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      Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets

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          Summary

          Introduction

          Severe acute respiratory syndrome (SARS) caused large outbreaks of atypical pneumonia in 2003, with the largest localized outbreak occurring in Beijing, China. Lymphopenia was prominent amongst the laboratory abnormalities reported in acute SARS.

          Methods

          The effect of SARS on peripheral blood lymphocytes and their subsets was examined in 271 SARS coronavirus-infected individuals.

          Results

          There was a significant decrease in the CD45+, CD3+, CD4+, CD8+, CD19+ and CD16+/56+ cell counts over the five weeks of the SARS illness although CD4+/CD8+ ratios did not change significantly. The lymphopenia was prolonged, reaching a nadir during days 7–9 in the second week of illness before returning towards normal after five weeks, with the lowest mean CD4+ cell count of 317 cells × 10 6/L at day 7, and CD8+ cell count of 239 cells × 10 6/L at day 8. Patients with more severe clinical illness, or patients who died, had significantly more profound CD4+ and CD8+ lymphopenia.

          Discussion

          Lymphopenia is a prominent part of SARS-CoV infection and lymphocyte counts may be useful in predicting the severity and clinical outcomes. Possible reasons for the SARS-associated lymphopenia may be direct infection of lymphocytes by SARS-CoV, lymphocyte sequestration in the lung or cytokine-mediated lymphocyte trafficking. There may also be immune-mediated lymphocyte destruction, bone marrow or thymus suppression, or apoptosis.

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          Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

          Christian Drosten, Stephan Günther, Wolfgang Preiser … (2003)
          The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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            A novel coronavirus associated with severe acute respiratory syndrome.

            Thomas G Ksiazek, Dean Erdman, Cynthia Goldsmith … (2003)
            A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus. Copyright 2003 Massachusetts Medical Society
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              Identification of severe acute respiratory syndrome in Canada.

              Susan M Poutanen, Donald Low, Bonnie Henry … (2003)
              Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation. Copyright 2003 Massachusetts Medical Society
              Article 0 comments Cited 507 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zhongping He
                Journal
                Journal ID (nlm-ta): Int J Infect Dis
                Journal ID (iso-abbrev): Int. J. Infect. Dis
                Title: International Journal of Infectious Diseases
                Publisher: International Society for Infectious Diseases. Published by Elsevier Ltd.
                ISSN (Print): 1201-9712
                ISSN (Electronic): 1878-3511
                Publication date PMC-release: 10 August 2005
                Publication date (Print): November 2005
                Publication date (Electronic): 10 August 2005
                Volume: 9
                Issue: 6
                Pages: 323-330
                Affiliations
                [a ]Capital University of Medical Sciences Affiliated Beijing YouAn Hospital, Beijing 100054, PR China
                [b ]Beijing Ditan Hospital, Beijing 100011, PR China
                [c ]Department of Microbiology, Peking University Health Science Center, Beijing 100083, PR China
                [d ]Center for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead NSW 2145, Australia
                Author notes
                [* ]Corresponding author. Tel.: +86 10 82801617; fax: +86 10 82802221. zhongpinghe@ 123456yahoo.com
                Article
                Publisher ID: S1201-9712(05)00072-X
                DOI: 10.1016/j.ijid.2004.07.014
                PMC ID: 7110876
                PubMed ID: 16095942
                SO-VID: 0581e06d-e1d8-449b-b2df-d773c29e622b
                Copyright statement: Copyright © 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
                License:

                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
                Date received : 4 February 2004
                Date revision received : 5 July 2004
                Date accepted : 20 July 2004
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: sars coronavirus,lymphocytes,cd4+ and cd8+ lymphopenia
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: sars coronavirus, lymphocytes, cd4+ and cd8+ lymphopenia

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