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      Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity

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          Abstract

          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS-CoV-2 coinfection in K18-hACE2 mice. Our data indicate enhance susceptibility of IAV-infected mice to developing severe disease upon coinfection with SARS-CoV-2 two days later. In contrast to nonfatal influenza and lower mortality rates due to SARS-CoV-2 alone, this coinfection results in severe morbidity and nearly complete mortality. Coinfection is associated with elevated influenza viral loads in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. This protection is antibody-dependent. These data experimentally support the necessity of seasonal influenza vaccination for reducing the risk of severe influenza/COVID-19 comorbidity during the COVID-19 pandemic.

          Abstract

          Influenza A virus (IAV) and SARS-CoV-2 coinfection is a possible scenario during influenza season. Here, the authors show in a mouse model that IAV infection increases the risk of severe disease upon SARS-CoV-2 infection two days later. IAV vaccination, especially antibody-dependent, protects from severe disease during coinfection.

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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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            Co-infections in people with COVID-19: a systematic review and meta-analysis

            Highlights • SARS-CoV-2, the cause of COVID19 disease, has spread globally since late 2019 • Bacterial coinfections associated with mortality in previous influenza pandemics • Proportion of COVID19 patients with bacterial coinfection less than in flu pandemics • Higher proportion of critically-ill with bacterial coinfections than in mixed setting • Bacterial co-pathogen profiles different to those in influenza co-infections • Fungal coinfection diagnosis difficult so high level suspicion in critically-ill
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              SARS-CoV-2 infection of hACE2 transgenic mice causes severe lung inflammation and impaired function

              Although animal models have been evaluated for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, none have fully recapitulated the severe lung disease phenotypes seen in hospitalized human cases. Here, we evaluate transgenic mice expressing the human ACE2 receptor driven by the cytokeratin-18 gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils, and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of NF-kB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.
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                Author and article information

                Contributors
                tomeri@iibr.gov.il
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                5 October 2021
                5 October 2021
                2021
                : 12
                : 5819
                Affiliations
                [1 ]GRID grid.419290.7, ISNI 0000 0000 9943 3463, Departments of Infectious Diseases, , Israel Institute for Biological Research, ; Ness-Ziona, 7410001 Israel
                [2 ]GRID grid.419290.7, ISNI 0000 0000 9943 3463, Department of Biochemistry and Molecular Genetics, , Israel Institute for Biological Research, ; Ness-Ziona, 7410001 Israel
                Author information
                http://orcid.org/0000-0003-0664-8628
                http://orcid.org/0000-0001-8578-8551
                http://orcid.org/0000-0002-3010-3372
                http://orcid.org/0000-0001-5143-9660
                http://orcid.org/0000-0003-0246-4477
                Article
                26113
                10.1038/s41467-021-26113-1
                8492774
                34611155
                b36651ef-e1cb-475c-8e56-670346f79323
                © The Author(s) 2021

                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
                : 6 July 2021
                : 16 September 2021
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                © The Author(s) 2021

                Uncategorized
                antibodies,influenza virus,sars-cov-2,viral host response
                Uncategorized
                antibodies, influenza virus, sars-cov-2, viral host response

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