emerging topic of this domain. On the other hand, dimensions of wildfire research related to human behaviour—particularly issues of emergency training, risk perception and wildfire hazard education—seem to be notably underdeveloped in this field, making this one of its most apparent knowledge gaps. A scoping review of all reviews and meta-analysis of this field demonstrates that this sub-topic is also virtually non-existent on the research synthesis front. This meta-synthesis further reveals how a western, deductive view excludes socioecological and traditional knowledge of fire.
... In order to provide a finer-grained level of insight into different streams of transportation research (compared to the previous macro-level analyses) and to identify temporal patterns, also in order to identify the most influential studies within each stream of this research, we applied the ground-breaking article co-citation methodology of Chen (2004) for visualising knowledge domains, as implemented in CiteSpace (Chen 2006). Co-citation is a form of document coupling defined as the frequency with which two documents are cited together by third publications (Boyack and Klavans 2010;Haghani and Varamini 2021;Small 1973). ...
Fifty years of evolution of transportation research is revisited based on bibliometric indicators of nearly 50,000 articles, the collective publication of all transportation journals. A multitude of objective indicators all consistently determined four major divisions in the field: (i) network analysis and traffic flow, (ii) economics of transportation and logistics, (iii) travel behaviour, and (iv) road safety. Trending themes of research within the abovementioned divisions respectively are: (i) macroscopic fundamental diagram and public transport network design, (ii) nil (no distinct trending topic), (iii) land-use, active transportation, residential self-selection, travel experience/satisfaction, social exclusion and transport/spatial equity, and (iv) statistical modelling of road accidents. Furthermore, clusters of research related to topics of (a) shared mobility, (b) electric mobility, and (c) autonomous mobility constitute trending topics that are each a cross between multiple divisions of the field. These outcomes document major directions to which the transportation research is headed. Additional outcome is determination of influential outsiders, seminal articles published by non-transportation journals that have proven instrumental in the development of transportation science.
... When two articles appear in the reference list of a third article, they are co-cited by that third article. Two articles that are frequently co-cited by such third citing articles are deemed likely to be thematically similar or related [195,196]. Within a domain of research, identification of groups of references that have frequently been co-cited is often used as an indication of clusters/streams of research activities. When such analysis is conducted at different time intervals, the added temporal component can also provide insight into the variation of trends during various periods of the development of a field. ...
Scholarly literature on terrorism is analysed in its full scope with three main goals: (i) to objectively determine the structural makeup of the field, (ii) to document its current and past temporal trends; and (iii) to identify underrepresented areas. The size of the literature is estimated to have exceeded 18,000 items. At the highest level of aggregation, the field is found to be composed of three major divisions representing: (a) political, ideological and criminological, (b) economic, (s) psychological; and (d) emergency response aspects of terrorism research. The literature has been largely driven and guided by outside political events. Two major spikes in the intensity of this research are distinctly identifiable. The extent of research triggered by and linked to the September 11 attacks has been such that it has generated its own stream of research, although, activities associated with this cluster have notably slowed down since 2010. Two major research streams—one linked to “domestic terrorism” and a newer stream linked to “economic impacts of terrorism (particularly, on tourism and financial markets)”—are identified as currently the trendiest topics of this research. Research on “right-wing/far-right” terrorism, although not new in this domain, shows clear signs of re-emergence and surge of activities. The analyses also identify gaps where further research is required. Most notable on that front is the striking paucity of empirical research on human behavior (i.e., civilian response) during (or in the aftermath of) terror attacks. Largely overlooked in this domain is the potential role of individual mental preparedness and/or peace-time training in mitigating the impact of terror events and increasing communities' self-efficacy in the face of terror. The multitude of dimensions that branch out from this single notion could potentially form a new cluster of terrorism research—possibly, a multidisciplinary crossover between the existing psychology and emergency response divisions—whose findings can help better prepare the public and reduce impacts of terror attacks on civilian communities. Some of these dimensions include (a) developing scales/inventories for measuring public preparedness level to react to terror attacks, (b) determining best response strategies to various forms of terror attacks, (c) identifying public misconceptions about best response, (d) examining public conformity and acceptance of training programs, (e) identifying effective means/media of raising awareness, (f) break down knowledge retainment barriers, and (g) determining best means of utilising bystander role as “zero responders” during terror attacks and capitalising on civilians’ altruistic tendencies for terror impact mitigation.
... They also use WoS as a data source. Haghani and Varamini [16] also use WoS and go forward to the end of August 2020 to study scientific developments related to the pandemic using scientometrics. Hossain [17] also reviewed 422 papers up to April 2020 using the same source of data. ...
The COVID-19 pandemic has wreaked havoc in every country in the world, with serious health-related, economic, and social consequences. Since its outbreak in March 2020, many researchers from different fields have joined forces to provide a wide range of solutions, and the support for this work from artificial intelligence (AI) and other emerging concepts linked to intelligent data analysis has been decisive. The enormous amount of research and the high number of publications during this period makes it difficult to obtain an overall view of the different applications of AI to the management of COVID-19 and an understanding of how research in this field has been evolving. Therefore, in this paper, we carry out a scientometric analysis of this area supported by text mining, including a review of 18,955 publications related to AI and COVID-19 from the Scopus database from March 2020 to June 2021 inclusive. For this purpose, we used VOSviewer software, which was developed by researchers at Leiden University in the Netherlands. This allowed us to examine the exponential growth in research on this issue and its distribution by country, and to highlight the clear hegemony of the United States (USA) and China in this respect. We used an automatic process to extract topics of research interest and observed that the most important current lines of research focused on patient-based solutions. We also identified the most relevant journals in terms of the COVID-19 pandemic, demonstrated the growing value of open-access publication, and highlighted the most influential authors by means of an analysis of citations and co-citations. This study provides an overview of the current status of research on the application of AI to the pandemic.
... In order to provide a finer-grained level of insight into different streams of transportation research (compared to the previous macro-level analyses) and to identify temporal patterns, also in order to identify the most influential studies within each stream of this research, we applied the ground-breaking article co-citation methodology of Chen (2004) for visualising knowledge domains, as implemented in CiteSpace (Chen 2006). Co-citation is a form of document coupling defined as the frequency with which two documents are cited together by third publications (Boyack and Klavans 2010;Haghani and Varamini 2021;Small 1973). ...
Fifty years of evolution of the transportation field is revisited at a macro scale using scientometric analysis of all publications in all 39 journals indexed in the category of Transportation by the Web of Science. The size of the literature is estimated to have reached 50,000 documents. At the highest level of aggregation, four major divisions of the literature are differentiated through these analyses, namely (i) network analysis and traffic flow, (ii) economics of transportation and logistics, (iii) travel behaviour, and (iv) road safety. Influential and emerging authors of each division are identified. Temporal trends in transportation research are also investigated via document co-citation analysis. This analysis identifies various major streams of transportation research while determining their approximate time of emergence and duration of activity. It documents topics that have been most trendy at any period of time during the last fifty years. Three clusters associated with the travel behaviour division (collectively embodying topics of land-use, active transportation, residential self-selection, traveller experience/satisfaction, social exclusion and transport/spatial equity), one cluster of statistical modelling of road accidents, and a cluster of network modelling linked predominantly to the notion of macroscopic fundamental diagram demonstrate characteristics of being current hot topics of the field. Three smaller clusters linked predominantly to electric mobility and autonomous/automated vehicles show characteristics of being emerging hot topics. A cluster labelled shared mobility is the youngest emerging cluster. Influential articles within each cluster of references are identified. Additional outcomes are the determination the influential outsiders of the transportation field.
Purpose
The purpose is to explore the essential reasons for the differences between book awakening phenomena, to develop the critical factors in awakening the slumbering collections and to provide a reliable basis for maximizing book value and optimizing collection allocation.
Design/methodology/approach
The research employs the integrated learning algorithm XGBoost to measure driving factors. In the process of book circulation, the characteristics of collections and readers are worthy of attention. Therefore, this study also carries out feature selection and model construction from the two dimensions of books and readers.
Findings
The results show that reader features have a stronger impetus for the collection awakening phenomenon than collection features. Among reader features, education level, gender and major subject are the main factors, which are followed closely by the activity level; among collection features, publication date and price are the main driving factors. The indicators of book popularity are not significant, whose effect on the phenomenon of collection awakening is almost negligible.
Originality/value
This study aims to augment the theory of zero circulation from the theoretical level and, for the first time, seeks to define the phenomenon of collection awakening. This study attempts to present novel ideas for research in the field of libraries and to provide references for optimizing collection and maximizing the value of books.
A "Sleeping Beauty" (SB) in science is a metaphor for a scholarly publication that remains relatively unnoticed by the related communities for a long time;-the publication is "sleeping". However, suddenly due to the appearance of some phenomenon, such a "forgotten" publication may become a center of scientific attention;-the SB is "awakened". Currently, there are specific scientific areas for which sleeping beauties (SBs) are awakened. For example, as the world is experiencing the COVID-19 global pandemic (triggered by SARS-CoV-2), publications on coronaviruses appear to be awakened. Thus, one can raise questions of scientific interest: are these publications coronavirus related SBs? Moreover, while much literature exists on other coronaviruses, there seems to be no comprehensive investigation on COVID-19,-in particular in the context of SBs. Nowadays, such SB papers can be even used for sustaining literature reviews and/or scientific claims about COVID-19. In our study, in order to pinpoint pertinent SBs, we use the "beauty score" (B-score) measure. The Activity Index (AI) and the Relative Specialization Index (RSI) are also calculated to compare countries where such SBs appear. Results show that most of these SBs were published previously to the present epidemic time (triggered by SARS-CoV or SARS-CoV-1), and are awakened in 2020. Besides outlining the most important SBs, we show from what countries and institutions they originate, and the most prolific author(s) of such SBs. The citation trend of SBs that have the highest B-score is also discussed.
Background
The COVID-19 pandemic has resulted in a high death toll. We aimed to describe the place and cause of death during the COVID-19 pandemic.
Methods
This national death registry included all adult (aged ≥18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Analyses were based upon ICD-10 codes corresponding to the underlying cause of death as stated on the Medical Certificate of Cause of Death. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death.
Findings
Between 2nd March and 30th June 2020, there was an excess mortality of 57860 (a proportional increase of 35%) compared with the expected deaths, of which 50603 (86.2%) were COVID-19 related. Almost half the excess deaths occurred in care homes (25611 deaths) where deaths were 55% higher than expected. One fifth of the excess deaths occurred in hospital (15938 deaths; a proportional increase of 21%) with the remainder occurring at home (16190 deaths; a proportional increase of 39%). At home, only 14% of 16190 excess deaths were related to COVID-19, with 5 963 deaths due to cancer and 2485 deaths due to cardiac disease, very few of which involved COVID-19. In care homes or hospices, 61% of the 25611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease and most of these (4315 deaths) involved COVID-19. In hospital, there were 16174 fewer deaths than expected which did not involve COVID-19, and there were 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.
Interpretation
The COVID-19 pandemic has resulted in a substantial increase in the absolute numbers of deaths occurring at home and care homes. There was a huge burden of excess deaths occurring in care homes, which were poorly characterised, and were likely to be, at least in part, the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, which suggests avoidance of hospital care for non-COVID-19 conditions.
Abstract Currently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets and/or contact routes. The report by the World Health Organization (WHO) Joint Mission on Coronavirus Disease 2019 (COVID-19) in China supports person-to-person droplet and fomite transmission during close unprotected contact with the vast majority of the investigated infection clusters occurring within families, with a household secondary attack rate varying between 3 and 10%, a finding that is not consistent with airborne transmission. The reproduction number (R0) for the SARS-CoV-2 is estimated to be between 2.2–2.7, compatible with other respiratory viruses associated with a droplet/contact mode of transmission and very different than an airborne virus like measles with a R0 widely cited to be between 12 and 18. Based on the scientific evidence accumulated to date, our view is that SARS-CoV-2 is not spread by the airborne route to any significant extent and the use of particulate respirators offers no advantage over medical masks as a component of personal protective equipment for the routine care of patients with COVID-19 in the health care setting. Moreover, prolonged use of particulate respirators may result in unintended harms. In conjunction with appropriate hand hygiene, personal protective equipment (PPE) used by health care workers caring for patients with COVID-19 must be used with attention to detail and precision of execution to prevent lapses in adherence and active failures in the donning and doffing of the PPE.
Background:
The novel coronavirus, named as 2019-nCoV or coronavirus disease 2019 (COVID-19), has recently appeared in China and has spread worldwide, presenting a health threat to the global community. Therefore, it is important to understand the global scientific output of COVID-19 research during the early stage of the outbreak. Thus, to track the current hotspots, and highlight future directions, we performed a bibliometric analysis to obtain an approximate scenario of COVID-19 to date.
Methods:
Relevant studies to COVID-19 were obtained from the Scopus database during the early stage of the outbreak. We then analysed the data by using well-established bibliometric indices: document type, country, collaboration patterns, affiliation, journal name, and citation patterns. VOSviewer was applied to map and determine hot topics in this field.
Results:
The bibliometric analysis indicated that there were 19,044 publications on Scopus published on COVID-19 during the early stage of the outbreak (December 2019 up until June 19, 2020). Of all these publications, 9140 (48.0%) were articles; 4192 (22.0%) were letters; 1797 (9.4%) were reviews; 1754 (9.2%) were editorials; 1728 (9.1%) were notes; and 433 (2.3%) were others. The USA published the largest number of publications on COVID-19 (4479; 23.4%), followed by China (3310; 17.4%), Italy, (2314; 12.2%), and the UK (1981; 10.4%). British Medical Journal was the most productive. The Huazhong University of Science and Technology, Tongji Medical, and Harvard Medical School were the institutions that published the largest number of COVID-19 research. The most prevalent topics of research in COVID-19 include "clinical features studies", "pathological findings and therapeutic design", "care facilities preparation and infection control", and "maternal, perinatal and neonatal outcomes".
Conclusions:
This bibliometric study may reflect rapidly emerging topics on COVID-19 research, where substantial research activity has already begun extensively during the early stage of the outbreak. The findings reported here shed new light on the major progress in the near future for hot topics on COVID-19 research including clinical features studies, pathological findings and therapeutic design, care facilities preparation and infection control, and maternal, perinatal and neonatal outcomes.
This paper outlines the rapid integration of social scientists into a Canadian province’s COVID-19 response. We describe the motivating theory, deployment and initial outcomes of our team of Organisational Sociologist ethnographers, Human Factors experts and Infection Prevention and Control clinicians focused on understanding and improving Alberta’s responsiveness to the pandemic. Specifically, that interdisciplinary team is working alongside acute and primary care personnel, as well as public health leaders to deliver ‘situated interventions’ that flow from studying communications, interpretations and implementations across responding organisations. Acting in real time, the team is providing critical insights on policy communication and implementation to targeted members of the health system. Using our rapid and ongoing deployment as a case study of social science techniques applied to a pandemic, we describe how other health systems might leverage social science to improve their preparations and communications.
The COVID-19 pandemic has been characterized by an unprecedented amount of published scientific articles. The aim of this study is to assess the type of articles published during the first 3 months of the COVID-19 pandemic and to compare them with articles published during 2009 H1N1 swine influenza pandemic. Two operators independently extracted and assessed all articles on COVID-19 and on H1N1 swine influenza that had an abstract and were indexed in PubMed during the first 3 months of these pandemics. Of the 2482 articles retrieved on COVID-19, 1165 were included. Over half of them were secondary articles (590, 50.6%). Common primary articles were: human medical research (340, 59.1%), in silico studies (182, 31.7%) and in vitro studies (26, 4.5%). Of the human medical research, the vast majority were observational studies and cases series, followed by single case reports and one randomized controlled trial. Secondary articles were mainly reviews, viewpoints and editorials (373, 63.2%). Limitations were reported in 42 out of 1165 abstracts (3.6%), with 10 abstracts reporting actual methodological limitations. In a similar timeframe, there were 223 articles published on the H1N1 pandemic in 2009. During the COVID-19 pandemic there was a higher prevalence of reviews and guidance articles and a lower prevalence of in vitro and animal research studies compared with the H1N1 pandemic. In conclusions, compared to the H1N1 pandemic, the majority of early publications on COVID-19 does not provide new information, possibly diluting the original data published on this disease and consequently slowing down the development of a valid knowledge base on this disease. Also, only a negligible number of published articles reports limitations in the abstracts, hindering a rapid interpretation of their shortcomings. Researchers, peer reviewers, and editors should take action to flatten the curve of secondary articles.
Objective
To study the frequency of neurological symptoms and complications in COVID-19 patients in a systematic review of the literature.Methods
Relevant studies were identified through electronic explorations of PubMed, medRxiv, and bioRxiv. Besides, three Chinese databases were searched. A snowballing method searching the bibliographies of the retrieved references was applied to identify potentially relevant articles. Articles published within 1 year prior to April 20th, 2020, were screened with no language restriction imposed. Databases were searched for terms related to SARS-CoV-2/COVID-19 and neurological manifestations, using a pre-established protocol registered on the International Prospective Register of Systematic Reviews database (ID: CRD42020187994).ResultsA total of 2441 articles were screened for relevant content, of which 92 full-text publications were included in the analyses of neurological manifestations of COVID-19. Headache, dizziness, taste and smell dysfunctions, and impaired consciousness were the most frequently described neurological symptoms, the latter more often among patients with a severe or critical disease course. To date, only smaller cohort studies or single cases have reported cerebrovascular events, seizures, meningoencephalitis, and immune-mediated neurological diseases, not suitable for quantitative analysis.Conclusion
The most frequent neurological symptoms reported in association with COVID-19 are non-specific for the infection with SARS-CoV-2. Although SARS-CoV-2 may have the potential to gain direct access to the nervous system, so far, SARS-CoV-2 was detected in the cerebrospinal fluid in two cases only. Standardized international registries are needed to clarify the clinical relevance of the neuropathogenicity of SARS-CoV-2 and to elucidate a possible impact of SARS-CoV-2 infection on common neurological disease, such as Alzheimer’s, Parkinson’s disease or multiple sclerosis.
As the current understanding of COVID-19 continues to evolve, a synthesis of the literature on the neurological impact of this novel virus may help inform clinical management and highlight potentially important avenues of investigation. Additionally, understanding the potential mechanisms of neurologic injury may guide efforts to better detect and ameliorate these complications. In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis. Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury. We also discuss evidence that suggests that SARS-CoV-2 may be a vasculotropic and neurotropic virus. Early reports suggest COVID-19 may be associated with severe neurologic complications, and several plausible mechanisms exist to account for these observations. A heightened awareness of the potential for neurologic involvement and further investigation into the relevant pathophysiology will be necessary to understand and ultimately mitigate SARS-CoV-2-associated neurologic injury.
Background
The incidence of elevated liver chemistries and the presence of the pre‐existing chronic liver disease (CLD) have been variably reported in COVID‐19.
Aims
To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID‐19.
Methods
A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID‐19.
Results
107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5‐5.1) among the 15 407 COVID‐19 patients. The pooled incidence of elevated liver chemistries in COVID‐19 was 23.1% (19.3‐27.3) at initial presentation. Additionally, 24.4% (13.5‐40) developed elevated liver chemistries during the illness. The pooled incidence of drug‐induced liver injury was 25.4% (14.2‐41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%‐5.2%). The odds of developing severe COVID‐19 in CLD patients was 0.81 (0.31‐2.09; P = 0.67) compared to non‐CLD patients. COVID‐19 patients with elevated liver chemistries had increased risk of mortality (OR‐3.46 [2.42‐4.95, P < 0.001]) and severe disease (OR‐2.87 [95% CI, 2.29‐3.6, P < 0.001]) compared to patients without elevated liver chemistries.
Conclusions
Elevated liver chemistries are common at presentation and during COVID‐19. The severity of elevated liver chemistries determines the outcome of COVID‐19. The presence of CLD does not alter the outcome of COVID‐19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.
Aim
To summarize what we know so far about coronavirus disease (COVID‐19) in children.
Method
We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory‐confirmed COVID‐19. We conducted random‐effects meta‐analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI.
Result
Forty‐six articles reporting 551 cases of COVID‐19 in children (aged 1 day‐17.5 years) were included. Eighty‐seven percent (95% CI: 77%‐95%) of patients had household exposure to COVID‐19. The most common symptoms and signs were fever (53%, 95% CI: 45%‐61%), cough (39%, 95% CI: 30%‐47%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%‐28%); however, 18% (95% CI: 11%‐27%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%‐43%) and ground glass opacities (28%, 95% CI: 18%‐39%), but 36% (95% CI: 28%‐45%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%‐92%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died.
Conclusion
Previously healthy children with COVID‐19 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID‐19 case. Children with COVID‐19 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.
Introduction
Within this large‐scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID‐19, SARS, and MERS to find unique features.
Method
We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed‐effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106).
Result
Overall 114 articles included in this study; 52 251 COVID‐19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID‐19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid‐19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X‐ray. The mortality rate in COVID‐19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients.
Conclusions
At the time of submission, the mortality rate in COVID‐19 confirmed cases is lower than in SARS‐ and MERS‐infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials.
The COVID-19 pandemic has sparked unprecedented mobilization of scientists, already generating thousands of new papers that join a litany of previous biomedical work in related areas. This deluge of information makes it hard for researchers to keep track of their own research area, let alone explore new directions. Standard search engines are designed primarily for targeted search and are not geared for discovery or making connections that are not obvious from reading individual papers. In this paper, we present our ongoing work on SciSight, a novel framework for exploratory search of COVID-19 research. Based on formative interviews with scientists and a review of existing tools, we build and integrate two key capabilities: first, exploring interactions between biomedical facets (e.g., proteins, genes, drugs, diseases, patient characteristics); and second, discovering groups of researchers and how they are connected. We extract entities using a language model pre-trained on several biomedical information extraction tasks, and enrich them with data from the Microsoft Academic Graph (MAG). To find research groups automatically, we use hierarchical clustering with overlap to allow authors, as they do, to belong to multiple groups. Finally, we introduce a novel presentation of these groups based on both topical and social affinities, allowing users to drill down from groups to papers to associations between entities, and update query suggestions on the fly with the goal of facilitating exploratory navigation. SciSight has thus far served over 10K users with over 30K page views and 13% returning users. Preliminary user interviews with biomedical researchers suggest that SciSight complements current approaches and helps find new and relevant knowledge.
A recent outbreak of a novel Coronavirus responsible for a Severe Acute Respiratory Syndrome (SARS-CoV-2) is spreading globally. The aim of this study was to systematically review main clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric age. An electronic search was conducted in PubMed database. Papers published between 1 January and 1 May 2020 including children aged 0–18 years were selected. Sixty-two studies and three reviews were included, with a total sample size of 7480 children (2428/4660 males, 52.1%; weighted mean age 7.6 years). Patients showed mainly mild (608/1432, 42.5%) and moderate (567/1432, 39.6%) signs of the infection. About 2% of children were admitted to the pediatric intensive care unit. The most commonly described symptoms were fever (51.6%) and cough (47.3%). Laboratory findings were often unremarkable. Children underwent a chest CT scan in 73.9% of all cases, and 32.7% resulted normal. Overall, the estimated mortality was 0.08%. A higher proportion of newborns was severely ill (12%) and dyspnea was the most common reported sign (40%).
Conclusion: SARS-CoV-2 affects children less severely than adults. Laboratory and radiology findings are mainly nonspecific. Larger epidemiological and clinical cohort studies are needed to better understand possible implications of COVID-19 infection in children.What is Known:
• A novel Coronavirus has been recently identified as responsible for a new Severe Acute Respiratory Syndrome (SARS-CoV-2) spreading globally.
• There is limited evidence on SARS-CoV2 infection in children.
What is New:
• Systematically reviewed available evidence showed that children with SARS-CoV-2 infection may have a less severe pattern of disease in comparison to adults.
• Blood tests and radiology findings are mainly nonspecific in children but may help to identify those who are severely ill.
At the end of 2019, a novel coronavirus began to spread in Wuhan, Hubei Province, China. The confirmed cases increased nationwide rapidly, in part due to the increased population mobility during the Chinese Lunar New Year festival. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Soon, transmission from person to person was confirmed and the virus spread to many other countries. To date, many cases have been reported in the pediatric age group, most of which were from China. The management and treatment strategies have also been improved, which we believe would be helpful to pediatric series in other countries as well. However, the characteristics of neonatal and childhood infection still have not been evaluated in detail. This review summarizes the current understanding of SARS-CoV-2 infection in neonates and children from January 24 to May 1, as an experience from China.
Background
The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system.
Methods
In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates.
Findings
We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2–5; range 0–15; I²=74%). The pooled prevalence of digestive symptoms was 15% (10–21; range: 2–57; I²=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9–32; range 1–53; I²=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of gastrointestinal symptoms (odds ratio [OR] 1·60 [95% CI 1·09–2·36]; p=0·0020; I²=44%) and liver injury (2·20 [1·60–3·02]; p<0·00001; I²=36%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4–19; range 3–23; I²=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22–5·48]; p=0·030; I²=73%). Patients with gastrointestinal involvement had a higher prevalence of complication (OR 2·51 [95% CI 1·62–3·89]; p<0·0001; I²=0%).
Interpretation
Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients.
Funding
None.
As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives 1. Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.
The COVID-19 pandemic represents a massive global health crisis. Because the crisis requires large-scale behaviour change and places significant psychological burdens on individuals, insights from the social and behavioural sciences can be used to help align human behaviour with the recommendations of epidemiologists and public health experts. Here we discuss evidence from a selection of research topics relevant to pandemics, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping. In each section, we note the nature and quality of prior research, including uncertainty and unsettled issues. We identify several insights for effective response to the COVID-19 pandemic and highlight important gaps researchers should move quickly to fill in the coming weeks and months.
Background
Cutaneous manifestations of COVID‐19 disease are poorly characterized.
Objectives
To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings
Methods
Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis.
Results
Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular).
Conclusions
We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases.
We present an analysis on the uptake of open access on COVID-819 related literature as well as the social media attention they gather when9compared with non OA papers. We use a dataset of publications curated by10Dimensions and analyze articles and preprints. Our sample includes 11,68611publications of which 67.5% are openly accessible. OA publications tend to re-12ceive the largest share of social media attention as measured by the Altmetric13Attention Score. 37.6% of OA publications are bronze, which means toll jour-14nals are providing free access. MedRxiv contributes to 36.3% of documents in15repositories but papers in BiorXiv exhibit on average higher AAS. We predict16the growth of COVID-19 literature in the following 30 days estimating ARIMA17models for the overall publications set, OA vs. non OA and by location of the18document (repository vs. journal). We estimate that COVID-19 publications19will double in the next 20 days, but non OA publications will grow at a higher20rate than OA publications. We conclude by discussing the implications of such21findings on the dissemination and communication of research findings to mit-22igate the coronavirus outbreak
Background:
Surgeons urgently need guidance on how to deliver surgical services safely and effectively during the COVID-19 pandemic. The aim was to identify the key domains that should be considered when developing pandemic preparedness plans for surgical services.
Methods:
A scoping search was conducted to identify published articles relating to management of surgical patients during pandemics. Key informant interviews were conducted with surgeons and anaesthetists with direct experience of working during infectious disease outbreaks, in order to identify key challenges and solutions to delivering effective surgical services during the COVID-19 pandemic.
Results:
Thirteen articles were identified from the scoping search, and surgeons and anaesthetists representing 11 territories were interviewed. To mount an effective response to COVID-19, a pandemic response plan for surgical services should be developed in advance. Key domains that should be included are: provision of staff training (such as patient transfers, donning and doffing personal protection equipment, recognizing and managing COVID-19 infection); support for the overall hospital response to COVID-19 (reduction in non-urgent activities such as clinics, endoscopy, non-urgent elective surgery); establishment of a team-based approach for running emergency services; and recognition and management of COVID-19 infection in patients treated as an emergency and those who have had surgery. A backlog of procedures after the end of the COVID-19 pandemic is inevitable, and hospitals should plan how to address this effectively to ensure that patients having elective treatment have the best possible outcomes.
Conclusion:
Hospitals should prepare detailed context-specific pandemic preparedness plans addressing the identified domains. Specific guidance should be updated continuously to reflect emerging evidence during the COVID-19 pandemic.
Importance
The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.
Objective
To study the neurologic manifestations of patients with COVID-19.
Design, Setting, and Participants
This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection.
Main Outcomes and Measures
Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations.
Results
Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]).
Conclusions and Relevance
Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.
Objective
To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19.
Methods
We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I². Publication bias was assessed using Egger's test.
Results
43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% [95% CI 78.4–87.7]), cough (60.3% [54.2–66.3]), and fatigue (38.0% [29.8–46.5]) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% [58.2–78.2]), decreased lymphocyte count (57.4% [44.8–69.5]) and increased lactate dehydrogenase (51.6% [31.4–71.6]). Ground-glass opacities (80.0% [67.3–90.4]) and bilateral pneumonia (73.2% [63.4–82.1]) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4–34.9) and 3.6% (1.1–7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender.
Conclusions
The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.
Objective
To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection.Methods
Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS).ResultsA total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001).Conclusion
Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.
Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses³. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity, but also aided the control, of severe acute respiratory syndrome (SARS) in 2003⁵. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on body site-specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 × 10⁸ RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples, in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat and lung samples from the same patient, proving independent replication. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (14 days in all), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts the prospects of COVID-19 containment in perspective.
A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans1,2. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2)3,4. Here we determined the crystal structure of the SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.
Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.
Background:
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.
Methods:
We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.
Results:
The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy.
Conclusion:
The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
Background
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.
Methods
We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.
ResultsThe Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.
Conclusion
The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.
Background
A relatively high mortality of severe coronavirus disease 2019 (COVID‐19) is worrying, the application of heparin in COVID‐19 has been recommended by some expert consensus due to the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated.
Methods
Coagulation results, medications and outcomes of consecutive patients being classified as severe COVID‐19 in Tongji hospital were retrospectively analysed. The 28‐day mortality between heparin users and nonusers were compared, also in different risk of coagulopaphy which was stratified by the sepsis‐induced coagulopathy (SIC) score or D‐dimer result.
Results
There were 449 patients with severe COVID‐19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin, LMWH) for 7 days or longer. The D‐dimer, prothrombin time and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference on 28‐day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P=0.910). But the 28‐day mortality of heparin users were lower than nonusers In patients with SIC score ≥4 (40.0% vs 64.2%, P=0.029), or D‐dimer > 6 fold of upper limit of normal (32.8% vs 52.4%, P=0.017).
Conclusions
Anticoagulant therapy mainly with LMWH appears to be associated with better prognosis in severe COVID‐19 patients meeting SIC criteria or with markedly elevated D‐dimer.
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2. SARS-CoV-2 has spread globally. Here, the authors characterize the entry pathway of SARS-CoV-2, show that the SARS-CoV-2 spike protein is less stable than that of SARS-CoV, and show limited cross-neutralization activities between SARS-CoV and SARS-CoV-2 sera.
Objective
To describe the place and cause of death during the COVID-19 pandemic to assess its impact on excess mortality.
Methods
This national death registry included all adult (aged≥18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death.
Results
Between 2nd March and 30th June 2020, there was an excess mortality of 57860 (a proportional increase of 35%) compared with the expected deaths, of which 50603 (87%) were COVID-19 related. At home, only 14% of 16190 excess deaths were related to COVID-19, with 5 963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% of the 25611 excess deaths related to COVID-19, 5539 of which were due to respiratory disease and most of these (4315 deaths) involved COVID-19. In hospital, there were 16174 fewer deaths than expected which did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.
Conclusion
The COVID-19 pandemic has resulted a large excess of deaths in care homes, which were poorly characterised and likely the result of undiagnosed COVID-19. There was a smaller, but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.
During the current century, each major coronavirus outbreak has triggered a quick and immediate surge of academic publications on its respective topic. The spike in research publications following the 2019 Novel Coronavirus (Covid-19) outbreak, however, has been like no other. The global crisis caused by the Covid-19 pandemic has mobilised scientific efforts at an unprecedented scale. In less than 5 months, more than 12,000 research items and in less than seven months, more than 30,000 items were indexed, while it is projected that the number could exceed 80,000 by the end of 2020, should the current trend continues. With the health crisis affecting all aspects of life, research on Covid-19 seems to have become a focal point of interest across many academic disciplines. Here, scientometric aspects of the Covid-19 literature are analysed and contrasted with those of the two previous major coronavirus diseases, i.e., Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The focus is on the co-occurrence of key-terms, bibliographic coupling and citation relations of journals and collaborations between countries. Interesting recurring patterns across all three literatures were discovered. All three outbreaks have commonly generated three distinct cohorts of studies: (i) studies linked to public health response and epidemic control, (ii) studies on chemical constitution of the virus; and (iii) studies related to treatment, vaccine and clinical care. While studies affiliated with category (i) seem to have been relatively earliest to emerge, they have overall received relatively smaller number of citations compared to publications the two other categories. Covid-19 studies seem to have been disseminated across a broader variety of journals and across a more diverse range of subject areas. Clear links are observed between the geographical origins of each outbreak as well as the local geographical severity of each outbreak and the magnitude of research originated from regions. Covid-19 studies also display the involvement of authors from a broader variety of countries compared to SARS and MERS. Considering the speed at which the Covid-19-related literature is accumulating, an interesting dimension that warrants further exploration could be to assess if the quality and rigour of these publications have been affected.
Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)—229E, HKU1, NL63 and OC43—circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined.
Abbreviations
2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette–Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children’s Fund; USA, United States of America; WHO, World Health Organization
The Pandemic of COVID-19, an infectious disease caused by SARS-CoV-2 motivated the scientific community to work together in order to gather, organize, process and distribute data on the novel biomedical hazard. Here, we analyzed how the scientific community responded to this challenge by quantifying distribution and availability patterns of the academic information related to COVID-19. The aim of this study was to assess the quality of the information flow and scientific collaboration, two factors we believe to be critical for finding new solutions for the ongoing pandemic. The RISmed R package, and a custom Python script were used to fetch metadata on articles indexed in PubMed and published on Rxiv preprint server. Scopus was manually searched and the metadata was exported in BibTex file. Publication rate and publication status, affiliation and author count per article, and submission-to-publication time were analysed in R. Biblioshiny application was used to create a world collaboration map. Preliminary data suggest that COVID-19 pandemic resulted in generation of a large amount of scientific data, and demonstrates potential problems regarding the information velocity, availability, and scientific collaboration in the early stages of the pandemic. More specifically, the results indicate precarious overload of the standard publication systems, significant problems with data availability and apparent deficient collaboration. In conclusion, we believe the scientific community could have used the data more efficiently in order to create proper foundations for finding new solutions for the COVID-19 pandemic. Moreover, we believe we can learn from this on the go and adopt open science principles and a more mindful approach to COVID-19-related data to accelerate the discovery of more efficient solutions. We take this opportunity to invite our colleagues to contribute to this global scientific collaboration by publishing their findings with maximal transparency.
Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).
COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20th May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide.
The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic.
In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).
Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.
Chest computed tomography (CT) is frequently used in diagnosing coronavirus disease 2019 (COVID-19) for detecting abnormal changes in the lungs and monitoring disease progression during the treatment process. Furthermore, CT imaging appearances are correlated with patients presenting with different clinical scenarios, such as early versus advanced stages, asymptomatic versus symptomatic patients, and severe versus nonsevere situations. However, its role as a screening and diagnostic tool in COVID-19 remains to be clarified. This article provides a systematic review and meta-analysis of the current literature on chest CT imaging findings with the aim of highlighting the contribution and judicious use of CT in the diagnosis of COVID-19. A search of PubMed/Medline, Web of Science, ScienceDirect, Google Scholar and Scopus was performed to identify studies reporting chest imaging findings in COVID-19. Chest imaging abnormalities associated with COVID-19 were extracted from the eligible studies and diagnostic value of CT in detecting these abnormal changes was compared between studies consisting of both COVID-19 and non-COVID-19 patients. A random-effects model was used to perform meta-analysis for calculation of pooled mean values and 95% confidence intervals (95% CI) of abnormal imaging findings. Fifty-five studies met the selection criteria and were included in the analysis. Pulmonary lesions more often involved bilateral lungs (78%, 95% CI: 45-100%) and were more likely to have a peripheral (65.35%, 95% CI: 25.93-100%) and peripheral plus central distribution (31.12%, 95% CI: 1.96-74.07%), but less likely to have a central distribution (3.57%, 95% CI: 0.99-9.80%). Ground glass opacities (GGO) (58.05%, 95% CI: 16.67-100%), consolidation (44.18%, 95% CI: 1.61-71.46%) and GGO plus consolidation (52.99%, 95% CI: 19.05-76.79%) were the most common findings reported in 94.5% (52/55) of the studies, followed by air bronchogram (42.50%, 95% CI: 7.78-80.39%), linear opacities (41.29%, 95% CI: 7.44-65.06%), crazy-paving pattern (23.57%, 95% CI: 3.13-91.67%) and interlobular septal thickening (22.91%, 95% CI: 0.90-80.49%). CT has low specificity in differentiating pneumonia-related lung changes due to significant overlap between COVID-19 and non-COVID-19 patients with no significant differences in most of the imaging findings between these two groups (P>0.05). Furthermore, normal CT (13.31%, 95% CI: 0.74-38.36%) was reported in 26 (47.3%) studies. Despite widespread use of CT in the diagnosis of COVID-19 patients based on the current literature, CT findings are not pathognomonic as it lacks specificity in differentiating imaging appearances caused by different types of pneumonia. Further, there is a relatively high percentage of normal CT scans. Use of CT as a first-line diagnostic or screening tool in COVID-19 is not recommended.
The COVID-19 global pandemic has generated an abundance of research quickly following the outbreak. Within only a few months, more than a thousand studies on this topic have already appeared in the scientific literature. In this short review, we analyse the bibliometric aspects of these studies on a macro level, as well as those addressing Coronaviruses in general. Furthermore, through a scoping analysis of the literature on COVID-19, we identify the main safety-related dimensions that these studies have thus far addressed. Our findings show that across various research domains, and apart from the medical and clinical aspects such as the safety of vaccines and treatments, issues related to patient transport safety, occupational safety of healthcare professionals, biosafety of laboratories and facilities, social safety, food safety, and particularly mental/psychological health and domestic safety have thus far attracted most attention of the scientific community in relation to the COVID-19 pandemic. Our analysis also uncovers various potentially significant safety problems caused by this global health emergency which currently have attracted only limited scientific focus but may warrant more attention. These include matters such as cyber safety, economic safety, and supply-chain safety. These findings highlight why, from an academic research perspective, a holistic interdisciplinary approach and a collective scientific effort is required to help understand and mitigate the various safety impacts of this crisis whose implications reach far beyond the bio-medical risks. Such holistic safety-scientific understanding of the COVID-19 crisis can furthermore be instrumental to be better prepared for a future pandemic.
Crises are no excuse for lowering scientific standards
Background Recent studies have suggested that chest computed tomography (CT) scans could be used as a primary screening or diagnostic tool for coronavirus disease 2019 (COVID-19) in epidemic areas. Purpose To perform a meta-analysis to evaluate diagnostic performance measures, including predictive values, of chest CT and initial reverse transcriptase-polymerase chain reaction (RT-PCR). Materials and Methods MEDLINE and Embase were searched from January 1, 2020 to April 3, 2020 for studies on COVID-19 that reported the sensitivity and/or specificity of CT scans and/or RT-PCR assays. The pooled sensitivity and specificity were estimated by using random-effects models. The actual prevalence (i.e., the proportion of confirmed patients among those tested) in eight countries was obtained from web sources, and the predictive values were calculated. Meta-regression was performed to reveal the effect of potential explanatory factors on the diagnostic performance measures. Results The pooled sensitivity was 94% (95% CI: 91%, 96%; I
2
=95%) for chest CT and 89% (95% CI: 81%, 94%; I
2
=90%) for RT-PCR. The pooled specificity was 37% (95% CI: 26%, 50%; I
2
=83%) for chest CT. The prevalence of COVID-19 outside China ranged from 1.0% to 22.9%. For chest CT scans, the positive predictive value (PPV) ranged from 1.5% to 30.7%, and the negative predictive value (NPV) ranged from 95.4% to 99.8%. For RT-PCR,the PPV ranged from 47.3% to 96.4%, while the NPV ranged from 96.8% to 99.9%. The sensitivity of CT was affected by the distribution of disease severity, the proportion of patients with comorbidities, and the proportion of asymptomatic patients (all p < 0.05). The sensitivity of RT-PCR was negatively associated with the proportion of elderly patients (p = 0.01). Conclusion Outside of China where there is a low-prevalence of COVID-19 (1-22.9%), chest CT screening of patients with suspected disease had low positive predictive value (1.5-30.7%).
Importance
The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.
Observations
No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.
Conclusions and Relevance
The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.
Introduction
COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available.
Methods
We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.
Results
We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.
Conclusion
The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.
Importance
In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited.
Objective
To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy.
Design, Setting, and Participants
Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020.
Exposures
SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs.
Main Outcomes and Measures
Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network.
Results
Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, −27 [95% CI, −42 to −12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001).
Conclusions and Relevance
In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.
Background & Aims
Infection with SARS-CoV-2 causes COVID-19, which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool, and also summarized data from a cohort of patients with COVID-19 in Hong Kong.
Methods
We collected data from the cohort of patients with COVID-19 in Hong Kong (n=59; diagnosis from February 2 through Feb 29, 2020), and searched PubMed, Embase, Cochrane and three Chinese databases through March 11, 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model.
Results
Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P=.02). The median fecal viral load was 5.1 log10cpm in patients with diarrhea vs 3.9 log10cpm in patients without diarrhea (P=.06). In a meta-analysis of 60 studies, comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% CI, 12.3%–24.5%); 11.8% of patients with non-severe COVID-19 had gastrointestinal symptoms (95% CI, 4.1%–29.1%) and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9%–36.7%). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3%–57.9%); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6%–85.1%).
Conclusions
In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients—even in stool collected after respiratory samples tested negative. Healthcare workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19—even during patient recovery.
Importance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system.
Observations
Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality.
Conclusions and Relevance
Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.
In the current absence of medical treatment and vaccination, the unfolding COVID-19 pandemic can only be brought under control by massive and rapid behaviour change. To achieve this we need to systematically monitor and understand how different individuals perceive risk and what prompts them to act upon it, argues Cornelia Betsch.