SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19
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Abstract
Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still >70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity.
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SciScore for 10.1101/2020.07.21.20159178: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All patients in this study were diagnosed and treated according to the Guidelines of the Diagnosis and Treatment of New Coronavirus Pneumonia (version 7) published by the National Health Committee of the People’s Republic of China25. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein were tested by capture chemiluminescence immunoassays (CLIA) by MAGLUMI(tm) 2000 … SciScore for 10.1101/2020.07.21.20159178: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All patients in this study were diagnosed and treated according to the Guidelines of the Diagnosis and Treatment of New Coronavirus Pneumonia (version 7) published by the National Health Committee of the People’s Republic of China25. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein were tested by capture chemiluminescence immunoassays (CLIA) by MAGLUMI(tm) 2000 Plus (Snibe, Shenzhen, China) as reported 26. IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Virus neutralization test (VNT) assay: Vero E6 cells (1×104 per well) were seeded in 96-well plates one night prior to use. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources SARS-CoV-2 (Strain BetaCoV/Wuhan/WIV04/2019, National Virus Resource Center number: IVCAS 6.7512) at 100 TCID50 was incubated in absence or presence of diluted plasma for 1 h at 37 °C. SARS-CoV-2suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has some limitations as follows. First, we did not have enough samples at 9-11 weeks because the patients were placed in mandatory isolation for two more weeks after discharge from the hospital, followed by another two more weeks at home after leaving mandatory isolation. Second, due to the limited availability of the BSL3 laboratory, not all samples could be assessed in virus neutralization tests. In conclusion, antibodies appear to have antiviral effects in the early stages of SARS-CoV-2 infection; and the most symptomatic patients with COVID-19 remain positive for IgG-S and exhibit sufficient neutralizing activity at six months after the onset of illness. These results support the notion that naturally infected patients have the ability to combat re-infection and vaccines may be able to produce sufficient protection. Please note, that analyses which terminated their observation earlier than ours and extrapolates the long-term trend based on this contraction phase without considering or determining the consolidation phase, bear the inherent risk to come to wrong over-pessimistic conclusions concerning the durability of humoral immune responses.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.07.21.20159178: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Intriguingly, the two unusual patients were young women diagnosed with symptomatic COVID-19 accompanied with lung lesions (Fig. 1D, lower panel). Table 2: Resources
Antibodies Sentences Resources We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being … SciScore for 10.1101/2020.07.21.20159178: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Intriguingly, the two unusual patients were young women diagnosed with symptomatic COVID-19 accompanied with lung lesions (Fig. 1D, lower panel). Table 2: Resources
Antibodies Sentences Resources We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being infected. IgGsuggested: NoneHowever, studies using pseudovirus particle-based systems 12,13 suggest that plasma derived from convalescent patients have potent neutralizing activity that was related to IgG molecules recognizing the RBD of the S protein, suggesting that IgG-RBD-S antibodies have a high likelihood to fulfill neutralizing functions (nAbs). IgG-RBD-Ssuggested: NoneResults: Symptomatic COVID-19 patients exhibit an early and rapid IgM-S and IgG-N response and maintain high levels of IgG-S/N for at least six months after disease onset In order to investigate antibody responses towards SARS-CoV-2 over time, a total of 585 samples obtained from 349 symptomatic COVID-19 patients, collected up to 26 weeks after disease onset, were analyzed for IgM and IgG recognizing the RBD of the spike protein (denoted IgM-S and IgGS, respectively) as well as IgM and IgG binding the nucleocapsid protein (IgM-N and IgG-N, respectively). IgG binding the nucleocapsid protein (IgM-N and IgG-Nsuggested: NoneDuring the first week after symptom onset, the four antibodies were tested positive with different frequencies: IgM-S (66%) > IgG-N (33%) > IgM-N (22%) > IgG-S (11%) (Fig. 1A). > IgG-Nsuggested: NoneWe further analyzed whether a combined antibody tests may support clinical diagnostics (Fig. S1). S1suggested: NoneThe IgG-RBD-S titer demonstrated by far the highest positive correlation with antibody neutralization activity (r=0.6932, p<0.0001), compared to IgM-S (r=0.2220, p<0.05) and IgG-N (r=0.3621, p=0.0001) (Fig. IgM-S (r=0.2220, p<0.05) and IgG-Nsuggested: NoneThus, the vast majority of COVID-19 patients raised IgG-RBD-S-binding antibodies with neutralizing capacity, which were maintained over the observational period of 6 months (Fig. 3A & Fig. raised IgG-RBD-S-bindingsuggested: NoneAlthough only the future will show how long protective immunity will last after natural infections or prophylactic vaccination against SARS-CoV2, our data suggests that SARS-CoV-2-specific antibody responses are quite similar to responses against many other viruses that induce immunity in humans, including the ‘common-cold’ Corona Viruses that have been shown to mediate protective immunity at for many months to years 23,24. SARS-CoV2suggested: (Abcam Cat# ab273074, AB_2847846)Data from additional tools added to each annotation on a weekly basis.
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