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      Different T cell related immunological profiles in COVID ‐19 patients compared to healthy controls

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          Abstract

          In various pathological conditions, cellular immunity plays an important role in immune responses. Among immune cells, T lymphocytes pdomote cellular and humoral responses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19 disease pathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS‐CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n=20), ICU hospitalized patients (n=30), non-ICU hospitalized patients (n=30), and normal subjects (n=20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.

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          Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

          Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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            A new coronavirus associated with human respiratory disease in China

            Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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              COVID-19: consider cytokine storm syndromes and immunosuppression

              As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).
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                Author and article information

                Journal
                Int Immunopharmacol
                Int Immunopharmacol
                International Immunopharmacology
                Published by Elsevier B.V.
                1567-5769
                1878-1705
                28 May 2021
                28 May 2021
                : 107828
                Affiliations
                [a ]Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [b ]Department of Biochemistry, Faculty of Materials Engineering, Islamic Azad University, Najafabad Branch, Najafabad, Iran
                [c ]Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
                [d ]Clinical Sciences Department, College of Medicine, University of Sharjah, UAE
                [e ]Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russia
                [f ]Department of Aquatic Management, Faculty of Fisheries and Marine Science Universitas Negeri Gorontalo, Gorontalo, Indonesia
                [g ]Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran
                [h ]Department of Microbiology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
                [i ]Department of Biology, Faculty of Sciences, Yazd University, Yazd, Iran
                [j ]Department of Biosciences, Mody University of Science and Technology, Lakshmangarh, Rajasthan, India
                [k ]Department of Medical Biotechnology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
                [l ]Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [m ]Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
                [n ]Department of Anesthesiology, Faculty of Medicine, Imam Reza Medical Research & Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
                [o ]Department of Basic Science, Faculty of Medicine, Maragheh University of Medical Sciences, Maragheh, Iran
                [p ]Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
                Author notes
                [* ]Corresponding author.at: Department of Basic Science, Faculty of Medicine, Maragheh University of Medical Sciences, Maragheh, Iran
                [1]

                These authors contributed equally to this study.

                Article
                S1567-5769(21)00464-1 107828
                10.1016/j.intimp.2021.107828
                8162824
                34091116
                e87e6845-8872-4272-928f-3a808440c36b
                © 2021 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
                : 23 March 2021
                : 25 May 2021
                : 25 May 2021
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                covid-19,t cells,cell mediated immunity,inflammation
                Pharmacology & Pharmaceutical medicine
                covid-19, t cells, cell mediated immunity, inflammation

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