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1.
Preprint in English | EuropePMC | ID: ppcovidwho-292311

ABSTRACT

Background: The Corona-Vakzin-Konsortium project (CoVaKo) analyses the efficacy and safety of COVID-19 vaccines in a real-world setting and breakthrough infections in Bavaria, Germany. A subproject of CoVaKo aims to identify adverse events of the COVID-19 vaccine and to compare these to adverse events of other vaccines in an online survey. A prior feasibility study was conducted to test study materials for comprehensibility, visual design and motivation to participate and secondly, to test practical implementation and realization in primary care practices and vaccination centres. Methods: : A mixed-methods design was used. Three focus groups with general population participants were performed to evaluate the study materials and survey. Second, a test-roll-out was conducted in vaccination centres and primary care practices, which involved implementation and quantitative evaluation of the online survey. Third, interviews were conducted with participating general practitioners and heads of vaccination centres four weeks after the test-roll-out. Results: : Parts of the study information and registration form proved incomprehensible in the recruitment material and/or online survey. For example, headings were misleading since the COVID-19 vaccination was overemphasized in the title as compared to other vaccinations. Participants requested more information on the procedure and completion time. In 31 days, 2199 participants who received either a COVID-19 vaccination (99 %) or at least one of the control vaccinations (1 %) registered for the study. Participants (strongly) agreed that the registration process was easy to understand, that all relevant information was provided, the completion time was reasonable and technical framework manageable. Physicians and heads of the vaccination centres perceived the study as easy to integrate into their workflow and most of them were willing to participate in the main study. Conclusions: : Our study indicated that capturing adverse events after vaccinations with an online survey is feasible. Testing of materials and surveys provided valuable improvements. Participation of health professionals is important to ensure practicality of the procedures. Flexible adaptation of the study organization to changing structures and requirements is necessary for a successful implementation, especially due to dynamic changes in COVID-19 vaccination strategies. Trial registration: The trial was retrospectively registered at “Deutsches Register Klinischer Studien” (DRKS-ID: DRKS00025881) on Oct 14, 2021.

2.
Diagnostics (Basel) ; 11(10)2021 Oct 06.
Article in English | MEDLINE | ID: covidwho-1463578

ABSTRACT

Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a "test establishment setting" to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup (n = 856) of the larger population based TiKoCo-19 cohort (n = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn't provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn't provide satisfactory quantitative correlations.

3.
Vaccines (Basel) ; 9(10)2021 Sep 24.
Article in English | MEDLINE | ID: covidwho-1438758

ABSTRACT

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty®), have proven to be highly immunogenic and efficient but also show marked reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r2 = 0.04) and DiaSorin-IgG (r2 = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.

6.
Viruses ; 13(6)2021 06 10.
Article in English | MEDLINE | ID: covidwho-1264531

ABSTRACT

SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/mortality , Population Surveillance/methods , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/immunology , Female , Germany/epidemiology , Humans , Latent Class Analysis , Male , Middle Aged , Prospective Studies , Seasons , Seroepidemiologic Studies , Surveys and Questionnaires , Young Adult
7.
Eur J Clin Microbiol Infect Dis ; 40(9): 1983-1997, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1263157

ABSTRACT

SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.


Subject(s)
Antibodies, Viral/blood , Bacterial Infections/diagnosis , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Respiratory Tract Infections/diagnosis , Antibodies, Bacterial/blood , Bacterial Infections/blood , COVID-19/blood , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Respiratory Tract Infections/blood , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
9.
Transfusion ; 61(2): 368-374, 2021 02.
Article in English | MEDLINE | ID: covidwho-894804

ABSTRACT

BACKGROUND: The frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia in blood donors is uncertain. Thus, assays for SARS-CoV-2 RNA detection in blood, validated on commercially available polymerase chain reaction (PCR) systems, are required to allow a good comparability of data. STUDY DESIGN AND METHODS: The cobas SARS-CoV-2 dual-target reverse transcriptase PCR (RT-PCR) assay, licensed for respiratory swab SARS-CoV-2 RNA testing, was validated for detection of viral RNA in blood. For the validation panel, SARS-CoV-2-positive plasma samples were prepared by spiking SARS-CoV-2-positive respiratory specimens in negative human plasma. The 95% limit of detection (LOD95) was determined by probit analysis. For clinical validation, coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donors and patients with COVID-19 with a severe disease course treated in an intensive care unit (ICU) were included. RESULTS: The validation of the SARS-CoV-2 RT-PCR assay for blood demonstrated high sensitivity and specificity and intra- and inter-assay precision and efficiency. The LOD95 for SARS-CoV-2 RNA was 5.0 genome copies/mL (95% confidence interval [CI], 3.3-12 copies/mL) for target 1 and 4.3 genome copies/mL (95% CI, 2.9-10 copies/mL) for target 2. In a cohort of 39 CCP donors with 66 CCP donations no SARS-CoV-2 RNA in plasma was detected. Screening of 25 blood samples of 19 ICU patients with COVID-19 showed six positive results for SARS-CoV-2 RNA in at least one target of the assay. CONCLUSION: The SARS-CoV-2 RNA assay, only licensed for respiratory swabs, performed on a PCR system for high-throughput testing, showed a good assay performance for blood testing.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , SARS-CoV-2/pathogenicity , Aged , Aged, 80 and over , Blood Donors , Female , Humans , Immunization, Passive , Male , Middle Aged , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics
10.
Eur J Clin Microbiol Infect Dis ; 40(4): 751-759, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-880323

ABSTRACT

SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, only a limited number of validated serological assays were available in the early phase of the pandemic. Here, we evaluated a novel flow cytometric approach to assess spike-specific antibody responses.HEK 293T cells expressing SARS-CoV-2 spike protein in its natural confirmation on the surface were used to detect specific IgG and IgM antibody responses in patient sera by flow cytometry. A soluble angiotensin-converting-enzyme 2 (ACE-2) variant was developed as external standard to quantify spike-specific antibody responses on different assay platforms. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2-infected patients. The external standard allowed robust quantification of antibody responses among different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits. The flow cytometric assay also provides a blueprint for rapid development of serological tests to other emerging viral infections.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin G/immunology , Immunoglobulin M/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Enzyme-Linked Immunosorbent Assay , Flow Cytometry/methods , HEK293 Cells , Humans , Reference Standards , Reproducibility of Results , Sensitivity and Specificity
11.
Euro Surveill ; 25(39)2020 10.
Article in English | MEDLINE | ID: covidwho-808986

ABSTRACT

We found that a single nucleotide polymorphism (SNP) in the nucleoprotein gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a patient interfered with detection in a widely used commercial assay. Some 0.2% of the isolates in the EpiCoV database contain this SNP. Although SARS-CoV-2 was still detected by the other probe in the assay, this underlines the necessity of targeting two independent essential regions of a pathogen for reliable detection.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Nucleoproteins/genetics , Pandemics , Pneumonia, Viral/diagnosis , Point Mutation , Polymorphism, Single Nucleotide , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Viral Proteins/genetics , Base Sequence , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Contact Tracing , Coronavirus Infections/virology , DNA Primers , Diagnostic Errors , False Negative Reactions , Female , Genes, Viral , Humans , Middle Aged , Nasopharynx/virology , Nucleoproteins/analysis , Phylogeny , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction/methods , Romania , SARS-CoV-2 , Travel-Related Illness , Viral Proteins/analysis
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