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      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China

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          Abstract

          Importance

          An ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice.

          Methods

          We conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves.

          Results

          A total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge= 117) or non-survivors (in-hospital death=28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively.

          Conclusion

          We find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19.

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          Most cited references15

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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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              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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                Author and article information

                Contributors
                Journal
                J Infect
                J. Infect
                The Journal of Infection
                The British Infection Association. Published by Elsevier Ltd.
                0163-4453
                1532-2742
                18 April 2020
                18 April 2020
                Affiliations
                [a ]Hubei Provincial Hospital of traditional Chinese and Western medicine, 11 lingjiao hu road, jianghan district, Wuhan 430015, China
                [b ]Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
                Author notes
                [* ]Corresponding author. hbszxyjhyy11@ 123456163.com
                Article
                S0163-4453(20)30223-1
                10.1016/j.jinf.2020.04.012
                7166040
                32315725
                128fdd5f-f2fb-49da-b628-da9c935fefb3
                © 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

                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
                : 13 April 2020
                Categories
                Article

                Infectious disease & Microbiology
                covid-19,t cell subsets,retrospective study,immunity
                Infectious disease & Microbiology
                covid-19, t cell subsets, retrospective study, immunity

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