scholarly journals Changes in SARS-CoV-2 Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

2020 ◽  
Author(s):  
Craig Fenwick ◽  
Antony Croxatto ◽  
Alix T. Coste ◽  
Florence Pojer ◽  
Cyril Andre ◽  
...  
Keyword(s):  
General Population ◽  
Acute Infection ◽  
Population Based ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Igg Antibody ◽  
S Protein ◽  
N Protein ◽  
Total Cohort

We have determined SARS-CoV-2-specific antibody responses in a cohort of 96 individuals with acute infection and in 578 individuals enrolled in a seroprevalence population study in Switzerland including three groups, i.e. subjects with previous RT-PCR confirmed SARS-CoV-2 infections (n=90), positive patient contacts (n=177) and random selected subjects (n=311). SARS-CoV-2 antibody responses specific to the Spike (S), in the monomeric and native trimeric forms, and/or the nucleocapsid (N) proteins were equally sensitive in the acute infection phase. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection and substantially underestimated the proportion of SARS-CoV-2 infections in the groups of patient positive contacts, i.e. 10.9 to 32.2% reduction and in the random selected general population, i.e. up to 45% reduction. The overall reduction in seroprevalence targeting only anti-N IgG antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.

scholarly journals Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

2020 ◽  
Author(s):  
Craig Fenwick ◽  
Antony Croxatto ◽  
Alix T. Coste ◽  
Florence Pojer ◽  
Cyril André ◽  
...  
Keyword(s):  
General Population ◽  
Antibody Response ◽  
Specific Antibody ◽  
Post Infection ◽  
Acute Infection ◽  
Population Based ◽  
Antibody Responses ◽  
S Protein ◽  
N Protein ◽  
Protein Assays

SARS-CoV-2-specific antibody responses to the Spike (S) protein monomer, S protein native trimeric form or the nucleocapsid (N) proteins were evaluated in cohorts of individuals with acute infection (n=93) and in individuals enrolled in a post-infection seroprevalence population study (n=578) in Switzerland. Commercial assays specific for the S1 monomer, for the N protein and a newly developed Luminex assay using the S protein trimer were found to be equally sensitive in antibody detection in the acute infection phase samples. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection cohort. Seroprevalence in a ‘positive patient contacts’ group (n=177) was underestimated by N protein assays by 10.9 to 32.2% and the ‘random selected’ general population group (n=311) was reduced up to 45% reduction relative to S protein assays. The overall reduction in seroprevalence targeting only anti-N antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was significantly more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies. IMPORTANCE In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and post-infection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection but that responses against N appear to wane in the post-infection phase while those against S protein persist over time. The most sensitive serological assay in both acute and post-infection phases used the native S protein trimer as binding antigen that has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe that these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response.

scholarly journals Seroepidemiological Study of Novel Corona Virus (CoVID-19) in Tehran, Iran

2021 ◽  
Author(s):  
Zeinab Tabanejad ◽  
Sorena Darvish ◽  
Zeinab Borjian Boroujeni ◽  
Seyed Saeed Asadi ◽  
Morteza Mesri ◽  
...  
Keyword(s):  
False Negative ◽  
Underlying Disease ◽  
Population Based ◽  
Immunological Methods ◽  
Age Group ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Igg Antibody ◽  
Cross Sectional ◽  
Exposed Population

AbstractA novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to all countries of the world, including Iran. Although new anti-coronavirus antibodies in patients may be identified by immunological methods with sufficient sensitivity and specificity, the conclusive diagnosis of the disease is by the molecular RT-PCR process. We used a population-based seroepidemiological survey to quantify the proportion of the exposed population with SARS-CoV-2 antibodies and evaluated whether the antibodies are a marker of total or partial immunity to the proportion of the population that remains susceptible to the virus. This cross-sectional study was conducted to investigate the seroprevalence of CoVID-19 in Tehran, the capital of Iran, between April and end of October 2020. Specimens of clotted and heparinized blood (2ml) were collected from the patients. The serum and plasma were separated and stored at − 80LJ°C until use. We examined serum anti-SARS-CoV-2 IgG and IgM antibodies from 1375 in-patients admitted to our hospitals using ELISA kits. In total, 1375 participants were enrolled in this study, and SARS-CoV-2 antibodies were detected using IgM-IgG antibody assay in 291 patients. Among the seropositive patients studied, 187 were men (64.3%), and 104 were women (35.7%) (P<0.05). The mean age of the patients was 49±8.4 years; the majority (27%) were in age group 31-40 years. Also, the lowest frequency of cases was reported in the age group of 1-10 years (P <0.05). We determined the seroprevalence of SARS-CoV-2 for IgM or IgG antibodies to be 21.2%. Diabetes mellitus was the most common underlying disease among SARS-CoV-2 patients [P=0.05; Odd Ratio=1.61(0.90-2.91)]. Conventional serological assays in SARS-CoV-2 cases, such as the enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, have a high-throughput advantage and minimize false-negative rates that occur with the RT-PCR method. This study determined the seroprevalence of SARS-CoV-2 antibodies to be 21%. Control of diabetes among other cases factors shall play important role in management and control of COVID-19.

scholarly journals Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection

2020 ◽  
Author(s):  
Xiaomei Zhang ◽  
Xian Wu ◽  
Dan Wang ◽  
Minya Lu ◽  
Xin Hou ◽  
...  
Keyword(s):  
Early Stage ◽  
False Negative ◽  
False Negative Rate ◽  
Antibody Detection ◽  
Igg Antibodies ◽  
Protein Subunit ◽  
Igg Antibody ◽  
S Protein ◽  
N Protein ◽  
Acute Myocardial Injury

AbstractRapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p≤0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.

scholarly journals Incorporating false negative tests in epidemiological models for SARS-CoV-2 transmission and reconciling with seroprevalence estimates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rupam Bhattacharyya ◽  
Ritoban Kundu ◽  
Ritwik Bhaduri ◽  
Debashree Ray ◽  
Lauren J. Beesley ◽  
...  
Keyword(s):  
False Negative ◽  
Population Based ◽  
Training Data ◽  
Epidemiological Models ◽  
Rt Pcr ◽  
Antibody Prevalence ◽  
Igg Antibody ◽  
False Negatives ◽  
Seir Model ◽  
Study Population

AbstractSusceptible-Exposed-Infected-Removed (SEIR)-type epidemiologic models, modeling unascertained infections latently, can predict unreported cases and deaths assuming perfect testing. We apply a method we developed to account for the high false negative rates of diagnostic RT-PCR tests for detecting an active SARS-CoV-2 infection in a classic SEIR model. The number of unascertained cases and false negatives being unobservable in a real study, population-based serosurveys can help validate model projections. Applying our method to training data from Delhi, India, during March 15–June 30, 2020, we estimate the underreporting factor for cases at 34–53 (deaths: 8–13) on July 10, 2020, largely consistent with the findings of the first round of serosurveys for Delhi (done during June 27–July 10, 2020) with an estimated 22.86% IgG antibody prevalence, yielding estimated underreporting factors of 30–42 for cases. Together, these imply approximately 96–98% cases in Delhi remained unreported (July 10, 2020). Updated calculations using training data during March 15-December 31, 2020 yield estimated underreporting factor for cases at 13–22 (deaths: 3–7) on January 23, 2021, which are again consistent with the latest (fifth) round of serosurveys for Delhi (done during January 15–23, 2021) with an estimated 56.13% IgG antibody prevalence, yielding an estimated range for the underreporting factor for cases at 17–21. Together, these updated estimates imply approximately 92–96% cases in Delhi remained unreported (January 23, 2021). Such model-based estimates, updated with latest data, provide a viable alternative to repeated resource-intensive serosurveys for tracking unreported cases and deaths and gauging the true extent of the pandemic.

scholarly journals Dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the Czech unvaccinated population: nationwide prospective seroconversion (PROSECO) study

2021 ◽  
Author(s):  
Pavel Piler ◽  
Vojtěch Thon ◽  
Lenka Andrýsková ◽  
Kamil Doležel ◽  
David Kostka ◽  
...  
Keyword(s):  
Czech Republic ◽  
Population Based ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
The Czech Republic ◽  
Global Pandemic ◽  
Government Data ◽  
Low Incidence ◽  
Study Participants ◽  
Second Wave

AbstractBackgroundAlthough the Czech Republic weathered the first wave of the COVID-19 epidemic with relatively low incidence, the second wave of the global pandemic saw it rank among countries bearing the greatest COVID-19 burden, both in Europe and on a worldwide scale. The aim of the nationwide prospective seroconversion (PROSECO) study was to investigate the dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the Czech population.MethodsAll clients of the second largest health insurance company in the Czech Republic were sent a written invitation to participate in this longitudinal study. The study includes the first 30,054 persons who provided a blood sample between October 2020 and March 2021. Seroprevalence was compared between calendar periods of blood sample collection, RT-PCR test results, sociodemographic factors, and other characteristics.FindingsThe data show a dramatic increase in seropositivity over time, from 28% in October/November 2020 to 43% in December 2020/January 2021 to 51% in February/March 2021. These trends were consistent with government data on cumulative viral antigenic prevalence in the population captured by PCR testing – although the seroprevalence rates established in this study were considerably higher than those listed in government data. Data pooled across the entire study period exhibited minor differences in seropositivity between sexes, age groups and body mass index categories; results were similar between test providing laboratories. Seropositivity was substantially higher among symptomatic vs. asymptomatic persons (76% vs. 34%). At least one third of all seropositive participants were asymptomatic, and 28% participants who developed antibodies against SARS-CoV-2 never underwent PCR testing.InterpretationAntibody response provides a better marker of past SARS-CoV-2 infection than PCR testing data. Our data on seroconversion confirm the rapidly increasing prevalence in the Czech population during the dramatically rising pandemic wave prior to the beginning of massive vaccination. The planned second and third assessment of the study participants (April 2021 – September 2021, October 2021 – March 2022) will provide valuable evidence on the seroprevalence changes following vaccination and persistence of antibodies resulting from natural infection and vaccination.Research in contextEvidence before this studySimilarly to most European countries, the first COVID-19 epidemic wave in the Czech Republic produced a relatively low incidence (86.9 confirmed cases per 100,000 persons over three months). At the peaks of the second wave, however, over 100 confirmed cases per 100,000 persons were diagnosed daily and the Czech Republic ranked among the countries with the greatest burden of COVID-19 in Europe and in the world. Only a few nationwide population-based studies have been published covering the second wave of the epidemic in Europe, and none of them from the Central and Eastern European region.Added value of this studyThe PROSECO study will provide key data from the heavily affected Central European region and contribute to the epidemiological and serological characteristics of the SARS-CoV-2 infection. All 30,054 study participants were recruited between October 2020 and March 2021, thus covering all three epidemic peaks (November 2020, January and March 2021) of the second COVID-19 epidemic wave. This allows us to follow the dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the immunologically naive and unvaccinated population during the COVID-19 pandemic. The study participants will be re-assessed in the second (April 2021 – September 2021) and third (October 2021 – March 2022) PROSECO phases to further study the post-infection/post-vaccination dynamics of seroconversion in/after a period of massive vaccination.Implications of all the available evidenceData from the first phase of the PROSECO study indicate that the percentage of the population that has been exposed to the SARS-CoV-2 may be substantially higher than estimates based on official data on cumulative viral positivity incidence as at least one third of seropositive participants were asymptomatic, and 28% of participants who developed antibodies against SARS-CoV-2 never underwent PCR testing. Regional seroprevalence data provide key information to inform, in combination with other surveillance data, public health policies and will be instrumental for the successful management of the subsequent phases of the global pandemic.The number of seropositive participants who never underwent RT-PCR testing demonstrates the importance of serological population-based studies describing the spread and exposure to the virus in the population over time.

scholarly journals Can we predict antibody responses in SARS-CoV-2? A cohort analysis

2021 ◽  
Author(s):  
Mary Gaeddert ◽  
Philip Kitchen ◽  
Tobias Broger ◽  
Stefan Weber ◽  
Ralf Bartenschlager ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Cohort Analysis ◽  
Antibody Responses ◽  
High Antibody ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Median Increase ◽  
Antibody Titers

AbstractBackgroundAfter infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.MethodsWe recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.Results281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.ConclusionsWhile age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.

scholarly journals Evolution of IgG antibody response against Toxoplasma gondii tissue cyst in acute and chronic human infections

1998 ◽  
Vol 40 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Margarita VILLAVEDRA ◽  
Hernán CAROL ◽  
Alberto NIETO
Keyword(s):  
Toxoplasma Gondii ◽  
Acute Infection ◽  
Chronic Phase ◽  
Tissue Cyst ◽  
Specific Response ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Wide Range ◽  
Toxoplasmic Infection ◽  
Human Infections

The recognition profile of the tissue cysts antigens by IgG antibodies was studied during acute and chronic human toxoplasmic infection. Thus the IgG response against Toxoplasma gondii was investigated by immunoblotting in two patients accidentally infected with the RH strain as well as in group of naturally infected patients at acute and chronic phase. There was an overall coincidence of molecular mass among antigens of tachyzoites and tissue cysts recognized by these sera, however, they appear not to be the same molecules. The response against tissue cysts starts early during acute infection, and the reactivity of antibodies is strong against a wide range of antigens. Six bands (between 82 and 151 kDa) were exclusively recognized by chronic phase sera but only the 132 kDa band was positive in more than 50% of the sera analysed. A mixture of these antigens could be used to discriminate between the two infection phases. The most important antigens recognized by the acute and the chronic phase sera were 4 clusters in the ranges 20-24 kDa, 34-39 kDa, 58-80 kDa and 105-130 kDa as well as two additional antigens of 18 and 29 kDa. Both accidentally infected patients and some of the naturally infected patients showed a weak specific response against tissue cyst antigens.

scholarly journals Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)-associated coronavirus infection

2004 ◽  
Vol 53 (5) ◽  
pp. 435-438 ◽  
Author(s):  
Weijun Chen ◽  
Zuyuan Xu ◽  
Jingsong Mu ◽  
Ling Yang ◽  
Haixue Gan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Time Course ◽  
Recovery Phase ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Blood Samples ◽  
Convalescent Phase ◽  
Coronavirus Infection

To understand the time-course of viraemia and antibody responses to severe acute respiratory syndrome-associated coronavirus (SARS-CoV), RT-PCR and ELISA were used to assay 376 blood samples from 135 SARS patients at various stages of the illness, including samples from patients who were in their early convalescent phase. The results showed that IgM antibodies decreased and became undetectable 11 weeks into the recovery phase. IgG antibodies, however, remained detectable for a period beyond 11 weeks and were found in 100 % of patients in the early convalescent phase. SARS-CoV viraemia mainly appeared 1 week after the onset of illness and then decreased over a period of 1 month, becoming undetectable in the blood samples of the convalescent patients. At the peak of viraemia, viral RNA was detectable in 75 % of blood samples from patients who were clinically diagnosed with SARS 1 or 2 weeks before the test.

scholarly journals Symptoms of COVID-19 infection and magnitude of antibody response in a large community-based study

2021 ◽  
Author(s):  
Thomas W. McDade ◽  
Joshua M. Schrock ◽  
Richard D’Aquila ◽  
Brian Mustanski ◽  
Nanette Benbow ◽  
...  
Keyword(s):  
General Population ◽  
Antibody Response ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Community Based ◽  
Large Community ◽  
Asymptomatic Infections ◽  
Low Levels ◽  
Specific Symptoms ◽  
The City

AbstractBackgroundThe majority of COVID-19 cases are asymptomatic, or minimally symptomatic with management in the home. Little is known about the frequency of specific symptoms in the general population, and how symptoms predict the magnitude of antibody response to SARS-CoV-2 infection.MethodsWe quantified IgG antibodies against the SARS-CoV-2 receptor binding domain (RBD) in home-collected dried blood spot samples from 3,365 adults participating in a community-based seroprevalence study in the city of Chicago, USA, collected between June 24 and November 11, 2020.Results17.8% of the sample was seropositive for SARS-CoV-2. A cluster of symptoms (loss of sense of smell or taste, fever, shortness of breath, muscle or body aches, cough, fatigue, diarrhea, headache) was associated with stronger anti-RBD IgG responses among the seropositives. 39.2% of infections were asymptomatic, and 2 or fewer symptoms were reported for 66.7% of infections. Total number of symptoms was positively but weakly associated with IgG response: Median anti-RBD IgG was 0.95 ug/mL for individuals with 3 or more symptoms, in comparison with 0.61 ug/mL for asymptomatic infections.ConclusionWe document high rates of asymptomatic and mild infection in a large community-based cohort, and relatively low levels of anti-SARS-CoV-2 IgG antibody in the general population of previously exposed individuals.

scholarly journals A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against Plasmodium vivax antigens in a multiplexed bead-based assay using Luminex technology (Bio-Plex 200 or MAGPIX)

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0238010
Author(s):  
Ramin Mazhari ◽  
Jessica Brewster ◽  
Rich Fong ◽  
Caitlin Bourke ◽  
Zoe S. J. Liu ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Magnetic Beads ◽  
Antibody Responses ◽  
Strongly Correlated ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Standard Curve ◽  
Luminex Technology ◽  
Specific Igg ◽  
Comparability Of Results

Multiplexed bead-based assays that use Luminex® xMAP® technology have become popular for measuring antibodies against proteins of interest in many fields, including malaria and more recently SARS-CoV-2/COVID-19. There are currently two formats that are widely used: non-magnetic beads or magnetic beads. Data are lacking regarding the comparability of results obtained using these two types of beads, and for assays run on different instruments. Whilst non-magnetic beads can only be run on flow-based instruments (such as the Luminex® 100/200™ or Bio-Plex® 200), magnetic beads can be run on both these and the newer MAGPIX® instruments. In this study we utilized a panel of purified recombinant Plasmodium vivax proteins and samples from malaria-endemic areas to measure P. vivax-specific IgG responses using different combinations of beads and instruments. We directly compared: i) non-magnetic versus magnetic beads run on a Bio-Plex® 200, ii) magnetic beads run on the Bio-Plex® 200 versus MAGPIX® and iii) non-magnetic beads run on a Bio-Plex® 200 versus magnetic beads run on the MAGPIX®. We also performed an external comparison of our optimized assay. We observed that IgG antibody responses, measured against our panel of P. vivax proteins, were moderately-strongly correlated in all three of our comparisons (pearson r>0.5 for 18/19 proteins), however higher amounts of protein were required for coupling to magnetic beads. Our external comparison indicated that results generated in different laboratories using the same coupled beads are also highly comparable (pearson r>0.7), particularly if a reference standard curve is used.

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