scholarly journals Accurate SARS-CoV-2 seroprevalence surveys require robust multi-antigen assays

2020 ◽  
Author(s):  
Christos Fotis ◽  
Nikolaos Meimetis ◽  
Nikos Tsolakos ◽  
Marianna Politou ◽  
Karolina Akinosoglou ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Blood Donors ◽  
Clinical Performance ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Accurate Identification ◽  
Serological Tests ◽  
Partial Agreement ◽  
Multiplex Immunoassay ◽  
Single Antigen

AbstractThere is a plethora of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) serological tests based either on nucleocapsid phosphoprotein (N), S1-subunit of spike glycoprotein (S1) or receptor binding domain (RBD). Although these single-antigen based tests demonstrate high clinical performance, there is growing evidence regarding their limitations in epidemiological serosurveys. To address this, we developed a Luminex-based multiplex immunoassay that detects total antibodies (IgG/IgM/IgA) against the N, S1 and RBD antigens and used it to compare antibody responses in 1,225 blood donors across Greece. Seroprevalence based on single-antigen readouts was strongly influenced by both the antigen type and cut-off value and ranged widely [0.8% (95% CI, 0.4-1.5%)-7.5% (95% CI, 6.0-8.9%)]. A multi-antigen approach requiring partial agreement between RBD and N or S1 readouts (RBD&N|S1 rule) was less affected by cut-off selection, resulting in robust seroprevalence estimation [0.6% (95% CI, 0.3-1.1%)-1.2% (95% CI, 0.7-2.0%)] and accurate identification of seroconverted individuals.

scholarly journals Accurate SARS-CoV-2 seroprevalence surveys require robust multi-antigen assays

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christos Fotis ◽  
Nikolaos Meimetis ◽  
Nikos Tsolakos ◽  
Marianna Politou ◽  
Karolina Akinosoglou ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Blood Donors ◽  
Clinical Performance ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Accurate Identification ◽  
Serological Tests ◽  
Partial Agreement ◽  
Multiplex Immunoassay ◽  
Single Antigen

AbstractThere is a plethora of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) serological tests based either on nucleocapsid phosphoprotein (N), S1-subunit of spike glycoprotein (S1) or receptor binding domain (RBD). Although these single-antigen based tests demonstrate high clinical performance, there is growing evidence regarding their limitations in epidemiological serosurveys. To address this, we developed a Luminex-based multiplex immunoassay that detects total antibodies (IgG/IgM/IgA) against the N, S1 and RBD antigens and used it to compare antibody responses in 1225 blood donors across Greece. Seroprevalence based on single-antigen readouts was strongly influenced by both the antigen type and cut-off value and ranged widely [0.8% (95% CI 0.4–1.5%)–7.5% (95% CI 6.0–8.9%)]. A multi-antigen approach requiring partial agreement between RBD and N or S1 readouts (RBD&N|S1 rule) was less affected by cut-off selection, resulting in robust seroprevalence estimation [0.6% (95% CI 0.3–1.1%)–1.2% (95% CI 0.7–2.0%)] and accurate identification of seroconverted individuals.

scholarly journals Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Science ◽  
2020 ◽  
Vol 369 (6506) ◽  
pp. 956-963 ◽  
Author(s):  
Thomas F. Rogers ◽  
Fangzhu Zhao ◽  
Deli Huang ◽  
Nathan Beutler ◽  
Alison Burns ◽  
...  
Keyword(s):  
Animal Model ◽  
Severe Acute Respiratory Syndrome ◽  
Global Health ◽  
Neutralizing Antibodies ◽  
Small Animal ◽  
Passive Transfer ◽  
Antibody Responses ◽  
High Dose ◽  
Receptor Binding Domain ◽  
Small Animal Model

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.

scholarly journals Low Seroprevalence of SARS-CoV-2 in Rhode Island Blood Donors Determined using Multiple Serological Assay Formats

2020 ◽  
Author(s):  
Daniel J Nesbitt ◽  
Daniel Jin ◽  
Joseph W Hogan ◽  
Philip A Chan ◽  
Melissa J Simon ◽  
...  
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Rhode Island ◽  
High Throughput ◽  
Blood Donors ◽  
Health Policies ◽  
Antibody Testing ◽  
Serological Tests ◽  
Public Health Policies ◽  
Seropositive Rate

Epidemic projections and public health policies addressing Coronavirus disease (COVID)-19 have been implemented without data reporting on the seroconversion of the population since scalable antibody testing has only recently become available. We measured the percentage of severe acute respiratory syndrome- Coronavirus-2 (SARS-CoV-2) seropositive individuals from 2,008 blood donors drawn in the state of Rhode Island (RI). We utilized multiple antibody testing platforms, including lateral flow immunoassays (LFAs), enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). We report than an estimated seropositive rate of RI blood donors of approximately 0.6% existed in April-May of 2020. These data imply that seroconversion, and thus infection, is likely not widespread within this population. Daily new case rates peaked in RI in late April 2020. We conclude that IgG LFAs and HTSAs are suitable to conduct seroprevalence assays in random populations. More studies will be needed using validated serological tests to improve the precision and report the kinetic progression of seroprevalence estimates.

scholarly journals A Highly Sensitive and Specific SARS-CoV-2 Spike- and Nucleoprotein-Based Fluorescent Multiplex Immunoassay (FMIA) to Measure IgG, IgA, and IgM Class Antibodies

2021 ◽  
Author(s):  
Anna Solastie ◽  
Camilla Virta ◽  
Anu Haveri ◽  
Nina Ekström ◽  
Anu Kantele ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Performance ◽  
Neutralizing Antibody ◽  
Serological Assay ◽  
Multiplex Immunoassay ◽  
Reliable Estimation ◽  
Highly Sensitive ◽  
Antibody Titers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays with excellent clinical performance are essential for reliable estimation of the persistence of immunity after infection or vaccination. In this paper we present a thoroughly validated SARS-CoV-2 serological assay with excellent clinical performance and good comparability to neutralizing antibody titers.

scholarly journals Low Seroprevalence of SARS-CoV-2 in Rhode Island Blood Donors Determined Using Multiple Serological Assay Formats

2020 ◽  
Author(s):  
Daniel J. Nesbitt ◽  
Daniel P. Jin ◽  
Joseph W. Hogan ◽  
Philip A Chan ◽  
Melissa J Simon ◽  
...  
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Statistical Method ◽  
Rhode Island ◽  
High Throughput ◽  
Blood Donors ◽  
Health Policies ◽  
Antibody Testing ◽  
Serological Tests ◽  
Public Health Policies

Abstract Background: Epidemic projections and public health policies addressing Coronavirus disease (COVID)-19 have been implemented without data reporting on the seroconversion of the population since scalable antibody testing has only recently become available. Methods: We measured the percentage of severe acute respiratory syndrome- Coronavirus-2 (SARS-CoV-2) seropositive individuals from 2,008 blood donors drawn in the state of Rhode Island (RI). We utilized multiple antibody testing platforms, including lateral flow immunoassays (LFAs), enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). To estimate seroprevalence, we utilized the Bayesian statistical method to adjust for sensitivity and specificity of the commercial tests used.Results: We report than an estimated seropositive rate of RI blood donors of approximately 0.6% existed in April-May of 2020. Daily new case rates peaked in RI in late April 2020. We found HTSAs and LFAs were positively correlated with ELISA assays to detect antibodies specific to SARS-CoV-2 in blood donors. Conclusions: These data imply that seroconversion, and thus infection, is likely not widespread within this population. We conclude that IgG LFAs and HTSAs are suitable to conduct seroprevalence assays in random populations. More studies will be needed using validated serological tests to improve the precision and report the kinetic progression of seroprevalence estimates.

scholarly journals “Evaluation of a COVID-19 IgM and IgG Rapid Test and Assessment of Specific Antibody Response in COVID-19 patients, Tunisia 2020”

2021 ◽  
Author(s):  
letaief hejer ◽  
Sonia Dhaouadi ◽  
Aicha Hechaichi ◽  
Mouna Safer ◽  
Chahida Harizi ◽  
...  
Keyword(s):  
Antibody Response ◽  
Clinical Performance ◽  
Rapid Test ◽  
Antibody Test ◽  
Antibody Responses ◽  
Rt Pcr ◽  
Serological Tests ◽  
Clinical Sensitivity ◽  
Negative Results ◽  
Finger Stick

Abstract Background COVID-19 pandemic is a massive global health emergency. Although RT-PCR is the gold standard for diagnosing suspected cases, there is a need of serological tests to investigate antibody responses. Many serologic immunoassays have been developed to detect antibodies to SARS-CoV2, including rapid tests. This study assessed the clinical performance of the SARS-CoV-2 antibody test (colloidal gold immunochromatography, LEPU TECHNOLOGY) and evaluated the kinetic antibody response in COVID-19 patients.Methods: Samples collected by finger stick; obtained from RT-PCR confirmed cases and samples of negative controls were tested with the IgM/IgG Detection Kit . Results: The kit shows a clinical sensitivity of 65.7 % [59.7%-71.3%] and a specificity of 96.3% [93.0%-98.3%]. The predictive positive value and negative predictive value were respectively 95.2% [91.0%-97.8%] and 71.4% [66.1%-76.2%]. The seroconversion of specific IgM and IgG antibodies were observed as early as the 2nd day after symptom onset.Conclusions: This test is quite useful for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. Longitudinal studies on antibody responses during and post infection are needed.

scholarly journals Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19

2020 ◽  
Vol 5 (52) ◽  
pp. eabe5511
Author(s):  
Baweleta Isho ◽  
Kento T. Abe ◽  
Michelle Zuo ◽  
Alainna J. Jamal ◽  
Bhavisha Rathod ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Receptor Binding ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Surrogate Measure ◽  
Antibody Levels ◽  
Negative Controls

Although the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) immunoglobulin G (IgG), IgA, and IgM responses to the SARS-CoV-2 spike protein (full-length trimer) and its receptor binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed coronavirus disease 2019 (COVID-19) ranging from 3 to 115 days postsymptom onset (PSO), compared with negative controls. Anti–SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16 to 30 days PSO. Longitudinal analysis revealed that anti–SARS-CoV-2 IgA and IgM antibodies rapidly decayed, whereas IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Last, IgG, IgM, and, to a lesser extent, IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in most of the patients with COVID-19 for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

scholarly journals SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

2021 ◽  
Author(s):  
Kevin O. Saunders ◽  
Esther Lee ◽  
Robert Parks ◽  
David R. Martinez ◽  
Dapeng Li ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Neutralization Titer ◽  
The Uk ◽  
Further Development

SUMMARYBetacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.

scholarly journals Low Seroprevalence of SARS-CoV-2 in Rhode Island blood donors during may 2020 as determined using multiple serological assay formats

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel J. Nesbitt ◽  
Daniel P. Jin ◽  
Joseph W. Hogan ◽  
Jenny Yang ◽  
Haidee Chen ◽  
...  
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Statistical Method ◽  
Rhode Island ◽  
High Throughput ◽  
Blood Donors ◽  
Health Policies ◽  
Antibody Testing ◽  
Serological Tests ◽  
Public Health Policies

Abstract Background Epidemic projections and public health policies addressing Coronavirus disease (COVID)-19 have been implemented without data reporting on the seroconversion of the population since scalable antibody testing has only recently become available. Methods We measured the percentage of severe acute respiratory syndrome- Coronavirus-2 (SARS-CoV-2) seropositive individuals from 2008 blood donors drawn in the state of Rhode Island (RI). We utilized multiple antibody testing platforms, including lateral flow immunoassays (LFAs), enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). To estimate seroprevalence, we utilized the Bayesian statistical method to adjust for sensitivity and specificity of the commercial tests used. Results We report than an estimated seropositive rate of RI blood donors of approximately 0.6% existed in April–May of 2020. Daily new case rates peaked in RI in late April 2020. We found HTSAs and LFAs were positively correlated with ELISA assays to detect antibodies specific to SARS-CoV-2 in blood donors. Conclusions These data imply that seroconversion, and thus infection, is likely not widespread within this population. We conclude that IgG LFAs and HTSAs are suitable to conduct seroprevalence assays in random populations. More studies will be needed using validated serological tests to improve the precision and report the kinetic progression of seroprevalence estimates.

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