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1.
Microbiol Spectr ; : e0059722, 2022 Oct 12.
Article in English | MEDLINE | ID: covidwho-2063980

ABSTRACT

Determination of antibody levels against the nucleocapsid (N) and spike (S) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to estimate the humoral immune response after SARS-CoV-2 infection or vaccination. Differences in the design and specification of antibody assays challenge the interpretation of test results, and comparative studies are often limited to single time points per patient. We determined the longitudinal kinetics of antibody levels of 145 unvaccinated coronavirus disease 2019 (COVID-19) patients at four visits over 1 year upon convalescence using 8 commercial SARS-CoV-2 antibody assays (from Abbott, DiaSorin, Roche, Siemens, and Technoclone), as well as a virus neutralization test (VNT). A linear regression model was used to investigate whether antibody results obtained in the first 6 months after disease onset could predict the VNT results at 12 months. Spike protein-specific antibody tests showed good correlation to the VNT at individual time points (rS, 0.74 to 0.92). While longitudinal assay comparison with the Roche Elecsys anti-SARS-CoV-2 S test showed almost constant antibody concentrations over 12 months, the VNT and all other tests indicated a decline in serum antibody levels (median decrease to 14% to 36% of baseline). The antibody level at 3 months was the best predictor of the VNT results at 12 months after disease onset. The current standardization to a WHO calibrator for normalization to binding antibody units (BAU) is not sufficient for the harmonization of SARS-CoV-2 antibody tests. Assay-specific differences in absolute values and trends over time need to be considered when interpreting the course of antibody levels in patients. IMPORTANCE Determination of antibodies against SARS-CoV-2 will play an important role in detecting a sufficient immune response. Although all the manufacturers expressed antibody levels in binding antibody units per milliliter, thus suggesting comparable results, we found discrepant behavior between the eight investigated assays when we followed the antibody levels in a cohort of 145 convalescent patients over 1 year. While one assay yielded constant antibody levels, the others showed decreasing antibody levels to a varying extent. Therefore, the comparability of the assays must be improved regarding the long-term kinetics of antibody levels. This is a prerequisite for establishing reliable antibody level cutoffs for sufficient individual protection against SARS-CoV-2.

2.
Diagn Microbiol Infect Dis ; 102(4): 115650, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1648986

ABSTRACT

Massive vaccination programs are being carried out to limit the SARS-CoV-2 pandemic that started in December 2019. Serological tests are of major importance as an indicator of circulation of the virus and to assess how vaccine-induced immunity progresses. An Enzyme-Linked Immunosorbent Assay (ELISA) and a Lateral Flow Assay (LFA) have been developed based on the SARS-CoV-2 recombinant Receptor Binding Domain (RBD) and the combination of Spike and Nucleoprotein, respectively. The validation with 1272 serum samples by comparison with INgezim COVID 19 DR showed good diagnostic performance (sensitivity: 93.2%-97.2%; specificity: 98.3%-99.3%) for detection of previous contact with SARS-CoV-2. Moreover, according to our results, these assays can help in the serosurveillance during and after vaccination, by detecting the humoral immune response as soon as 15 days postvaccination and identifying low-respondents. Hence, these tests could play a key role in the progression to a COVID-19 free world, helping to adjust future vaccination protocols.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , COVID-19/prevention & control , Humans , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus , Vaccination
3.
J Clin Virol Plus ; 2(1): 100058, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1561656

ABSTRACT

The presence of neutralizing antibodies against SARS-CoV-2 in a large number of people is - besides cellular immunity - important to overcome the SARS-CoV-2 pandemic. While determination of neutralizing antibodies via virus neutralization tests are laborious, assays to determine the antibody levels serologically are fully automated and widely available. Correlations between these methodologies were recently given by the manufacturers, however performance in samples close to the cut off value have not yet been fully validated. Thus, we analysed 22 borderline and low positive (<100 BAU/ml) samples and 9 high positive (≥ 100 BAU/ml) from infected and/or vaccinated individuals and compared the SARS-CoV-2 IgG II Quant assay (Abbott), LIAISON SARS-CoV-2 TrimericS IgG (Diasorin), Elecsys Anti-SARS-CoV-2 S (Roche), and SARS-CoV-2 IgG (Siemens) with results obtained from a virus neutralization test. Based on the cut off values given by Abbott, Diasorin, Roche, and Siemens, the positive serologic results were concordant with the virus neutralization test in 100%, 76%, 88%, and 71%, respectively, while in turn, negative ones were in agreement in 29%, 79%, 93%, and 86%, respectively. In conclusion, weakly positive, serologic results are challenging to correctly predict the presence of neutralizing antibodies. Our study suggests, that different cut off values (for positivity vs. presence of neutralizing antibodies) could improve the test's performance, but determination thereof requires more samples to be analysed.

4.
BMC Infect Dis ; 21(1): 915, 2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1398841

ABSTRACT

BACKGROUND: The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening. METHOD: A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study. Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days. RESULTS: Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%). Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%). In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ2 = 23.848, df = 2, p < 0.001) was observed (χ2 = 23.848, df = 2, p < 0.001)-with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3. CONCLUSIONS: During the study period (May 11th-August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Asymptomatic Infections , Austria/epidemiology , Humans , Personnel, Hospital , Prospective Studies , Seroepidemiologic Studies
5.
Aging Dis ; 12(3): 710-717, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1315005

ABSTRACT

In December 2019, the People's Republic of China and the World Health Organization first reported on a cluster of pneumonia with an unknown cause. Nine months later more than 1.4 million people have died from COVID 19. In this work, the effects of the COVID 19 pandemic on five nursing homes in Austria, which cared for 889 residents in the first half of 2020, were examined. The research question was whether the measures taken were appropriate to prevent an outbreak within the individual facilities. To detect previously unrecognized infections, the present study evaluated the prevalence of neutralizing antibodies against the SARS-CoV-2 virus in residents and employees of the nursing homes. Following the analysis of blood samples, the prospectively collected data was connected to data from screening examinations and data from contact tracing. The present study demonstrated an overall prevalence of neutralizing antibodies against the SARS-CoV-2 virus in nursing homes of 3.7%. Whereas the prevalence in those facilities that have never been hit by an outbreak is 0%, the prevalence in those facilities with an outbreak is up to 4.9%. Neutralizing antibodies against SARS-CoV-2 were detected in 35 persons. A retrospective analysis of all 5 included nursing homes demonstrated that upon regular clinical screening in combination with PCRs an infection with SARS-COV-2 was detected in 66 residents and 24 employees from different professional groups. In only 25 of the 35 persons with neutralizing antibodies against SARS-CoV-2 an infection was proven in advance. This study suggests that specific measures can prevent transmission within a health care facility. Nevertheless, the results also show that a risk reduction to 0% cannot be achieved. In preparation for further pandemic waves there is still the need to reduce the probability of a transmission in nursing homes with specific test strategies.

7.
EBioMedicine ; 67: 103348, 2021 May.
Article in English | MEDLINE | ID: covidwho-1201238

ABSTRACT

BACKGROUND: Antibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody tests have primarily provided qualitative results, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups. METHODS: We have developed two quantitative, easy-to-implement SARS-CoV-2 antibody tests, based on the spike receptor binding domain and the nucleocapsid protein. Comprehensive evaluation of antigens from several biotechnological platforms enabled the identification of superior antigen designs for reliable serodiagnostic. Cut-off modelling based on unprecedented large and heterogeneous multicentric validation cohorts allowed us to define optimal thresholds for the tests' broad applications in different aspects of clinical use, such as seroprevalence studies and convalescent plasma donor qualification. FINDINGS: Both developed serotests individually performed similarly-well as fully-automated CE-marked test systems. Our described sensitivity-improved orthogonal test approach assures highest specificity (99.8%); thereby enabling robust serodiagnosis in low-prevalence settings with simple test formats. The inclusion of a calibrator permits accurate quantitative monitoring of antibody concentrations in samples collected at different time points during the acute and convalescent phase of COVID-19 and disclosed antibody level thresholds that correlate well with robust neutralization of authentic SARS-CoV-2 virus. INTERPRETATION: We demonstrate that antigen source and purity strongly impact serotest performance. Comprehensive biotechnology-assisted selection of antigens and in-depth characterisation of the assays allowed us to overcome limitations of simple ELISA-based antibody test formats based on chromometric reporters, to yield comparable assay performance as fully-automated platforms. FUNDING: WWTF, Project No. COV20-016; BOKU, LBI/LBG.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Binding Sites , CHO Cells , COVID-19/immunology , Cricetulus , Early Diagnosis , HEK293 Cells , Humans , Immunoglobulin G/blood , Middle Aged , Sensitivity and Specificity , Young Adult
8.
Clin Chem Lab Med ; 59(8): 1453-1462, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1175446

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and induce a specific antibody response. Serological assays detecting IgG against the receptor binding domain (RBD) of the spike (S) protein are useful to monitor the immune response after infection or vaccination. The objective of our study was to evaluate the clinical performance of the Siemens SARS-CoV-2 IgG (sCOVG) assay. METHODS: Sensitivity and specificity of the Siemens sCOVG test were evaluated on 178 patients with SARS-CoV-2-infection and 160 pre-pandemic samples in comparison with its predecessor test COV2G. Furthermore, correlation with virus neutralization titers was investigated on 134 samples of convalescent COVID-19 patients. RESULTS: Specificity of the sCOVG test was 99.4% and sensitivity was 90.5% (COV2G assay 78.7%; p<0.0001). S1-RBD antibody levels showed a good correlation with virus neutralization titers (r=0.843; p<0.0001) and an overall qualitative agreement of 98.5%. Finally, median S1-RBD IgG levels increase with age and were significantly higher in hospitalized COVID-19 patients (median levels general ward: 25.7 U/mL; intensive care: 59.5 U/mL) than in outpatients (3.8 U/mL; p<0.0001). CONCLUSIONS: Performance characteristics of the sCOVG assay have been improved compared to the predecessor test COV2G. Quantitative SARS-CoV-2 S1-RBD IgG levels could be used as a surrogate for virus neutralization capacity. Further harmonization of antibody quantification might assist to monitor the humoral immune response after COVID-19 disease or vaccination.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , Immunoglobulin G/immunology , Neutralization Tests , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/pathology , COVID-19/virology , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Protein Subunits/immunology , Reagent Kits, Diagnostic , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Severity of Illness Index , Young Adult
9.
Wien Klin Wochenschr ; 133(17-18): 923-930, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1173916

ABSTRACT

BACKGROUND: Chronic kidney disease patients show a high mortality in cases of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV­2) infection. Thus, information on the sero-status of nephrology personnel might be crucial for patient protection; however, limited information exists about the presence of SARS-CoV­2 antibodies in asymptomatic individuals. METHODS: We examined the seroprevalence of SARS-CoV­2 IgG and IgM antibodies among healthcare workers of a tertiary care kidney center during the the first peak phase of the corona virus disease 2019 (COVID-19) crisis in Austria using an orthogonal test strategy and a total of 12 commercial nucleocapsid protein or spike glycoprotein-based assays as well as Western blotting and a neutralization assay. RESULTS: At baseline 60 of 235 study participants (25.5%, 95% confidence interval, CI 20.4-31.5%) were judged to be borderline positive or positive for IgM or IgG using a high sensitivity/low specificity threshold in one test system. Follow-up analysis after about 2 weeks revealed IgG positivity in 12 (5.1%, 95% CI: 2.9-8.8%) and IgM positivity in 6 (2.6%, 95% CI: 1.1-5.6) in at least one assay. Of the healthcare workers 2.1% (95% CI: 0.8-5.0%) showed IgG nucleocapsid antibodies in at least 2 assays. By contrast, positive controls with proven COVID-19 showed antibody positivity among almost all test systems. Moreover, serum samples obtained from healthcare workers did not show SARS-CoV­2 neutralizing capacity, in contrast to positive controls. CONCLUSION: Using a broad spectrum of antibody tests the present study revealed inconsistent results for SARS-CoV­2 seroprevalence among asymptomatic individuals, while this was not the case among COVID-19 patients. TRIAL REGISTRATION NUMBER: CONEC, ClinicalTrials.gov number NCT04347694.


Subject(s)
COVID-19 , Nephrology , Antibodies, Viral , Health Personnel , Humans , SARS-CoV-2 , Seroepidemiologic Studies
10.
J Virol ; 95(4)2021 01 28.
Article in English | MEDLINE | ID: covidwho-1075935

ABSTRACT

Swine influenza A virus (swIAV) infection causes substantial economic loss and disease burden in humans and animals. The 2009 pandemic H1N1 (pH1N1) influenza A virus is now endemic in both populations. In this study, we evaluated the efficacy of different vaccines in reducing nasal shedding in pigs following pH1N1 virus challenge. We also assessed transmission from immunized and challenged pigs to naive, directly in-contact pigs. Pigs were immunized with either adjuvanted, whole inactivated virus (WIV) vaccines or virus-vectored (ChAdOx1 and MVA) vaccines expressing either the homologous or heterologous influenza A virus hemagglutinin (HA) glycoprotein, as well as an influenza virus pseudotype (S-FLU) vaccine expressing heterologous HA. Only two vaccines containing homologous HA, which also induced high hemagglutination inhibitory antibody titers, significantly reduced virus shedding in challenged animals. Nevertheless, virus transmission from challenged to naive, in-contact animals occurred in all groups, although it was delayed in groups of vaccinated animals with reduced virus shedding.IMPORTANCE This study was designed to determine whether vaccination of pigs with conventional WIV or virus-vectored vaccines reduces pH1N1 swine influenza A virus shedding following challenge and can prevent transmission to naive in-contact animals. Even when viral shedding was significantly reduced following challenge, infection was transmissible to susceptible cohoused recipients. This knowledge is important to inform disease surveillance and control strategies and to determine the vaccine coverage required in a population, thereby defining disease moderation or herd protection. WIV or virus-vectored vaccines homologous to the challenge strain significantly reduced virus shedding from directly infected pigs, but vaccination did not completely prevent transmission to cohoused naive pigs.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines/administration & dosage , Orthomyxoviridae Infections/transmission , Swine Diseases/transmission , Virus Shedding , Adjuvants, Immunologic/administration & dosage , Animals , Female , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/isolation & purification , Orthomyxoviridae Infections/prevention & control , Swine , Swine Diseases/prevention & control , Vaccination , Vaccines, Attenuated/administration & dosage , Vaccines, Inactivated/administration & dosage
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