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      Convalescent plasma in Covid-19: Possible mechanisms of action

      review-article
      a , a , b , a , a , c , d , e , a , f , g , a , b , h , i , a , b , *
      Autoimmunity Reviews
      The Author(s). Published by Elsevier B.V.
      Coronavirus, COVID-19, SARS-Cov-2, Convalescent plasma, Cytokines, Intravenous immunoglobulins, Neutralizing antibodies, ACE-2 receptor, 2019-nCoV, 2019 novel coronavirus, ACE-2, Angiotensin converting enzyme-2., ADE, Antibody-dependent enhancement., BAFF, B cell–activating factor., BCR, B-cell receptor., COVID-19, Coronavirus disease 2019., CP, Convalescent plasma., DCs, Dendritic cells., HIV, Human immunodeficiency virus., ICU, Intensive care unit., IgG, Immunoglobulin G., IgM, Immunoglobulin M., IVIg, Intravenous immunoglobulin., MERS, Middle East respiratory syndrome., MERS-CoV, MERS coronavirus., NAbs, Neutralizing antibodies., NAT, Nucleic acid test., S1-RBD, Spike1-receptor binding protein, SARS, Severe acute respiratory syndrome coronavirus., SARS-CoV, SARS coronavirus.

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          Abstract

          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, antibiotics and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system ( i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of PC are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality.

          Highlights

          • Coronavirus disease 19 (COVID-19) is an emerging viral threat with major repercussions for public health.

          • There is not specific treatment for COVID-19.

          • Convalescent plasma (CP) emerges as the first option of management for hospitalized patients with COVID-19.

          • Transference of neutralizing antibodies helps to control COVID-19 infection and modulates inflammatory response.

          • Other plasma components may enhance the antiviral and anti-inflammatory properties of CP.

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          Most cited references85

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

              Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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                Author and article information

                Contributors
                Journal
                Autoimmun Rev
                Autoimmun Rev
                Autoimmunity Reviews
                The Author(s). Published by Elsevier B.V.
                1568-9972
                1873-0183
                5 May 2020
                5 May 2020
                : 102554
                Affiliations
                [a ]Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
                [b ]Clínica del Occidente, Bogota, Colombia
                [c ]Instituto Distrital de Ciencia Biotecnología e Investigación en Salud, IDCBIS, Bogota, Colombia
                [d ]GenomaCES, Universidad CES, Medellin, Colombia
                [e ]Fundación Universitaria de Ciencias de la Salud (FUCS), Bogota, Colombia
                [f ]Internal Medicine Department, Universidad CES, Medellin, Colombia
                [g ]Epidemiology and Biostatistics Research Group, Universidad CES, Medellin, Colombia
                [h ]Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to Tel-Aviv University, Tel Aviv, Israel
                [i ]Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, Saint-Petersburg, Russian Federation
                Author notes
                [* ]Corresponding author at: Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 26-63-B-51, 110010 Bogota, Colombia. juan.anaya@ 123456urosario.edu.co
                Article
                S1568-9972(20)30116-6 102554
                10.1016/j.autrev.2020.102554
                7198427
                32380316
                66f96682-b2d1-4534-8daa-66567e93b84f
                © 2020 The Author(s). Published by Elsevier B.V.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 11 April 2020
                Categories
                Article

                Immunology
                coronavirus,covid-19,sars-cov-2,convalescent plasma,cytokines,intravenous immunoglobulins,neutralizing antibodies,ace-2 receptor,2019-ncov, 2019 novel coronavirus,ace-2, angiotensin converting enzyme-2.,ade, antibody-dependent enhancement.,baff, b cell–activating factor.,bcr, b-cell receptor.,covid-19, coronavirus disease 2019.,cp, convalescent plasma.,dcs, dendritic cells.,hiv, human immunodeficiency virus.,icu, intensive care unit.,igg, immunoglobulin g.,igm, immunoglobulin m.,ivig, intravenous immunoglobulin.,mers, middle east respiratory syndrome.,mers-cov, mers coronavirus.,nabs, neutralizing antibodies.,nat, nucleic acid test.,s1-rbd, spike1-receptor binding protein,sars, severe acute respiratory syndrome coronavirus.,sars-cov, sars coronavirus.

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