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      Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

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          Abstract

          Background

          The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.

          Methods

          The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort.

          Results

          The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%).

          Conclusions

          The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.

          Abstract

          The time kinetics of humoral responses against the novel coronavirus (SARS-CoV-2) are characterized in patients with COVID-19 by nucleocapsid-based ELISA. The antibody testing can aid in the diagnosis of COVID-19 when combined with qPCR, including in subclinical cases.

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          Most cited references15

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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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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
            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

              Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
              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.
              Article 0 comments Cited 10831 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Infect Dis
                Journal ID (iso-abbrev): Clin. Infect. Dis
                Journal ID (publisher-id): cid
                Title: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Publisher: Oxford University Press (US )
                ISSN (Print): 1058-4838
                ISSN (Electronic): 1537-6591
                Publication date (Electronic): 21 March 2020
                Publication date PMC-release: 21 March 2020
                Electronic Location Identifier: ciaa310
                Affiliations
                [1 ] National Health Commission (NHC) K ey Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China
                [2 ] Laboratory of Infectious Diseases Center of Beijing Ditan Hospital, Capital Medical University , Beijing, China
                [3 ] Department of Laboratory Medicine and Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China
                [4 ] Third Medical Center of Chinese People's Liberation Army General Hospital , Beijing, China
                [5 ] NHC Key Laboratory of Systems Biology of Pathogens, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China
                [6 ] Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine , New Haven, Connecticut, USA
                [7 ] Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China
                [8 ] Emergency Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China
                [9 ] Emergency Department of Infectious Diseases of Beijing Ditan Hospital, Capital Medical University , Beijing, China
                [10 ] Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                Author notes
                Correspondence: J. Wang, No. 9 Dong Dan San Tiao, Dongcheng District, Beijing 100730, P. R. China ( jianwei.wang@ 123456ipbcams.ac.cn ).

                L. G, L. R, S. Y., M. X., D. C., and F. Y. contributed equally to this work.

                L. S., L. W., and J. W. contributed equally to this work.

                Article
                Publisher ID: ciaa310
                DOI: 10.1093/cid/ciaa310
                PMC ID: 7184472
                PubMed ID: 32198501
                SO-VID: f9af4262-083d-4a89-8496-35b66ecc9fd3
                Copyright © © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
                License:

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                Date received : 22 February 2020
                Date: 17 March 2020
                Date accepted : 19 March 2020
                Date: 17 April 2020
                Page count
                Pages: 9
                Funding
                Funded by: Chinese Academy of Medical Sciences, DOI 10.13039/501100005150;
                Award ID: 2016-I2M-1–014
                Funded by: Central Research Institute Fund of CAMS;
                Award ID: 2020HY320001
                Funded by: National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China;
                Award ID: 2017ZX10103004
                Categories
                Subject: Major Article
                Subject: AcademicSubjects/MED00290
                Custom metadata
                article-lifecycle PAP
                edited-state corrected-proof

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: novel coronavirus,covid-19,antibody,elisa,diagnosis
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: novel coronavirus, covid-19, antibody, elisa, diagnosis

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