| Title | Venue | Year | Impact | Source |
3651 | Do not violate the International Health Regulations during the COVID-19 outbreak | Lancet | 2020 | | LitCov and CORD-19 |
3652 | Care of the pregnant woman with COVID-19 in labor and delivery: anesthesia, emergency cesarean delivery, differential diagnosis in the acutely ill parturient, care of the newborn, and protection of the healthcare personnel COVID-19 in pregnancy can cause severe maternal morbidity in up to 9% of affected gravidae. Chest imaging is helpful in pregnant women who have a high pretest probability of COVID-19, but are RT-PCR negative. Vertical transmission is unlikely, but active measures are needed to prevent neonatal infection. We present an algorithm of care for the acutely ill parturient. We present a protocol for intrapartum care of the pregnant woman in labor. | Am J Obstet Gynecol | 2020 | | LitCov and CORD-19 |
3653 | Ongoing Clinical Trials for the Management of the COVID-19 Pandemic COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response. | Trends Pharmacol Sci | 2020 | | LitCov and CORD-19 |
3654 | The Role of Zinc in Antiviral Immunity Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types, representing an integral component of approximately 10% of the human proteome, and encompassing hundreds of key enzymes and transcription factors. Zinc deficiency is strikingly common, affecting up to a quarter of the population in developing countries, but also affecting distinct populations in the developed world as a result of lifestyle, age, and disease-mediated factors. Consequently, zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections such as HIV or hepatitis C virus. This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings; however, there remains much to be learned regarding the antiviral mechanisms and clinical benefit of zinc supplementation as a preventative and therapeutic treatment for viral infections. | Adv Nutr | 2019 | | CORD-19 |
3655 | Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results IMPORTANCE: Vitamin D treatment has been found to decrease the incidence of viral respiratory tract infection, especially in patients with vitamin D deficiency. Whether vitamin D is associated with coronavirus disease 2019 (COVID-19) incidence is unknown. OBJECTIVE: To examine whether the last vitamin D status before COVID-19 testing is associated with COVID-19 test results. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study at an urban academic medical center included patients with a 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol level measured within 1 year before being tested for COVID-19 from March 3 to April 10, 2020. EXPOSURES: Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL or 1,25-dihydroxycholecalciferol less than 18 pg/mL before COVID-19 testing. Treatment changes were defined by changes in vitamin D type and dose between the date of the last vitamin D level measurement and the date of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize the most recent vitamin D status before COVID-19 testing as likely deficient (last level deficient and treatment not increased), likely sufficient (last level not deficient and treatment not decreased), and 2 groups with uncertain deficiency (last level deficient and treatment increased, and last level not deficient and treatment decreased). MAIN OUTCOMES AND MEASURES: The outcome was a positive COVID-19 polymerase chain reaction test result. Multivariable analysis tested whether vitamin D status before COVID-19 testing was associated with testing positive for COVID-19, controlling for demographic and comorbidity indicators. RESULTS: A total of 489 patients (mean [SD] age, 49.2 [18.4] years; 366 [75%] women; and 331 [68%] race other than White) had a vitamin D level measured in the year before COVID-19 testing. Vitamin D status before COVID-19 testing was categorized as likely deficient for 124 participants (25%), likely sufficient for 287 (59%), and uncertain for 78 (16%). Overall, 71 participants (15%) tested positive for COVID-19. In multivariate analysis, testing positive for COVID-19 was associated with increasing age up to age 50 years (relative risk, 1.06; 95% CI, 1.01-1.09; P = .02); non-White race (relative risk, 2.54; 95% CI, 1.26-5.12; P = .009), and likely deficient vitamin D status (relative risk, 1.77; 95% CI, 1.12-2.81; P = .02) compared with likely sufficient vitamin D status. Predicted COVID-19 rates in the deficient group were 21.6% (95% CI, 14.0%-29.2%) vs 12.2%(95% CI, 8.9%-15.4%) in the sufficient group. CONCLUSIONS AND RELEVANCE: In this single-center, retrospective cohort study, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that suggests that randomized trials may be needed to determine whether vitamin D affects COVID-19 risk. | JAMA Netw Open | 2020 | | LitCov and CORD-19 |
3656 | Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection N/A | JAMA | 2020 | | LitCov and CORD-19 |
3657 | Chest CT Features of COVID-19 in Rome, Italy BACKGROUND: The standard for diagnosis of SARS-CoV-2 virus is reverse transcription polymerase chain reaction (RT-PCR) test, but chest CT may play a complimentary role in the early detection of COVID-19 pneumonia. PURPOSE: To investigate CT features of patients with COVID-19 in Rome, Italy, and to compare the accuracy of CT with RT-PCR. METHODS: In this prospective study from March 4, 2020, until March 19, 2020, consecutive patients with suspected COVID-19 infection and respiratory symptoms were enrolled. Exclusion criteria were: chest CT with contrast medium performed for vascular indications, patients who refused chest CT or hospitalization, and severe CT motion artifact. All patients underwent RT-PCR and chest CT. Diagnostic performance of CT was calculated using RT-PCR as reference. Chest CT features were calculated in a subgroup of RT-PCR-positive and CT-positive patients. CT features of hospitalized patients and patient in home isolation were compared by using Pearson chi squared test. RESULTS: Our study population comprised 158 consecutive study participants (83 male and 75 female, mean age 57 y ±17). Fever was observed in 97/158 (61%), cough in 88/158 (56%), dyspnea in 52/158 (33%), lymphocytopenia in 95/158 (60%), increased C-reactive protein level in 139/158 (88%), and elevated lactate dehydrogenase in 128/158 (81%) study participants. Sensitivity, specificity, and accuracy of CT were 97% (60/62)[95% IC, 88-99%], 56% (54/96)[95% IC,45-66%] and 72% (114/158)[95% IC 64-78%], respectively. In the subgroup of RT-PCR-positive and CT-positive patients, ground-glass opacities (GGO) were present in 58/58 (100%), multilobe and posterior involvement were both present in 54/58 (93%), bilateral pneumonia in 53/58 (91%), and subsegmental vessel enlargement (> 3 mm) in 52/58 (89%) of study participants. CONCLUSION: The typical pattern of COVID-19 pneumonia in Rome, Italy, was peripherally ground-glass opacities with multilobe and posterior involvement, bilateral distribution, and subsegmental vessel enlargement (> 3 mm). Chest CT sensitivity was high (97%) but with lower specificity (56%). | Radiology | 2020 | | LitCov and CORD-19 |
3658 | Impact of Online Information on Self-Isolation Intention During the COVID-19 Pandemic: Cross-Sectional Study BACKGROUND: During the coronavirus disease (COVID-19) pandemic, governments issued movement restrictions and placed areas into quarantine to combat the spread of the disease. In addition, individuals were encouraged to adopt personal health measures such as social isolation. Information regarding the disease and recommended avoidance measures were distributed through a variety of channels including social media, news websites, and emails. Previous research suggests that the vast amount of available information can be confusing, potentially resulting in overconcern and information overload. OBJECTIVE: This study investigates the impact of online information on the individual-level intention to voluntarily self-isolate during the pandemic. Using the protection-motivation theory as a framework, we propose a model outlining the effects of cyberchondria and information overload on individuals’ perceptions and motivations. METHODS: To test the proposed model, we collected data with an online survey (N=225) and analyzed it using partial least square-structural equation modeling. The effects of social media and living situation were tested through multigroup analysis. RESULTS: Cyberchondria and information overload had a significant impact on individuals’ threat and coping perceptions, and through them on self-isolation intention. Among the appraisal constructs, perceived severity (P=.002) and self-efficacy (P=.003) positively impacted self-isolation intention, while response cost (P<.001) affected the intention negatively. Cyberchondria (P=.003) and information overload (P=.003) indirectly affected self-isolation intention through the aforementioned perceptions. Using social media as an information source increased both cyberchondria and information overload. No differences in perceptions were found between people living alone and those living with their families. CONCLUSIONS: During COVID-19, frequent use of social media contributed to information overload and overconcern among individuals. To boost individuals’ motivation to adopt preventive measures such as self-isolation, actions should focus on lowering individuals’ perceived response costs in addition to informing them about the severity of the situation. | J Med Internet Res | 2020 | | LitCov and CORD-19 |
3659 | Discriminating self from non-self in nucleic acid sensing Innate immunity against pathogens relies on an array of immune receptors to detect molecular patterns that are characteristic of the pathogens, including receptors that are specialized in the detection of foreign nucleic acids. In vertebrates, nucleic acid sensing is the dominant antiviral defence pathway. Stimulation of nucleic acid receptors results in antiviral immune responses with the production of type I interferon (IFN), as well as the expression of IFN-stimulated genes, which encode molecules such as cell-autonomous antiviral effector proteins. This Review summarizes the tremendous progress that has been made in understanding how this sophisticated immune sensory system discriminates self from non-self nucleic acids in order to reliably detect pathogenic viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri.2016.78) contains supplementary material, which is available to authorized users. | Nat Rev Immunol | 2016 | | CORD-19 |
3660 | Deciphering the impact of COVID-19 pandemic on food security, agriculture and livelihoods: A review of the evidence from developing countries With COVID-19 now spreading in developing countries, massive consequences on health and livelihoods are feared. Food security is the most important and crucial aspect of sustainable development. The agricultural sector forms the backbone of the economy and provides livelihood to a large section in developing countries. Therefore, the disruption in food security and the agricultural sector will have far-reaching impacts on these countries. Owing to the importance of these sectors, this paper performs a comprehensive assessment of the effect of COVID-19 on food security and agriculture. The research suggests coping and mitigation mechanisms that can be adopted to sustain livelihoods. | Curr Res Environ Sustain | 2020 | | LitCov and CORD-19 |
3661 | Obesity aggravates COVID-19: A systematic review and meta-analysis OBJECTIVE: Obesity and COVID‐19 are both world epidemics now. There may be some potential relationships between them, but we knew little. This work was to explore the relationship through literature searching, systematic review, and meta‐analysis. METHODS: Pubmed, Embase, WOS, Cochrane, CNKI, Wanfang, and Sinomed databases were searched to collect the literature concerning obesity and COVID‐19. Systematic review and meta‐analysis were conducted after literature screening, quality assessment, and data extraction. RESULTS: 180 articles were initially searched after duplicate removal and 9 were finally included in our analysis. Results show that severe COVID‐19 patients have higher BMI than non‐severe ones(WMD =2.67, 95%CI[1.52‐3.82]); COVID‐19 patients with obesity were more severe and have a worse outcome than those without(OR=2.31, 95%CI[1.3‐4.12]). CONCLUSION: Obesity may aggravate COVID‐19. This article is protected by copyright. All rights reserved. | J Med Virol | 2020 | | LitCov and CORD-19 |
3662 | Repurposing of clinically approved drugs for treatment of COVID-19 in a 2019-novel coronavirus-related coronavirus model BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC(50)] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10(−4)vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37 t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10(−4)vs. 1.00 ± 0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted. | Chin Med J (Engl) | 2020 | | LitCov and CORD-19 |
3663 | Antiviral Natural Products and Herbal Medicines ABSTRACT Viral infections play an important role in human diseases, and recent outbreaks in the advent of globalization and ease of travel have underscored their prevention as a critical issue in safeguarding public health. Despite the progress made in immunization and drug development, many viruses lack preventive vaccines and efficient antiviral therapies, which are often beset by the generation of viral escape mutants. Thus, identifying novel antiviral drugs is of critical importance and natural products are an excellent source for such discoveries. In this mini-review, we summarize the antiviral effects reported for several natural products and herbal medicines. | J Tradit Complement Med | 2014 | | CORD-19 |
3664 | Unveiling the roles of autophagy in innate and adaptive immunity Cells digest portions of their interiors in a process known as autophagy to recycle nutrients, remodel and dispose of unwanted cytoplasmic constituents. This ancient pathway, conserved from yeast to humans, is now emerging as a central player in the immunological control of bacterial, parasitic and viral infections. The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. This Review describes the mechanisms of autophagy and highlights recent advances relevant to the role of autophagy in innate and adaptive immunity. | Nat Rev Immunol | 2007 | | CORD-19 |
3665 | A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) coronavirus is a major public health challenge. Rapid tests for detecting existing SARS-CoV-2 infections and assessing virus spread are critical. Approaches to detect viral RNA based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) have potential as simple, scalable, and broadly applicable testing methods. Compared to RT quantitative polymerase chain reaction (RT-qPCR)–based methods, RT-LAMP assays require incubation at a constant temperature, thus eliminating the need for sophisticated instrumentation. Here, we tested a two-color RT-LAMP assay protocol for detecting SARS-CoV-2 viral RNA using a primer set specific for the N gene. We tested our RT-LAMP assay on surplus RNA samples isolated from 768 pharyngeal swab specimens collected from individuals being tested for COVID-19. We determined the sensitivity and specificity of the RT-LAMP assay for detecting SARS-CoV-2 viral RNA. Compared to an RT-qPCR assay using a sensitive primer set, we found that the RT-LAMP assay reliably detected SARS-CoV-2 RNA with an RT-qPCR cycle threshold (CT) number of up to 30, with a sensitivity of 97.5% and a specificity of 99.7%. We also developed a swab–to–RT-LAMP assay that did not require a prior RNA isolation step, which retained excellent specificity (99.5%) but showed lower sensitivity (86% for CT < 30) than the RT-LAMP assay. In addition, we developed a multiplexed sequencing protocol (LAMP-sequencing) as a diagnostic validation procedure to detect and record the outcome of RT-LAMP reactions. | Sci Transl Med | 2020 | | LitCov and CORD-19 |
3666 | Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care. | Proc Natl Acad Sci U S A | 2020 | | LitCov and CORD-19 |
3667 | COVID-19: Coagulopathy, Risk of Thrombosis and the Rationale for Anticoagulation The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19. | Clin Appl Thromb Hemost | 2020 | | LitCov and CORD-19 |
3668 | Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials N/A | JAMA | 2012 | | CORD-19 |
3669 | Benchmarking atlas-level data integration in single-cell genomics Single-cell atlases often include samples that span locations, laboratories and conditions, leading to complex, nested batch effects in data. Thus, joint analysis of atlas datasets requires reliable data integration. To guide integration method choice, we benchmarked 68 method and preprocessing combinations on 85 batches of gene expression, chromatin accessibility and simulation data from 23 publications, altogether representing >1.2 million cells distributed in 13 atlas-level integration tasks. We evaluated methods according to scalability, usability and their ability to remove batch effects while retaining biological variation using 14 evaluation metrics. We show that highly variable gene selection improves the performance of data integration methods, whereas scaling pushes methods to prioritize batch removal over conservation of biological variation. Overall, scANVI, Scanorama, scVI and scGen perform well, particularly on complex integration tasks, while single-cell ATAC-sequencing integration performance is strongly affected by choice of feature space. Our freely available Python module and benchmarking pipeline can identify optimal data integration methods for new data, benchmark new methods and improve method development. | Nat Methods | 2021 | | CORD-19 |
3670 | COVID-19: too little, too late? | Lancet | 2020 | | LitCov and CORD-19 |
3671 | Impact of SARS-CoV-2 on the mental health of healthcare professionals: a systematic review N/A | Rev Esp Salud Publica | 2020 | | LitCov and CORD-19 |
3672 | The benefits of meditation and mindfulness practices during times of crisis such as COVID-19 Meditation and mindfulness are practices that can support healthcare professionals, patients, carers and the general public during times of crisis such as the current global pandemic caused by COVID-19. While there are many forms of meditation and mindfulness, of particular interest to healthcare professionals are those with an evidence base such as mindfulness-based stress reduction (MBSR). Systematic reviews of such practices have shown improvements in measures of anxiety, depression and pain scores. Structural and functional brain changes have been demonstrated in the brains of people with a long-term traditional meditation practice, and in people who have completed a MBSR programme. Mindfulness and meditation practices translate well to different populations across the lifespan and range of ability. Introducing a mindfulness and meditation practice during this pandemic has the potential to complement treatment and is a low-cost beneficial method of providing support with anxiety for all. | Ir J Psychol Med | 2020 | | LitCov and CORD-19 |
3673 | Loneliness and Mental Health During the COVID-19 Pandemic: A Study Among Dutch Older Adults OBJECTIVES: With the spread of COVID-19, the Netherlands implemented a policy to keep citizens physically distanced. We hypothesize that consequent reduction in the frequency of social contacts, personal losses and the experience of general threats in society reduced well-being. METHODS: Data were collected from 1,679 Dutch community-dwelling participants aged 65 to 102 years old comprising a longitudinal online panel. Social and emotional loneliness and mental health were measured in May 2020, i.e., two months after the implementation of the measures, and earlier in October and November 2019. RESULTS: In this pandemic, not only loneliness of older people increased, but mental health remained roughly stable. The policy measures for physical distancing did not cause much social isolation but personal losses, worries about the pandemic, and a decline in trust in societal institutions were associated with increased mental health problems and especially emotional loneliness. DISCUSSION: The consequences of long-term social isolation and well-being must be closely monitored. | J Gerontol B Psychol Sci Soc S | 2020 | | LitCov and CORD-19 |
3674 | COVID-19 can present with a rash and be mistaken for dengue | J Am Acad Dermatol | 2020 | | LitCov and CORD-19 |
3675 | Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2 The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19. | Viruses | 2020 | | LitCov and CORD-19 |
3676 | COVID-19 and Beyond: Micropractices for Burnout Prevention and Emotional Wellness | J Am Coll Radiol | 2020 | | LitCov and CORD-19 |
3677 | Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings PURPOSE: To investigate the epidemiological and clinical characteristics of COVID-19 patients with abnormal imaging findings. METHODS: Patients confirmed with SARS-CoV-2 infection in Zhejiang province from January 17 to February 8 who had undergone CT or X-ray were enrolled. Epidemiological and clinical data were analyzed among those with abnormal or normal imaging findings. RESULTS: Excluding 72 patients with normal images, 230 of 573 patients showed abnormalities affecting more than two lung lobes. The median radiographic score was 2.0, and there was a negative correlation between that score and the oxygenation index (ρ = −0.657, P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with a higher rate of coexisting condition (28.8%), a lower rate of exposure history, and longer time between onset and confirmation (5 days) than non-pneumonia patients (all P < 0.05). A higher rate of fever, cough, expectoration and headache, a lower level of lymphocytes, albumin, and serum sodium levels and a higher total bilirubin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels and a lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels, and higher serum creatinine and radiographic score at admission were predictive factors for the severe/critical subtype. CONCLUSION: Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiographic scores can effectively predict severe/critical types. | Int J Infect Dis | 2020 | | LitCov and CORD-19 |
3678 | 2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation INTRODUCTION: Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. OBJECTIVE: We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). RESULTS: Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. CONCLUSIONS: Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment. | Int J Infect Dis | 2020 | | LitCov and CORD-19 |
3679 | Interfering with disease: a progress report on siRNA-based therapeutics RNA interference (RNAi) quietly crept into biological research in the 1990s when unexpected gene-silencing phenomena in plants and flatworms first perplexed scientists. Following the demonstration of RNAi in mammalian cells in 2001, it was quickly realized that this highly specific mechanism of sequence-specific gene silencing might be harnessed to develop a new class of drugs that interfere with disease-causing or disease-promoting genes. Here we discuss the considerations that go into developing RNAi-based therapeutics starting from in vitro lead design and identification, to in vivo pre-clinical drug delivery and testing. We conclude by reviewing the latest clinical experience with RNAi therapeutics. | Nat Rev Drug Discov | 2007 | | CORD-19 |
3680 | India under COVID-19 lockdown | Lancet | 2020 | | LitCov and CORD-19 |
3681 | Labor and delivery guidance for COVID-19 This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19–positive woman, as well as the critically ill COVID-19–positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19–positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19–positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities. | Am J Obstet Gynecol MFM | 2020 | | LitCov and CORD-19 |
3682 | Strategies and Solutions for Team Sports Athletes in Isolation due to COVID-19 In December of 2019, there was an outbreak of a severe acute respiratory syndrome caused by the Coronavirus 2 (SARS-CoV-2 or COVID-19) in China. The virus rapidly spread into the whole World causing an unprecedented pandemic and forcing governments to impose a global quarantine, entering an extreme unknown situation. The organizational consequences of quarantine/isolation are: absence of organized training and competition, lack of communication among athletes and coaches, inability to move freely, lack of adequate sunlight exposure, inappropriate training conditions. Based on the current scientific, we strongly recommend encouraging the athlete to reset their mindset to understand quarantine as an opportunity for development, organizing appropriate guidance, educating and encourage athletes to apply appropriate preventive behavior and hygiene measures to promote immunity and ensuring good living isolation conditions. The athlete’s living space should be equipped with cardio and resistance training equipment (portable bicycle or rowing ergometer). Some forms of body mass resistance circuit-based training could promote aerobic adaptation. Sports skills training should be organized based on the athlete’s needs. Personalized conditioning training should be carried out with emphasis on neuromuscular performance. Athletes should also be educated about nutrition (Vitamin D and proteins) and hydration. Strategies should be developed to control body composition. Mental fatigue should be anticipated and mental controlled. Adequate methods of recovery should be provided. Daily monitoring should be established. This is an ideal situation in which to rethink personal life, understanding the situation, that can be promoted in these difficult times that affect practically the whole world. | Sports (Basel) | 2020 | | LitCov and CORD-19 |
3683 | Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19 The new coronavirus, classified as SARS-CoV-2 that emerged in Hubei province in China, causes a new coronavirus disease, which was termed COVID-19 by WHO on February 11, 2020. COVID-19 claimed almost 19000 lives around the world by March 25, 2020. | Acta Physiol (Oxf) | 2020 | | LitCov and CORD-19 |
3684 | Incidence, co-occurrence and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19 BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity. | PLoS Med | 2021 | | LitCov and CORD-19 |
3685 | Hydroxychloroquine and COVID-19 N/A | Postgrad Med J | 2020 | | LitCov and CORD-19 |
3686 | Clinical Characteristics of Children with COVID-19 in Hubei, China Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment. | Curr Med Sci | 2020 | | LitCov and CORD-19 |
3687 | How COVID-19 induces cytokine storm with high mortality The newly emerging coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, but has rapidly spread all over the world. Some COVID-19 patients encounter a severe symptom of acute respiratory distress syndrome (ARDS) with high mortality. This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells. We hypothesize that IL-6-STAT3 signaling is a promising therapeutic target for the cytokine storm in COVID-19, because IL-6 is a major STAT3 stimulator, particularly during inflammation. We herein review the pathogenic mechanism and potential therapeutic targets of ARDS in COVID-19 patients. | Inflamm Regen | 2020 | | LitCov and CORD-19 |
3688 | Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is commonly diagnosed by reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA in patient samples, but RNA extraction constitutes a major bottleneck in current testing. Methodological simplification could increase diagnostic availability and efficiency, benefitting patient care and infection control. Here, we describe methods circumventing RNA extraction in COVID-19 testing by performing RT-PCR directly on heat-inactivated or lysed samples. Our data, including benchmarking using 597 clinical patient samples and a standardised diagnostic system, demonstrate that direct RT-PCR is viable option to extraction-based tests. Using controlled amounts of active SARS-CoV-2, we confirm effectiveness of heat inactivation by plaque assay and evaluate various generic buffers as transport medium for direct RT-PCR. Significant savings in time and cost are achieved through RNA-extraction-free protocols that are directly compatible with established PCR-based testing pipelines. This could aid expansion of COVID-19 testing. | Nat Commun | 2020 | | LitCov and CORD-19 |
3689 | Social Media and Emergency Preparedness in Response to Novel Coronavirus N/A | JAMA | 2020 | | LitCov and CORD-19 |
3690 | TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection Transmembrane serine protease TMPRSS2 activates the spike protein of highly pathogenic human coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). In vitro, activation induces virus-cell membrane fusion at the cell surface. However, the roles of TMPRSS2 during coronavirus infection in vivo are unclear. Here, we used animal models of SARS-CoV and MERS-CoV infection to investigate the role of TMPRSS2. Th1-prone C57BL/6 mice and TMPRSS2-knockout (KO) mice were used for SARS-CoV infection, and transgenic mice expressing the human MERS-CoV receptor DPP4 (hDPP4-Tg mice) and TMPRSS2-KO hDPP4-Tg mice were used for MERS-CoV infection. After experimental infection, TMPRSS2-deficient mouse strains showed reduced body weight loss and viral kinetics in the lungs. Lack of TMPRSS2 affected the primary sites of infection and virus spread within the airway, accompanied by less severe immunopathology. However, TMPRSS2-KO mice showed weakened inflammatory chemokine and/or cytokine responses to intranasal stimulation with poly(I·C), a Toll-like receptor 3 agonist. In conclusion, TMPRSS2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology. IMPORTANCE Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type 2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy. | J Virol | 2019 | | CORD-19 |
3691 | Transmission cycles, host range, evolution and emergence of arboviral disease Many pandemics have been attributed to the ability of some RNA viruses to change their host range to include humans. Here, we review the mechanisms of disease emergence that are related to the host-range specificity of selected mosquito-borne alphaviruses and flaviviruses. We discuss viruses of medical importance, including Venezuelan equine and Japanese encephalitis viruses, dengue viruses and West Nile viruses. | Nat Rev Microbiol | 2004 | | CORD-19 |
3692 | Anxiety, depression, stress, fear and social support during COVID-19 pandemic among Jordanian healthcare workers The emergence of Coronavirus disease 2019 (COVID-19) has affected health-care workers’ psychological and mental health. Few studies have been conducted examining the psychological effect of COVID-19 on health-care worker psychological health in Jordan. Therefore, the present study aims to assess the respective levels of fear, anxiety, depression, stress, social support, and the associated factors, experienced by Jordanian health-care workers during the COVID-19 Pandemic. This study adopted a cross-sectional, correlational design to collect data from 365 health-care workers in Amman, Jordan, from August 16th to 23rd, 2020. Along with collecting sociodemographic characteristics, the Fear of COVID-19 Scale, the Depression, Anxiety, Stress Scale, and the Multidimensional Scale of Perceived Social Support electronically administered to participants. The majority of the participants (69.3%) were registered nurses. The mean overall score for the Fear of COVID-19 scale was 23.64 (SD + 6.85) which again exceeded the mid-point for the total score range (21), indicating elevated level fear of the COVID-19 pandemic. Participants had displayed extremely severe depression 40%, extremely severe anxiety 60%, and 35% severely distressed. Scores for depression (21.30 ± 10.86), anxiety (20.37 ± 10.80), stress (23.33 ± 10.87) were also high. Factors determined to be associated with psychological distress were being male, married, aged 40 years and older, and having more clinical experience. Assessment of social support indicated moderate-to-high levels of perceived support for all dimensions (significant other: 5.17 ± 1.28, family: 5.03 ± 1.30, friends: 5.05 ± 1.30). Weak significant correlations were found between social support and the other study variables (r < 0.22), indicating a weak association with fear, depression, anxiety, and stress, respectively. Overall, Jordanian health-care workers sample reported fear, depression, anxiety, and stress. The associated factors were being male, married, aged 40 years and older, and having more clinical experience. Regarding social support, participants primarily relied on support from their families, followed by support from friends. | PLoS One | 2021 | | LitCov and CORD-19 |
3693 | Well-being of Parents and Children During the COVID-19 Pandemic: A National Survey N/A | Pediatrics | 2020 | | LitCov and CORD-19 |
3694 | COVID-19 pandemic and prospects for recovery of the global aviation industry N/A | J Air Transp Manag | 2021 | | LitCov and CORD-19 |
3695 | Post-COVID-19 Syndrome and the Potential Benefits of Exercise The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19. | Int J Environ Res Public Healt | 2021 | | LitCov and CORD-19 |
3696 | Family-Centered Care During the COVID-19 Era Abstract Family support is more, not less, important during crisis. However, during the COVID-19 pandemic, maintaining public safety necessitates restricting the physical presence of families for hospitalized patients. In response, health systems must rapidly adapt family-centric procedures and tools to circumvent restrictions on physical presence. Strategies for maintaining family integrity must acknowledge clinicians’ limited time and attention to devote to learning new skills. Internet-based solutions can facilitate the routine, predictable, and structured communication which is central to family-centered care. But the reliance on technology may compromise patient privacy and exacerbate racial, socioeconomic, and geographic disparities for populations that lack access to reliable internet access, devices or technological literacy. We provide a toolbox of strategies for supporting family-centered inpatient care during physical distancing responsive to the current clinical climate. Innovations in the implementation of family involvement during hospitalizations may lead to long-term progress in the delivery of family-centered care. | J Pain Symptom Manage | 2020 | | LitCov and CORD-19 |
3697 | Comparison of the characteristics, morbidity and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study BACKGROUND: To date, influenza epidemics have been considered suitable for use as a model for the COVID-19 epidemic, given that they are respiratory diseases with similar modes of transmission. However, data directly comparing the two diseases are scarce. METHODS: We did a nationwide retrospective cohort study using the French national administrative database (PMSI), which includes discharge summaries for all hospital admissions in France. All patients hospitalised for COVID-19 from March 1 to April 30, 2020, and all patients hospitalised for influenza between Dec 1, 2018, and Feb 28, 2019, were included. The diagnosis of COVID-19 (International Classification of Diseases [10th edition] codes U07.10, U07.11, U07.12, U07.14, or U07.15) or influenza (J09, J10, or J11) comprised primary, related, or associated diagnosis. Comparisons of risk factors, clinical characteristics, and outcomes between patients hospitalised for COVID-19 and influenza were done, with data also stratified by age group. FINDINGS: 89 530 patients with COVID-19 and 45 819 patients with influenza were hospitalised in France during the respective study periods. The median age of patients was 68 years (IQR 52–82) for COVID-19 and 71 years (34–84) for influenza. Patients with COVID-19 were more frequently obese or overweight, and more frequently had diabetes, hypertension, and dyslipidaemia than patients with influenza, whereas those with influenza more frequently had heart failure, chronic respiratory disease, cirrhosis, and deficiency anaemia. Patients admitted to hospital with COVID-19 more frequently developed acute respiratory failure, pulmonary embolism, septic shock, or haemorrhagic stroke than patients with influenza, but less frequently developed myocardial infarction or atrial fibrillation. In-hospital mortality was higher in patients with COVID-19 than in patients with influenza (15 104 [16·9%] of 89 530 vs 2640 [5·8%] of 45 819), with a relative risk of death of 2·9 (95% CI 2·8–3·0) and an age-standardised mortality ratio of 2·82. Of the patients hospitalised, the proportion of paediatric patients (<18 years) was smaller for COVID-19 than for influenza (1227 [1·4%] vs 8942 [19·5%]), but a larger proportion of patients younger than 5 years needed intensive care support for COVID-19 than for influenza (14 [2·3%] of 613 vs 65 [0·9%] of 6973). In adolescents (11–17 years), the in-hospital mortality was ten-times higher for COVID-19 than for influenza (five [1·1% of 458 vs one [0·1%] of 804), and patients with COVID-19 were more frequently obese or overweight. INTERPRETATION: The presentation of patients with COVID-19 and seasonal influenza requiring hospitalisation differs considerably. Severe acute respiratory syndrome coronavirus 2 is likely to have a higher potential for respiratory pathogenicity, leading to more respiratory complications and to higher mortality. In children, although the rate of hospitalisation for COVID-19 appears to be lower than for influenza, in-hospital mortality is higher; however, low patient numbers limit this finding. These findings highlight the importance of appropriate preventive measures for COVID-19, as well as the need for a specific vaccine and treatment. FUNDING: French National Research Agency. | Lancet Respir Med | 2020 | | LitCov and CORD-19 |
3698 | In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines. | Science | 2020 | | LitCov and CORD-19 |
3699 | A Mouse Model of SARS-CoV-2 Infection and Pathogenesis Summary Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for animal model. Human Angiotensin converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) using CRISPR/Cas9 knock-in technology. Compared with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected- aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was evidenced to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis, and evaluating COVID-19 vaccines and therapeutics. | Cell Host Microbe | 2020 | | LitCov and CORD-19 |
3700 | Distribution of ACE2, CD147, CD26 and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension and COVID-19 risk factors BACKGROUND: Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide and novel clinical presentations of COVID‐19 are often reported. The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19. METHODS: We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4(+) and CD8(+) T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL or blood. Additionally, CD147‐related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2‐ and CD147‐related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID‐19 morbidity and severity patterns. | Allergy | 2020 | | LitCov and CORD-19 |