Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice

Long, Quanxin; Deng, Haijun; Chen, Juan; Hu, Jieli; Liu, Beizhong; Liao, Pu; Lin, Yong; Yu, Lihua; Zhan, Ming; Xu, Yingkun; Gong, Fang; Wu, Guicheng; Zhang, Xian-xiang; Chen, Yao-Kai; Li, Zhijie; Wang, Kun; Zhang, Xiaoli; Tian, Weizhong; Niu, Chunping; Yang, Qingjun; Xiang, Junyi; Du, Hongxin; Liu, Huawen; Lang, Chunhui; Luo, Xu; Wu, Shaobo; Chen, Xiaoping; Zheng, Zhou; Wang, Jing; Xue, Chengjun; Li, Xiaofeng; Wang, Li; Tang, Xiaojun; Zhang, Yong; Qiu, Jingfu; Liu, Xiamao; Li, Jinjing; Zhang, Dechun; Zhang, Fan; Cai, Xue-Fei; Wang, Deqiang; Hu, Yuan; Ren, Ji-Hua; Tang, Ni; Liu, Ping; Li, Qin; Huang, Aiping

doi:10.1101/2020.03.18.20038018

Cited by 156 publications

(216 citation statements)

References 11 publications

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“…19 Our data on the kinetics of antibody responses to SARS-CoV-2 infection build upon studies of hospitalised patients in China reporting a median 11 days to seroconversion for total antibody, with IgM and IgG seroconversion at days 12 and 14 respectively; 15 another similar study reports 100% IgG positivity by 19 days. 16 Our ELISA data show IgG titres rose over the first 3 weeks of infection and that IgM testing identified no additional cases. Methods to enhance sensitivity, especially shortly after symptom onset, could consider different sample types (e.g.…”

Section: Discussionmentioning

confidence: 59%

“…14 As a diagnostic tool, serology may have a role in combination with RT-PCR testing to improve sensitivity, particularly of cases presenting sometime after symptom onset. 15,16 Reproducible methods to detect and quantify vaccine-mediated anti-SARS-CoV-2 antibodies are also crucial, as vaccines enter clinical trials, evaluating the magnitude and durability of immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…Acute (≤28 days from symptom onset) and convalescent samples (>28 days) were included to optimise detection of SARS-CoV-2 specific IgM and IgG respectively ( Figure 1B). Acute samples were collected from patients a median 10 (range 4-27) days from symptom onset (n=16), and from recovering healthcare workers median 13 [range [8][9][10][11][12][13][14][15][16][17][18][19] Cases were classified following WHO criteria as critical (respiratory failure, septic shock, and/or multiple organ dysfunction/failure); severe (dyspnoea, respiratory frequency ≥30/minute, blood oxygen saturation ≤93%, PaO2/FiO2 ratio <300, and/or lung infiltrates >50% of the lung fields within 24-48 hours); or otherwise mild. 12 Among 22 acute cases, 9…”

Section: Samplesmentioning

confidence: 99%

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Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel

Adams

Ainsworth

Anand

et al. 2020

Preprint

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Background:The SARS-CoV-2 pandemic caused >1 million infections during January-March 2020. There is an urgent need for robust antibody detection approaches to support diagnostics, vaccine development, safe individual release from quarantine and population lock-down exit strategies. The early promise of lateral flow immunoassay (LFIA) devices has been questioned following concerns about sensitivity and specificity. Methods:We used a panel of plasma samples designated SARS-CoV-2 positive (from SARS-CoV-2 RT-PCR-positive individuals; n=40) and negative (samples banked in the UK prior to December-2019 (n=142)). We tested plasma for SARS-Cov-2 IgM and IgG antibodies by ELISA and using nine different commercially available LFIA devices. Results: ELISA detected SARS-CoV-2 IgM or IgG in 34/40 individuals with an RT-PCR-confirmed diagnosis of SARS-CoV-2 infection (sensitivity 85%, 95%CI 70-94%), vs 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 RT-PCRpositive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%).IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions:The performance of current LFIA devices is inadequate for most individual patient applications. ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following symptoms onset.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Samplesmentioning

confidence: 99%

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Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel

Adams

Ainsworth

Anand

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…When IgM and IgG levels are below the detection limit, the test results would be negative. Furthermore, IgM antibodies would gradually decrease and disappear after 2 weeks, so that the IgM level might be below its peak and not detectable in some cases.Meanwhile, the difference in individual immune response might result in the false negative results in suspected cases (19)(20). Patients who do not produce antibodies, or who produce antibodies relatively late, might have a relapse once their immunity is reduced.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the auxiliary diagnosis value of antibodies assays for the detection of novel coronavirus (SARS-Cov-2)

Gao

Yi²,

et al. 2020

Preprint

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Background: The spread of an novel coronavirus (SARS-CoV-2, previously named 2019-nCoV) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. Elucidating the diagnostic value of different methods, especially the auxiliary diagnosis value of antibodies assays for SARS-CoV-2 infection is helpful for improving the sensitivities of pathogenic-diagnosis, providing timely treatment, and differentiating the infected cases from the healthy, thus preventing further epidemics. Methods: Medical records from 38 patients with confirmed SARS-CoV-2 infection in the Second People's Hospital of Fuyang from January 22, 2020 to February 28, 2020 were collected and retrospectively analyzed. Specimens including throat swabs, sputum and serum were collected during the hospitalization period, viral RNAs and serum IgM-IgG antibodies to SARS-CoV-2 were measured respectively. The detectability of different methods as well as the auxiliary diagnosis value of antibodies test for SARS-CoV-2 infection were analyzed.Results: Among 38 patients, the total seropositive rate for IgM and IgG was 50.0% and 92.1%, respectively. Two patients remained seronegative throughout the course of illness. In the early phase of illness, the RNA test for sputum specimens possessed the highest detectability(92.3%), followed by the the RNA test for throat swabs (69.2%), and the antibodies assays presented lower positive rates(IgM, 23.0%, IgG, 53.8%).While, the sensitivity of antibodies assays overtook that of RNA test since day 8 after onset (IgM, 50.0%; IgG, 87.5%). Of note, the positive rate of throat swabs was only 13.0% for cases in later phase (≥15 d.a.o), and the sensitivities of IgM and IgG rose to 52.2% and 91.3%, respectively. Combined use of antibodies assay and qRT-PCR at the same time was able to improve the sensitivities of pathogenic-diagnosis, especially for the throat swabs group at the later stage of illness. Moreover, most of these cases with undetectable viral RNA in throat swabs specimens at the early stage of illness were able to be IgM/IgG seropositive after 7 days. Conclusions:The antibodies detection against SARS-CoV-2 offers vital clinical information for physicians, and could be used as an effective supplementary indicator

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“…Infection with SARS-CoV-2 elicits antibodies that bind to the virus [1][2][3][4][5][6]. But as is the case for all viruses [7][8][9][10], only some of these antibodies neutralize the virus's ability to enter cells [4,5,11,12].…”

Section: Introductionmentioning

confidence: 99%

Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 Spike protein for neutralization assays

Crawford

Eguia

Dingens

et al. 2020

Preprint

273

270

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AbstractSARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral and VSV particles, but the reagents and protocols are not widely available. Here we detail how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also make all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrate how these pseudotyped lentiviral particles can be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.

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Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice

Cited by 156 publications

References 11 publications

Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel

Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel

Evaluation of the auxiliary diagnosis value of antibodies assays for the detection of novel coronavirus (SARS-Cov-2)

Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 Spike protein for neutralization assays

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