Corpus overview


MeSH Disease

Human Phenotype


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    Clinical Utility of a Highly Sensitive Lateral Flow Immunoassay SERO as determined by Titer Analysis for the Detection of anti- SARS-CoV-2 Antibodies SERO at the Point-of-Care

    Authors: Amanda Haymond; Claudius Mueller; Hannah Steinberg; K. Alex Hodge; Caitlin W Lehman; Shih-Chao Lin; Lucia Collini; Heather Branscome; Tuong Vi Nguyen; Sally Rucker; Lauren Panny; Rafaela Flor; Raouf Guirguis; Richard Hoefer; Giovanni Lorenzin; Emanuel Petricoin; Fatah Kashanchi; Kylene Kehn-Hall; Paolo Lanzafame; Lance Liotta; Alessandra Luchini

    doi:10.1101/2020.07.30.20163824 Date: 2020-08-02 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19), caused by the severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2), became a pandemic in early 2020. Lateral flow immunoassays SERO for antibody testing SERO have been viewed as a cheap and rapidly deployable method for determining previous infection MESHD with SARS-CoV-2; however, these assays have shown unacceptably low sensitivity SERO. We report on nine lateral flow immunoassays SERO currently available and compare their titer sensitivity SERO in serum SERO to a best-practice enzyme-linked immunosorbent assay SERO ( ELISA SERO) and viral neutralization assay. For a small group of PCR-positive, we found two lateral flow immunoassay SERO devices with titer sensitivity SERO roughly equal to the ELISA SERO; these devices were positive for all PCR-positive patients harboring SARS-CoV-2 neutralizing antibodies SERO. One of these devices was deployed in Northern Italy to test its sensitivity SERO and specificity in a real-world clinical setting. Using the device with fingerstick blood SERO on a cohort of 27 hospitalized PCR-positive patients and seven hospitalized controls, ROC curve analysis gave AUC values of 0.7646 for IgG. For comparison, this assay was also tested with saliva from the same patient population and showed reduced discrimination between cases and controls with AUC values of 0.6841 for IgG. Furthermore, during viral neutralization testing, one patient was discovered to harbor autoantibodies to ACE2, with implications for how immune responses are profiled. We show here through a proof-of-concept study that these lateral flow devices can be as analytically sensitive as ELISAs SERO and adopted into hospital protocols; however, additional improvements to these devices remain necessary before their clinical deployment.

    Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor

    Authors: Abu Sajib

    id:202004.0369/v2 Date: 2020-08-02 Source:

    Respiratory transmission TRANS is the primary route of Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) infection MESHD. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease MESHD (COVID-19).

    Persistence of anti- SARS-CoV-2 antibodies SERO in non-hospitalized COVID-19 convalescent health care workers

    Authors: Margherita Bruni; Valentina Cecatiello; Angelica Diaz-Basabe; Georgia Lattanzi; Erika Mileti; Silvia Monzani; Laura Pirovano; Francesca Rizzelli; Clara Visintin; Giuseppina Bonizzi; Marco Giani; Marialuisa Lavitrano; Silvia Faravelli; Federico Forneris; Flavio Caprioli; Pier Giuseppe Pelicci; Gioacchino Natoli; Sebastiano Pasqualato; Marina Mapelli; Federica Facciotti

    doi:10.1101/2020.07.30.20164368 Date: 2020-08-01 Source: medRxiv

    Background. Coronavirus disease MESHD-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome MESHD CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody SERO response to SARS-CoV-2 can be detected early during the infection MESHD, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody SERO titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum SERO levels of pro-inflammatory mediators. Methods. An ELISA assay SERO has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies SERO as well as soluble pro-inflammatory mediators in the sera. Results. Specificity and sensitivity SERO of the ELISA assays SERO were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA SERO allowed quantification of IgM, IgG and IgA antibody SERO responses against all the viral antigens tested and showed a correlation between magnitude of the antibody SERO response and disease MESHD severity. Non-hospitalized subjects showed lower antibody SERO titers and blood SERO pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested SERO. Noteworthy, in non-severe COVID-19 infections MESHD, antibody SERO titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Conclusions. Rapid decline in antibody SERO titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection MESHD, suggesting that antibody SERO-mediated protection against re- infection MESHD with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing SERO to estimate the prevalence SERO of SARS-CoV-2 infection MESHD in the general population.

    High rate of major drug-drug interactions of lopinavir-ritonavir for COVID-19 treatment

    Authors: Juan Macias; Ana Pinilla; Francisco A Lao-Dominguez; Anais Corma; Enrique Contreras-Macias; Alejandro Gonzalez-Serna; Antonio Gutierrez-Pizarraya; Marta Fernandez-Fuertes; Ramon Morillo-Verdugo; Marta Trigo; Luis M Real; Juan A Pineda

    doi:10.1101/2020.07.30.20165027 Date: 2020-08-01 Source: medRxiv

    The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease MESHD 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection MESHD treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI: 69%-85%) patients, and in 33 (26%, 95% CI: 19%-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p=0.010). After adjustment, only the Charlson index was independently associated with death MESHD [adjusted OR (95% CI) for Charlson index [≥]5: 85 (10-731), p <0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases MESHD Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p=0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age TRANS and comorbidities. Patients managed by the Infectious Diseases MESHD Unit had lower risk of major DDI.

    Augmentation of anti-MDA5 antibody SERO implies severe disease MESHD in COVID-19 patients

    Authors: Changzheng Liu; Qian Wang; Yeming Wang; Geng Wang; Linghang Wang; Hong Chen; Tao Jiao; Chaojun Hu; Xiaobo Lei; Li Guo; Lili Ren; Mengtao Li; Xiaofeng Zeng; Dingyu Zhang; Bin Cao; Jianwei Wang

    doi:10.1101/2020.07.29.20164780 Date: 2020-08-01 Source: medRxiv

    Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV2) infection MESHD, which is associated with high mortality of coronavirus disease MESHD 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti- melanoma MESHD melanoma HP differentiation-associated gene 5 (MDA5) antibody SERO (Ab)-related dermatomyositis MESHD (DM), implying a shared autoinflammatory aberrance. However, it is unclear whether anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Here, we found that the positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% and the anti-MDA5 Ab positive patients tended to develop severe disease MESHD (88.6% vs 66.9%, P<0.0001). In particular, the titer of anti-MDA5 Ab was increased in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data reveal that anti-MDA5 Ab is prevalent in the COVID-19 patients and high titer of this antibody SERO is correlated with severe disease MESHD and unfavorable outcomes.

    Isolation Considered Epidemiological Model for the Prediction of COVID-19 Trend in Tokyo, Japan

    Authors: Motoaki Utamura; Makoto Koizumi; Seiichi Kirikami

    doi:10.1101/2020.07.31.20165829 Date: 2020-07-31 Source: medRxiv

    Background: Coronavirus Disease MESHD 2019 (COVID19) currently poses a global public health threat. Although no exception, Tokyo, Japan was affected at first by only a small epidemic. Medical collapse nevertheless nearly happened because no predictive method existed for counting patients. A standard SIR epidemiological model and its derivatives predict susceptible, infectious, and removed (recovered/ deaths MESHD) cases but ignore isolation of confirmed cases TRANS. Predicting COVID19 trends with hospitalized and infectious people in field separately is important to prepare beds and develop quarantine strategies. Methods: Time-series COVID19 data from February 28 to May 23, 2020 in Tokyo were adopted for this study. A novel epidemiological model based on delay differential equation was proposed. The model can evaluate patients in hospitals and infectious cases in the field. Various data such as daily new cases, cumulative infections MESHD, patients in hospital, and PCR test positivity ratios were used to examine the model. This approach derived an alternative formulation equivalent to the standard SIR model. Its results were compared quantitatively with those of the present isolation model. Results: The basic reproductive number TRANS, inferred as 2.30, is a dimensionless parameter composed of modeling parameters. Effects of intervention to mitigate the epidemic spread were assessed a posteriori. An exit policy of how and when to release a statement of emergency MESHD was also assessed using the model. Furthermore, results suggest that the rapid isolation of infectious cases has a large potential to effectively mitigate the spread of infection MESHD and restores social and economic activities safely. Conclusions: A novel mathematical model was proposed and examined using COVID19 data for Tokyo. Results show that shortening the period from infection MESHD to hospitalization is effective against outbreak without rigorous public health intervention and control. Faster and precise case cluster detection and wider and quicker introduction of testing measures are strongly recommended.

    Use of a humanized anti-CD6 monoclonal antibody SERO (itolizumab) in elderly TRANS patients with moderate COVID-19

    Authors: Mayra Ramos-Suzarte; Yayquier Diaz; Yordanis Martin; Nestor Antonio Calderon; William Santiago; Orlando Vinet; Yulieski La O; Jorge Perez; Augusto Oyarzabal; Yoan Perez; Geidy Lorenzo; Meylan Cepeda; Danay Saavedra; Zayma Mazorra; Daymys Estevez; Patricia Lorenzo-Luaces; Carmen Valenzuela; Armando Caballero; Kalet leon; Tania Crombet; Carlos Jorge Hidalgo

    doi:10.1101/2020.07.24.20153833 Date: 2020-07-30 Source: medRxiv

    Abstract Introduction: The Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease MESHD (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly TRANS with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection MESHD. During the outbreak, a local transmission TRANS event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly TRANS residents were positive for SARS-CoV-2. Methods: Based on the increased susceptibility to viral-induced cytokine release syndrome MESHD inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody SERO. Results: All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease MESHD was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age TRANS, comorbidities and severity of the disease MESHD. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion: Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum SERO levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death MESHD. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease MESHD worsening and mortality. The humanized antibody SERO itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome MESHD from other pathologies.

    EUAdb: a resource for COVID-19 test development

    Authors: Alyssa Woronik; Henry W Shaffer; Karin Kiontke; Jon M Laurent; Ronald Zambrano; Jef D Boeke; David H.A. Fitch

    doi:10.1101/2020.07.30.228890 Date: 2020-07-30 Source: bioRxiv

    Due to the sheer number of COVID-19 ( coronavirus disease MESHD 2019) cases, the prevalence SERO of asymptomatic TRANS cases and the fact that undocumented cases appear to be significant for transmission TRANS of the causal virus, SARS-CoV-2 ( severe acute respiratory syndrome MESHD coronavirus 2), there is an urgent need for increased SARS-CoV-2 testing capability that is both efficient and effective1. In response to the growing threat of the COVID-19 pandemic in February, 2020, the FDA (US Food and Drug Administration) began issuing Emergency MESHD Use Authorizations (EUAs) to laboratories and commercial manufacturers for the development and implementation of diagnostic tests1. So far, the gold standard assay for SARS-CoV-2 detection is the RT-qPCR (real-time quantitative polymerase chain reaction) test2. However, the authorized RT-qPCR test protocols vary widely, not only in the reagents, controls, and instruments they use, but also in the SARS-CoV-2 genes they target, what results constitute a positive SARS-CoV-2 infection MESHD, and their limit of detection (LoD). The FDA has provided a web site that lists most of the tests that have been issued EUAs, along with links to the authorization letters and summary documents describing these tests1. However, it is very challenging to use this site to compare or replicate these tests for a variety of reasons. First, at least 12 of 18 tests that were issued EUAs prior to March 31, 2020, are not listed there. Second, the data are not standardized and are only provided as longhand prose in the summary documents. Third, some details (e.g. primer sequences) are absent from several of the test descriptions. Fourth, for tests provided by commercial manufacturers, summary documents are completely missing. To address at least the first three issues, we have developed a database, EUAdb (, that holds standardized information about EUA-issued tests and is focused on RT-qPCR diagnostic tests, or "high complexity molecular-based laboratory developed tests"1. By providing a standardized ontology and curated data in a relational architecture, we seek to facilitate comparability and reproducibility, with the ultimate goal of consistent, universal and high-quality testing nationwide. Here, we document the basics of the EUAdb data architecture and simple data queries. The source files can be provided to anyone who wants to modify the database for his/her own research purposes. We ask that the original source of the files be made clear and that the database not be used in its original or modified forms for commercial purposes.

    Mathematical Modelling the Impact Evaluation ofLockdown on Infection MESHD Dynamics of COVID-19 inItaly.

    Authors: Daniyar Yergesh; Shirali Kadyrov; Hayot Saydaliev; Alibek Orynbassar

    doi:10.1101/2020.07.27.20162537 Date: 2020-07-29 Source: medRxiv

    The Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARSCoV-2), the cause of the coronavirus disease MESHD-2019 (COVID-19), within months of emergence from Wuhan, China, has rapidly spread, exacting a devastating human toll across around the world reaching the pandemic stage at the the beginning of March 2020. Thus, COVID-19s daily increasing cases and deaths MESHD have led to worldwide lockdown, quarantine and some restrictions. Covid-19 epidemic in Italy started as a small wave of 2 infected cases on January 31. It was followed by a bigger wave mainly from local transmissions TRANS reported in 6387 cases on March 8. It caused the government to impose a lockdown on 8 March to the whole country as a way to suppress the pandemic. This study aims to evaluate the impact of the lockdown and awareness dynamics on infection MESHD in Italy over the period of January 31 to July 17 and how the impact varies across different lockdown scenarios in both periods before and after implementation of the lockdown policy. The findings SEIR reveal that implementation lockdown has minimised the social distancing flattening the curve. The infections MESHD associated with COVID-19 decreases with quarantine initially then easing lockdown will not cause further increasing transmission TRANS until a certain period which is explained by public high awareness. Completely removing lockdown may lead to sharp transmission TRANS second wave. Policy implementation and limitation of the study were evaluated at the end of the paper. Keywords COVID-19 - Lockdown - Epidemic model - SEIR - Awareness - Dynamical systems.

    Clinical characteristics of neonates with coronavirus disease MESHD 2019 (COVID-19): a systematic review

    Authors: Yuan Hu; Jing Xiong; Yuan Shi

    doi:10.21203/ Date: 2020-07-29 Source: ResearchSquare

    This study aimed to summarize the existing literature on severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection in newborns to clarify the clinical features and outcomes of neonates with COVID-19. A systematic search was performed in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP databases from January 1, 2019 to April 30, 2020. The references of relevant studies were also searched. A descriptive summary was organized by aspects of clinical presentations (symptoms, laboratory examinations, and imaging) and outcomes. We identified 14 studies reporting 18 newborns with COVID-19. The most common clinical manifestations were fever MESHD fever HP (62.5%), shortness of breath (50.0%), diarrhea MESHD diarrhea HP/ vomiting MESHD vomiting HP/feeding intolerance(43.8%), cough MESHD cough HP (37.5%), dyspnea MESHD dyspnea HP (25.0%), and nasal congestion/runny nose/ sneeze MESHD sneeze HP(25.0%). Atypical symptoms included jaundice MESHD jaundice HP and convulsion. Lymphocyte numbers decreased in 5 cases, and radiographic findings were likely to show pneumonia MESHD pneumonia HP. All newborns recovered and discharged from the hospital, and there was no death MESHD.Conclusion: Clinical symptoms of neonatal SARS-CoV-2 infection MESHD are atypical, most of them are mild. Up to now, the prognosis of newborns is good, and there is no death MESHD. Intrauterine vertical transmission TRANS is possible, but confirmed evidence is still lacking. The Long-term follow-up of potential influences of SARS-CoV-2 infection MESHD on neonates need further exploration.

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MeSH Disease
Human Phenotype

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