Article

First Case of 2019 Novel Coronavirus in the United States

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Abstract

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

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... The nCOVID-19 depicts novel (n) corona (CO) virus (VI) disease (D) and the numeral 19 depicts the year of its outbreak, i.e., 2019. Gradual progress in identification, diagnosis, clinical studies, and management of this virus became a major concern, and the first US case of corona virus led to a symptomatic analysis with mild symptoms at initial stages progressively deteriorating to pneumonia up to the 9th day of infection (Holshue et al. 2020). Various reports have demonstrated horrific images of corona virus pandemic, which has now taken over countries like Italy and America, where death toll has reached alarming levels. ...
... An adenosine analog, remdesivir, is a monophosphoramidate prodrug (Lu 2020;Ren et al. 2020), which is metabolized into active form, GS-441524, inhibiting rial RNA production. Besides Ebola virus , remdesivir has reported to inhibit corona viruses like MERS-CoV as well as SARS-CoV, significantly, as per in-vitro studies ("Coronavirus"; Holshue et al. 2020;. A study involved 308 adult subjects, hospitalized with the COVID-19 infection, where the subjects were randomized to either remdesivir or placebo. ...
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The 2019 outbreak of corona virus disease began from Wuhan (China), transforming into a leading pandemic, posing an immense threat to the global population. The WHO coined the term nCOVID-19 for the disease on 11th February, 2020 and the International Committee of Taxonomy of Viruses named it SARS-CoV-2, on account of its similarity with SARS-CoV-1 of 2003. The infection is associated with fever, cough, pneumonia, lung damage, and ARDS along with clinical implications of lung opacities. Brief understanding of the entry target of virus, i.e., ACE2 receptors has enabled numerous treatment options as discussed in this review. The manuscript provides a holistic picture of treatment options in COVID-19, such as non-specific anti-viral drugs, immunosuppressive agents, anti-inflammatory candidates, anti-HCV, nucleotide inhibitors, antibodies and anti-parasitic, RNA-dependent RNA polymerase inhibitors, anti-retroviral, vitamins and hormones, JAK inhibitors, and blood plasma therapy. The text targets to enlist the investigations conducted on all the above categories of drugs, with respect to the COVID-19 pandemic, to accelerate their significance in hindering the disease progression. The data collected primarily targets recently published articles and most recent records of clinical trials, focusing on the last 10-year database. The current review provides a comprehensive view on the critical need of finding a suitable treatment for the currently prevalent COVID-19 disease, and an opportunity for the researchers to investigate the varying possibilities to find and optimized treatment approach to mitigate and ameliorate the chaos created by the pandemic worldwide.
... The COVID-19 pandemic caused by SARS-CoV-2 is rapidly spreading and evolving around the world. Though conventional antiviral drugs (Holshue et al., 2020;McKee et al., 2020;NIH, 2022), traditional Chinese medicine Wang and Yang, 2021;Shi et al., 2022), antibiotics (Mirzaei et al., 2020;Popp et al., 2021), and vaccines (Poland et al., 2020;Eyre et al., 2022;WHO, 2022a) have been applied in COVID-19 clinical therapy, the screening for drugs targeting SARS-CoV-2 critical proteins remains a long and arduous process ...
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The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.
... The existence of competitiveness between ligands and receptors can be observed through the residues bound to the ligands, which indicates that if there are the same or more residues, the ligands will compete with each other. [28] On the other hand, the interaction of the ligand and the COVID-19 receptor was also seen with a docking simulation. The binding affinity of catechin and remdesivir to the coronavirus protease is shown in Table 2 where the binding affinity of catechin to the coronavirus protease protein is lower than that of remdesivir. ...
... The existence of competitiveness between ligands and receptors can be observed through the residues bound to the ligands, which indicates that if there are the same or more residues, the ligands will compete with each other. [28] On the other hand, the interaction of the ligand and the COVID-19 receptor was also seen with a docking simulation. The binding affinity of catechin and remdesivir to the coronavirus protease is shown in Table 2 where the binding affinity of catechin to the coronavirus protease protein is lower than that of remdesivir. ...
Article
Coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 attacking the lungs, which contain the most oxygen. The involvement of oxidative stress in the body and the role of antioxidant compounds, namely catechins, are thought to be able to prevent various diseases, including the COVID-19 infection virus. An in silico approach was employed between the catechins and the protein NADPH oxidase (Nox), followed by the coronavirus protease protein, to limit the generation of reactive oxygen species. This research using the in silico method seeks to predict the mechanism of action of catechin as a superoxide radical anion inhibitor and as an antiviral for COVID-19. This study carried out molecular docking simulations of catechin compounds against Nox and coronavirus proteases and then compared them with positive controls GKT136901 and remdesivir. The binding energy of catechin and Nox in a docking simulation is - 8.30 kcal/mol, which is somewhat lower than GKT136901's binding value of - 8.72 kcal/mol. Catechin and coronavirus proteases had binding energy of - 7.89 kcal/mol, which was greater than remdesivir's binding energy of - 7.50 kcal/mol. Based on in silico data, catechin as an antioxidant compound can be antiviral for COVID-19.
... The multivariate model was adjusted for sex, age, marital status, equivalent household income, educational level, occupation, self-rated health status and anxiety. Introduction , first identified at the end of 2019, is continuing to rage around the world (1)(2)(3)(4). Having experienced four waves of the disease through June 2021 there is an urgent need in Japan to understand the working and social environment and the health status of workers affected by the COVID-19 pandemic. ...
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Background The COVID-19 pandemic has resulted in treatment interruption for chronic diseases. The scale of COVID-19 in Japan has varied greatly in terms of the scale of infection and the speed of spread depending on the region. This study aimed to examine the relationship between local infection level and treatment interruption among Japanese workers. Methods Cross-sectional internet survey was conducted from December 22 to 26, 2020. Of 33,302 participants, 9,510 (5,392 males and 4,118 females) who responded that they required regular treatment were included in the analysis. The infection level in each participant's prefecture of residence was assessed based on the incidence rate (per 1,000 population) and the number of people infected. Age-sex and multivariate adjusted odds ratios (ORs) of regional infection levels associated with treatment interruption were estimated by multilevel logistic models, nested by prefecture of residence. The multivariate model was adjusted for sex, age, marital status, equivalent household income, educational level, occupation, self-rated health status and anxiety. Results The ORs of treatment interruption for the lowest and highest levels of infection in the region were 1.32 [95 % confidence interval (CI) were 1.09–1.59] for the overall morbidity rate (per 1,000) and 1.34 (95 % CI 1.10–1.63) for the overall number of people infected. Higher local infection levels were linked to a greater number of workers experiencing treatment interruption. Conclusions Higher local infection levels were linked to more workers experiencing treatment interruption. Our results suggest that apart from individual characteristics such as socioeconomic and health status, treatment interruption during the pandemic is also subject to contextual effects related to regional infection levels. Preventing community spread of COVID-19 may thus protect individuals from indirect effects of the pandemic, such as treatment interruption.
... The stock of SARS-CoV-2 strain 2019-nCoV/USA_WA1/2020 (CoV-2/WA1) was derived from one of the first patients diagnosed in the United States. This virus was originally isolated by Natalie Thornburg from the Centers for Disease Control and Prevention in Atlanta, GA (46). It was amplified on Vero E6 cells. ...
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The results of this study demonstrate that the late lineages of SARS-CoV-2 evolved to more efficient use of the TMPRSS2-mediated entry pathway and gradually lost an ability to employ the cathepsins/endosome-mediated entry. The acquisition of a furin cleavage site (FCS) by SARS-CoV-2-specific S protein made the virus a potent producer of syncytia. Their formation is also determined by expression of ACE2 and TMPRSS2 and is resistant to neutralizing human MAbs and immune sera.
... On December 31, 2019, China reported a cluster of mysterious cases of pneumonia, which later turned out to be Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and was first detected in a human in the United States on January 20, 2020 (Holshue et al., 2020). The World Health Organization (WHO) declared a global pandemic on March 11, 2020 ("WHO ", 2020). ...
Article
Antimicrobials like parabens, triclosan (TCS), and triclocarban (TCC) are of public health concern worldwide due to both their endocrine-disrupting properties and ability to promote antimicrobial drug resistance in human pathogens. The overall use of antimicrobials presumably has increased during the COVID-19 pandemic, whereas TCS and TCC may have experienced reductions in use due their recent ban from thousands of over-the-counter (OTC) personal care products by the U.S. Food and Drug Administration (FDA). No quantitative data are available on the use of parabens or the impact the FDA ban had on TCC and TCS. Here, we use wastewater samples (n = 1514) from 10 different communities in Arizona to measure the presence of the six different antimicrobial products (TCS, TCC, and four alkylated parabens [methylparaben (MePb), ethylparaben (EtPb), propylparaben (PrPb), butylparaben (BuPb)]) collected before and during the COVID-19 pandemic using a combination of solid-phase extraction, liquid chromatography/tandem mass spectrometry (LC-MS/MS), and isotope dilution for absolute quantitation. The average mass loadings of all antimicrobials combined (1,431 ± 22 mg/day per 1,000 people) after the onset of the local epidemic (March 2020 - October 2020) were significantly higher (945 ± 62 mg/day per 1,000 people; p < 0.05) than before the pandemic (January 2019 - February 2020). Overall, parabens (∑Pbs = 999 ± 16 mg/day per 1,000 people) were the most used antimicrobials followed by TCS (117 ± 14 mg/day per 1,000 people) and TCC (117 ± 14 mg/day per 1,000 people). After the 2017 U.S. FDA ban, we found a statistically significant (p < 0.05) reduction in the mass loadings of TCS (-89%) and TCC (-80%) but a rise in paraben use (+72%). Mass flows of 3 of a total of 4 parabens (MePb, EtPb, and PrPb) in wastewater were significantly higher upon the onset of the epidemic locally (p < 0.05). This is the first longitudinal study investigating the use of antimicrobials during the COVID-19 pandemic by using wastewater-based epidemiology. Whereas an overall increase in the use of antimicrobials was evident by analyzing Arizona wastewater, a notable reduction in use of TCS and TCC was evident, triggered by the U.S. FDA ban during the pandemic.
... The ongoing global pandemic of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health emergency of international concern (Organization and Fund (UNICEF) 2020a, 2020b). SARS-CoV-2 ribonucleic acid (RNA) has been detected in feces from both symptomatic and asymptomatic patients (Chen et al. 2020;Holshue et al. 2020;Jiehao et al. 2020;Tang et al. 2020;W. Wang et al. 2020;Zhang et al. 2020) and in wastewater (Ahmed et al. 2020;Lodder and Husman 2020;Medema et al. 2020). ...
... When remdesivir was administered intravenously to the first patient diagnosed with SARS-CoV-2 in the USA, no adverse effects were noted with some clinical benefits in the patients [77]. Evidence also showed an accelerated recovery rate of 4 days when remdesivir was employed [78]. ...
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The unprecedented outbreak of the severe acute respiratory syndrome (SARS) Coronavirus-2, across the globe, triggered a worldwide uproar in the search for immediate treatment strategies. With no specific drug and not much data available, alternative approaches such as drug repurposing came to the limelight. To date, extensive research on the repositioning of drugs has led to the identification of numerous drugs against various important protein targets of the coronavirus strains, with hopes of the drugs working against the major variants of concerns (alpha, beta, gamma, delta, omicron) of the virus. Advancements in computational sciences have led to improved scope of repurposing via techniques such as structure-based approaches including molecular docking, molecular dynamic simulations and quantitative structure activity relationships, network-based approaches, and artificial intelligence-based approaches with other core machine and deep learning algorithms. This review highlights the various approaches to repurposing drugs from a computational biological perspective, with various mechanisms of action of the drugs against some of the major protein targets of SARS-CoV-2. Additionally, clinical trials data on potential COVID-19 repurposed drugs are also highlighted with stress on the major SARS-CoV-2 targets and the structural effect of variants on these targets. The interaction modelling of some important repurposed drugs has also been elucidated. Furthermore, the merits and demerits of drug repurposing are also discussed, with a focus on the scope and applications of the latest advancements in repurposing.
... The first case of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in the United States on January 19, 2020. 1 To protect patients and providers and avoid overwhelming the health care system, most US hospital systems swiftly implemented measures to limit non-COVID-related services, including limiting in-person office visits and postponing elective surgeries. 2 These changes initially prompted concerns about the ability of hospitals, health systems, and physician practices to remain financially solvent amid major changes to billable services and revenue streams. ...
Article
Objective: To quantify the financial impact of the coronavirus disease (COVID-19) pandemic on an academic otolaryngology department. Methods: A year-over-year comparison was used to compare department revenue from April 2020 and April 2021 as a percentage of baseline April 2019 activity. Results: At the onset of the COVID-19 pandemic in April 2020, total department charges decreased by 83.4%, of which outpatient clinic charges were affected to the greatest extent. One year into pandemic recovery, department charges remained down 6.7% from baseline, and outpatient clinic charges remained down 9.9%. The reduction in outpatient clinic charges was mostly driven by a decrease in in-office procedure charges. Conclusion: Given that precautions to mitigate the risk of viral transmission in the health care setting are likely to be long-lived, it is important to consider the vulnerabilities of our specialty to mitigate financial losses going forward.
... We studied the air quality data at the study site from March 2019 to July 2020. The first confirmed case of COVID-19 in the USA was reported on January 20, 2020 (Holshue et al., 2020), and the first reported death occurred on February 29, 2020 (Centers for Disease Control and Prevention, 2020). We considered the period from January 1 to March 15, 2020, to be the pre-pandemic stage. ...
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Improved air quality has been the silver lining of the pandemic since early 2020. The air quality in northern New Jersey (NJ) was continuously measured during the COVID-19 pandemic and through the three stages of recovery, i.e., the Stay-at-home stage, Reopening stage 1, and Reopening stage 2. A significant change in air quality was observed during the Stay-at-home stage (March 16 to May 16, 2020) as most people stayed home and industrial activity decreased 60%. Compared to 2019, carbon dioxide (CO2) decreased 17%, carbon monoxide (CO) decreased 7%, and nitrogen oxides (NOx) decreased 51% during the Stay-at-home stage in 2020. However, the ground-level ozone (O3) increased in 2020 because of the reduced NOx emission and the possibly increased levels of volatile organic compounds (VOCs) due to warmer weather. With the step-by-step reopening process, the difference in local CO2 levels between 2019 and 2020 was reduced, and the NOx concentration returned to its 2019 level. The CO2 concentrations were positively correlated with CO, and the NOx concentrations were negatively correlated with O3. Under the COVID-19 pandemic in 2020, NJ consumed 14% less natural gas and 21% less gasoline; therefore, the CO2, CO, and NOx emissions and concentration levels were reduced besides the effects of meteorology parameters on air quality in metropolitan New Jersey. Our findings support that replacing fossil fuels with electric or renewable energy in the transportation systems and industry could be beneficial for the concentration reduction of certain greenhouse gases. Supplementary information: The online version contains supplementary material available at 10.1007/s11270-022-05764-w.
... 23 There is anecdotal experience with use of remdeswir, a broad spectrum anti RNA drug developed for Ebola in management of COVID-19. 34 More evidence is needed before these drugs are recommended. Other drugs proposed for therapy are arbidol (an antiviral drug available in Russia and China), intravenous immunoglobulin, interferons, chloroquine and plasma of patients recovered from COVID-19. ...
... The affliction caused by COVID-19 is extensive (Holshue et al. 2020). People commonly utilize SM as a forum to post and share their ideas and sentiments. ...
Article
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The COVID-19 infection, which began in December 2019, has claimed many lives and impacted all aspects of human life. With time, COVID-19 was identified as a pandemic outbreak by the World Health Organization (WHO), putting massive pressure on global health. During this ongoing pandemic, the exponential growth of social media platforms has provided valuable resources for distributing information, as well as a source for self-reported disease symptoms in public discourse. Therefore, there is an urgent need for effective approaches to detect self-reported symptoms or cases in social media content. In this study, we scrapped public discourse on COVID-19 symptoms in Twitter content. For this, we developed a huge dataset of COVID-19 self-reported symptoms and gold-annotated the tweets into four categories: confirmed, death, suspected, and recovered. Then, we use a machine and deep machine learning models, each with its own set of features, such as feature representation. Furthermore, the experimentations were achieved with recurrent neural networks (RNNs) variants and compared their performance with traditional machine learning algorithms. Experimental results report that optimizing the area under the curve (AUC) enhances model performance, and the long short-term memory (LSTM) has the highest accuracy in detecting COVID-19 symptoms in real-time public messaging. Thus, the LSTM classifier in the proposed pipeline achieves a classification accuracy of 90.7%, outperforming existing state-of-the-art algorithms for multi-class classification.
... This necessitates and calls for pragmatic thinking of leaders of HEIs and garnering and strengthening the cooperation of various stakeholders like policymakers and society. Commendable research is done by medical science and other health-related fields (Holshue et al., 2020;Meng et al., 2020). At the same time, a good amount of publications is also available that deals with closing down the educational institutions to control the spread of an infectious disease (De Luca et al., 2018;Kawano & Kakehashi, 2015;Wheeler et al., 2010). ...
Article
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The impact of COVID-19 is felt across and encompassing numerous dimensions of life; healthcare, education, job market, family and social life to name a few. With a modest beginning at a Chinese city, within a year, the disease infected and affected humanity all over the world. Though very commendable researches are undertaken by medical science and other health-related fields to understand, curtail and overcome its impact, the research is very limited on the impact of the pandemic on academia in general and on the issue related to Higher Education Institutions (HEI) in particular. This gap in literatur provided a compelling reason to the researchers to explore this phenomenal crises from its impact on HEI perspective and to make some practical recommendations in this regard. In this study, the researchers delved into the COVID impact on specific academic dimentions like teaching and learning, international student movement, student evaluation and academic research.
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Background: In March 2020, Qatar started reporting increased numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19). National preventive measures were implemented, and a testing plan was developed to respond to the pandemic with the Primary Health Care Corporation (PHCC) as the central element. PHCC is the main public primary healthcare provider in Qatar and it operates in 27 health centers with around 1.4 million registered individuals as of January 1, 2020. The latter population was distributed across four main nationality groups; Middle Eastern and North African (51.5%), Asian (41.2%), African (2.4%), and others (5.1%). At the primary healthcare level in Qatar, this study describes the epidemiological characteristics of individuals registered at PHCC who had contracted COVID-19 in 2020 during the first wave before the vaccination phase and examines the factors associated with the positivity rate. Methods: Retrospective data analysis was conducted for persons screened for SARS-CoV-2 in primary healthcare health centers in Qatar between March 11 and December 31, 2020. The study analyzed the demographic characteristics of the tested persons and noncommunicable disease burden, positivity rate by month, nationality, and age-group, and the factors associated with the positivity rate. Results: Between March 11 and December 31, 2020, PHCC tested 379,247 persons for SARS-CoV-2, with a median age (IQR) of 32 (21-42) years. Of these, 57.0% were from the Middle East and North Africa, and 32.5% were originally from Asia. Overall, 10.9% had diabetes mellitus and 11.3% had hypertension. The epidemiological curve showed a steep increase in the positivity rate from March till May 2020, at the highest rate of 37.5% in May 2020. The highest positivity rate was observed among Asian males at 15.7%. The positivity rate was the lowest among the age-group aged 60 years and above. It was almost the same among the tested persons for SARS-CoV-2 in the three main age groups (0-18, 19-39, 40-59) at 10.1%, 12.3%, and 12.2%, respectively. In a multi regression model, being a male was associated with a higher risk (OR 1.15; 95% CI 1.13-1.17). Asians were at higher risk than those originally from the Middle East and North Africa (OR 1.29; 95% CI 1.27-1.32). COVID-19 infection was higher among those presenting clinical symptoms than asymptomatic individuals (OR. 4.52; 95% CI 4.42-4.64). Conclusion: The epidemic among the PHCC-registered population predominantly affected younger ages and males, namely, coming from Asia. At the primary healthcare level, the COVID-19 infection rate was higher among those who presented with clinical symptoms. The lowest positivity rate among individuals >60 years may reflect the effectiveness of public health measures related to the high-risk group. Scaled-up testing at the primary healthcare level helped to detect more cases during the peak of the first wave and was reflected in a steady increase in the positivity rate flattened later due to the established public health measures.
By 9 February 2021, the Coronavirus has killed 2,336,650 people worldwide and it has been predicted that this number continues to increase in year 2021. The study aimed to identify therapeutic approaches and drugs that can potentially be used as interventions in Coronavirus 2019 (COVID-19) management. A systematic scoping review was conducted. Articles reporting clinical evidence of therapeutic management of COVID-19 were selected from three different research databases (Google Scholar, PubMed, and Science Direct). From the database search, 31 articles were selected based on the study inclusion and exclusion criteria. This review paper showed that remdesivir and ivermectin significantly reduced viral ribonucleic acid (RNA) activity. On the other hand, convalescent plasma (CP) significantly improved COVID-19 clinical symptoms. Additionally, the use of corticosteroid increased survival rates in COVID-19 patients with acute respiratory distress syndrome (ARDS). Findings also indicated that both hydroxychloroquine and favipiravir were effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, lopinavir–ritonavir combination was not effective against COVID-19. Finally, ribavirin, galidesivir, and sofosbuvir showed potential therapeutic benefit in treating COVID-19, but there is a lack of clinical evidence on their effectiveness against SARS-CoV-2. Remdesivir, ivermectin, favipiravir, hydroxychloroquine, dexamethasone, methylprednisolone, and CP are the therapeutic agents that can potentially be used in COVID-19 management.
Book
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We can also say that this book, prepared by our faculty members by adding their current experiences during the pandemic process, is one of the leading scientific publications about the COVID-19 pandemic.
Chapter
Prior 2019 to work date entire world is seriously influenced by an appalling illness called COVID sickness [Coronavirus disease-2019 (COVID-19)] which is brought about by another strain of coronavirus known as severe acute respiratory syndrome-Coronavirus-2. This pandemic was first seen in the Hubei area in Wuhan city of China. To date above 170 million individuals have been influenced by this infection and more than 3 million individuals died. The race of finding specific therapeutic drugs and efficacious vaccine candidates is still going on to tackle the pandemic-associated morbidities. This chapter discussed different clinically accessible medications (remdesivir, hydroxychloroquine, azithromycin, etc.) and immunizations (mRNA-1273, Sputanik, Pfizer, etc.) which are either in use or under trial for the treatment of COVID-19.
Article
Purpose: Coronavirus disease 2019 (COVID-19) is a recently declared worldwide pandemic. Triaging of patients into severe and non-severe could further help in targeted management. "Potential severe patients" is a category of patients who did not have severe symptoms at their initial diagnosis, but eventually progressed to be severe patients and are easily overlooked in the early stage. This work aimed to develop and evaluate a CT-based radiomics signature for the prediction of these potential severe COVID-19 patients. Methods: 150 COVID-19 patients were enrolled and randomly divided into cross-validation and independent test sets. First, Their clinical characteristics were screened using the univariate and multivariate logistic regression step by step. Then, radiomics features were extracted from the lesions on their chest CT images. Subsequently, the Inter- and intra-class correlation coefficients (ICC) analysis, minimum-redundancy maximum-relevance (mRMR) selection and the least absolute shrinkage and selection operator (LASSO) algorithm were used step by step for feature selection and construction of a radiomics signature. Finally, the screened clinical risk factors and constructed radiomics signature were combined for the Combined model and Radiomics+Clinics nomogram construction. The predictive performance of the Radiomics and Combined models were evaluated and compared using receiver operating characteristic curve (ROC) analysis, Hosmer-Lemeshow test and Delong test. Results: Clinical characteristics analysis resulted in the screening of five clinical risk factors. The combination of ICC, mRMR and LASSO methods resulted in the selection of ten radiomics features, which made up the radiomics signature. The differences in the radiomics signature between the potential severe and non-severe groups in cross-validation set and test sets were both p < 0.001. All Radiomics and Combined models showed a very good predictive performance with the accuracy and AUC of nearly or above 0.9. Additionally, we found no significant difference in the predictive performance between these two models. Conclusions: A CT-based radiomics signature for the prediction of potential severe COVID-19 patients was constructed and evaluated. Constructed Radiomics and Combined model showed good feasibility and accuracy. The Radiomics+Clinical nomogram, acted as a useful tool, may assist clinicians to better identify potential severe cases to target their management in the COVID-19 pandemic prevention and control. This article is protected by copyright. All rights reserved.
Chapter
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) is one of the worst human health problems faced by humanity in recent centuries. An end to this health crisis relies on our ability to monitor viral transmission dynamics to check spread, develop therapeutics and preventatives for treatment of SARS-CoV-2 infection and understand the pathophysiology of the disease for better management of the patients. Omics technologies have played a crucial part in understanding the different aspects of COVID-19 disease. While whole-genome sequencing of SARS-CoV-2 isolates from across the globe has aided in the development of molecular diagnostic assays and informed about the viral evolution, knowledge of structure and function of viral proteome fueled the development of small molecule and biologicals therapeutics as well as vaccines. Concurrently, metabolomic profiling of samples from COVID-19 patients experiencing a varying level of disease severity has provided a snapshot of the pathophysiology of the disease helping device effective treatment regimen. This chapter deals with genomic, proteomic, and metabolomic profiling of SRAS-CoV-2.
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In response to global efforts to control and exterminate infectious diseases, this study aims to provide insight into the productivity of remdesivir research and highlight future directions. To achieve this, there is a need to summarize and curate evidence from the literature. As a result, this study carried out comprehensive scientific research to detect trends in published articles related to remdesivir using a bibliometric analysis. Keywords associated with remdesivir were used to access pertinent published articles using the Scopus database. A total of 5321 research documents were retrieved, primarily as novel research articles (n = 2440; 46%). The number of publications increased exponentially from 2020 up to the present. The papers published by the top 12 institutions focusing on remdesivir accounted for 25.69% of the overall number of articles. The USA ranked as the most productive country, with 906 documents (37.1%), equivalent to one-third of the global publications in this field. The most productive institution was Icahn School of Medicine, Mount Sinai, in the USA (103 publications). The New England Journal of Medicine was the most cited, with an h-index of 13. The publication of research on remdesivir has gained momentum in the past year. The importance of remdesivir suggests that it needs continued research to help global health organizations detect areas requiring instant action to implement suitable measures. Furthermore, this study offers evolving hotspots and valuable insights into the scientific advances in this field and provides scaling-up analysis and evidence diffusion on remdesivir.
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Purpose This study aims to evaluate how brands communicate with consumers through the COVID-19 pandemic and how messaging has shifted over time. The authors identify a typology drawn from extant literature and use it to understand how brands shape consumers’ behavior. Design/methodology/approach Through a mix of interpretive and thematic analysis, the authors examine 858 US email advertisements and how these messages have evolved throughout the pandemic. Findings The authors findings demonstrate brand communication ranges from prosocial to brand messaging and brands employed different strategies at different phases of the pandemic. Specifically, while brands started out emphasizing socially desirable behavior before and directly after a national emergency was declared, COVID-19-related communications shifted to predominantly marketing-related messages later in the pandemic. Originality/value This study provides valuable insight into how brands adjust communication strategies through a prolonged cultural trauma and how these messages relate to authenticity, the triple bottom line and a social (versus branded) focus.
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Tüm dünyayı etkisi altına alan Covid-19 pandemisi, hem tanı almış hem de risk durumundaki bireylerde etkili ve kapsamlı bakım ve tedavi gerektirmektedir. Sağlık bakım sisteminin her basamağında yer alan ve Covid-19 pandemisinin etkili bir şekilde yürütülmesinde oldukça önemli rolü olan hemşirelerin hümanistik ve holistik bakış açısıyla bireylerin bakımını sağlamaları ve sürdürmeleri büyük önem taşımaktadır. Bu süreçte, hemşirelerin bakım uygulamalarına rehberlik edebilecek, yapılandırılmış zihinsel modellere dayanan klinik akıl yürütme ve karar verme becerilerini kullanabilecekleri hemşirelik sürecinde uygun rehberlerin ve sınıflama sistemlerinin kullanılması önerilmektedir. Bu derlemede, hemşirelerin Covid-19 tanılı bireylere bakım verirken, hemşirelik sürecinin hemşirelik tanısı belirleme ve planlama aşamalarında kullanabilecekleri rehberlere yer verilmesi amaçlanmaktadır.
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An efficient and enantioselective phosphonation protocol for construction of chiral α-aminophosphates and α-aminodiarylphosphine oxides has been developed based on chiral phosphoric acid-catalyzed dearomatization of isoquinolines. A series of chiral 1,2-dihydroisoquinolines...
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Since the summer of 2020, the rate of coronavirus cases in the United States has been higher in rural areas than in urban areas, raising concerns that patients with coronavirus disease 2019 (COVID-19) will overwhelm under-resourced rural hospitals. Using data from the University of Minnesota COVID-19 Hospitalization Tracking Project and the U.S. Department of Health and Human Services, we document disparities in COVID-19 hospitalization rates between rural and urban areas. We show that rural-urban differences in COVID-19 admission rates were minimal in the summer of 2020 but began to diverge in fall 2020. Rural areas had statistically higher hospitalization rates from September 2020 through early 2021, after which rural-urban admission rates re-converged. The insights in this article are relevant to policymakers as they consider the adequacy of hospital resources across rural and urban areas during the COVID-19 pandemic.
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This study explores the impact of the COVID-19 pandemic on telecommuting (working from home) and travel during the first year of the pandemic in the U.S.A. (from March 2020 to March 2021), with a particular focus on examining the variation in impact across different U.S. geographies. We divided 50 U.S. states into several clusters based on their geographic and telecommuting characteristics. Using K-means clustering, we identified four clusters comprising 6 small urban states, 8 large urban states, 18 urban–rural mixed states, and 17 rural states. Combining data from multiple sources, we observed that nearly one-third of the U.S. workforce worked from home during the pandemic, which was six times higher than the pre-pandemic period, and that these fractions varied across the clusters. More people worked from home in urban states compared with rural states. As well as telecommuting, we examined several activity travel trends across these clusters: reduction in the number of activity visits; changes in the number of trips and vehicle-miles traveled; and mode usage. Our analysis showed there was a greater reduction in the number of workplace and nonworkplace visits in urban states compared with rural states. The number of trips in all distance categories decreased except for long-distance trips, which increased during the summer and fall of 2020. The changes in overall mode usage frequency were similar across urban and rural states with a large drop in ride-hailing and transit use. This comprehensive study can provide a better understanding of the regional variation in the impact of the pandemic on telecommuting and travel, which can facilitate informed decision-making.
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Whether the stay-at-home order and face mask mandate are effective in slowing down the COVID-19 virus transmission is up for debate. To investigate this matter, we employ a unique angle. A two-wave logistic equation is proposed and then fitted to the cumulative case counts of all 50 states in the U.S. from the onset to early December of 2020 when vaccinating begins at large scale. The data period is confined to isolate the effects of executive orders from that of vaccination. The length of the first wave’s accelerating phase is regressed on variables describing the stay-at-home order and face mask mandate, along with control variables. A state’s lockdown duration is discovered to be negatively related to the time it takes for the virus to transit from accelerating to decelerating rates. This finding provides statistical support to the executive orders and can be useful in guiding risk management of future pandemics.
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Corona virus is causes respiratory infection which includes pneumonia, cold, sneezing and coughing and body temperature variation, digestion imbalance (diarrhea) and respiratory infection in humans. Corona virus transmitted human to human or human to animal via airborne droplets. Corona virus enters and affected in animals, some researchers have identified some specific types of cell in a nose that are the primary infection, and from mouth, sexually transmit contact through membrane and angiotensin converting enzyme-2(ACE)-2 exopeptidase receptor. WHO and European center for disease prevention and control (ECDC) advised to avoid public place and close contact to infected persons and pet animals. Initially, Corona virus (2019-nCoV) was isolated from Wuhan market China on 7 th Jan 2020. While the majority of cases result in mild symptoms, some progress to pneumonia and multiorgan failure. The death per number of diagnosed cases is estimated at between 1% and 5%, but varies by age and other health conditions. The infection is spread from one person to others via respiratory droplets, often produced during coughing and sneezing. It takes 2-14 days to develop symptoms from the day of exposure. Reverse transcription-polymerase chain reaction (RT-PCR) from a nasopharyngeal swab or oropharyngeal swab is the standard method of diagnosis. The infection can also be diagnosed from a combination of symptoms, risk factors, and a chest computed tomography scan showing features of pneumonia. Measures recommended to prevent the disease include frequent hand washing, maintaining distance from other people, and not touching one's face. The use of masks is recommended for those who are suspected to have the virus and to their caregivers, but not the general public. As of still, there is no vaccine or specific antiviral treatment for COVID-19; management involves treatment of symptoms, supportive care, and experimental measures. The World Health Organization declared the 2019-2020 CoV outbreak a pandemic and a Public Health Emergency of International Concern.
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creative commons attribution noncommercial License. Which allows others to remix, tweak, and build upon the work non commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Abstract Background: A novel corona virus (now known as
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Background and Objectives: Medical students are considered a high-risk group for COVID-19 anxiety due to their health and medical activities. The aim of this study was to determine the level of anxiety caused by the COVID-19 epidemic among medical students in rafsanjan. Materials and Methods: In this descriptive study, 400 students of Rafsanjan University of Medical Sciences were selected by regular stratified sampling and participated in the study. The data collection tool was a standard questionnaire. Data were analyzed using independent t-test, one-way analysis of variance, and non-parametric Kruskal-Wallis test. Results: 228 (57%) were girls and the rest were boys. 29% (116 people) had a history of corona. 62.3% (249 people) of family members or relatives of participants had a history of infection or death due to corona. 25.3% (101 people) of the participants were active in the field of corona control. The mean scores of anxiety and psychological and physical subscales were 12.97±8.03, 10.06±5.07, and 2.91±3.69, respectively. Conclusion: The results of the study indicated that there was anxiety among students. The reasons were more exposure to patients, contaminated work environment, wearing protective clothing and masks, and fear of contamination of oneself and family. Greater awareness of the disease, access to personal protective equipment, and vaccination are strategies that can be effective in reducing anxiety.
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The coronavirus pandemic of 2019 has already exerted an enormous impact. For over a year, the worldwide pandemic has ravaged the whole globe, with approximately 250 million verified human infection cases and a mortality rate surpassing 4 million. While the genetic makeup of the related pathogen (SARS-CoV-2) was identified, many unknown facets remain a mystery, comprising the virus's origin and evolutionary trend. There were many rumors that SARS-CoV-2 was human-borne and its evolution was predicted many years ago, but scientific investigation proved them wrong and concluded that bats might be the origin of SARS-CoV-2 and pangolins act as intermediary species to transmit the virus from bats to humans. Airborne droplets were found to be the leading cause of human-to-human transmission of this virus, but later studies showed that contaminated surfaces and other environmental factors are also involved in its transmission. The evolution of different SARS-CoV-2 variants worsens the condition and has become a challenge to overcome this pandemic. The emergence of COVID-19 is still a mystery, and scientists are unable to explain the exact origin of SARS-CoV-2. This review sheds light on the possible origin of SARS-CoV-2, its transmission, and the key factors that worsen the situation.
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This book, prepared by our faculty members byadding their current experiences during the pandemic process, is one of the leading scientific publications about the COVID-19 pandemic.
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The unprecedented worldwide spread of SARS-CoV-2 has imposed severe challenges on global health care systems. The roll-out and widespread administration of COVID-19 vaccines has been deemed a major milestone in the race to restrict the severity of the infection. Vaccines have as yet not entirely suppressed the relentless progression of the pandemic, due mainly to the emergence of new virus variants, and also secondary to the waning of protective antibody titers over time. Encouragingly, an increasing number of antiviral drugs, such as remdesivir and the newly developed drug combination, Paxlovid® (nirmatrelvir/ritonavir), as well as molnupiravir, have shown significant benefits for COVID-19 patient outcomes. Pre-exposure prophylaxis (PrEP) has been proven to be an effective preventive strategy in high-risk uninfected people exposed to HIV. Building on knowledge from what is already known about the use of PrEP for HIV disease, and from recently gleaned knowledge of antivirals used against COVID-19, we propose that SARS-CoV-2 PrEP, using specific antiviral and adjuvant drugs against SARS-CoV-2, may represent a novel preventive strategy for high-risk populations, including healthcare workers, immunodeficient individuals, and poor vaccine responders. Herein, we critically review the risk factors for severe COVID-19 and discuss PrEP strategies against SARS-CoV-2. In addition, we outline details of candidate anti-SARS-CoV-2 PrEP drugs, thus creating a framework with respect to the development of alternative and/or complementary strategies to prevent COVID-19, and contributing to the global armamentarium that has been developed to limit SARS-CoV-2 infection, severity, and transmission.
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Objectives To assess the economic and mental health impacts of COVID-19 in the presence of previous exposure to flooding events. Methods Starting in April 2018, the Texas Flood Registry (TFR) invited residents to complete an online survey regarding their experiences with Hurricane Harvey and subsequent flooding events. Starting in April 2020, participants nationwide were invited to complete a brief online survey on their experiences during the pandemic. This study includes participants in the TFR (N = 20,754) and the COVID-19 Registry (N = 8568) through October 2020 (joint N = 2929). Logistic regression and generalized estimating equations were used to examine the relationship between exposure to flooding events and the economic and mental health impacts of COVID-19. Results Among COVID-19 registrants, 21% experienced moderate to severe anxiety during the pandemic, and 7% and 12% of households had difficulty paying rent and bills, respectively. Approximately 17% of Black and 15% of Hispanic households had difficulty paying rent, compared to 5% of non-Hispanic white households. The odds of COVID-19 income loss are 1.20 (1.02, 1.40) times higher for those who previously had storm-related home damage compared to those who did not and 3.84 (3.25–4.55) times higher for those who experienced Harvey income loss compared to those who did not. For registrants for whom Harvey was a severe impact event, the odds of having more severe anxiety during the pandemic are 5.14 (4.02, 6.58) times higher than among registrants for whom Harvey was a no meaningful impact event. Conclusions Multiple crises can jointly and cumulatively shape health and wellbeing outcomes. This knowledge can help craft emergency preparation and intervention programs.
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Background . The ongoing pandemic of a new coronavirus infection (COVID-19) determines the relevance of the analysis of epidemiological patterns of SARS-CoV-2 spread among the population of the Russian Federation. Aim — study of the manifestations of the epidemic process of COVID-19 in the Russian Federation in 2020–2022. Materials and methods. A retrospective epidemiological analysis of the incidence of COVID-19 in the Russian Federation was carried out from 03/30/2020 to 04/24/2022. The data from the Rospotrebnadzor report No. 970 “Information on cases of infectious diseases in persons with suspected new coronavirus infection”, information portal Stopcoronavirus.rf, etc. were used. The presence of SARS-CoV-2 RNA was confirmed by real-time RT-PCR. Results and discussion. The analysis of the manifestations of the epidemic process of COVID-19 in the Russian Federation in 2020–2022 showed the presence of two stages which differed depending on the influence of the biological factor and the ongoing anti-epidemic measures. There was a pronounced trend in the development of the epidemic process, starting from megacities (Moscow, Moscow region and St. Petersburg), which are major transport hubs and centers of migration activity of the population, to the regions of the Russian Federation. The SARS-CoV-2 pathogenicity has been shown to decrease with each subsequent cycle of the rise in the incidence of COVID-19 against the background of the increased contagiousness of the virus. Conclusion. As a result of the study, risk areas (megacities) and risk groups were identified.
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December 2019, when the world was busy in welcoming New Year, unaware of the fact that the spark of COVID-19 has been ignited in Wuhan, China, will outbreak into wildfire to scorch the entire World. Nobody could have imagined that a single cell microorganism which even does not have any kind of cellular structure could be such a huge threat to human society. WHO and Public Health of Emergency of International Concern (PHEIC) declared COVID-19 as highly contagious within a month after reporting of the first case on January 11, 2020. As it started spreading across the globe, it was declared as a pandemic by WHO on March 12, 2020. Several scientists of government and nongovernment organizations started working toward the prevention and treatment of this novel disease. Its high rate of transmission, global spread, and high mortality rate started raising concerns worldwide. But as the disease was spreading at an extremely high rate through person-to-person contact, the main challenge was to develop fast and accurate diagnostic methods. Diagnostic tests during such pandemic are crucial as they help to evaluate the effectiveness of the prevention, treatment, and population-wise containment measures. This chapter discusses the various clinical methods that are currently being used worldwide to detect the presence of deadly Corona virus. The procedures of the tests are detailed and are compared based on their specificity, sensitivity, limit of detection (LOD), reliability, and affordability.
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Background The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely reuse PPE. Methylene blue (MB) is a light-activated dye with demonstrated antimicrobial activity used to sterilize blood plasma. Decontamination of respirators using photoactivated MB requires no specialized equipment, making it attractive for use in the field during outbreaks. Methods We examined decontamination of N95 and KN95 respirators using photoactivated MB and 3 variants of SARS-CoV-2, the virus that causes COVID-19; and 4 World Health Organization priority pathogens: Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Lassa virus. Virus inactivation by pretreating respirator material was also tested. Results Photoactivated MB inactivated all tested viruses on respirator material, albeit with varying efficiency. Virus applied to respirator material pre-treated with MB was also inactivated, thus MB pretreatment may potentially protect respirator wearers from virus exposure in real-time. Conclusions These results demonstrate that photoactivated MB represents a cost-effective, rapid, and widely deployable method to decontaminate N95 respirators for reuse during supply shortages.
Article
The gold-standard approach for diagnosing and confirming Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection is reverse transcription-polymerase chain reaction (RT-PCR). This method, however, is inefficient in detecting previous or dormant viral infections. The presence of antigen-specific antibodies is the fingerprint and cardinal sign for diagnosis and determination of exposure to infectious agents including Corona virus disease-2019 (COVID-19). This cross-sectional study examined the presence of SARS-CoV-2 spike-specific immunoglobulin G (IgG) among asymptomatic blood donors in Makkah region. A total of 4368 asymptomatic blood donors were enrolled. They were screened for spike-specific IgG using ELISA and COVID-19 RNA by real-time PCR. COVID-19 IgG was detected among 2248 subjects (51.5%) while COVID-19-RNA was detected among 473 (10.8%) subjects. The IgG frequency was significantly higher among males and non-Saudi residents (p < 0.001 each) with no significant variation in IgG positivity among blood donors with different blood groups. In addition, COVID-19 RNA frequency was significantly higher among donors below 40-years old (p = 0.047, χ2 = 3.95), and non-Saudi residents (p = 0.001, χ2 = 304.5). The COVID-19 IgG levels were significantly higher among the RNA-positive donors (p = 001), and non-Saudi residents (p = 0.041), with no variations with age or blood group (p > 0.05). This study reveals a very high prevalence of COVID-19 IgG and RNA among asymptomatic blood donors in Makkah, Saudi Arabia indicating a high exposure rate of the general population to COVID-19; particularly foreign residents. It sheds light on the spread on COVID-19 among apparently healthy individuals at the beginning of the pandemic and could help in designing various control measures to minimize viral spread.
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Introduction During the COVID-19 pandemic, health care shifted to virtual interactions with health professionals. The aim of this study was to examine the determinants of telehealth use in a nationally representative sample of the United States adult population. Methods The study used data from the 2020 National Health Interview Survey of 17,582 respondents aged ≥18. Andersen’s model of health services utilization was employed to examine predisposing, enabling, and needs factors associated with past-year telehealth use. Multivariable logistic regression was conducted to examine statistical associations. Results 32.5% of adults ( n = 6402; mean age 51.6, SE = 0.4) reported telehealth use. Predisposing factors: Women and married/partnered adults and those with higher levels of education had greater odds of using telehealth. Adults living in Midwest and South and adults living in medium-small and non-metropolitan areas had decreased odds of using telehealth. Enabling factors: Income and having a usual source of care were positively associated with telehealth use. A negative association was found for those with no insurance and telehealth use, whereas a positive association was found for military insurance. Needs factors: Odds of using telehealth were increased for adults who had well-visits and ER visits in the past 12 months. Mental health services quadrupled the odds of telehealth use. Odds of using telehealth increased with each additional chronic disease, including COVID-19. Conclusion There are disparities in telehealth use according to sex, education, rurality, access to care, and health needs. Tackling these disparities is pivotal to ensure barriers to telehealth use are not exacerbated post-pandemic.
Article
Objective To compare mortality trends in patients requiring Extracorporeal Membrane Oxygenation (ECMO) support between the first quarters of 2019 and 2020 and determine whether these trends might have predicted the severe acute respiratory syndrome coronavirus-2 (SARS)-Cov-2 pandemic in the United States. Methods We analyzed 5% Medicare claims data at aggregate, state, hospital, and encounter levels using MS-DRG (Medicare Severity-Diagnosis Related Group) codes for ECMO, combining state-level data with national census data. Necessity and sufficiency relations associated with change in mortality between the 2 years were modeled using qualitative comparative analysis (QCA). Multilevel, generalized linear modeling was used to evaluate mortality trends. Results Based on state-level data, there was a 3.36% increase in mortality between 2019 and 2020. Necessity and sufficiency evaluation of aggregate data at state and institutional levels did not identify any association or combinations of risk factors associated with this increase in mortality. However, multilevel and generalized linear models using disaggregated patient-level data to evaluate institution mortality and patient death, identified statistically significant differences between the first ( p = .019) and second ( p = .02) months of the 2 years, the first and second quarters ( p < .001 and p = .042, respectively), and the first 6 months ( p < .001) of 2019 and 2020. Conclusion Mortality in ECMO patients increased significantly during the first quarter of 2020 and may have served as an early warning of the SARS-Cov-2 pandemic. Granular data shared in real-time may be used to better predict public health threats.
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In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
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Background: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections. Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.
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Background: Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. Methods: We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. Results: A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. Conclusions: Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.).
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Background Recent outbreaks of Ebola virus disease in the Democratic Republic of the Congo (DRC) reinforce the desperate need to establish definitively the comparative safety and efficacy of different medical countermeasures (MCM). Methods Through a multipartner governance framework under WHO coordination, the Institut National de Recherche Biomédicale and NIAID collaborated with clinical partners (the MOH, ALIMA, MSF) to launch a randomized controlled trial in 2018 in the North Kivu/Ituri provinces of DRC. PCR+ participants receiving enhanced supportive care are being randomized 1:1:1:1 to receive either ZMapp™ (control arm), remdesivir, mAb114, or REG-EB3 according to standard treatment regimens. Stratification is by site, country, and baseline nucleoprotein (NP) PCR cycle threshold (CT) ≤ 22 or > 22. The primary objective is a comparison of 28-day mortality relative to the control arm. The planned accrual is for 125 patients per arm. Secondary objectives include an evaluation of the comparative safety and tolerability of the 4 investigational MCMs, relative changes in viral load over time, comparisons of treatment efficacy according to baseline risk categories, 58-day mortality, RNA clearance from semen, and an assessment of the validity of drug-class comparisons, including efficacy. The study is monitored by an independent data and safety monitoring committee (DSMB). Results Enrollment commenced in the Ebola Treatment Unit in Beni in November, 2018, with sites in Butembo and Katwa added in early 2019. Time from study concept initiation to study start was only 3.5 months. Ongoing hurdles encountered to date include maintenance of cold chain requirements for the MCMs and marked volatility in the security situation surrounding sites affecting staff and patient safety. Despite these challenges, data quality and completed follow-up have been remarkably high and by mid-April, 2019, accrual to date (see table) had already surpassed the predefined threshold triggering an interim DSMB review. Conclusion Scientifically rigorous and ethically sound clinical research can take place during disease outbreaks even within a conflict zone. Results about the relative efficacy of the evaluated investigational MCMs are pending the completion of the trial. Disclosures All Authors: No reported Disclosures.
Article
Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.
Centers for Disease Control and Prevention
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