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      Immune response in COVID-19: what is next?

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          Abstract

          The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future.

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          Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

          The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.
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            Antibody responses to SARS-CoV-2 in patients with COVID-19

            We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
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              An inflammatory cytokine signature predicts COVID-19 severity and survival

              Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
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                Author and article information

                Contributors
                melino@uniroma2.it
                yufangshi@sibs.ac.cn
                Journal
                Cell Death Differ
                Cell Death Differ
                Cell Death and Differentiation
                Nature Publishing Group UK (London )
                1350-9047
                1476-5403
                17 May 2022
                17 May 2022
                : 1-16
                Affiliations
                [1 ]GRID grid.452253.7, ISNI 0000 0004 1804 524X, The Third Affiliated Hospital of Soochow University/The First People’s Hospital of Changzhou, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine of Soochow University, Medical College, ; Suzhou, China
                [2 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, , Shanghai Institutes for Biological Sciences/Shanghai Jiao Tong University School of Medicine, University of Chinese Academy of Sciences, Chinese Academy of Sciences, ; Shanghai, China
                [3 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Beijing Institute of Biotechnology, , Research Unit of Cell Death Mechanism, Chinese Academy of Medical Sciences, ; 2021RU008, 20 Dongda Street, 100071 Beijing, China
                [4 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Deutsches Zentrum für Immuntherapie (DZI), , Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, ; Erlangen, Germany
                [5 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Internal Medicine 3 - Rheumatology and Immunology, , Friedrich-Alexander-Universität Erlangen‐Nürnberg (FAU) and Universitätsklinikum Erlangen, ; Erlangen, Germany
                [6 ]GRID grid.415788.7, ISNI 0000 0004 1756 9674, Ministry of Health, ; Rome, Italy
                [7 ]GRID grid.6530.0, ISNI 0000 0001 2300 0941, Department of Biology, , TOR, University of Rome Tor Vergata, ; 00133 Rome, Italy
                [8 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, INSERM-U1124, Université Paris, ; Paris, France
                [9 ]GRID grid.411081.d, ISNI 0000 0000 9471 1794, CHU de Québec - Université Laval Research Center, ; Québec City, QC Canada
                [10 ]GRID grid.10388.32, ISNI 0000 0001 2240 3300, Institute of Innate Immunity, , University Hospital Bonn, University of Bonn, ; 53127 Bonn, Germany
                [11 ]GRID grid.425088.3, Research and Development Center, GlaxoSmithKline (GSK), ; Siena, Italy
                [12 ]GRID grid.424247.3, ISNI 0000 0004 0438 0426, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), ; Bonn, Germany
                [13 ]GRID grid.10388.32, ISNI 0000 0001 2240 3300, Genomics & Immunoregulation, LIMES-Institute, University of Bonn, ; Bonn, Germany
                [14 ]GRID grid.452490.e, Department of Biomedical Sciences, , Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, ; 20072 Milan, Italy
                [15 ]IRCCS Humanitas Clinical Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy
                [16 ]GRID grid.4868.2, ISNI 0000 0001 2171 1133, William Harvey Research Institute, Queen Mary University, ; London, UK
                [17 ]GRID grid.415224.4, ISNI 0000 0001 2150 066X, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, ; Toronto, ON M5G 2M9 Canada
                [18 ]GRID grid.194645.b, ISNI 0000000121742757, Department of Pathology, , University of Hong Kong, Hong Kong, ; Pok Fu Lam, 999077 Hong Kong
                [19 ]GRID grid.6530.0, ISNI 0000 0001 2300 0941, Department of Experimental Medicine, , TOR, University of Rome Tor Vergata, ; 00133 Rome, Italy
                Author information
                http://orcid.org/0000-0003-1990-5857
                http://orcid.org/0000-0002-2571-9367
                http://orcid.org/0000-0003-2922-9370
                http://orcid.org/0000-0002-0258-2484
                http://orcid.org/0000-0003-4312-8955
                http://orcid.org/0000-0002-3128-9762
                http://orcid.org/0000-0003-2618-9342
                http://orcid.org/0000-0002-6881-396X
                http://orcid.org/0000-0002-9432-8044
                http://orcid.org/0000-0003-0228-5081
                http://orcid.org/0000-0003-0088-5788
                http://orcid.org/0000-0003-1488-5666
                http://orcid.org/0000-0003-2812-9853
                http://orcid.org/0000-0001-5578-236X
                http://orcid.org/0000-0001-9428-5972
                http://orcid.org/0000-0001-8964-319X
                Article
                1015
                10.1038/s41418-022-01015-x
                9110941
                35581387
                dcb661f4-484c-45e2-b30e-e7ccbafa39aa
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 April 2022
                : 16 April 2022
                : 26 April 2022
                Funding
                Funded by: the National Key R&D Program of China (2021YFA1100600), Jiangsu Province International Science and Technology Cooperation Program (BZ2019017), National Center for International Research-Cambridge-Su Genomic Research Center (2017B01012) and the State Key Laboratory of Radiation Medicine and Protection, Soochow University (GZN1201903).
                Funded by: the National Key R&D Program of China (2021YFA1100600), the Scientific Innovation Project of the Chinese Academy of Sciences (XDA16020403), the National Natural Science Foundation of China (81861138015, 81530043, 31961133024, 81930085 32150710523, and 81571612), Ministry of Health Italy-China cooperation grant & AIRC IG#20473 to GM.
                Funded by: the National Natural Science Foundation of China (32000626), Fellowship of China Postdoctoral Science Foundation (2020M671261)
                Funded by: from the Fondation Recherche Médicale and the Agence Nationale de la Recherche (COVID-I²A) and from Canada Research Chair program
                Funded by: Regione Lazio through LazioInnova Progetto Gruppo di Ricerca n 85-2017-14986; n 33 & 55-2021-T0002E0001, by grants CRC1454 432325352 and CRC1403 414786233 from the Deutsche Forschungsgemeinschaft (DFG) and the grant COVIMMUNE by the Bundesministerium für Bildung und Forschung (BMBF).
                Funded by: CRC1454 432325352 from the DFG and the grant COVIM by the BMBF
                Funded by: a grant from the Italian Ministry of Health
                Funded by: the Associazione Italiana per la Ricerca contro il Cancro (AIRC) to GM (IG#20473; 2018-2022)), to IA (AIRC Start-Up ID 23219; 2020-2024).
                Categories
                Review Article

                Cell biology
                infectious diseases,antimicrobial responses
                Cell biology
                infectious diseases, antimicrobial responses

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