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      High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses

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          Abstract

          Objectives

          We aimed to gain an understanding of the paradox of the immunity in COVID‐19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation.

          Methods

          A total of 280 hospitalised patients with COVID‐19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single‐cell RNA sequencing (scRNA‐seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID‐19 patients.

          Results

          The levels of soluble CD25 (sCD25), IL‐6, IL‐8, IL‐10 and TNF‐α were higher in severe COVID‐19 patients than non‐severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV‐infected mice with high levels of sCD25 demonstrated insufficient anti‐viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25 +CD8 + T cells that also expressed the highest level of PD‐1 with pro‐inflammatory potential. The counterpart human CD25 +PD‐1 + T cells were expanded in BALF of COVID‐19 patients with severe disease compared to those with modest disease.

          Conclusion

          These results suggest that high levels of sCD25 in COVID‐19 patients probably result from insufficient anti‐viral immunity and indicate an expansion of pro‐inflammatory T cells that contribute to disease severity.

          Abstract

          High levels of soluble CD25 in COVID‐19 patients were found being associated with severe disease and prolonged viral shedding. We discovered that the elevation of sCD25 was caused by the insufficient anti‐viral T‐cell immune response and the resulting expansion of CD25 +PD−1 +CD8 + T cells. CD25 +PD−1 +CD8 + T cells that expressed CD38 and Ki‐67 participated pro‐inflammatory response and drove disease severity.

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

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          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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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

              Guang Chen, Di Wu, Wei. Guo … (2020)
              Journal of Clinical Investigation
              Article 0 comments Cited 2166 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Min Xie: xie_m@126.com
                Di Yu:
                ORCID: https://orcid.org/0000-0003-1721-8922
                di.yu@uq.edu.au
                Journal
                Journal ID (nlm-ta): Clin Transl Immunology
                Journal ID (iso-abbrev): Clin Transl Immunology
                Journal ID (doi): 10.1002/(ISSN)2050-0068
                Journal ID (publisher-id): CTI2
                Title: Clinical & Translational Immunology
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2050-0068
                Publication date (Electronic): 15 February 2021
                Publication date Collection: 2021
                Volume: 10
                Issue: 2 ( doiID: 10.1002/cti2.v10.2 )
                Affiliations
                [ 1 ] Department of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
                [ 2 ] Key Laboratory of Respiratory Diseases National Ministry of Health of the People's Republic of China National Clinical Research Center for Respiratory Disease Wuhan China
                [ 3 ] The University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD Australia
                [ 4 ] Department of Otolaryngology‐Head and Neck Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
                [ 5 ] Shandong Artificial Intelligence Institute Qilu University of Technology (Shandong Academy of Sciences) Jinan China
                [ 6 ] Department of Immunology and Infectious Disease John Curtin School of Medical Research Australian National University Canberra ACT Australia
                [ 7 ] China–Australia Centre for Personalised Immunology Shanghai Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai
                [ 8 ] Department of Infectious Diseases Huashan Hospital Fudan University Shanghai China
                [ 9 ] Department of Radiology Shanghai Public Health Clinical Center Fudan University Shanghai China
                [ 10 ] Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
                [ 11 ] Immunology Division Garvan Institute of Medical Research Darlinghurst NSW Australia
                [ 12 ] St Vincent’s Clinical School University of New South Wales Sydney NSW Australia
                Author notes
                [*] [* ] Correspondence

                D Yu, The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.

                E‐mail: di.yu@ 123456uq.edu.au

                M Xie, Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

                E‐mail: xie_m@ 123456126.com

                [†]

                Equal contributors and joint first authors.

                Article
                Publisher ID: CTI21251
                DOI: 10.1002/cti2.1251
                PMC ID: 7883478
                SO-VID: 0a7128b4-e1db-460c-bc8c-6df58c9ba4ff
                Copyright statement: © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Figures: 6, Tables: 3, Pages: 17, Words: 20382
                Product
                Funding
                Funded by: Eureka TechIN
                Funded by: Bellberry‐Viertel Fellowship
                Funded by: National Health and Medical Research Council , open-funder-registry 10.13039/501100000925;
                Award ID: GNT1147769
                Funded by: Natural Science Foundation of Shandong Province , open-funder-registry 10.13039/501100007129;
                Award ID: ZR2020ZD41
                Categories
                Subject: Original Article
                Subject: Original Article
                Custom metadata
                source-schema-version-number 2.0
                cover-date 2021
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:15.02.2021

                Keywords: cd25+pd‐1+ cd8+ t cell,covid‐19 patients,disease severity,sars‐cov‐2,soluble cd25
                Data availability:
                Keywords: cd25+pd‐1+ cd8+ t cell, covid‐19 patients, disease severity, sars‐cov‐2, soluble cd25

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