Corpus overview


MeSH Disease

Human Phenotype


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    SARS-CoV-2 antigens expressed in plants detect antibody SERO responses in COVID-19 patients

    Authors: Mohau S Makatsa; Marius B Tincho; Jerome M Wendoh; Sherazaan D Ismail; Rofhiwa Nesamari; Francisco Pera; Scott de Beer; Anura David; Sarika Jugwanth; Maemu P Gededzha; Nakampe Mampeule; Ian Sanne; Wendy Stevens; Lesley Scott; Jonathan Blackburn; Elizabeth S Mayne; Roanne S Keeton; Wendy A Burgers

    doi:10.1101/2020.08.04.20167940 Date: 2020-08-04 Source: medRxiv

    Background: The SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods, with over 16 million confirmed cases TRANS and at least 650 000 deaths MESHD from COVID-19 in the first 7 months of the pandemic. Developing tools to measure seroprevalence SERO and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay SERO using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. Methods: We established an indirect enzyme-linked immunosorbent assay SERO ( ELISA SERO) using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody SERO responses in sera from South African patients (n=77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of six weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease MESHD. In addition, we tested the reactivity of pre-pandemic plasma SERO (n=58) and compared the performance SERO of our in-house ELISA SERO with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies SERO by a validated, high sensitivity SERO commercial ELISA SERO, and OD values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma SERO, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA SERO. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. Conclusions: We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody SERO responses to SARS-CoV-2 in infected patients in our setting.

    High SARS-CoV-2 seroprevalence SERO in Health Care Workers but relatively low numbers of deaths MESHD in urban Malawi

    Authors: Marah Grace Chibwana; Khuzwayo Chidiwa Jere; Jonathan Mandolo; Vincent Katunga-Phiri; Dumizulu Tembo; Ndaona Mitole; Samantha Musasa; Simon Sichone; Agness Lakudzala; Lusako Sibale; Prisca Matambo; Innocent Kadwala; Rachel Louise Byrne; Alice Mbewe; Marc Y.R. Henrion; Ben Morton; Chimota Phiri; Jane Mallewa; Henry C Mwandumba; Emily R Adams; Stephen B Gordon; Kondwani Charles Jambo

    doi:10.1101/2020.07.30.20164970 Date: 2020-08-01 Source: medRxiv

    Background In low-income countries, like Malawi, important public health measures including social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD, there are no reliable estimates of the true burden of infection MESHD and death MESHD. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection MESHD in urban Malawi. Methods Five hundred otherwise asymptomatic TRANS HCWs were recruited from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples SERO were collected all participants. A commercial ELISA SERO was used to measure SARS-CoV-2 IgG antibodies SERO in serum SERO. We run local negative samples (2018 - 2019) to verify the specificity of the assay. To estimate the seroprevalence SERO of SARS CoV-2 antibodies SERO, we adjusted the proportion of positive results based on local specificity of the assay. Results Eighty-four participants tested positive for SARS-CoV-2 antibodies SERO. The HCW with a positive SARS-CoV-2 antibody SERO result came from different parts of the city. The adjusted seroprevalence SERO of SARS-CoV-2 antibodies SERO was 12.3% [CI 9.0-15.7]. Using age TRANS-stratified infection MESHD fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence SERO, the number of predicted deaths MESHD was 8 times the number of reported deaths MESHD. Conclusion The high seroprevalence SERO of SARS-CoV-2 antibodies SERO among HCW and the discrepancy in the predicted versus reported deaths MESHD, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

    Sex-specificity of mortality risk factors among hospitalized COVID-19 patients in New York City: prospective cohort study

    Authors: Tomi Jun; Sharon Nirenberg; Patricia Kovatch; Kuan-lin Huang

    doi:10.1101/2020.07.29.20164640 Date: 2020-08-01 Source: medRxiv

    Objective: To identify sex-specific effects of risk factors for in-hospital mortality among COVID-19 patients admitted to a hospital system in New York City. Design: Prospective observational cohort study with in-hospital mortality as the primary outcome. Setting: Five acute care hospitals within a single academic medical system in New York City. Participants: 3,086 hospital inpatients with COVID-19 admitted on or before April 13, 2020 and followed through June 2, 2020. Follow-up till discharge or death MESHD was complete for 99.3% of the cohort. Results: The majority of the cohort was male TRANS (59.6%). Men were younger (median 64 vs. 70, p<0.001) and less likely to have comorbidities such as hypertension MESHD hypertension HP (32.5% vs. 39.9%, p<0.001), diabetes (22.6% vs. 26%, p=0.03), and obesity MESHD obesity HP (6.9% vs. 9.8%, p=0.004) compared to women. Women had lower median values of laboratory markers associated with inflammation MESHD compared to men: white blood SERO cells (5.95 vs. 6.8 K/uL, p<0.001), procalcitonin (0.14 vs 0.21 ng/mL, p<0.001), lactate dehydrogenase (375 vs. 428 U/L, p<0.001), C-reactive protein (87.7 vs. 123.2 mg/L, p<0.001). Unadjusted mortality was similar between men and women (28.8% vs. 28.5%, p=0.84), but more men required intensive care than women (25.2% vs. 19%, p<0.001). Male TRANS sex was an independent risk factor for mortality (OR 1.26, 95% 1.04-1.51) after adjustment for demographics, comorbidities, and baseline hypoxia MESHD. There were significant interactions between sex and coronary artery disease MESHD (p=0.038), obesity MESHD obesity HP (p=0.01), baseline hypoxia MESHD (p<0.001), ferritin (p=0.002), lactate dehydrogenase (p=0.003), and procalcitonin (p=0.03). Except for procalcitonin, which had the opposite association, each of these factors was associated with disproportionately higher mortality among women. Conclusions: Male TRANS sex was an independent predictor of mortality, consistent with prior studies. Notably, there were significant sex-specific interactions which indicated a disproportionate increase in mortality among women with coronary artery disease MESHD, obesity MESHD obesity HP, and hypoxia MESHD. These new findings highlight patient subgroups for further study and help explain the recognized sex differences in COVID-19 outcomes.

    Model stability of COVID-19 mortality prediction with biomarkers

    Authors: Chenyan Huang; Xi Long; Zhuozhao Zhan; Edwin van den Heuvel

    doi:10.1101/2020.07.29.20161323 Date: 2020-07-30 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19) is an unprecedented and fast evolving pandemic, which has caused a large number of critically ill patients and deaths MESHD globally. It is an acute public health crisis leading to overloaded critical care capacity. Timely prediction of the clinical outcome ( death MESHD/survival) of hospital-admitted COVID-19 patients can provide early warnings to clinicians, allowing improved allocation of medical resources. In a recently published paper, an interpretable machine learning model was presented to predict the mortality of COVID-19 patients with blood SERO biomarkers, where the model was trained and tested on relatively small data sets. However, the model or performance SERO stability was not explored and assessed. By re-analyzing the data, we reveal that the reported mortality prediction performance SERO was likely over-optimistic and its uncertainty was underestimated or overlooked, with a large variability in predicting deaths MESHD.

    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.

    Seroprevalence SERO of anti-SARS-CoV-2 IgG antibodies SERO in Kenyan blood SERO donors

    Authors: Sophie Uyoga; Ifedayo M.O. Adetifa; Henry K. Karanja; James Nyagwange; James Tuju; Perpetual Wanjiku; Rashid Aman; Mercy Mwangangi; Patrick Amoth; Kadondi Kasera; Wangari Ng'ang'a; Charles Rombo; Christine K. Yegon; Khamisi Kithi; Elizabeth Odhiambo; Thomas Rotich; Irene Orgut; Sammy Kihara; Mark Otiende; Christian Bottomley; Zonia N. Mupe; Eunice W. Kagucia; Katherine Gallagher; Anthony Etyang; Shirine Voller; John Gitonga; Daisy Mugo; Charles N. Agoti; Edward Otieno; Leonard Ndwiga; Teresa Lambe; Daniel Wright; Edwine Barasa; Benjamin Tsofa; Philip Bejon; Lynette I. Ochola-Oyier; Ambrose Agweyu; J. Anthony G. Scott; George M Warimwe

    doi:10.1101/2020.07.27.20162693 Date: 2020-07-29 Source: medRxiv

    Background There are no data on SARS-CoV-2 seroprevalence SERO in Africa though the COVID-19 epidemic curve and reported mortality differ from patterns seen elsewhere. We estimated the anti- SARS-CoV-2 antibody SERO prevalence SERO among blood SERO donors in Kenya. Methods We measured anti-SARS-CoV-2 spike IgG prevalence SERO by ELISA SERO on residual blood SERO donor samples obtained between April 30 and June 16, 2020. Assay sensitivity SERO and specificity were 83% (95% CI 59, 96%) and 99.0% (95% CI 98.1, 99.5%), respectively. National seroprevalence SERO was estimated using Bayesian multilevel regression and post-stratification to account for non-random sampling with respect to age TRANS, sex and region, adjusted for assay performance SERO. Results Complete data were available for 3098 of 3174 donors, aged TRANS 15-64 years. By comparison with the Kenyan population, the sample over-represented males TRANS (82% versus 49%), adults TRANS aged TRANS 25-34 years (40% versus 27%) and residents of coastal Counties (49% versus 9%). Crude overall seroprevalence SERO was 5.6% (174/3098). Population-weighted, test-adjusted national seroprevalence SERO was 5.2% (95% CI 3.7, 7.1%). Seroprevalence SERO was highest in the 3 largest urban Counties; Mombasa (9.3% [95% CI 6.4, 13.2%)], Nairobi (8.5% [95% CI 4.9, 13.5%]) and Kisumu (6.5% [95% CI 3.3, 11.2%]). Conclusions We estimate that 1 in 20 adults TRANS in Kenya had SARS-CoV-2 antibodies SERO during the study period. By the median date of our survey, only 2093 COVID-19 cases and 71 deaths MESHD had been reported through the national screening system. This contrasts, by several orders of magnitude, with the numbers of cases and deaths MESHD reported in parts of Europe and America when seroprevalence SERO was similar.

    A Comprehensive Evaluation of Early Predictors of Disease Progression MESHD in Patients with COVID-19: A Case Control Study

    Authors: Qiang Tang; Yanwei Liu; Yingfeng Fu; Ziyang Di; Kailiang Xu; Bo Tang; Hui Wu; Maojun Di

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

    Background: The 2019 coronavirus disease MESHD (COVID-19) has become an unprecedented public health crisis with nearly 16 million confirmed cases TRANS and 630,000 deaths MESHD worldwide. Methods: We retrospectively investigated the demographic, clinical, laboratory, radiological and treatment data of COVID-19 patients consecutively enrolled from January 18 to May 15, 2020, in Taihe and Jinzhou central hospital. Results: Of all 197 patients, the median age TRANS was 66.5 years (IQR 7-76), and 120 (60.9%) patients were males TRANS. We identified 88 (44.7%) of 197 COVID-19 patients as the disease progression MESHD (aggravation) cases. The aggravation cases tend to have more medical comorbidity: hypertension MESHD hypertension HP (34.1%), diabetes (30.7%), and presented with dyspnea MESHD dyspnea HP (34.1%), neutrophilia HP (60.2%), and lymphocytopenia (73.9%), compared with those without. And the patients with disease progression MESHD showed significantly higher level of Fibrinogen (Fbg), D-dimer, IL-6, C-reactive protein (CRP), procalcitonin (PCT), and serum SERO ferritin, and were more prone to develop organ damage in the liver, kidney, and heart (P<0.05). Multivariable regression showed that advanced age TRANS, comorbidities, lymphopenia MESHD lymphopenia HP, and elevated level of Fbg, lactate dehydrogenase (LDH), Cardiac troponin (CTnI), IL-6, serum SERO ferritin were the significant predictors of disease progression MESHD. Further, we investigated antibody SERO responses to SARS-CoV-2 and found that the levels of IgM and IgG were significantly higher in the disease progression MESHD cases compared to non-progression cases from 3 weeks after symptom onset TRANS. In addition, the disease progression MESHD group tended to peak later and has a more vigorous IgM/IgG response against SARS-CoV-2. Further, we performed Kaplan-Meier analysis and found that 61.6% of patients had not experienced ICU transfer or survival from hospital within 25 days from admission.Conclusions: Investigating the potential factors of advanced age TRANS, comorbidities and elevated level of IL-6, serum SERO ferritin and Kaplan-Meier analysis enables early identification and management of patients with poor prognosis. Detection of the dynamic antibody SERO may offer vital clinical information during the course of SARS-CoV-2 and provide prognostic value for patients infection MESHD.  

    An early warning tool for predicting mortality risk of COVID-19 patients using machine learning

    Authors: Muhammad E. H. Chowdhury; Tawsifur Rahman; Amith Khandakar; Somaya Al-Madeed; Susu M. Zughaier; Suhail A. R. Doi; Hanadi Hassen; Mohammad T. Islam

    id:2007.15559v1 Date: 2020-07-29 Source: arXiv

    COVID-19 pandemic has created an extreme pressure on the global healthcare services. Fast, reliable and early clinical assessment of the severity of the disease MESHD can help in allocating and prioritizing resources to reduce mortality. In order to study the important blood SERO biomarkers for predicting disease MESHD mortality, a retrospective study was conducted on 375 COVID-19 positive patients admitted to Tongji Hospital (China) from January 10 to February 18, 2020. Demographic and clinical characteristics, and patient outcomes were investigated using machine learning tools to identify key biomarkers to predict the mortality of individual patient. A nomogram was developed for predicting the mortality risk among COVID-19 patients. Lactate dehydrogenase, neutrophils (%), lymphocyte (%), high sensitive C-reactive protein, and age TRANS - acquired at hospital admission were identified as key predictors of death MESHD by multi-tree XGBoost model. The area under curve (AUC) of the nomogram for the derivation and validation cohort were 0.961 and 0.991, respectively. An integrated score (LNLCA) was calculated with the corresponding death MESHD probability. COVID-19 patients were divided into three subgroups: low-, moderate- and high-risk groups using LNLCA cut-off values of 10.4 and 12.65 with the death MESHD probability less than 5%, 5% to 50%, and above 50%, respectively. The prognostic model, nomogram and LNLCA score can help in early detection of high mortality risk of COVID-19 patients, which will help doctors to improve the management of patient stratification.

    Longitudinal COVID-19 Surveillance and Characterization in the Workplace with Public Health and Diagnostic Endpoints

    Authors: Manjula Gunawardana; Jessica Breslin; John M Cortez; Sofia Rivera; Simon Webster; F Javier Ibarrondo; Otto O Yang; Richard B Pyles; Christina M Ramirez; Amy P Adler; Peter A Anton; Marc M Baum

    doi:10.1101/2020.07.25.20160812 Date: 2020-07-28 Source: medRxiv

    Background The rapid spread of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease MESHD 2019 (COVID-19) have precipitated a global pandemic heavily challenging our social behavior, economy, and healthcare infrastructure. Public health practices currently represent the primary interventions for managing the spread of the pandemic. We hypothesized that frequent, longitudinal workplace disease MESHD surveillance would represent an effective approach to controlling SARS-CoV-2 transmission TRANS among employees and their household members, reducing potential economic consequences and loss of productivity of standard isolation methods, while providing new insights into viral-host dynamics. Methodology and Findings On March 23, 2020 a clinical study (OCIS-05) was initiated at a small Southern California organization. Results from the first 3 months of the ongoing study are presented here. Study participants (27 employees and 27 household members) consented to provide frequent nasal or oral swab samples that were analyzed by RT-qPCR for SARS-CoV-2 RNA using CDC protocols. Only participants testing negative were allowed to enter the "safe zone" workplace facility. Optional blood SERO samples were collected at baseline and throughout the 3-month study. Serum SERO virus-specific antibody SERO concentrations (IgG, IgM, and IgA) were measured using a selective, sensitive, and quantitative ELISA assay SERO developed in house. A COVID-19 infection MESHD model, based on traditional SEIR compartmental models combined with Bayesian non-linear mixed models and modern machine learning, was used to predict the number of employees and household members who would have become infected in the absence of workplace surveillance. Two study participants were found to be infected by SARS-CoV-2 during the study. One subject, a household member, tested positive clinically by RT-qPCR prior to enrollment and experienced typical COVID-19 symptoms that did not require hospitalization. While on study, the participant was SARS-CoV-2 RNA positive for at least 71 days and had elevated virus-specific antibody SERO concentrations (medians: IgM, 9.83 ug mL-1; IgG, 11.5 ug mL-1; IgA, 1.29 ug mL-1) in serum samples SERO collected at three timepoints. A single, unrelated employee became positive for SARS-CoV-2 RNA over the course of the study, but remained asymptomatic TRANS with low associated viral RNA copy numbers. The participant did not have detectable serum SERO IgM and IgG concentrations, and IgA concentrations decayed rapidly (half-life: 1.3 d). The employee was not allowed entry to the safe zone workplace until testing negative three consecutive times over 7 d. No other employees or household members contracted COVID-19 over the course of the study. Our model predicted that under the current prevalence SERO in Los Angeles County without surveillance intervention, up to 7 employees (95% CI = 3-10) would have become infected with at most 1 of them requiring hospitalizations and 0 deaths MESHD. Conclusions Our clinical study met its primary objectives by using intense longitudinal testing to provide a safe work environment during the COVID-19 pandemic, and elucidating SARS-CoV-2 dynamics in recovering and asymptomatic TRANS participants. The surveillance plan outlined here is scalable and transferrable. The study represents a powerful example on how an innovative public health initiative can be dovetailed with scientific discovery.

    Exploration of prognostic factors for critical COVID-19 patients:a nomogram analysis 

    Authors: Lili Wang; Chun Liu; Zhengquan Wang; Yi Lin; Rui Fan

    doi:10.21203/ Date: 2020-07-24 Source: ResearchSquare

    To discuss influencing factors on critical COVID-19 patient’s prognosis, construct a basic model and predict their mortality risks. Retrospectively analyzed the general condition and respective laboratory biomarkers of critical patients with duration≥24 h from Feb. 10th, 2020 to Mar. 30th, 2020 to separate them into a survival group and death MESHD group based on their clinical features. Multiple logistic regression analysis was performed to assess risk factors for critical COVID-19 patient’s and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) was created to evaluate the accuracy of the nomogram. Multi-factor Logistic recovery analysis results show: Age TRANS, Peripheral blood SERO leucocyte count,Lymphocyte percentage, Thrombocyte count and Hyper C-reactive protein are single danger factors of critical COVID-19 patient’s mortality risk (p<0.05). ROC curve indicates Nomogram predictive model AUC is 0.958 (95%CI: 0.923-0.993), which has high predictive value. Findings from this study suggest advanced age TRANS, high peripheral blood SERO leucocyte count, high hyper C-reactive protein, low lymphocyte percentage and low thrombocyte count are risk factors of critical COVID-19 patient’s death MESHD.The Nomogram model is helpful for timely intervention to reduce the incidence of critical COVID-19 patients. 

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MeSH Disease
Human Phenotype

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