| Title | Venue | Year | Impact | Source |
| 1951 | Novel coronavirus: From discovery to clinical diagnostics A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV. | Infect Genet Evol | 2020 | | LitCov and CORD-19 |
| 1952 | Structure of replicating SARS-CoV-2 polymerase N/A | Nature | 2020 | | LitCov and CORD-19 |
| 1953 | The worldwide air transportation network: Anomalous centrality, community structure and cities' global roles N/A | Proc Natl Acad Sci U S A | 2005 | | CORD-19 |
| 1954 | First cases of COVID-19 in the WHO European Region, 24 January to 21 February 2020 In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters’ index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. | Euro Surveill | 2020 | | LitCov and CORD-19 |
| 1955 | Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists | Intensive Care Med | 2020 | | LitCov and CORD-19 |
| 1956 | Immediate impact of stay-at-home orders to control COVID-19 transmission on socioeconomic conditions, food insecurity, mental health and intimate partner violence in Bangladeshi women and their families: an interrupted time series BACKGROUND: Stay-at-home orders (lockdowns) have been deployed globally to control COVID-19 transmission, and might impair economic conditions and mental health, and exacerbate risk of food insecurity and intimate partner violence. The effect of lockdowns in low-income and middle-income countries must be understood to ensure safe deployment of these interventions in less affluent settings. We aimed to determine the immediate impact of COVID-19 lockdown orders on women and their families in rural Bangladesh. METHODS: An interrupted time series was used to compare data collected from families in Rupganj upazila, rural Bangladesh (randomly selected from participants in a randomised controlled trial), on income, food security, and mental health a median of 1 year and 2 years before the COVID-19 pandemic to data collected during the lockdown. We also assessed women's experiences of intimate partner violence during the pandemic. RESULTS: Between May 19 and June 18, 2020, we randomly selected and invited the mothers of 3016 children to participate in the study, 2424 of whom provided consent. 2414 (99·9%, 95% CI 99·6–99·9) of 2417 mothers were aware of, and adhering to, the stay-at-home advice. 2321 (96·0%, 95·2–96·7) of 2417 mothers reported a reduction in paid work for the family. Median monthly family income fell from US$212 at baseline to $59 during lockdown, and the proportion of families earning less than $1·90 per day rose from five (0·2%, 0·0–0·5) of 2422 to 992 (47·3%, 45·2–49·5) of 2096 (p<0·0001 comparing baseline with lockdown period). Before the pandemic, 136 (5·6%, 4·7–6·6) of 2420 and 65 (2·7%, 2·1–3·4) of 2420 families experienced moderate and severe food insecurity, respectively. This increased to 881 (36·5%, 34·5–38·4) of 2417 and 371 (15·3%, 13·9–16·8) of 2417 during the lockdown; the number of families experiencing any level of food insecurity increased by 51·7% (48·1–55·4; p<0·0001). Mothers' depression and anxiety symptoms increased during the lockdown. Among women experiencing emotional or moderate physical violence, over half reported it had increased since the lockdown. INTERPRETATION: COVID-19 lockdowns present significant economic, psychosocial, and physical risks to the wellbeing of women and their families across economic strata in rural Bangladesh. Beyond supporting only the most socioeconomically deprived, support is needed for all affected families. FUNDING: National Health and Medical Research Council, Australia. | Lancet Glob Health | 2020 | | LitCov and CORD-19 |
| 1957 | Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19 Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens. | Elife | 2020 | | LitCov and CORD-19 |
| 1958 | Vaccine confidence in the time of COVID-19 In the early months of the COVID-19 epidemic, some have wondered if the force of this global experience will solve the problem of vaccine refusal that has vexed and preoccupied the global public health community for the last several decades. Drawing on historical and epidemiological analyses, we critique contemporary approaches to reducing vaccine hesitancy and articulate our notion of vaccine confidence as an expanded way of conceptualizing the problem and how to respond to it. Intervening on the rush of vaccine optimism we see pervading present discourse around the COVID-19 epidemic, we call for a re-imagination of the culture of public health and the meaning of vaccine safety regulations. Public confidence in vaccination programs depends on the work they do for the community—social, political, and moral as well as biological. The concept of public health and its programs must be broader than the delivery of the vaccine technology itself. The narrative work and policy actions entailed in actualizing such changes will, we expect, be essential in achieving a true vaccine confidence, however the public reacts to the specific vaccine that may be developed for COVID-19. | Eur J Epidemiol | 2020 | | LitCov and CORD-19 |
| 1959 | PCR-based diagnostics for infectious diseases: uses, limitations and future applications in acute-care settings Molecular diagnostics are revolutionising the clinical practice of infectious disease. Their effects will be significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes. PCR is the most well-developed molecular technique up to now, and has a wide range of already fulfilled, and potential, clinical applications, including specific or broad-spectrum pathogen detection, evaluation of emerging novel infections, surveillance, early detection of biothreat agents, and antimicrobial resistance profiling. PCR-based methods may also be cost effective relative to traditional testing procedures. Further advancement of technology is needed to improve automation, optimise detection sensitivity and specificity, and expand the capacity to detect multiple targets simultaneously (multiplexing). This review provides an up-to-date look at the general principles, diagnostic value, and limitations of the most current PCR-based platforms as they evolve from bench to bedside. | Lancet Infect Dis | 2004 | | CORD-19 |
| 1960 | Computational analysis of SARS-CoV-2/COVID-19 surveillance by wastewater-based epidemiology locally and globally: Feasibility, economy, opportunities and challenges Abstract With the economic and practical limits of medical screening for SARS-CoV-2/COVID-19 coming sharply into focus worldwide, scientists are turning now to wastewater-based epidemiology (WBE) as a potential tool for assessing and managing the pandemic. We employed computational analysis and modeling to examine the feasibility, economy, opportunities and challenges of enumerating active coronavirus infections locally and globally using WBE. Depending on local conditions, detection in community wastewater of one symptomatic/asymptomatic infected case per 100 to 2,000,000 non-infected people is theoretically feasible, with some practical successes now being reported from around the world. Computer simulations for past, present and emerging epidemic hotspots (e.g., Wuhan, Milan, Madrid, New York City, Teheran, Seattle, Detroit and New Orleans) identified temperature, average in-sewer travel time and per-capita water use as key variables. WBE surveillance of populations is shown to be orders of magnitude cheaper and faster than clinical screening, yet cannot fully replace it. Cost savings worldwide for one-time national surveillance campaigns are estimated to be in the million to billion US dollar range (US$), depending on a nation's population size and number of testing rounds conducted. For resource poor regions and nations, WBE may represent the only viable means of effective surveillance. Important limitations of WBE rest with its inability to identify individuals and to pinpoint their specific locations. Not compensating for temperature effects renders WBE data vulnerable to severe under-/over-estimation of infected cases. Effective surveillance may be envisioned as a two-step process in which WBE serves to identify and enumerate infected cases, where after clinical testing then serves to identify infected individuals in WBE-revealed hotspots. Data provided here demonstrate this approach to save money, be broadly applicable worldwide, and potentially aid in precision management of the pandemic, thereby helping to accelerate the global economic recovery that billions of people rely upon for their livelihoods. | Sci Total Environ | 2020 | | LitCov and CORD-19 |
| 1961 | Clinical characteristics of novel COVID-19 in newborns, infants and children | Pediatr Neonatol | 2020 | | LitCov and CORD-19 |
| 1962 | Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field. In this work, a review was done on the most recent publications concerning their antioxidant and anti-inflammatory activities. At the same time a survey of the methods generally used for the evaluation of antioxidant activity and some of the mechanisms involved in the anti-inflammatory activities of essential oils are also reported. | Molecules | 2010 | | CORD-19 |
| 1963 | Solid supported lipid bilayers: From biophysical studies to sensor design The lipid bilayer is one of the most eloquent and important self-assembled structures in nature. It not only provides a protective container for cells and sub-cellular compartments, but also hosts much of the machinery for cellular communication and transport across the cell membrane. Solid supported lipid bilayers provide an excellent model system for studying the surface chemistry of the cell. Moreover, they are accessible to a wide variety of surface-specific analytical techniques. This makes it possible to investigate processes such as cell signaling, ligand–receptor interactions, enzymatic reactions occurring at the cell surface, as well as pathogen attack. In this review, the following membrane systems are discussed: black lipid membranes, solid supported lipid bilayers, hybrid lipid bilayers, and polymer cushioned lipid bilayers. Examples of how supported lipid membrane technology is interfaced with array based systems by photolithographic patterning, spatial addressing, microcontact printing, and microfluidic patterning are explored. Also, the use of supported lipid bilayers in microfluidic devices for the development of lab-on-a-chip based platforms is examined. Finally, the utility of lipid bilayers in nanotechnology and future directions in this area are discussed. | Surf Sci Rep | 2006 | | CORD-19 |
| 1964 | Resilience, COVID-19-related stress, anxiety and depression during the pandemic in a large population enriched for healthcare providers COVID-19 pandemic is a global calamity posing an unprecedented opportunity to study resilience. We developed a brief resilience survey probing self-reliance, emotion-regulation, interpersonal-relationship patterns and neighborhood-environment, and applied it online during the acute COVID-19 outbreak (April 6–15, 2020), on a crowdsourcing research website (www.covid19resilience.org) advertised through social media. We evaluated level of stress (worries) regarding COVID-19: (1) contracting, (2) dying from, (3) currently having, (4) family member contracting, (5) unknowingly infecting others with (6) experiencing significant financial burden following. Anxiety (GAD7) and depression (PHQ2) were measured. Totally, 3042 participants (n = 1964 females, age range 18–79, mean age = 39) completed the resilience and COVID-19-related stress survey and 1350 of them (mean age = 41, SD = 13; n = 997 females) completed GAD7 and PHQ2. Participants significantly endorsed more distress about family contracting COVID-19 (48.5%) and unknowingly infecting others (36%), than getting COVID-19 themselves (19.9%), p < 0.0005 covarying for demographics and proxy COVID-19 exposures like getting tested and knowing infected individuals. Patterns of COVID-19 related worries, rates of anxiety (GAD7 > 10, 22.2%) and depression (PHQ2 > 2, 16.1%) did not differ between healthcare providers and non-healthcare providers. Higher resilience scores were associated with lower COVID-19 related worries (main effect F(1,3054) = 134.9; p < 0.00001, covarying for confounders). Increase in 1 SD on resilience score was associated with reduced rate of anxiety (65%) and depression (69%), across healthcare and non-healthcare professionals. Findings provide empirical evidence on mental health associated with COVID-19 outbreak in a large convenience sample, setting a stage for longitudinal studies evaluating mental health trajectories following COVID-19 pandemic. | Transl Psychiatry | 2020 | | LitCov and CORD-19 |
| 1965 | People with Suspected COVID-19 Symptoms Were More Likely Depressed and Had Lower Health-Related Quality of Life: The Potential Benefit of Health Literacy The coronavirus disease 2019 (COVID-19) epidemic affects people’s health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted from 14 February to 2 March 2020. 3947 participants were recruited from outpatient departments of nine hospitals and health centers across Vietnam. The interviews were conducted using printed questionnaires including participants’ characteristics, clinical parameters, health behaviors, HL, depression, and HRQoL. People with S-COVID-19-S had a higher depression likelihood (OR, 2.88; p < 0.001), lower HRQoL-score (B, −7.92; p < 0.001). In comparison to people without S-COVID-19-S and low HL, those with S-COVID-19-S and low HL had 9.70 times higher depression likelihood (p < 0.001), 20.62 lower HRQoL-score (p < 0.001), for the people without S-COVID-19-S, 1 score increment of HL resulted in 5% lower depression likelihood (p < 0.001) and 0.45 higher HRQoL-score (p < 0.001), while for those people with S-COVID-19-S, 1 score increment of HL resulted in a 4% lower depression likelihood (p = 0.004) and 0.43 higher HRQoL-score (p < 0.001). People with S-COVID-19-S had a higher depression likelihood and lower HRQoL than those without. HL shows a protective effect on depression and HRQoL during the epidemic. | J Clin Med | 2020 | | LitCov and CORD-19 |
| 1966 | Molecular Evolution of Human Coronavirus Genomes Human coronaviruses (HCoVs), including SARS-CoV and MERS-CoV, are zoonotic pathogens that originated in wild animals. HCoVs have large genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ in number and sequence even among closely related CoVs. Thus, in addition to recombination and mutation, HCoV genomes evolve through gene gains and losses. In this review we summarize recent findings on the molecular evolution of HCoV genomes, with special attention to recombination and adaptive events that generated new viral species and contributed to host shifts and to HCoV emergence. VIDEO ABSTRACT: | Trends Microbiol | 2016 | | CORD-19 |
| 1967 | Global epidemiology of COVID-19: disease incidence, daily cumulative index, mortality and their association with country healthcare resources and economic status ABSTRACT It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were <10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and once-daily press conferences by the government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of 29 February 2020) with a DCI of 1 case per day in Taiwan, which is much lower than that of nearby countries such as the Republic of Korea and Japan. In addition, the incidence and mortality were correlated with the DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19. | Int J Antimicrob Agents | 2020 | | LitCov and CORD-19 |
| 1968 | Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 BACKGROUND: There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. OBJECTIVE: Develop evidence-based rapid guidelines intended to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19. METHODS: IDSA formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. CONCLUSIONS: The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments. | Clin Infect Dis | 2020 | | LitCov and CORD-19 |
| 1969 | Approved Antiviral Drugs over the Past 50 Years N/A | Clin Microbiol Rev | 2016 | | CORD-19 |
| 1970 | Human kidney is a target for novel SARS-CoV-2 infection It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI. | Nat Commun | 2021 | | LitCov and CORD-19 |
| 1971 | Targeting cancer stem cell pathways for cancer therapy Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs. | Signal Transduct Target Ther | 2020 | | CORD-19 |
| 1972 | Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia The lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists. | Lancet Rheumatol | 2020 | | LitCov and CORD-19 |
| 1973 | A decade after SARS: strategies for controlling emerging coronaviruses Two novel coronaviruses have emerged in humans in the 21(st) century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome human coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and have high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, a priority in the field is the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains. This review will: describe the emergence and identification of novel human coronaviruses over the last 10 years; review their key biological features, including tropism and receptor use; and summarize approaches to develop broadly effective vaccines. | Nat Rev Microbiol | 2013 | | CORD-19 |
| 1974 | KEGG: integrating viruses and cellular organisms KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations. | Nucleic Acids Res | 2020 | | CORD-19 |
| 1975 | SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19 N/A | Nature | 2020 | | LitCov and CORD-19 |
| 1976 | Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development BACKGROUND: Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. METHODS: We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. FINDINGS: Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. INTERPRETATION: MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases. | EBioMedicine | 2020 | | LitCov and CORD-19 |
| 1977 | COVID-19 and Cardiovascular Complications Abstract The coronavirus disease 2019 (COVID-19) has become a global pandemic. It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important. | J Cardiothorac Vasc Anesth | 2020 | | LitCov and CORD-19 |
| 1978 | Psychological Outcomes Associated with Stay-at-Home Orders and the Perceived Impact of COVID-19 on Daily Life The COVID-19 pandemic has resulted in the widespread implementation of extraordinary physical distancing interventions (e.g., stay-at-home orders) to slow the spread of the virus. Although vital, these interventions may be socially and economically disruptive, contributing to adverse psychological outcomes. This study examined relations of both stay-at-home orders and the perceived impact of COVID-19 on daily life to psychological outcomes (depression, health anxiety, financial worry, social support, and loneliness) in a nationwide U.S. community adult sample (N = 500; 47% women, mean age = 40). Participants completed questionnaires assessing psychological outcomes, stay-at-home order status, and COVID-19’s impact on their daily life. Being under a stay-at-home order was associated with greater health anxiety, financial worry, and loneliness. Moreover, the perceived impact of COVID-19 on daily life was positively associated with health anxiety, financial worry, and social support, but negatively associated with loneliness. Findings highlight the importance of social connection to mitigate negative psychological consequences of the COVID-19 pandemic. | Psychiatry Res | 2020 | | LitCov and CORD-19 |
| 1979 | Role of vitamin D in preventing of COVID-19 infection, progression and severity The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p = 0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels 75-125 nmol/L. In conclusion, there not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis. | J Infect Public Health | 2020 | | LitCov and CORD-19 |
| 1980 | Hepatocellular carcinoma N/A | Nat Rev Dis Primers | 2016 | | CORD-19 |
| 1981 | Quantitative Real-Time PCR Changes in mRNA expression levels occur during physiological and pathological processes in the cardiovascular system. An increase inDNAtranscription results in increasedmRNAlevels and will subsequently result in increased protein levels that regulate processes inside and outside the cell. To determine alterations in mRNA levels, traditional methods such as Northern blot and ribonuclease protection assay can be used; however, large amounts of RNA are necessary and the methods are very labor intensive. In this chapter, we focus on the newest advancements in reverse transcription polymerase chain reaction (rt-pcr) technology, the real-time PCR or quantitative PCR, using small amounts of RNA to determine expression levels.We discuss the technique in general and describe two different approaches. | Cardiovascular Research | 2006 | | CORD-19 |
| 1982 | Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic AIMS: Analyze the relationship between obesity and influenza. METHODS: Basal hormone milieu, defective response of both innate and adaptive immune system and sedentariness are major determinants in the severity of influenza viral infection in obese patients. Being overweight not only increases the risk of infection and of complications for the single obese person, but a large prevalence of obese individuals within the population might increase the chance of appearance of more virulent viral strain, prolongs the virus shedding throughout the total population and eventually might increase overall mortality rate of an influenza pandemic. RESULTS: Waiting for the development of a vaccination against COVID-19, isolation of positive cases and social distancing are the primary interventions. Nonetheless, evidence from previous influenza pandemics suggests the following interventions aimed at improving immune response: (1) lose weight with a mild caloric restriction; (2) include AMPK activators and PPAR gamma activators in the drug treatment for obesity associated with diabetes; and (3) practice mild-to-moderate physical exercise. CONCLUSIONS: Due to prolonged viral shedding, quarantine in obese subjects should likely be longer than normal weight individuals. | Acta Diabetol | 2020 | | LitCov and CORD-19 |
| 1983 | Managing uncertainty during a global pandemic: An international business perspective Despite the perennial need to understand and manage uncertainty in international business, there is no comprehensive framework that incorporates different types of uncertainty, their antecedents and outcomes, and the different coping strategies used by managers and their outcomes. This makes it difficult for international business managers to understand the types of uncertainty in their businesses and develop appropriate strategies to deal with it effectively, especially during times such as the ongoing Covid-19 pandemic. This paper uses an extensive review of the international business literature to address the above research gap by identifying the different types of uncertainty, their antecedents and outcomes, the coping strategies used to mitigate their impact, and the consequences of these actions. The authors also use examples from the current Covid-19 crisis to assess the firms’ responses and their consequences. The paper concludes with some implications for international business managers and directions for future research. | J Bus Res | 2020 | | LitCov and CORD-19 |
| 1984 | Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization Abstract BACKGROUD & AIMS: Although SARS-CoV-2 infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with COVID-19 in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of ACE2 in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity. | Gastroenterology | 2020 | | LitCov and CORD-19 |
| 1985 | SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway While severe acute respiratory syndrome coronavirus (SARS-CoV) was initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that virus entry may also involve endocytosis. We have found that SARS-CoV enters cells via pH- and receptor-dependent endocytosis. Treatment of cells with either SARS-CoV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic pathway inhibitors and dominant-negative Eps15 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/cr.2008.15) contains supplementary material, which is available to authorized users. | Cell Res | 2008 | | CORD-19 |
| 1986 | Evolving epidemiology and transmission dynamics of COVID-19 outside Hubei province, China: a descriptive and modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R(t)) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020. | Lancet Infect Dis | 2020 | | LitCov and CORD-19 |
| 1987 | Initial impacts of global risk mitigation measures taken during the combatting of the COVID-19 pandemic Abstract This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11 2020, to limit the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, providing an update on the current knowledge for authorities, sectors and first responders on the effectiveness of said measures, and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio-economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures. | Saf Sci | 2020 | | LitCov and CORD-19 |
| 1988 | Looking beyond COVID-19 vaccine phase 3 trials N/A | Nat Med | 2021 | | LitCov and CORD-19 |
| 1989 | Economic impacts of Wuhan 2019-nCoV on China and the world Uncertainties over the Wuhan 2019 Novel Coronavirus (2019-nCoV), which has killed 1,017 people and sickened more than 43,100 as of Feb 11,1 has interrupted global trade and supply chains, depressed asset prices, and forced multinational businesses to make hard decisions with limited information. This article is protected by copyright. All rights reserved. | J Med Virol | 2020 | | LitCov and CORD-19 |
| 1990 | The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome N/A | J Thromb Haemost | 2020 | | LitCov and CORD-19 |
| 1991 | Getting the message right on nature-based solutions to climate change N/A | Glob Chang Biol | 2021 | | CORD-19 |
| 1992 | Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration N/A | Pharmaceutics | 2020 | | CORD-19 |
| 1993 | Phase-adjusted estimation of the number of COVID-19 cases in Wuhan, China An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R(0) of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of R(t). In the first assumption, R(t) was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with R(t) = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, R(t) was assumed to gradually decrease at different phases from high level of transmission (R(t) = 3.1, 2.6, and 1.9) to below 1 (R(t) = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce R(t) to an ideal level and control the infection. | Cell Discov | 2020 | | LitCov and CORD-19 |
| 1994 | CT Imaging and Differential Diagnosis of COVID-19 Since the beginning of 2020, coronavirus disease 2019 (COVID-19) has spread throughout China. This study explains the findings from lung computed tomography images of some patients with COVID-19 treated in this medical institution and discusses the difference between COVID-19 and other lung diseases. | Can Assoc Radiol J | 2020 | | LitCov and CORD-19 |
| 1995 | Asymptomatic cases in a family cluster with SARS-CoV-2 infection | Lancet Infect Dis | 2020 | | LitCov and CORD-19 |
| 1996 | Sedentary Lifestyle: Overview of Updated Evidence of Potential Health Risks One-third of the global population aged 15 years and older engages in insufficient physical activities, which affects health. However, the health risks posed by sedentary behaviors are not well known. The mean daily duration of sedentary behavior is 8.3 hours among the Korean population and 7.7 hours among the American adult population. Sedentary lifestyles are spreading worldwide because of a lack of available spaces for exercise, increased occupational sedentary behaviors such as office work, and the increased penetration of television and video devices. Consequently, the associated health problems are on the rise. A sedentary lifestyle affects the human body through various mechanisms. Sedentary behaviors reduce lipoprotein lipase activity, muscle glucose, protein transporter activities, impair lipid metabolism, and diminish carbohydrate metabolism. Furthermore, it decreases cardiac output and systemic blood flow while activating the sympathetic nervous system, ultimately reducing insulin sensitivity and vascular function. It also alters the insulin-like growth factor axis and the circulation levels of sex hormones, which elevates the incidence of hormone-related cancers. Increased sedentary time impairs the gravitostat, the body’s weight homeostat, and weight gain, adiposity, and elevated chronic inflammation caused by sedentary behavior are risk factors for cancer. Sedentary behaviors have wide-ranging adverse impacts on the human body including increased all-cause mortality, cardiovascular disease mortality, cancer risk, and risks of metabolic disorders such as diabetes mellitus, hypertension, and dyslipidemia; musculoskeletal disorders such as arthralgia and osteoporosis; depression; and, cognitive impairment. Therefore, reducing sedentary behaviors and increasing physical activity are both important to promote public health. | Korean J Fam Med | 2020 | | CORD-19 |
| 1997 | Stunting in childhood: an overview of global burden, trends, determinants and drivers of decline N/A | Am J Clin Nutr | 2020 | | CORD-19 |
| 1998 | Evaluation of Nucleocapsid and Spike Protein-Based Enzyme-Linked Immunosorbent Assays for Detecting Antibodies against SARS-CoV-2 At present, PCR-based nucleic acid detection cannot meet the demands for coronavirus infectious disease (COVID-19) diagnosis. Two hundred fourteen confirmed COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command of the People’s Liberation Army between 18 January and 26 February 2020 were recruited. Two enzyme-linked immunosorbent assay (ELISA) kits based on recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, and their diagnostic feasibility was evaluated. Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, respectively. The positive rates of the rN-based and rS-based ELISAs for antibody (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of the rS-based ELISA for IgM detection was significantly higher than that of the rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG ELISAs was less than 60% during the early stage of the illness, 0 to 10 d.p.o., and that of IgM and IgG was obviously increased after 10 d.p.o. ELISA has a high sensitivity, especially for the detection of serum samples from patients after 10 d.p.o., so it could be an important supplementary method for COVID-19 diagnosis. | J Clin Microbiol | 2020 | | LitCov and CORD-19 |
| 1999 | Stress resilience during the coronavirus pandemic The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19) is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers. We not only advocate for an increased focus on mental health during the coronavirus pandemic but also highlight the urgent need of augmenting our focus on resilience and on strategies to enhance it. | Eur Neuropsychopharmacol | 2020 | | LitCov and CORD-19 |
| 2000 | KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update N/A | Am J Kidney Dis | 2020 | | CORD-19 |
