ABSTRACT
Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.
Subject(s)
COVID-19ABSTRACT
Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the START button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.
Subject(s)
COVID-19ABSTRACT
Background: The COIVD-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies remain elevated with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome.Method: By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgM/IgG responses against 20 SARS-CoV-2 proteins in 1,034 hospitalized COVID-19 patients on admission, who were followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality.Results: We found that high level of IgM against ORF7b at the time of hospitalization is an independent predictor of patient survival ( p trend = 0.002), while levels of IgG responses to 6 non-structural proteins and 1 accessory protein, i. e., NSP4, NSP7, NSP9, NSP10, RdRp (NSP12), NSP14, and ORF3b, possess significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory markers for disease severity (all with p trend < 0.05). Spline regression analysis indicated that the correlation between ORF7b IgM, NSP9 IgG, and NSP10 IgG and the risk of COVID-19 mortality shows linear ( p = 0.0013, 0.0073 and 0.0003, respectively). Their AUCs for predictions, determined by computational cross-validations (validation1), were 0.74 (cut-off = 7.59), 0.66 (cut-off = 9.13), and 0.68 (cut-off = 6.29), respectively. Further validations were conducted in the second and third serial samples of these cases (validation2A, n = 633, validation2B, n = 382), with high accuracy of prediction for outcome.Conclusion: These findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.Funding Statement: This work was supported by grants from the Fundamental Research Funds for the Central Universities (HUST COVID-19 Rapid Response Call No. 2020kfyXGYJ040) and Wuhan Bureau of Science and Technology (No. 2020020601012218).Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (IRB ID:TJ-C20200128).
Subject(s)
COVID-19ABSTRACT
The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology.Funding: This work was partially supported by the National Key Research and Development Program of China Grant (No.2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, 31370813, 31900112 and 21907065).Conflict of Interest: The authors declare no competing interests.Ethical Approval: The study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (ITJ-C20200128). Written informed consent was obtained from all participants enrolled in this study.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 specific IgG responses play critical roles for patients to recover from COVID-19, in-depth dissecting of the IgG responses on systems level is of great interest. Herein, we adopted a newly developed high-throughput epitope mapping technology (AbMap), analyzed 55 COVID-19 convalescent sera and 226 antibody samples enriched by specific proteins or peptides from these sera. We revealed three areas that are rich of IgG epitopes, two are on Spike protein but outside of RBD, and one is on Nucleocapsid protein. We identified 29 significant epitopes on Spike protein, from two of these significant epitopes, two critical epitope residues were found, i. e., D936 and P1263, which are highly related to the infectivity of SARS-CoV-2. In summary, we provided the first global map of IgG binding epitopes for SARS-CoV-2 at single amino acid resolution. This map will facilitate the precise development of therapeutic antibodies and vaccines.
Subject(s)
COVID-19ABSTRACT
Neutralization antibodies and vaccines for treating COVID-19 are desperately needed. For precise development of antibodies and vaccines, the key is to understand which part of SARS-CoV-2 Spike protein is highly immunogenic on a systematic way. We generate a linear epitope landscape of Spike protein by analyzing serum IgG response of 1,051 COVID-19 patients with a peptide microarray. We reveal two regions that rich of linear epitopes, i.e., CTD and a region close to the S2’ cleavage site and fusion peptide. Unexpectedly, we find RBD is lack of linear epitope. Besides 3 moderate immunogenic peptides from RBD, 16 highly immunogenic peptides from other regions of Spike protein are determined. These peptides could serve as the base for precise development of antibodies and vaccines for COVID-19 on a systematic level.Funding: This work was partially supported by National Key Research and Development Program of China Grant (No. 2016YFA0500600), Science and Technology Commission of Shanghai Municipality (No. 19441911900), Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2020YQ10), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813).Conflict of Interest: The authors declare no competing interest.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 outbreak is a world-wide pandemic. The Spike protein plays central role in cell entry of the virus, and triggers significant immuno-response. Our understanding of the immune-response against S protein is still very limited. Herein, we constructed a peptide microarray and analyzed 55 convalescent sera, three areas with rich linear epitopes were identified. Potent neutralizing antibodies enriched from sera by 3 peptides, which do not belong to RBD were revealed.