scholarly journals Anti-Spike, anti-Nucleocapsid and neutralizing antibodies in SARS-CoV-2 inpatients and asymptomatic carriers

2020 ◽  
Author(s):  
Etienne Brochot ◽  
Baptiste Demey ◽  
Antoine Touzé ◽  
Sandrine Belouzard ◽  
Jean Dubuisson ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Asymptomatic Carrier ◽  
Secondary Infection ◽  
List Type ◽  
Receptor Binding Domain ◽  
Plasma Therapy ◽  
Specific Antibodies ◽  
Asymptomatic Carriers ◽  
Kinetics Of

SummaryObjectiveThe objective of this study was to monitor the anti-SARS-CoV-2 antibody response in infected patients.MethodsIn order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We also monitored the presence of neutralizing antibodies in these samples as well as 25 asymptomatic carrier samples using retroviral particles pseudotyped with the spike of the SARS-CoV-2.ResultsWe observed that specific antibodies were detectable in all inpatients two weeks post-symptom onset. The detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Neutralizing antibodies reached a plateau two weeks post-symptom onset and then declined in the majority of inpatients. Furthermore, neutralizing antibodies were undetectable in 56% of asymptomatic carriers.ConclusionsOur results raise questions concerning the role played by neutralizing antibodies in COVID-19 cure and protection against secondary infection. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.HighlightsSpecific antibodies are detectable in 100% COVID-19 inpatients two weeks post-symptom onset.The detection of the SARS-CoV-2 Nucleocapsid and Receptor Binding Domain is more sensitive than the detection of the S1 or S2 subunits.Neutralizing antibodies reach a plateau two weeks post-symptom onset and then decline in the majority of inpatients.Neutralizing antibodies are undetectable in the majority of asymptomatic carriers.

scholarly journals Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiandan Xiang ◽  
Boyun Liang ◽  
Yaohui Fang ◽  
Sihong Lu ◽  
Sumeng Li ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Protein S ◽  
Igg Antibodies ◽  
Neutralizing Activity ◽  
Specific Igg ◽  
One Year ◽  
Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

scholarly journals Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients

2020 ◽  
Vol 5 (52) ◽  
pp. eabe0367 ◽  
Author(s):  
Anita S. Iyer ◽  
Forrest K. Jones ◽  
Ariana Nodoushani ◽  
Meagan Kelly ◽  
Margaret Becker ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Binding Domain ◽  
Antibody Responses ◽  
Human Antibody ◽  
Receptor Binding Domain ◽  
Recent Infection

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.

scholarly journals Limited window for donation of convalescent plasma with high live-virus neutralizing antibodies for COVID-19 immunotherapy

2020 ◽  
Author(s):  
Abhinay Gontu ◽  
Sreenidhi Srinivasan ◽  
Eric Salazar ◽  
Meera Surendran Nair ◽  
Ruth H. Nissly ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Igg Antibody ◽  
Plasma Therapy ◽  
Live Virus ◽  
Viral Neutralization ◽  
Knowledge Deficit ◽  
Neutralizing Capacity ◽  
Optimal Window

ABSTRACTThe optimal timeframe for donating convalescent plasma to be used for COVID-19 immunotherapy is unknown. To address this important knowledge deficit, we determined in vitro live-virus neutralizing capacity and persistence of IgM and IgG antibody responses against the receptor-binding domain and S1 ectodomain of the SARS-CoV-2 spike glycoprotein in 540 convalescent plasma samples obtained from 175 COVID-19 plasma donors for up to 142 days post-symptom onset. Robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 persist, in the aggregate, for at least 100 days post-symptom onset. However, a notable acceleration in decline in virus neutralization titers ≥160, a value suitable for convalescent plasma therapy, was observed starting 60 days after first symptom onset. Together, these findings better define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor, including age and COVID-19 disease severity score.One Sentence SummaryEvaluation of SARS-CoV-2 anti-spike protein IgM, IgG, and live-virus neutralizing titer profiles reveals that the optimal window for donating convalescent plasma for use in immunotherapy is within the first 60 days of symptom onset.

scholarly journals Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis

Kidney360 ◽  
2021 ◽  
Vol 2 (12) ◽  
pp. 1917-1927
Author(s):  
Ana Cecilia Bardossy ◽  
Lauren Korhonen ◽  
Sabrina Schatzman ◽  
Paige Gable ◽  
Carolyn Herzig ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Clinical Course ◽  
Rt Pcr ◽  
Convenience Sample ◽  
Content Type ◽  
Specific Antibodies ◽  
Viral Culture ◽  
Maintenance Dialysis ◽  
Dialysis Facilities

BackgroundPatients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity.MethodsFrom August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens.ResultsFifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duration of RT-PCR positivity from diagnosis was 18 days (interquartile range [IQR], 8‒24 days). Ten participants had at least one, for a total of 41, positive RT-PCR specimens ≥10 days after symptoms onset. Of these 41 specimens, 21 underwent viral culture; one (5%) was positive 14 days after symptom onset. Thirteen participants developed SARS-CoV-2–specific antibodies, 11 of which included neutralizing antibodies. RT-PCRs remained positive after seroconversion in eight participants and after detection of neutralizing antibodies in four participants; however, all of these samples were culture negative.ConclusionsPatients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2–RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR–positive results in the presence of SARS-CoV-2–specific antibodies, but without replication-competent virus detected.

scholarly journals Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class

2021 ◽  
Author(s):  
Micah Rapp ◽  
Yicheng Guo ◽  
Eswar R. Reddem ◽  
Lihong Liu ◽  
Pengfei Wang ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Neutralizing Antibodies ◽  
Structural Basis ◽  
List Type ◽  
Receptor Binding Domain ◽  
Heavy Chains ◽  
Vh Gene ◽  
Antibody Class ◽  
Insight Into ◽  
Potent Neutralization

SUMMARYAntibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent SARS-CoV-2-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determined structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three utilized VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy chain N53I enhancing binding and light chain tyrosines recognizing F486RBD. Despite these similarities, class members bound both RBD-up and -down conformations of the spike, with a subset of antibodies utilizing elongated CDRH3s to recognize glycan N343 on a neighboring RBD – a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2-antibody class thus utilizes modular recognition encoded by modular genetic elements to effect potent neutralization, with VH-gene component specifying recognition of RBD and CDRH3 component specifying quaternary interactions.HighlightsDetermine structures of VH1-2-derived antibodies 2-43, 2-15, and H4 in complex with SARS-CoV-2 spikeDefine a multi-donor VH1-2-antibody class with modular components for RBD and quaternary recognitionReveal structural basis of RBD-up and RBD-down recognition within the classShow somatic hypermutations and avidity to be critical for potencyDelineate changes in spike conformation induced by CDRH3-mediated quaternary recognition

Key features of tests for detection of SARS-CoV2 antibodies

2021 ◽  
pp. 13-17
Author(s):  
V. S. Berestovskaya ◽  
T. V. Vavilova ◽  
A. V. Gubanova ◽  
N. Yu. Chernysh
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
World Health ◽  
Receptor Binding Domain ◽  
Test Format ◽  
Specific Antibodies ◽  
The World ◽  
Quantitative Results ◽  
Key Features ◽  
Health Organization

On March 11, 2020, the World Health Organization recognized the outbreak of the disease COVID-19 (Coronavirus Disease 2019) and the spread of the new coronavirus (SARS-CoV-2), which caused this disease, as a pandemic. The SARS-CoV-2 virus stimulates the production of antigen-specific antibodies for which commercial tests have been developed. The issue of diagnosing antibodies to SARS-CoV-2 became especially acute together with the beginning of mass vaccination of the population. Due to the fact that the reading of the result depends on the test format, it is necessary to understand how the antigenic target, the composition of the immunoglobulins and the way of expressing the result affect its interpretation. When analyzing the literature, it was found that with COVID-19, antibodies to the nucleocapsid antigen of SARS-CoV-2 can be detected somewhat earlier than antibodies to the spike antigen; virus-neutralizing antibodies are directed to the receptor-binding domain, seroconversion of immunoglobulins M and G begins simultaneously, and tests for total antibodies are potentially more sensitive due to the ability to capture antibodies with various features of the immune response. The problem of incomparability of quantitative results obtained on different systems is also noted. These factors must be taken into account when choosing a test for detecting antibodies to SARS-CoV-2, which will adequately solve a specific clinical and epidemiological problem.

scholarly journals Titers, Prevalence, and Duration of SARS-CoV-2 Antibodies in a Local COVID-19 Outbreak and Following Vaccination

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 587
Author(s):  
Jodi F. Hedges ◽  
Macy A. Thompson ◽  
Deann T. Snyder ◽  
Amanda Robison ◽  
Matthew P. Taylor ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Herd Immunity ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Specific Antibodies ◽  
Neutralization Capacity ◽  
Protein Receptor ◽  
Asymptomatic Infections ◽  
Antibody Levels

Information concerning the development of neutralizing antibodies and their duration will be critical to establishing herd immunity for COVID-19. We sought to evaluate SARS-CoV-2 spike protein receptor-binding domain (RBD)-specific antibodies, their duration, and capacity for SARS-CoV-2 neutralization in volunteers while the pandemic spread within our community starting in March 2020. Those participants with the highest starting titers had the longest-lasting response, up to 12 months post-diagnosis. SARS-CoV-2 neutralization capacity was correlated with anti-RBD antibody levels. The majority of our participants with confirmed COVID-19 diagnosis had very mild or asymptomatic infections. We also detected low and largely non-neutralizing anti-RBD IgG titers in a few participants with no known COVID-19 diagnosis. Finally, we found that antibody responses induced by vaccination were significantly higher than those induced by natural infection. Thus, our study suggests that vaccination is still critical even for those naturally infected or diagnosed with COVID-19.

scholarly journals SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence

2020 ◽  
Vol 222 (9) ◽  
pp. 1452-1461 ◽  
Author(s):  
Gerco den Hartog ◽  
Rutger M Schepp ◽  
Marjan Kuijer ◽  
Corine GeurtsvanKessel ◽  
Josine van Beek ◽  
...  
Keyword(s):  
Multiplex Assay ◽  
Spike Protein ◽  
Antibody Detection ◽  
Receptor Binding Domain ◽  
Test Results ◽  
Protein Subunits ◽  
Specific Antibodies ◽  
Single Antigen ◽  
Specific Igg ◽  
Kinetics Of

Abstract Background The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. Results Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. Conclusions The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.

scholarly journals The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients

2020 ◽  
Vol 5 (48) ◽  
pp. eabc8413 ◽  
Author(s):  
Lakshmanane Premkumar ◽  
Bruno Segovia-Chumbez ◽  
Ramesh Jadi ◽  
David R. Martinez ◽  
Rajendra Raut ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Severe Disease ◽  
Population Level ◽  
Respiratory Illness ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Specific Antibodies

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.

scholarly journals The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan

2021 ◽  
Author(s):  
Yudai Kaneko ◽  
Akira Sugiyama ◽  
Toshiya Tanaka ◽  
Kazushige Fukui ◽  
Akashi Taguchi ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Early Stage ◽  
Binding Domain ◽  
Structural Proteins ◽  
Receptor Binding Domain ◽  
Antibody Testing ◽  
Serum Samples ◽  
Iga Antibodies

Objectives: To compare the temporal changes of IgM, IgG, and IgA antibodies against the SARS-CoV-2 nucleoprotein, S1 subunit, and receptor binding domain and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with COVID-19. Methods: A total of five patients in Nissan Tamagawa Hospital, Tokyo, Japan confirmed COVID-19 from August 8, 2020 to August 14, 2020 were investigated. Serum samples were acquired multiple times from 0 to 76 days after symptom onset. Using a fully automated CLIA analyzer, we measured the levels of IgG, IgA, and IgM against the SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2. Results: The levels of IgG antibodies against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA antibodies increasing before IgG and IgM in 3/5 cases. The NAb levels against SARS-CoV-2 increased and kept above 10 AU/mL more than around 70 days after symptom onset in all cases. Furthermore, in the early stage, NAb levels were more than cut off value in 4/5 COVID-19 patients some of whose antibodies against RBD didn't exceed 10 AU/mL. Conclusions: Our findings indicate that patients with COVID-19 should be examined for IgG, IgA and IgM antibodies against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 in addition to conventional antibody testing methods for SARS-CoV-2 (IgG and IgM kits) to analyze the diversity of patients' immune mechanisms.

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