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    IP-10 and MCP-1 as biomarkers predicting disease severity of COVID-19

    Authors: Yu Chen; Jinglan Wang; Chenxi Liu; Longxiang Su; Dong Zhang; Junping Fan; Yanli Yang; Meng Xiao; Jing Xie; Yingchun Xu; Yongzhe Li; Shuyang Zhang

    doi:10.21203/rs.3.rs-57499/v1 Date: 2020-08-11 Source: ResearchSquare

    Background: COVID-19 is a viral respiratory disease MESHD caused by the severe acute respiratory syndrome-Coronavirus type 2 MESHD (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis MESHD arterial thrombosis HP because of the activation of many factors involved in it, including inflammation MESHD, platelet activation and endothelial dysfunction. Therefore, this study focused on coagulation and thrombosis MESHD-related indicators (IP-10, MCP-1 and MIP1a) in COVID-19, with the hope to find biomarkers that can predict patients’ outcome.Methods: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill MESHD patients. The serum SERO IP-10, MCP-1 and MIP1a level in both groups was detected using the enzyme-linked immunosorbent assay SERO ( ELISA SERO) kit. The clinical symptoms, laboratory test results and the outcome of COVID-19 patients were retrospectively analyzed.Results: The serum SERO IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1a between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death MESHD.Conclusions: IP-10 and MCP-1 are biomarkers predicting the severity of COVID-19 disease and could be related to the risk of death in COVID-19 patients. In addition, anti-IP-10 antibody SERO treatment may represent a new approach in COVID-19 patients, especially the ones with thrombotic MESHD events.

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

    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 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.

    Asymptomatic TRANS COVID-19; We Don’t Know What We Don’t Know

    Authors: Olen R. Brown

    id:10.20944/preprints202007.0681.v1 Date: 2020-07-28 Source: Preprints.org

    Decisions affecting the COVID-19 pandemic, by the individual and those with highest authority, are being made on the basis of unreliable data. Data about cases and deaths MESHD are collected daily but represent only a sample of reality. Statistics convert sample data into more reliable estimates. However, statistics have no magical powers; reliability requires dependable data. It is futile to rail against this darkness; COVID-19 is not a scientific experiment. However, we must do better both with data collection and data analysis. In this review, I focus on one element of the data, the asymptomatic TRANS case of COVID-19. Without reliable information about this number, decision makers are significantly blinded. By its nature, the asymptomatic TRANS case is hidden but contaminating to understanding COVID-19. The true case rate and death rate per case are unknowable without knowing the fraction of cases that are asymptomatic TRANS. The best estimate of asymptomatic TRANS cases is in the CDC document: COVID-19 Pandemic Planning Scenarios. For four different scenarios the estimates range from 10% to 70%, with the best estimate of 40% for asymptomatic TRANS cases. However, even the definition of the asymptomatic TRANS case is problematic. In simplest terms, two elements are required: an infection MESHD and no symptoms. How is “no symptoms” to be usefully defined? It appears to be analogous to pontificating about black swans from studying only white swans. It implies infection MESHD, but how is infection defined? Is it presence of the virus, replication of the virus, or presence of antibodies SERO? Is asymptomatic TRANS disease an oxymoron? Without extensive, purposeful screening for specifically defined, essential symptoms and appropriate virus and antibody testing SERO over time, the class of asymptomatic TRANS cases remains unknown. Current estimates range from <20% to ˃80%. If low, it can be ignored; if high, it dramatically and proportionately lowers the case rate and the death MESHD rate per case. Consequentially, the asymptomatic TRANS rate dramatically affects our societal and political responses. In this focused review, we assess the limitations of the published estimates, bring attention to the importance of obtaining accurate data, and exhort that high priority be given in the scientific community to understanding the issue, asymptomatic TRANS COVID-19 cases.

    Antibody Testing SERO Documents the Silent Spread of SARS-CoV-2in New York Prior to the First Reported Case

    Authors: Kathrine Meyers; Lihong Liu; Wen-Hsuan Lin; Yang Luo; Michael Yin; Yumeng Wu; Sandeep Wontakal; Alex Rai; Francesca La Carpia; Sebastian Fernando; Mitra Dowlatshahi; Elad Elkayam; Ankur Garg; Leemor Joshua-Tor; John Wolk; Barbara Alpert; Marie-Laure Romney; Brianna Costabile; Edoardo Gelardi; Francesca Vallese; Oliver Clarke; Filippo Mancia; Anne-Catrin Uhlemann; Magdalena Sobieszczyk; Alan Perelson; Yaoxing Huang; Eldad Hod; David Ho

    doi:10.21203/rs.3.rs-39880/v1 Date: 2020-07-02 Source: ResearchSquare

    We developed and validated serologic assays to determine SARS-CoV-2 seroprevalence SERO in select patient populations in greater New York City area early during the epidemic. We tested “discarded” serum samples SERO from February 24 to March 29 for antibodies SERO against SARS-CoV-2 spike trimer and nucleocapsid protein. Using known durations for antibody SERO development, incubation period TRANS, serial interval TRANS, and reproductive ratio for this pandemic, we determined that introduction of SARS-CoV-2 into New York likely occurred between January 23 and February 4, 2020. SARS-CoV-2 spread silently for 4–5 weeks before the first community acquired infection MESHD was reported. A novel coronavirus emerged in December 2019 in Wuhan, China1,2 and devasted Hubei Province in early 2020 before spreading to every province within China and nearly every country in the world3. This pathogen, now termed severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has caused a global pandemic, with ~ 10 million cases and over 500,000 deaths MESHD reported through June 30, 20203. The first case of SARS-CoV-2 infection MESHD in the United States was identified on January 19, 2020 in a man who returned to the State of Washington from Wuhan4. In the ensuing months, the U.S. has become a hotspot of the pandemic, presently accounting for almost one third of the total caseload and over one fourth of the deaths3. The first confirmed case TRANS in New York was reported on March 1 in a traveler recently returned from Iran. The first community-acquired SARS-CoV-2 infection MESHD was diagnosed on March 3 in a 50-year-old male TRANS who lived in New Rochelle and worked in New York City (https://www1.nyc.gov/site/doh/covid/covid-19-data-archive.page.) In the ensuing 18 weeks, New York City has suffered a peak daily infection number of ~ 4,500 (Fig. 1a) and a cumulative caseload of ~ 400,000 to date. The time period when SARS-CoV-2 gained entry into this epicenter of the pandemic remains unclear.

    Prevalence SERO, specificity, and clinical association of anti-phospholipid antibodies SERO in COVID-19 patients: are the antibodies SERO really guilty?

    Authors: Maria Orietta Borghi; Asmaa Beltagy; Emirena Garrafa; Daniele Curreli; Germana Cecchini; Caterina Bodio; Claudia Grossi; Simonetta Blengino; Angela Tincani; Franco Franceschini; Laura Andreoli; Maria Grazia Lazzaroni; Silvia Piantoni; Stefania Masneri; Francesca Crisafulli; Dulio Brugnoni; Maria Lorenza Muiesan; Massimo Salvetti; Gianfranco Parati; Erminio Torresani; Michael Mahler; Francesca Heilbron; Francesca Pregnolato; Martino Pengo; Francesco Tedesco; Nicola Pozzi; Pier Luigi Meroni

    doi:10.1101/2020.06.17.20134114 Date: 2020-06-19 Source: medRxiv

    Background. Critically ill MESHD patients with coronavirus disease MESHD 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy MESHD which leads to organ failure MESHD and death MESHD. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies SERO (aPL) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant HP lupus anticoagulant MESHD) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-{beta}2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies SERO was not investigated systematically. Epitope specificity of anti-{beta}2GPI antibodies SERO was not reported. Objective. To evaluate the prevalence SERO and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-{beta}2GPI antibodies SERO. Methods. ELISA SERO and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic MESHD events. Results. Anti-{beta}2GPI IgG/IgA/IgM were the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM were detected in 5.7/6.6% by ELISA SERO. Comparable values were found by chemiluminescence. aPS MESHD/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA SERO. No association between thrombosis MESHD and aPL was found. Reactivity against domain 1 and 4-5 of {beta}2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-{beta}2GPI nor with thrombosis MESHD. Conclusions. aPL show a low prevalence SERO in COVID-19 patients and are not associated with major thrombotic MESHD events. aPL in COVID-19 patients are mainly directed against {beta}2GPI but display an epitope specificity different from antibodies SERO in antiphospholipid syndrome.

    In-depth virological assessment of kidney transplant recipients with COVID-19 MESHD

    Authors: Ilies Benotmane; Gabriela Gautier-Vargas; Maris-Josee Wendling; Peggy Perrin; Aurelie Velay; Xavier Bassand; Dimitri Bedo; Clement Baldacini; Mylene Sagnard; Dogan-Firat Bozman; Margaux Della-Chiesa; Morgane Solis; Floriane Gallais; Noelle Cognard; Jerome Olagne; Heloise Delagreverie; Louise Gontard; Baptiste Panaget; David Marx; Francoise Heibel; Laura Braun-Parvez; Bruno Moulin; Sophie Caillard; Samira Fafi-Kremer

    doi:10.1101/2020.06.17.20132076 Date: 2020-06-19 Source: medRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease MESHD 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody SERO kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma SERO viral loads via RT-PCR and SARS-CoV-2 serology via ELISA SERO and study their association with severe forms of COVID-19 and death MESHD in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma SERO viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset TRANS. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma SERO viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies SERO the second week after symptom onset TRANS that persisted for two months. We conclude that plasma SERO viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.

    Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples

    Authors: Xiaotian Tan; Cory Lin; Jie Zhang; Maung Kyaw Khaing Oo; Xudong Fan

    doi:10.1101/2020.04.20.052233 Date: 2020-04-22 Source: bioRxiv

    COVID-19 pandemic has caused tens of thousands of deaths MESHD and is now a severe threat to global health. Clinical practice has demonstrated that the SARS-CoV-2 S1 specific antibodies SERO and viral antigens can be used as diagnostic and prognostic markers of COVID-19. However, the popular point-of-care biomarker detection technologies, such as the lateral-flow test strips, provide only yes/no information and have very limited sensitivities SERO. Thus, it has a high false negative rate and cannot be used for the quantitative evaluation of patients immune response. Conventional ELISA SERO ( enzyme-linked immunosorbent assay SERO), on the other hand, can provide quantitative, accurate, and sensitive results, but it involves complicated and expensive instruments and long assay time. In addition, samples need to be sent to centralized labs, which significantly increases the turn-around time. Here, we present a microfluidic ELISA SERO technology for rapid (15-20 minutes), quantitative, sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen - S protein in serum SERO. We also characterized various humanized monoclonal IgG, and identified a candidate with a high binding affinity towards SARS-CoV-2 S1 protein that can serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. Furthermore, we demonstrated that our microfluidic ELISA SERO platform can be used for rapid affinity evaluation of monoclonal anti-S1 antibodies SERO. The microfluidic ELISA SERO device is highly portable and requires less than 10 L of samples for each channel. Therefore, our technology will greatly facilitate rapid and quantitative analysis of COVID-19 patients and vaccine recipients at point-of-care.

    COVID-19 experience: first Italian survey on healthcare staff members from a Mother- Child TRANS Research hospital using combined molecular and rapid immunoassays SERO test

    Authors: Manola Comar; Marco Brumat; Maria Pina Concas; Giorgia Argentini; Annamonica Bianco; Livia Bicego; Roberta Bottega; Petra Carli; Andrea Cassone; Eulalia Catamo; Massimiliano Cocca; Massimo Del Pin; Mariateresa Di Stazio; Agnese Feresin; Martina La Bianca; Sara Morassut; Anna Morgan; Giulia Pelliccione; Vincenzo Petix; Giulia Ragusa; Antonietta Robino; Stefano Russian; Beatrice Spedicati; Sarah Suergiu; Marianela Urriza; Fulvia Vascotto; Paola Toscani; Giorgia Girotto; Paolo Gasparini

    doi:10.1101/2020.04.19.20071563 Date: 2020-04-22 Source: medRxiv

    The fast spread of the novel coronavirus (SARS-CoV-2) has become a global threat hitting the worldwide fragile health care system. In Italy, there is a continued COVID-19 growth of cases and deaths MESHD that requires control measures for the correct management of the epidemiological emergency. To contribute to increasing the overall knowledge of COVID-19, systematic tests in the general population are required. Here, we describe the first Italian survey performed in 727 employees belonging to a Mother- Child TRANS Research hospital tested for both viral (nasopharyngeal and oropharyngeal swabs) and antibody SERO presence. Individuals were divided into three risk categories (high, medium and low) according to their job activity. Only one subject was positive at the swab test while 17.2% of the cohort was positive for the presence of antibodies SERO. Results highlighted that the presence of Positive antibodies SERO is significantly associated with high and medium risk exposure occupation (p-value=0.026) as well as cold and conjunctivitis HP conjunctivitis MESHD symptoms (p-value=0.016 and 0.042 respectively). Moreover, among healthcare professionals, the category of medical doctors showed a significant association with the presence of antibodies SERO against SARS-CoV-2 (p-value=0.0127). Finally, we detected a rapid decrease in antibody SERO intensity between two assessments performed within a very short period (p-value=0.009). Overall, the present study increases our knowledge of the epidemiological data of COVID-19 infection MESHD in Italy, suggesting a high prevalence SERO of immune individuals (i.e. at least among at-risk categories) and the efficacy of the combined diagnostic protocol to monitor the possible outbreak.

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