Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.

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Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection

10.1101/2020.08.06.20169367 ◽

2020 ◽

Cited By ~ 16

Author(s):

Katharine HD Crawford ◽

Adam S Dingens ◽

Rachel Eguia ◽

Caitlin R Wolf ◽

Naomi Wilcox ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Neutralizing Antibody ◽

Spike Protein ◽

Early Immune Response ◽

Antibody Titers ◽

Antibody Levels ◽

Time Frames ◽

Initial Peak

Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ≈30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

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SARS-CoV-2 serology across scales: a framework for unbiased seroprevalence estimation incorporating antibody kinetics and epidemic recency

10.1101/2021.09.09.21263139 ◽

2021 ◽

Author(s):

Saki Takahashi ◽

Michael J Peluso ◽

Jill Hakim ◽

Keirstinne Turcios ◽

Owen Janson ◽

...

Keyword(s):

Large Scale ◽

Statistical Approach ◽

Population Level ◽

Individual Level ◽

Antibody Titers ◽

Severe Infections ◽

Study Designs ◽

Antibody Levels ◽

Antibody Kinetics ◽

Parameter Values

Serosurveys are a key resource for measuring SARS-CoV-2 cumulative incidence. A growing body of evidence suggests that asymptomatic and mild infections (together making up over 95% of all infections) are associated with lower antibody titers than severe infections. Antibody levels also peak a few weeks after infection and decay gradually. We developed a statistical approach to produce adjusted estimates of seroprevalence from raw serosurvey results that account for these sources of spectrum bias. We incorporate data on antibody responses on multiple assays from a post-infection longitudinal cohort, along with epidemic time series to account for the timing of a serosurvey relative to how recently individuals may have been infected. We applied this method to produce adjusted seroprevalence estimates from five large-scale SARS-CoV-2 serosurveys across different settings and study designs. We identify substantial differences between reported and adjusted estimates of over two-fold in the results of some surveys, and provide a tool for practitioners to generate adjusted estimates with pre-set or custom parameter values. While unprecedented efforts have been launched to generate SARS-CoV-2 seroprevalence estimates over this past year, interpretation of results from these studies requires properly accounting for both population-level epidemiologic context and individual-level immune dynamics.

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Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa618 ◽

2020 ◽

Cited By ~ 7

Author(s):

Katharine H D Crawford ◽

Adam S Dingens ◽

Rachel Eguia ◽

Caitlin R Wolf ◽

Naomi Wilcox ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Symptom Onset ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Neutralizing Antibody ◽

Spike Protein ◽

Antibody Titers ◽

Antibody Levels ◽

Time Frames ◽

Initial Peak

Abstract Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

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Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽

10.3390/v13020284 ◽

2021 ◽

Vol 13 (2) ◽

pp. 284

Author(s):

Hulda R. Jonsdottir ◽

Michel Bielecki ◽

Denise Siegrist ◽

Thomas W. Buehrer ◽

Roland Züst ◽

...

Keyword(s):

Young Adults ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Humoral Response ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Asymptomatic Infection ◽

Homogeneous Population ◽

Humoral Immune ◽

Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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Third doses of COVID-19 vaccines reduce infection and transmission of SARS-CoV-2 and could prevent future surges in some populations

10.1101/2021.10.25.21265500 ◽

2021 ◽

Author(s):

Billy J Gardner ◽

A. Marm Kilpatrick

Keyword(s):

Vaccine Coverage ◽

Severe Disease ◽

Neutralizing Antibody ◽

Reproductive Number ◽

Vaccine Protection ◽

Contact Rates ◽

Previous Infection ◽

Antibody Titers ◽

Protection Against Infection ◽

The Impact

Background Vaccines have greatly reduced the impact of COVID-19 globally. Unfortunately, evidence indicates that immunity wanes following vaccination, especially with the Delta variant (B.1.617.2). Protection against severe disease and death remain high, but protection against milder disease and infection have dropped significantly. A third booster dose of two-dose vaccines has been approved in several countries to individuals at higher risk of severe disease to protect those individuals, but the benefit to boosting immunity in younger healthy individuals and the effects on transmission are less clear. Methods Here we use relationships between neutralizing antibody titers and vaccine protection against infection and transmission, combined with data on waning and boosting of neutralizing antibody titers to examine the impact of a third dose of the Pfizer vaccine on infection and transmission and its impact on the pathogen effective reproductive number Rt. Findings Eight months of waning reduced protection of the Pfizer vaccine against all infections from 80.0% (95% CI: 77% to 83%) to 60.4% (95% CI: 53% to 67%); a third dose (which increased neutralizing antibody titers 25.9- fold relative to levels after 8 months of waning) increased protection to 87.2% (95% CI: 83% to 91%). Increased protection against infection and transmission from third doses reduced Rt by 21% to 66% depending on vaccine coverage and previous infection and reduced Rt below 1 when vaccination coverage was high or contact rates were well below pre-pandemic levels. Interpretation A third dose of the Pfizer vaccine could reduce transmission of SARS-CoV-2, which would reduce infection in unvaccinated individuals and breakthrough infections in vaccinated individuals. While vaccination of unvaccinated individuals, especially in developing countries, would be more effective for reducing disease than providing a third dose to vaccinated individuals, the benefit of a third dose in reducing transmission is sizeable and increases with vaccine coverage and contact rates among individuals.

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Prevalence and Persistence of Maternal Dengue Neutralizing Antibodies in Infants From Central and Southern Thailand: A Retrospective Cohort Study

Asia Pacific Journal of Public Health ◽

10.1177/1010539519853396 ◽

2019 ◽

Vol 31 (4) ◽

pp. 288-295 ◽

Cited By ~ 1

Author(s):

Adrienne Guignard ◽

François Haguinet ◽

Stéphanie Wéry ◽

Phirangkul Kerdpanich

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Development ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Maternal Antibodies ◽

Childhood Immunization ◽

Serum Samples ◽

Denv Serotypes ◽

Antibody Titers ◽

Antibody Kinetics

Understanding maternal dengue virus (DENV) neutralizing antibody kinetics in infants remains timely to develop a safe and effective childhood immunization. This retrospective study evaluated the prevalence and persistence of maternal antibody titers against DENV serotypes 1 to 4 in 139 Thai infants at 2, 6, and 7 months of age, using serum samples collected in a vaccination trial ( http://clinicaltrials.gov ; NCT00197275). Neutralizing antibodies against all 4 DENV serotypes were detected in 87.8% and 22.9% of infants at 2 and 7 months, respectively. At 2 months, DENV-4 neutralizing antibody geometric mean titers were notably lower (80) compared with DENV-1 to DENV-3 (277-471). Our results corroborate previous findings that DENV-1 to DENV-4 maternal antibodies persist at 7 months despite titers decrease from 2 months onwards. As persisting maternal antibodies may inhibit immune responses in DENV-vaccinated infants, a comprehensive understanding of DENV antibody kinetics is required in the perspective of vaccine development for infants.

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Neutralizing Antibody Responses in COVID-19 Convalescent Sera

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa673 ◽

2020 ◽

Vol 223 (1) ◽

pp. 47-55 ◽

Cited By ~ 1

Author(s):

William T Lee ◽

Roxanne C Girardin ◽

Alan P Dupuis ◽

Karen E Kulas ◽

Anne F Payne ◽

...

Keyword(s):

Neutralizing Antibodies ◽

High Titer ◽

Experimental Treatment ◽

Neutralizing Antibody ◽

Maximal Activity ◽

The United States ◽

Enzyme Linked Immunosorbent Assay ◽

United States Food ◽

Antibody Titers ◽

Antibody Levels

Abstract Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.

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IL-6 and IL-10 Levels, Rather Than Viral Load and Neutralizing Antibody Titers, Determine the Fate of Patients With Severe Fever With Thrombocytopenia Syndrome Virus Infection in South Korea

Frontiers in Immunology ◽

10.3389/fimmu.2021.711847 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jeong Rae Yoo ◽

Tae-Jin Kim ◽

Sang Taek Heo ◽

Kyung-Ah Hwang ◽

Hyunjoo Oh ◽

...

Keyword(s):

Viral Load ◽

Close Contact ◽

Multiorgan Failure ◽

Severe Disease ◽

Elevated Serum ◽

Gastrointestinal Symptoms ◽

Neutralizing Antibody ◽

Haemaphysalis Longicornis ◽

Antibody Titers ◽

Severe Fever

Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death).

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Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

10.21203/rs.3.rs-916427/v1 ◽

2021 ◽

Author(s):

Annika Fendler ◽

Lewis Au ◽

Scott Shepherd ◽

Fiona Byrne ◽

Maddalena Cerrone ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Cellular Responses ◽

Patients With Cancer ◽

Cell Immunity ◽

Clinical Annotation ◽

Antibody Titers ◽

Antibody Levels ◽

Immune Profiling ◽

Reactive Antibody

Abstract Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

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Defining Antibody Seroprevalence and Duration of Humoral Responses to SARS-CoV-2 Infection and/or Vaccination in a Greek Community

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph19010407 ◽

2021 ◽

Vol 19 (1) ◽

pp. 407

Author(s):

Ourania S. Kotsiou ◽

Dimitrios Papagiannis ◽

Evangelos C. Fradelos ◽

Dimitra I. Siachpazidou ◽

Garifallia Perlepe ◽

...

Keyword(s):

Immune Response ◽

Antibody Response ◽

Severe Disease ◽

Vaccination Status ◽

Antibody Responses ◽

Antibody Testing ◽

Mild Disease ◽

Antibody Titers ◽

Humoral Responses ◽

Pandemic Wave

Background: In this work we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). Methods: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination and 27% of participants were both previously infected and vaccinated. All previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. Conclusions: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization

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