scholarly journals IgG Antibodies Develop to Spike but Not to the Nucleocapsid Viral Protein in Many Asymptomatic and Light COVID-19 Cases

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1945
Author(s):  
Maria Tutukina ◽  
Anna Kaznadzey ◽  
Maria Kireeva ◽  
Ilya Mazo
Keyword(s):  
Disease Severity ◽  
Nucleocapsid Protein ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
N Protein ◽  
Main Target ◽  
Viral Nucleocapsid ◽  
Different Levels ◽  
Antibody Ratio ◽  
Severe Lung

Since SARS-CoV-2 appeared in late 2019, many studies on the immune response to COVID-19 have been conducted, but the asymptomatic or light symptom cases were somewhat understudied as respective individuals often did not seek medical help. Here, we analyze the production of the IgG antibodies to viral nucleocapsid (N) protein and receptor-binding domain (RBD) of the spike protein and assess the serum neutralization capabilities in a cohort of patients with different levels of disease severity. In half of light or asymptomatic cases the antibodies to the nucleocapsid protein, which serve as the main target in many modern test systems, were not detected. They were detected in all cases of moderate or severe symptoms, and severe lung lesions correlated with respective higher signals. Antibodies to RBD were present in the absolute majority of samples, with levels being sometimes higher in light symptom cases. We thus suggest that the anti-RBD/anti-N antibody ratio may serve as an indicator of the disease severity. Anti-RBD IgG remained detectable after a year or more since the infection, even with a slight tendency to raise over time, and the respective signal correlated with the serum capacity to inhibit the RBD interaction with the ACE-2 receptor.

scholarly journals DYNAMICS OF ANTIBODIES TO VARIOUS ANTIGENS OF THE SARS-COV-2 CORONAVIRUS IN PATIENTS WITH CONFIRMED COVID-19 INFECTION

2020 ◽  
Author(s):  
L.I. Novikova ◽  
◽  
S.S. Bochkareva ◽  
A.V. Aleshkin ◽  
S.IU. Kombarova ◽  
...  
Keyword(s):  
Venous Blood ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
N Protein ◽  
Test Systems ◽  
Igm Antibodies ◽  
Short Period ◽  
Virion Antigen ◽  
High Level ◽  
Different Levels

Presence of IgG and IgM antibodies in venous blood of 76 patients with confirmed presence of SARS-CoV-2 was determined. The study was carried out by ELISA using Russian test systems. Revealed different levels of IgM antibodies to N-protein and RBD (receptor binding domain of the Spike protein). The level of IgM to RBD did not reach high values, while the level of IgM to N-protein sharply increased in a short period of time to high values by the 3rd week of the disease and decreased only by the 8th week. The dynamics of IgG antibodies to the whole virion antigen and the recombinant spikes was similar, reaching high values at 4-5 weeks of the disease, however, the dynamics of IgG to the N-protein differed, showing a slight increase by the 1st week of the disease and a low level throughout the entire period of observation. Different dynamics of production of IgG and IgM antibodies to N-protein and RBD were noted. The amount of IgM to the N-protein increased sharply and reached a high level, while the amount of IgG increased smoothly and did not show a high level. The opposite picture was observed for antibodies to RBD. The characteristic dynamics of IgG, measured using test systems withsorbed whole virion or recombinant spike proteins, suggests duration of the disease

scholarly journals Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ariel Munitz ◽  
L. Edry-Botzer ◽  
M. Itan ◽  
R. Tur-Kaspa ◽  
D. Dicker ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Neutralizing Antibodies ◽  
Host Response ◽  
Humoral Response ◽  
Rapid Onset ◽  
Response Analysis ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Viral Receptor ◽  
Iga Antibodies

AbstractDespite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

scholarly journals Antibody response patterns in COVID-19 patients with different levels of disease severity—Japan

2020 ◽  
Author(s):  
Kazuo Imai ◽  
Yutaro Kitagawa ◽  
Sakiko Tabata ◽  
Katsumi Kubota ◽  
Mayu Nagura-Ikeda ◽  
...  
Keyword(s):  
Antibody Response ◽  
Disease Severity ◽  
Cross Reactivity ◽  
Response Patterns ◽  
Igg Antibodies ◽  
Past Infection ◽  
Infection Pattern ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Different Levels

AbstractBackgroundWe analyzed antibody response patterns according to level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan.MethodsWe analyzed 611 serum specimens from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). IgM and IgG antibodies against nucleocapsid protein (N) and spike 1 protein (S1) were detected by enzyme-linked immunosorbent assays.FindingsThe peaks of fitting curves for the OD values of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared with N. The OD values of IgM against N and IgG against both N and S1 were significantly higher in the severe and critical cases than in the mild cases at 11 days after symptom onset. The seroconversion rates of IgG were higher than those of IgM against both N and S1 during the clinical course based on the optimal cut-off values defined in this study. The seroconversion rates of IgG and IgM against N and S1 were higher in the severe and critical cases than in the mild cases.ConclusionOur findings show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and there were low seroconversion rates of antibodies against N and S1 in the mild cases. The antibody response patterns in our population suggest a second infection pattern, leading us to hypothesize that cross-reactivity occurs between SARS-CoV-2 and past infection with other human coronaviruses.

Immune response to SARS-CoV-2 and the risk of COVID-19 among different groups of healthcare workers

2021 ◽  
Vol 61 (5) ◽  
pp. 286-304
Author(s):  
Liliya M. Fatkhutdinova ◽  
Gulnara G. Badamshina ◽  
Elena P. Sizova ◽  
Marina A. Patyashina ◽  
Lidiya V. Stavropolskaya ◽  
...  
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Nucleocapsid Protein ◽  
Comparison Group ◽  
Igg Antibodies ◽  
N Protein ◽  
Study Results ◽  
History Of ◽  
Coronavirus Infection ◽  
The Republic

Introduction. To date, issues related to the protection of medical workers from COVID-19 infection, including immunological protection, are of particular interest. The aim of the study was to explore seroprevalence of the IgG to SARS-CoV-2 N-protein in various groups of medical workers with the following assessment of the risk of COVID-19, depending on the seropositivity and occupational group. Materials and methods. The study of the strength of immunity to COVID-19 was carried out within the framework of the large-scale Rospotrebnadzor program to assess population immunity to the SARS-CoV-2 virus in the population of the Russian Federation, considering the protocol recommended by WHO, on the basis of the laboratories of the Center for Hygiene and Epidemiology in the Republic of Tatarstan. From the sample of the study conducted in the Republic of Tatarstan, medical workers (301) were selected without a history of a new coronavirus infection and with no clinical symptoms of this disease at the time of biomaterial sampling (June 2020); the absence of the transferred new coronavirus infection was verified by the Unified State Information System "Electronic Health of the Republic of Tatarstan". The comparison group included 52 employees belonging to the engineering and technical personnel and not employed in medical institutions who met the above inclusion criteria. In the aggregate, the observation group (medical workers and the comparison group) included 12.1% of the participants in the population study. Results. The rate of seropositivity was 36.5% in the control groups, 23.7% - in doctors, and 38.9% - in nurses. Compared to doctors, seroprevalence was higher in nurses. The employment of medical workers in temporary infectious diseases hospitals did not affect the production of the IgG to SARS-CoV-2 N-protein. A relatively low prevalence of seropositivity among doctors of temporary infectious diseases hospitals was revealed. The probability of seroconversion decreased with age and did not depend on gender or history of recent contacts with COVID-19 patients. The survival analysis showed that the probability of remaining healthy by the end of the follow-up was the lowest among doctors from medical and preventive institutions that did not serve as temporary infectious diseases hospitals. The risk of COVID-19 in seronegative individuals was higher, but without statistical significance. Conclusion. According to the data of immunological studies for the presence of IgG antibodies to the nucleocapsid protein of the SARS-CoV-2 virus, it was found that the prevalence of seroprevalence in nurses is significantly higher than that of doctors, nurses of medical and prophylactic organizations of young age have higher seroprevalence to the nucleocapsid protein of the SARS-CoV-2. According to prospective observation, it was revealed that doctors of medical and prophylactic organizations that are not classified as temporary infectious diseases hospitals have a higher risk of developing a symptomatic form of COVID-19, which may be due to both the insufficient effectiveness of anti-epidemic measures and the peculiarities of the immune response and approaches, used to evaluate it. In the current epidemic situation, the detection of IgG antibodies to the SARS-CoV-2 virus can be used to decide on the distribution of responsibilities among medical personnel.

scholarly journals Persistence of robust humoral immune response in COVID-19 convalescent individuals over 12 months after infection

2021 ◽  
Author(s):  
Kei Miyakawa ◽  
Sousuke Kubo ◽  
Sundararaj Stanleyraj Jeremiah ◽  
Hirofumi Go ◽  
Yutaro Yamaoka ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Virus Antibody ◽  
Neutralization Activity ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Viral Nucleocapsid

SARS-CoV-2 infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). Here we report the persistence of nAb responses over 12 months after infection despite its decreasing trend noticed from 6 months. The study included sera from 358 individuals who had been infected with SARS-CoV-2 between January and May 2020. Samples were collected at 6 and 12 months after onset. The titers of IgG to the viral nucleocapsid protein (NP) and receptor-binding domain of the spike protein (RBD) were measured by CLEIA. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. While the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility of reinfection to the variants of concerns (VOCs). COVID-19 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

scholarly journals Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins

2020 ◽  
Author(s):  
Yang Li ◽  
Zhaowei Xu ◽  
Qing Lei ◽  
Dan-yun Lai ◽  
Hongyan Hou ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Antibody Response ◽  
Disease Severity ◽  
Sharp Decrease ◽  
Antibody Responses ◽  
Structural Proteins ◽  
List Type ◽  
Accessory Proteins ◽  
Igg Antibodies ◽  
N Protein

SummaryThe 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.HighlightsAn antibody response landscape against SARS-CoV-2 proteome was constructedNon-structural/accessory proteins elicit prevalent antibody responses but likely through a different mechanism to that of structural proteinsIgG antibodies against non-structural/accessory proteins are more associated with disease severity and clinical outcomeFor non-survivors, the levels of IgG antibodies against S1 and N decline significantly before death

scholarly journals Persistence of robust humoral immune response in COVID-19 convalescent individuals over twelve months after infection

2021 ◽  
Author(s):  
Kei Miyakawa ◽  
Sousuke Kubo ◽  
Sundararaj Stanleyraj Jeremiah ◽  
Hirofumi Go ◽  
Yutaro Yamaoka ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Neutralization Activity ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Viral Nucleocapsid

Abstract Background SARS-CoV-2 infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). Here, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. Methods The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of IgG to the viral nucleocapsid protein (NP) and receptor-binding domain of the spike protein (RBD) were measured by CLEIA. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. Results Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. While the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). Conclusions COVID-19 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

scholarly journals A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sisi Kang ◽  
Mei Yang ◽  
Suhua He ◽  
Yueming Wang ◽  
Xiaoxue Chen ◽  
...  
Keyword(s):  
Risk Factor ◽  
Monoclonal Antibodies ◽  
Nucleocapsid Protein ◽  
Rna Binding ◽  
Complex Structure ◽  
Antibody Responses ◽  
N Protein ◽  
Human Antibodies ◽  
Quick Recovery ◽  
Viral Nucleocapsid

AbstractAlthough human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

scholarly journals Glycosylation is a key in SARS-CoV-2 infection

2021 ◽  
Author(s):  
Celso A. Reis ◽  
Rudolf Tauber ◽  
Véronique Blanchard
Keyword(s):  
Adaptive Immune Response ◽  
Protective Role ◽  
Host Cells ◽  
Target Cells ◽  
Receptor Binding Domain ◽  
Serological Testing ◽  
Virus Binding ◽  
Adaptive Immune ◽  
Cytokine Cascade ◽  
Different Levels

AbstractSARS-CoV-2 causes the respiratory syndrome COVID-19 and is responsible for the current pandemic. The S protein of SARS-CoV-2-mediating virus binding to target cells and subsequent viral uptake is extensively glycosylated. Here we focus on how glycosylation of both SARS-CoV-2 and target cells crucially impacts SARS-CoV-2 infection at different levels: (1) virus binding and entry to host cells, with glycosaminoglycans of host cells acting as a necessary co-factor for SARS-CoV-2 infection by interacting with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, (2) innate and adaptive immune response where glycosylation plays both a protective role and contributes to immune evasion by masking of viral polypeptide epitopes and may add to the cytokine cascade via non-fucosylated IgG, and (3) therapy and vaccination where a monoclonal antibody-neutralizing SARS-CoV-2 was shown to interact also with a distinct glycan epitope on the SARS-CoV-2 spike protein. These evidences highlight the importance of ensuring that glycans are considered when tackling this disease, particularly in the development of vaccines, therapeutic strategies and serological testing.

scholarly journals Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2

2021 ◽  
Author(s):  
Peter G. Kremsner ◽  
Philipp Mann ◽  
Arne Kroidl ◽  
Isabel Leroux-Roels ◽  
Christoph Schindler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Lipid Nanoparticles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Phase 1 Study ◽  
S Protein ◽  
Dosage Escalation

Summary Background We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). Results In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.

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