Corpus overview


MeSH Disease

Human Phenotype


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    SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic

    Authors: Jochen Schneider; Hrvoje Mijocevic; Kurt Ulm; Bernhardt Ulm; Simon Weidlich; Silvia Wuerstle; Kathrin Rothe; Matthias Treiber; Roman Iakoubov; Ulrich Mayr; Tobias Lahmer; Sebastian Rasch; Alexander Herner; Egon Burian; Fabian Lohöfer; Rickmer Braren; Marcus Makowski; Roland Schmid; Ulrike Protzer; Christoph Spinner; Fabian Geisler

    doi:10.21203/ Date: 2020-07-30 Source: ResearchSquare

    Background: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates HP with high sensitivity SERO, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. Methods: IgM/IgG chemiluminescent immunoassay SERO was performed for 107 patients with confirmed (group A: PCR+; CT±) and 46 patients with suspected (group B: repetitive PCR-; CT+) COVID-19, admitted to a German university hospital during the pandemic’s first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia MESHD pneumonia HP was used to assess the probability of COVID-19. Results: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset TRANS (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p<0.01). Compared to hospitalized patients with a non-complicated course, seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 9%, 26%, 65%, 77% and 92% in group A, compared with 0%, 10%, 20%, 40% and 50% in group B (p<0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology >14 days after symptom onset TRANS (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity SERO of SARS-CoV-2 serology was superior to PCR >17d after symptom onset TRANS. Conclusions: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates HP in PCR negative patients. However, sensitivity SERO of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2 nd week following symptom onset TRANS.

    COVIDOSE: Low-dose tocilizumab in the treatment of Covid-19

    Authors: Garth W Strohbehn; Brian L Heiss; Sherin J Rouhani; Jonathan A Trujillo; Jovian Yu; Alec J Kacew; Emily F Higgs; Jeffrey C Bloodworth; Alexandra Cabanov; Rachel C Wright; Adriana Koziol; Alexandra Weiss; Keith Danahey; Theodore G Karrison; Cuoghi C Edens; Iazsmin Bauer Ventura; Natasha N Pettit; Bhakti Patel; Jennifer Pisano; Mary E Strek; Thomas F Gajewski; Mark J Ratain; Pankti D Reid

    doi:10.1101/2020.07.20.20157503 Date: 2020-07-26 Source: medRxiv

    Background Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the high mortality of coronavirus disease MESHD 2019 (Covid-19). Tocilizumab, an IL-6 receptor blocking monoclonal antibody SERO, has been repurposed for Covid-19, but prospective trials and dose-finding studies in Covid-19 are lacking. Methods We conducted a phase 2 trial of low-dose tocilizumab in hospitalized adult TRANS patients with Covid-19, radiographic pulmonary infiltrate HP, fever MESHD fever HP, and C-reactive protein (CRP) >= 40 mg/L who did not require mechanical ventilation. Dose cohorts were determined by a trial Operations Committee, stratified by CRP and epidemiologic risk factors. A range of doses from 40 to 200 mg (low-dose tocilizumab) was evaluated, with allowance for one repeat dose at 24-48 hours. The primary objective was to assess the relationship of dose to fever MESHD fever HP resolution and CRP response. Outcomes were compared with retrospective controls with Covid-19. Correlative studies evaluating host antibody SERO response were performed in parallel. Findings A total of 32 patients received low-dose tocilizumab. This cohort had improved fever MESHD fever HP resolution (75.0% vs. 34.2%, p = 0.001) and CRP decline (86.2% vs. 14.3%, p < 0.001) in the 24-48 hours following drug administration, as compared to the retrospective controls (N=41). The probabilities of fever MESHD fever HP resolution or CRP decline did not appear to be dose-related in this small study (p=0.80 and p=0.10, respectively). Within the 28-day follow-up, 5 (15.6%) patients died. For patients who recovered, median time to clinical recovery was 3 days (IQR, 2-5). Clinically presumed and/or cultured bacterial superinfections MESHD were reported in 5 (15.6%) patients. Correlative biological studies demonstrated that tocilizumab-treated patients produced anti- SARS-CoV-2 antibodies SERO comparable to controls. Interpretation Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with Covid-19. Results of this trial and its correlative biological studies provide rationale for a randomized, controlled trial of low-dose tocilizumab in Covid-19.

    Initial experience in Mexico with convalescent plasma SERO in COVID-19 patients with severe respiratory failure HP, a retrospective case series

    Authors: Michel F. Martinez-Resendez; Fernando Castilleja-Leal; Alejandro Torres-Quintanilla; Augusto Rojas-Martinez; Gerardo Garcia-Rivas; Rocio Ortiz-Lopez; Victor Trevino; Reynaldo Lara-Medrano; Hiram Villanueva-Lozano; Teresa Ramirez-Elizondo; Victor Sanchez-Nava; Francisco Moreno-Hoyos; Alfonso Martinez-Thomae; Martin Hernandez-Torre; Carlos Diaz-Olachea; Servando Cardona-Huerta; Sylvia de la Rosa-Pacheco; Carlos Diaz-Garza; Paola Reynoso-Lobo; Alma R. Marroquin-Escamilla; Jessica G. Herrera-Gamboa; Fatima M. Alvarado-Monroy; Claudia D. Aguayo-Millan; Francisco F. Villegas-Macedo; Jesus E. Flores-Osorio; Daniel Davila-Gonzalez; Maria E. Diaz-Sanchez; Guillermo Torre-Amione

    doi:10.1101/2020.07.14.20144469 Date: 2020-07-20 Source: medRxiv

    Introduction: Hospital mortality due to COVID-19 in Mexico is high (32%) and as of today, effective treatment options are limited. More effective treatments that shorten hospital stay and reduce mortality are needed. Initial reports for the use of convalescent plasma SERO (CP) therapy for COVID-19 appear promising. We describe a case series of eight patients with impending respiratory failure HP, who underwent CP therapy. Methods: Six male TRANS and two female TRANS ( ages TRANS 31 to 79) patients that were admitted to the intensive-care unit for severe COVID-19 were transfused with two doses of CP (250 mL per dose, anti-SARS-CoV-2 IgG titers > 1:100). Donors were six SARS-CoV-2 infected males TRANS who remained asymptomatic TRANS for > 7 days and were negative for two nasopharyngeal RT-PCR tests. Clinical characteristics, inflammatory and cellular injury markers, chest X-ray findings and viral loads were analyzed before and after CP administration. Viral load association to disease MESHD severity was further analyzed on a separate cohort of asymptomatic TRANS vs hospitalized patients with COVID-19. Results: Eight patients with respiratory failure HP were successfully discharged with a median length of stay of 22.5 (IQR 18.25-29.00). After CP therapy, we observed a reduction of C-reactive protein (CRP) (median, 22.80 mg/dL vs. 1.63 mg/dL), and of procalcitonin (median, 0.27 ng/mL vs. 0.13 ng/mL). High- Sensitivity SERO Cardiac Troponin I (hs-cTnI), Brain Natriuretic Peptide (BNP) and Lactate Dehydrogenase (LDH) were lower, and a mild reduction of pulmonary infiltrates HP by chest X-ray was observed. Lastly, a reduction of viral load was after CP therapy was found. (log, median [IQR], 1.2 [0.70-2.20] vs. 0.25 [0.00-1.78]). We observed no adverse effects. Conclusions: CP could potentially be an effective therapeutic option for patients with severe COVID-19. Clinical benefit needs to be studied further through randomized controlled trials.


    Authors: Antoni Sisó-Almirall; Belchin Kostov; Minerva Mas-Heredia; Sergi Vilanova-Rotllan; Ethel Sequeira-Aymar; Mireia Sans-Corrales; Elisenda Sant-Arderiu; Laia Cayuelas-Redondo; Angela Martínez-Pérez; Noemí García Plana; August Anguita-Guimet; Jaume Benavent-Àreu

    doi:10.1101/2020.06.18.20134510 Date: 2020-06-20 Source: medRxiv

    Background In addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease MESHD early to limit contagion in the community. Aim To determine clinical factors of a poor prognosis in patients with COVID-19 infection MESHD. Design and Setting Descriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000. Method Examination of the medical records of patients with COVID-19 infections MESHD infections confirmed TRANS confirmed by polymerase chain reaction. Results We included 322 patients (mean age TRANS 56.7 years, 50% female TRANS, 115 (35.7%) aged TRANS [≥] 65 years). The best predictors of ICU admission or death MESHD were greater age TRANS, male TRANS sex (OR=2.99; 95%CI=1.55 to 6.01), fever MESHD fever HP (OR=2.18; 95%CI=1.06 to 4.80), dyspnoea (OR=2.22; 95%CI=1.14 to 4.24), low oxygen saturation (OR=2.94; 95%CI=1.34 to 6.42), auscultatory alterations (OR=2.21; 95%CI=1.00 to 5.29), heart disease MESHD (OR=4.37; 95%CI=1.68 to 11.13), autoimmune disease MESHD (OR=4.03; 95%CI=1.41 to 11.10), diabetes (OR=4.00; 95%CI=1.89 to 8.36), hypertension MESHD hypertension HP (OR=3.92; 95%CI=2.07 to 7.53), bilateral pulmonary infiltrates HP (OR=3.56; 95%CI=1.70 to 7.96), elevated lactate-dehydrogenase (OR=3.02; 95%CI=1.30 to 7.68), elevated C-reactive protein (OR=2.94; 95%CI=1.47 to 5.97), elevated D-dimer (OR=2.66; 95%CI=1.15 to 6.51) and low platelet count (OR=2.41; 95%CI=1.12 to 5.14). Myalgia MESHD Myalgia HP or artralgia (OR=0.28; 95%CI=0.10 to 0.66), dysgeusia MESHD (OR=0.28; 95%CI=0.05 to 0.92) and anosmia HP (OR=0.23; 95%CI=0.04 to 0.75) were protective factors. Conclusion Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection MESHD will be key to early treatment and isolation and the tracing of contacts TRANS.

    Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Alum Induces Protective Immunity and Reduces Immune Enhancement

    Authors: Wen-Hsiang Chen; Xinrong Tao; Anurodh Agrawal; Abdullah Algaissi; Bi-Hung Peng; Jeroen Pollet; Ulrich Strych; Maria Elena Bottazzi; Peter J Hotez; Sara Lustigman; Lanying Du; Shibo Jiang; Chien-Te K Tseng

    doi:10.1101/2020.05.15.098079 Date: 2020-05-15 Source: bioRxiv

    We developed a severe acute respiratory syndrome MESHD (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high-level neutralizing antibodies SERO against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ∼ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies SERO and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody SERO titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates HP. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

    Authors: Brandi Williamson; Friederike Feldmann; Benjamin Schwarz; Kimberly Meade-White; Danielle Porter; Jonathan Schulz; Neeltje van Doremalen; Ian Leighton; Claude Kwe Yinda; Lizzette Perez-Perez; Atsushi Okumura; Jamie Lovaglio; Patrick Hanley; Greg Saturday; Catharine Bosio; Sarah Anzick; Kent Barbian; Tomas Chilar; Craig Martens; Dana Scott; Vincent Munster; Emmie de Wit

    doi:10.1101/2020.04.15.043166 Date: 2020-04-15 Source: bioRxiv

    BackgroundEffective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection MESHD. MethodsTo evaluate the effect of remdesivir treatment on SARS-CoV-2 disease MESHD outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection MESHD that results in transient lower respiratory tract disease MESHD. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. ResultsIn contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease MESHD and had reduced pulmonary infiltrates HP on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. ConclusionsTherapeutic remdesivir treatment initiated early during infection MESHD has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia MESHD pneumonia HP.

    Respiratory disease and virus MESHD shedding in rhesus macaques inoculated with SARS-CoV-2

    Authors: Vincent Munster; Friederike Feldmann; Brandi Williamson; Neeltje van Doremalen; Lizzette Perez-Perez,; Jonathan Schultz; Kimberly Meade-White; Atsushi Okumura; Julie Callison; Beniah Brumbaugh; Victoria Avanzato; Rebecca Rosenke; Patrick Hanley; Greg Saturday; Dana Scott; Elizabeth Fischer; Emmie de Wit

    doi:10.1101/2020.03.21.001628 Date: 2020-03-21 Source: bioRxiv

    An outbreak of a novel coronavirus, now named SARS-CoV-2, causing respiratory disease MESHD and a [~]2% case fatality rate started in Wuhan, China in December 2019. Following unprecedented rapid global spread, the World Health Organization declared COVID-19 a pandemic on March 11, 2020. Although data on disease MESHD in humans are emerging at a steady pace, certain aspects of the pathogenesis of SARS-CoV-2 can only be studied in detail in animal models, where repeated sampling and tissue collection is possible. Here, we show that SARS-CoV-2 causes respiratory disease MESHD in infected rhesus macaques, with disease MESHD lasting 8-16 days. Pulmonary infiltrates HP, a hallmark of human disease MESHD, were visible in lung radiographs of all animals. High viral loads were detected in swabs from the nose and throat of all animals as well as in bronchoalveolar lavages; in one animal we observed prolonged rectal shedding. Taken together, the rhesus macaque recapitulates moderate disease MESHD observed in the majority of human cases. The establishment of the rhesus macaque as a model of COVID-19 will increase our understanding of the pathogenesis of this disease MESHD and will aid development and testing of medical countermeasures.

    Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia MESHD Pneumonia HP (COVID-19)

    Authors: Weiren Luo; Hong Yu; Jizhou Gou; Xiaoxing Li; Yan Sun; Jinxiu Li; Lei Liu

    id:202002.0407/v4 Date: 2020-03-09 Source:

    Background Critical patients with novel coronavirus pneumonia MESHD pneumonia HP ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis MESHD on gross examination. The haemorrhagic necrosis MESHD was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis MESHD, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction MESHD. Small vessels hyperplasia MESHD, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma SERO cells infiltrating into pulmonary HP interstitium. Bronchiolitis MESHD Bronchiolitis HP and alveolitis with proliferation, atrophy MESHD, desquamation and squamous metaplasia MESHD of epithelial cells. Atrophy MESHD, vacuolar degeneration, proliferation, desquamation and squamous metaplasia MESHD in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema MESHD edema HP fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis MESHD. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease MESHD.

    Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China.

    Authors: Dawei Wang; Yimei Yin; Chang Hu; Xing Liu; Xingguo Zhang; Shuliang Zhou; Mingzhi Jian; Haibo Xu; John Prowle; Bo Hu; Yirong Li; Zhi-Yong Peng

    doi:10.21203/ Date: 2020-03-04 Source: ResearchSquare

    Background In December 2019, Coronavirus Disease MESHD 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. Methods Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan, and Xi-shui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic and clinical data were collected. Clinical course of survivors and non-survivors were compared. Risk factors for death MESHD were analyzed. Results A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever MESHD fever HP, cough MESHD cough HP, dyspnea MESHD dyspnea HP, lymphopenia MESHD lymphopenia HP and radiological multilobar pulmonary infiltrates HP. In severe cases, thrombocytopenia MESHD thrombocytopenia HP, acute kidney injury MESHD acute kidney injury HP, acute myocardial injury or adult respiratory distress syndrome MESHD adult TRANS respiratory distress HP syndrome were observed. During week 2, in mild cases, fever MESHD fever HP, cough MESHD cough HP and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia MESHD lymphopenia HP persisted. In severe cases, leukocytosis MESHD leukocytosis HP, neutrophilia HP and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia MESHD lymphopenia HP. However, severe cases showed persistent lymphopenia MESHD lymphopenia HP, severe acute respiratory dyspnea MESHD dyspnea HP syndrome MESHD , refractory shock MESHD shock HP, anuric acute kidney injury MESHD acute kidney injury HP, coagulopathy, thrombocytopenia MESHD thrombocytopenia HP and death MESHD. Older age TRANS and male TRANS sex were independent risk factors for poor outcome of the illness. Conclusions A period of 7–13 days after illness onset is the critical stage in COVID-19 course. Age TRANS and male TRANS gender TRANS were independent risk factors for death MESHD of COVID-19.

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MeSH Disease
Human Phenotype

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