Corpus overview


MeSH Disease

Human Phenotype


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    Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma SERO in severe COVID-19

    Authors: Purbita Bandopadhyay; Ranit D'Rozario; Abhishake Lahiri; Jafar Sarif; Yogiraj Ray; Shekhar Ranjan Paul; Rammohan Roy; Rajsekhar Maiti; Kausik Chaudhuri; Sougata Bagchi; Ayan Maiti; Md. Masoom Parwez; Biswanath Sharma Sarkar; Devlina Roy; Rahul Chakraborty; Janani Srinivasa Vasudevan; Sachin Sharma; Durba Biswas; Chikam Maiti; Bibhuti Saha; Prasun Bhattacharya; Rajesh Pandey; Shilpak Chatterjee; Sandip Paul; Dipyaman Ganguly; Sarah Dorothea Müller; Uwe Gerd Liebert; Naveed Ishaque; Lars Kaderali; Leif Erik Sander; Sven Laudi; Christian Drosten; Roland Eils; Christian Conrad; Ulf Landmesser; Irina Lehmann

    doi:10.1101/2020.09.21.20199109 Date: 2020-09-23 Source: medRxiv

    In a randomized control trial on convalescent plasma SERO therapy (CPT) in severe COVID-19, we characterized the nature, in terms of abundance of forty eight cytokines, and dimensions, in terms of their interrelationships, of the hyper-immune activation-associated cytokine storm in patients suffering from acute respiratory distress syndrome MESHD respiratory distress HP syndrome. We found plasma SERO MCP3 level to be a key correlate for mitigation of hypoxia MESHD, irrespective of therapeutic regimen. We also identified an anti-inflammatory role of CPT independent of its neutralizing antibody SERO content, and a linear regression analysis revealed that neutralizing antibodies SERO as well as the anti-inflammatory effect of CPT both contribute to marked immediate reductions in hypoxia MESHD, as compared to patients on standard therapy.

    KIM-1/TIM-1 is a Receptor for SARS-CoV-2 in Lung and Kidney MESHD

    Authors: Takaharu Ichimura; Yutaro Mori; Philipp Aschauer; Krishna M Padmanabha Das; Robert F Padera Jr.; Astrid Weins; Mahmoud L Nasr; Joseph V Bonventre; Gerald Choon Huat Koh; Thean Yen Tan; Chuin Siau; Andrzej Horban; Justyna Dominika Kowalska; Michela Sali; Massimiliano Papi; Jayashree Kalpathy-Cramer; Fredrik Nyberg; Jose D Posada; Martina Recalde; Elena Roel; Karishma Shah; Nigam Shah; Lisa M Schilling; Vignesh Subbian; David Vizcaya; Lin Zhang; Ying Zhang; Hong Zhu; Li Liu; Peter Rijnbeek; George Hripcsak; Jennifer C.E Lane; Edward Burn; Christian Reich; Marc A Suchard; Talita Duarte-Salles; Krisitn Kosta; Patrick B Ryan; DANIEL PRIETO-ALHAMBRA; Christoph Lange; Georg Laue; Clemes Lier; Matthias Lindner; Georgios Marinos; Robert Markewitz; Jacob Nattermann; Rainer Noth; Peter Pickkers; Klaus F. Rabe; Alina Renz; Christoph Roecken; Jan Rupp; Annika Schaffarzyk; Alexander Scheffold; Jonas Schulte-Schrepping; Domagoj Schunck; Dirk Skowasch; Thomas Ulas; Klaus-Peter Wandinger; Michael Wittig; Johannes Zimmermann; Hauke Busch; Bimba F. Hoyer; Christoph Kaleta; Jan Heyckendorf; Matthijs Kox; Jan Rybniker; Stefan Schreiber; Joachim Schultze; Philip Rosenstiel; - HCA Lung Biological Network; - Deutsche COVID-19 Omics Initiative (DeCOI)

    doi:10.1101/2020.09.16.20190694 Date: 2020-09-18 Source: medRxiv

    SARS-CoV-2 precipitates respiratory distress HP by infection of airway epithelial cells and is often accompanied by acute kidney injury HP acute kidney injury MESHD. We report that Kidney Injury MESHD Molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1) is expressed in lung and kidney epithelial cells in COVID-19 patients and is a receptor for SARS-CoV-2. Human and mouse lung and kidney epithelial cells express KIM-1 and endocytose nanoparticles displaying the SARS-CoV-2 spike protein (virosomes). Uptake was inhibited both by anti-KIM-1 antibodies SERO and by TW-37, our newly discovered inhibitor of KIM-1-mediated endocytosis. Enhanced KIM-1 expression by human kidney tubuloids increased uptake of virosomes. KIM-1 positive cells express less angiotensin-converting enzyme 2 (ACE2), the well-known receptor for SARS-CoV-2. Using microscale thermophoresis, the EC50 for KIM-1-SARS-CoV-2 spike protein, and receptor binding domain (RBD) interactions, were 19 and 10 nM respectively. Thus KIM-1 is an alternative receptor to ACE2 for SARS-CoV-2. KIM-1 targeted therapeutics may prevent and/or treat COVID-19.

    Detection of SARS-CoV-2 in peritoneal fluid from patients with kidney disease MESHD and COVID-19: report of two cases

    Authors: Margarita Ibarra-Hernandez; María de la Luz Alcantar-Vallín; Rodolfo I. Cabrera-Silva; Karina Sánchez-Reyes; Monserrat Alvarez-Zavala; Judith C. De Arcos-Jiménez; Luz A. González-Hernández; Vida V. Ruiz-Herrera; Sara A. Aguirre-Díaz; Roxana García-Salcido; Guillermo García-García; Jaime F. Andrade-Villanueva

    doi:10.21203/ Date: 2020-09-16 Source: ResearchSquare

    Background: Coronavirus disease-2019 (COVID-19) has a broad clinical presentation, involving multiple organs besides the respiratory system. Currently, there is little evidence available on the presence of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in peritoneal fluid (PF). In this study, we describe the detection of SARS-CoV-2 in the PF of two patients with COVID 19 and kidney disease MESHD.Case presentation: Case 1: A 71-year-old woman with a history of end-stage kidney disease MESHD who presented with a 15-day evolution of progressive dyspnea HP dyspnea MESHD, accompanied by dry cough MESHD cough HP and fever HP fever MESHD; IgM antibodies SERO to SARS-CoV-2 were detected on admission. Real-time SARS-CoV-2 polymerase chain reaction (qRT-PCR) in the PF was positive. Three days after admission the patient's respiratory distress HP improved and she was discharged after 8 days of hospitalization.Case 2: A 78-year-old woman, with type 2 diabetes MESHD, hypertension HP hypertension MESHD, a 15-day history of polypnea, and a 5-day onset of fever HP fever MESHD and dyspnea HP dyspnea MESHD. IgM and IgG antibodies SERO to SARS-CoV-2 were detected on admission, as well as a positive nasopharyngeal qRT-PCR test for SARS-CoV-2. During hospitalization she developed acute kidney injury HP acute kidney injury MESHD, requiring peritoneal dialysis, SARS-CoV-2 was confirmed in PF by qRT-PCRConclusions: These two cases highlights the importance of increasing the level of awareness for the presence and possible SARS-CoV-2 transmission TRANS through non-respiratory routes, like peritoneal fluid.Emphasis should be given to appropriate preventive strategies for minimizing the risk of transmission TRANS of COVID-19 from patients on peritoneal dialysis in both inpatient and outpatient settings.

    A COVID-19 antibody SERO curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation

    Authors: Sisi Kang; Mei Yang; Suhua He; Yueming Wang; Xiaoxue Chen; Yaoqing Chen; Zhongsi Hong; Jing Liu; Guanmin Jiang; Qiuyue Chen; Ziliang Zhou; Zhechong Zhou; Zhaoxia Huang; Xi Huang; Huanhuan He; Weihong Zheng; Hua-Xin Liao; Fei Xiao; Hong Shan; Shoudeng Chen; Shunhua Long; Fang Gong; Luo Li; Yang Wu; Wei Xu; Xia Cai; Di Qu; Zhenghong Yuan; Qingzhu Gao; Guiji Zhang; Changlong He; Yaru Nai; Kun Deng; Li Du; Ni Tang; Youhua Xie; Ailong Huang; Aishun Jin; Louis M. Weiss; Jonathan R. Lai; Kartik Chandran

    doi:10.1101/2020.09.10.292318 Date: 2020-09-11 Source: bioRxiv

    Although human antibodies SERO elicited by severe acute respiratory distress HP respiratory distress MESHD syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection MESHD, little is known about the function of N-directed antibodies SERO. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies SERO (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody SERO responses to SARS-CoV-2 N MESHD protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation MESHD, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody SERO to N protein.

    Impaired cellular immunity to SARS-CoV-2 in severe COVID-19 patients

    Authors: Ling Ni; Meng-Li Cheng; Hui Zhao; Yu Feng; Jingyuan Liu; Fang Ye; Qing Ye; Gengzhen Zhu; Xiaoli Li; Pengzhi Wang; Jing Shao; Yong-qiang Deng; Peng Wei; Fang Chen; Cheng-feng Qin; Guoqing Wang; Fan Li; Hui Zeng; Chen Dong

    doi:10.1101/2020.08.10.20171371 Date: 2020-08-12 Source: medRxiv

    The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, the basis of which remains largely unclear. Currently, though convalescent individuals have been shown with both cellular and humoral immune responses, there is very limited understanding on the immune responses, especially adaptive immune responses, in patients with severe COVID-19. Here, we examined 10 blood SERO samples from COVID-19 patients with acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD). The majority of them (70%) mounted SARS-CoV-2-specific humoral immunity with production of neutralizing antibodies SERO. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, accompanied with decreased IFNg expression in CD4+ T cells in peripheral blood SERO from severe patients. Most notably, we failed in detecting SARS-CoV-2-specific IFNg production by peripheral blood SERO lymphocytes from these patients. Our work thus indicates that COVID-19 patients with severe symptoms are associated with defective cellular immunity, which not only provides insights on understanding the pathogenesis of COVID-19, but also has implications in developing an effective vaccine to SARS-CoV-2.

    Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission TRANS associated with increased mortality in Western Europe and the United States

    Authors: Yuan Hu; Lee W Riley

    doi:10.1101/2020.07.13.20152959 Date: 2020-07-15 Source: medRxiv

    Mechanisms underlying the acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD)-like clinical manifestations leading to deaths in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility TRANS and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody SERO-dependent enhancement (ADE) response, which could explain the ARDS MESHD-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies SERO against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.

    Antibody SERO responses to SARS-CoV2 are distinct in children TRANS with MIS-C compared to adults TRANS with COVID-19

    Authors: Stuart P Weisberg; Thomas Connors; Yun Zhu; Matthew Baldwin; Wen-Hsuan Lin; Sandeep Wontakal; Peter A Szabo; Steven B Wells; Pranay Dogra; Joshua I Gray; Emma Idzikowski; Francesca Bovier; Julia Davis-Porada; Rei Matsumoto; Maya Meimei Li Poon; Michael P Chait; Cyrille Mathieu; Branka Horvat; Didier Decimo; Zachary C Bitan; Francesca La Carpia; Stephen A Ferrara; Emily Mace; Joshua Milner; Anne Moscona; Eldad A Hod; Matteo Porotto; Donna L Farber

    doi:10.1101/2020.07.12.20151068 Date: 2020-07-14 Source: medRxiv

    Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age TRANS. While children TRANS are largely spared from severe respiratory disease MESHD, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome MESHD ( MIS-C MESHD) similar to Kawasaki's disease MESHD. Here, we show distinct antibody SERO (Ab) responses in children TRANS with MIS-C compared to adults TRANS with severe COVID-19 causing acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD), and those who recovered from mild disease. There was a reduced breadth and specificity of anti- SARS-CoV-2-specific antibodies SERO in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children TRANS and adults TRANS who develop severe disease, with implications for optimizing treatments based on symptom and age TRANS.

    Placental SARS-CoV-2 in a patient with mild COVID-19 disease

    Authors: Albert L. Hsu; Minhui Guan; Eric Johannesen; Amanda J. Stephens; Nabila Khaleel; Nikki Kagan; Breanna C. Tuhlei; Xiu-Feng Wan

    doi:10.1101/2020.07.11.20149344 Date: 2020-07-14 Source: medRxiv

    Background: The full impact of COVID-19 on pregnancy remains uncharacterized. Current literature suggests minimal maternal, fetal, and neonatal morbidity and mortality,1 and COVID-19 manifestations appear similar between pregnant and non-pregnant women.2 We present a case of placental SARS-CoV-2 virus in a woman with an uncomplicated pregnancy and mild COVID-19 disease. Methods: A pregnant woman was evaluated at University of Missouri Women and Childrens Hospital. Institutional review board approval was obtained; information was obtained from medical records. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect SARS-CoV-2. A gynecological pathologist examined the placenta and performed histolopathology. Sections were formalin-fixed and paraffin-embedded; slides were cut and subjected to hematoxylin-and-eosin or immunohistochemistry (IHC) staining. IHC was performed with specific monoclonal antibodies SERO to detect SARS-CoV-2 antigen or to identify trophoblasts. Findings: A 29 year-old multigravida presented at 40-4/7 weeks for labor induction. With myalgias HP myalgias MESHD two days prior, she tested positive for SARS-CoV-2. Her parents TRANS were in self-isolation for COVID-19 positivity; husband was asymptomatic TRANS and tested negative for COVID-19, but exposed to a workplace (meatpacking facility) outbreak. Prenatal course was uncomplicated, with no gestational hypertension HP hypertension MESHD. She was afebrile and asymptomatic TRANS with normal vital signs throughout hospitalization. Her myalgias HP myalgias MESHD improved prior to admission. A liveborn male TRANS infant was delivered vaginally. Newborn course was uneventful; he was appropriate for gestational age TRANS, physical was unremarkable, and he was discharged home at 36 hours. COVID-19 RT-PCR test was negative at 24 hours. At one-week follow-up, newborn was breastfeeding well, with no fevers HP or respiratory distress HP. Overall placental histology is consistent with acute uterine hypoxia MESHD (subchorionic laminar necrosis MESHD) superimposed on chronic uterine hypoxia MESHD (extra-villous trophoblasts and focal chronic villitis MESHD). IHC using SARS-CoV-2 nucleocapsid-specific monoclonal antibody SERO demonstrated SARS-CoV-2 antigens throughout the placenta in chorionic villi endothelial cells, and rarely in CK7-expressing trophoblasts. Negative control placenta (November 2019 delivery) and ferret nasal turbinate tissues (not shown) were negative for SARS-CoV-2. Interpretation: In this report, SARS-CoV-2 was found in the placenta, but newborn was COVID-19 negative. Our case shows maternal vascular malperfusion, with no features of fetal vascular malperfusion. To our knowledge, this is the first report of placental COVID-19 despite mild COVID-19 disease in pregnancy (with no symptoms of COVID-19 aside from myalgias HP myalgias MESHD); specifically, this patient had no fever HP fever MESHD, cough HP cough MESHD, or shortness of breath MESHD, but only myalgias HP myalgias MESHD and sick contacts. Despite her having mild COVID-19 disease in pregnancy, we demonstrate placental vasculopathy MESHD and presence of SARS-CoV-2 virus across the placenta. Evidence of placental COVID-19 raises concern for possible placental vasculopathy MESHD (potentially leading to fetal growth restriction, pre- eclampsia HP eclampsia MESHD, and other pregnancy complications) as well as for potential vertical transmission TRANS -- especially for pregnant women who may be exposed to COVID-19 in early pregnancy. Further studies are urgently needed, to determine whether women with mild, pre-symptomatic, or asymptomatic TRANS COVID-19 may have SARS-CoV-2 virus that can cross the placenta, cause fetal vascular malperfusion, and possibly affect the fetus. This raises important public health and public policy questions of whether future pregnancy guidance should include stricter pandemic precautions, such as screening for a wider array of COVID-19 symptoms, increased antenatal surveillance, and possibly routine COVID-19 testing on a regular basis throughout pregnancy.

    SARS-CoV-2 assays to detect functional antibody SERO responses that block ACE2 recognition in vaccinated animals and infected MESHD patients

    Authors: Daniel W Kulp; Susanne Walker; Neethu Chokkalingam; Emma L Reuschel; Mansi Purwar; Ziyang Xu; Ebony Y Gary; Kevin Y. Kim; Katherine Schultheis; Jewell Walters; Stephanie Ramos; Trevor R.F. Smith; Kate Broderick; Pablo Tebas; Ami Patel; David B Weiner

    doi:10.1101/2020.06.17.158527 Date: 2020-06-20 Source: bioRxiv

    SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2 MESHD) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress HP and significant mortality. The global outbreak of this novel coronavirus has now infected >8 million people worldwide with >2 million cases in the US (June 17th, 2020). There is an urgent need for vaccines and therapeutics to combat the spread of this coronavirus. Similarly, the development of diagnostic and research tools to determine infection MESHD and vaccine efficacy are critically needed. Molecular assays have been developed to determine viral genetic material present in patients. Serological assays SERO have been developed to determine humoral responses to the spike protein or receptor binding domain (RBD). Detection of functional antibodies SERO can be accomplished through neutralization of live SARS-CoV2 virus, but requires significant expertise, an infectible stable cell line, a specialized BioSafety Level 3 (BSL-3) facility. As large numbers of people return from quarantine, it is critical to have rapid diagnostics that can be widely adopted and employed to assess functional antibody SERO levels in the returning workforce. This type of surrogate neutralization diagnostic can also be used to assess humoral immune responses induced in patients from the large number of vaccine and immunotherapy trials currently on-going. Here we describe a rapid serological diagnostic assay for determining antibody SERO receptor blocking and demonstrate the broad utility of the assay by measuring the antibody SERO functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients.

    Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma SERO. A proof of concept single arm multicenter interventional trial

    Authors: Cesare Perotti; Fausto Baldanti; Raffaele Bruno; Claudia Delfante; Elena Seminari; Salvatore Casari; Elena Percivalle; Claudia Glingani; Valeria Musella; Mirko Belliato; Martina Garuti; Federica Meloni; Marilena Frigato; Antonio Di Sabatino; Catherine Klersy; Giuseppe De Donno; Massimo Franchini

    doi:10.1101/2020.05.26.20113373 Date: 2020-05-29 Source: medRxiv

    BACKGROUND Hyperimmune plasma SERO from Covid-19 convalescent is a potential treatment for severe Covid-19. METHODS We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma SERO ( neutralizing antibodies SERO titer [≥]1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety. RESULTS The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged TRANS 63, 61% male TRANS, 30 on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related). CONCLUSIONS Hyperimmune plasma SERO in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma SERO banking, development of standardized pharmaceutical products and monoclonal antibodies SERO.

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MeSH Disease
Human Phenotype

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