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2.
Preprint | EuropePMC | ID: ppcovidwho-296948

ABSTRACT

Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has been described. Here, we analyze titers of neutralizing antibodies of sera from convalescent or vaccinated individuals against the new B.1.1.529 variant and compared them with titers against other Variants of Concern (B.1.1.7, B.1.351, B.1617.2) using replication competent SARS-CoV-2 variants. We found that sera from vaccinated individuals neutralized the B.1.1.529 variant to a much lesser extent than any other variant analyzed. Neutralization capacity against B.1.1.529 was maintained best against sera from super immune individuals (infected and vaccinated or vaccinated and infected).

3.
Commun Med (London) ; 1(1): 4, 2021.
Article in English | MEDLINE | ID: covidwho-1555629

ABSTRACT

Background: In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. Methods: Between April 21st and 27th 2020, a cross-sectional epidemiologic study targeting the full population of Ischgl (n = 1867), of which 79% could be included (n = 1473, incl. 214 children), was performed. For each individual, the study involved a SARS-CoV-2 PCR, antibody testing and structured questionnaires. A mathematical model was used to help understand the influence of the determined seroprevalence on virus transmission. Results: The seroprevalence was 42.4% (95% confidence interval (CI) 39.8-44.7). Individuals under 18 showed a significantly lower seroprevalence of 27.1% (95% CI 21.3-33.6) than adults (45%; 95% CI 42.2-47.7; OR of 0.455, 95% CI 0.356-0.682, p < 0.001). Of the seropositive individuals, 83.7% had not been diagnosed to have had SARS-CoV-2 infection previously. The clinical course was generally mild. Over the previous two months, two COVID-19-related deaths had been recorded, corresponding to an infection fatality rate of 0.25% (95% CI 0.03-0.91). Only 8 (0.5 %) individuals were newly diagnosed to be infected with SARS-CoV-2 during this study. Conclusions: Ischgl was hit early and hard by SARS-CoV-2 leading to a high local seroprevalence of 42.4%, which was lower in individuals below the age of 18 than in adults. Mathematical modeling suggests that a drastic decline of newly infected individuals in Ischgl by the end of April occurred due to the dual impact from the non-pharmacological interventions and a high immunization of the Ischgl population.

4.
Wien Klin Wochenschr ; 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1527469

ABSTRACT

BACKGROUND: Short-term antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown previously. The further development remains to be determined. METHODS: We prospectively followed 29 coronavirus disease 2019 cases, mean age 44 ± 13.2 years. Except for one participant in whom rheumatoid arthritis existed, all other cases were previously healthy. We determined anti-viral binding antibodies at 2-10 weeks, 3 months, 6 months, and 12 months after disease onset as well as neutralizing antibodies (NAb) against wild type at 6 and 12 months and the B.1.1.7 and B.1.351 variants at month 12. Three binding antibody assays were used, targeting the nucleocapsid protein (NCP), the S1 subunit of the spike protein, and the receptor binding domain (RBD). RESULTS: Antibodies to the RBD persisted for 12 months in all cases with increasing concentrations, whereas antibodies to S1 dropped below cut-off point in 7 participants and NCP antibodies were above cut-off point in only 5 subjects at month 12. The NAb against wild type were detected in all but 2 samples at 12 months of follow-up but clearly less frequently when targeting the variants. In 5 participants who were vaccinated against COVID-19 there was a strong increase of antibodies against S1 and RBD as well as an increase of NAb titres against wild type and the variants. CONCLUSION: There was a persisting antibody response against SARS-CoV­2 up to 12 months after COVID-19 with declining concentrations except for RBD and a strong increase of all antibody concentrations after vaccination.

5.
Wien Klin Wochenschr ; 2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1482216

ABSTRACT

BACKGROUND: Seroepidemiological studies provide important insight into the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) in our society. We aimed to determine seropositivity of SARS-CoV­2 antibodies and its cross-sectional correlates in a large cohort of blood donors. METHODS: In this observational cohort study, we tested healthy blood donors residing in Tyrol, Austria, for SARS-CoV­2 antibodies using the Abbott SARS-CoV­2 IgG chemiluminescent microparticle immunoassay. We estimated 95% confidence intervals (95% CI) of seroprevalences using bootstrapping and tested for differences by participant characteristics using logistic regression. FINDINGS: Between 8 June and 4 September 2020, we screened 5345 healthy individuals at local blood donor sessions (mean age 42.7 years, SD 13.5 years, 46.7% female). Overall seroprevalence was 3.1% (95% CI 2.7-3.6%, 165 cases), which is 5.1-fold higher (95% CI 4.5-6.0%) than the case number identified by the health authorities in the state-wide testing program (0.6%; 4536 out of 757,634). Seroprevalence was higher in the district Landeck (16.6%, P < 0.001) and in individuals aged < 25 years (4.7%, P = 0.043), but did not differ by gender, blood types, or medication intake. The odds ratio for seropositivity was 2.51 for participants who had travelled to Ischgl (1.49-4.21, P = 0.001), 1.39 who had travelled to other federal states (1.00-1.93, P = 0.052), and 2.41 who had travelled abroad (1.61-3.63, P < 0.001). Compared to participants who had a suspected/confirmed SARS-CoV­2 infection but were seronegative, seropositive participants more frequently reported loss of smell (odds ratio = 2.49, 1.32-4.68, P = 0.005) and taste (odds ratio = 2.76, 1.54-4.92, P = 0.001). CONCLUSION: In summer 2020, SARS-CoV­2 seroprevalence in Tyrolean blood donors was 3.1%. Our study revealed regional variation and associations with young age, travel history and specific symptoms.

6.
J Infect Dis ; 224(5): 764-770, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1413436

ABSTRACT

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5-1.5 months (baseline) and 7-8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/immunology , Austria , Cohort Studies , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Young Adult
7.
EBioMedicine ; 70: 103539, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1356205

ABSTRACT

BACKGROUND: In recent months numerous health care professional acquired COVID-19 at the workplace resulting in significant shortages in medical and nursing staff. We investigated how prior COVID-19 affects SARS-CoV-2 vaccination and how such knowledge could facilitate frugal vaccination strategies. METHODS: In a cohort of 41 healthcare professionals with (n=14) and without (n=27) previous SARS-CoV-2 infection, we assessed the immune status before, during and after vaccination with BNT162b2. The humoral immune response was assessed by receptor binding domain ELISA and different SARS-CoV-2 neutralisation assays using wildtype and pseudo-typed viruses. T cell immunity against SARS-CoV-2 surface and nucleocapsid peptides were studied using interferon-γ release assays and intracellular flow cytometry. Vaccine-related side effects were captured. FINDINGS: Prior COVID-19 resulted in improved vaccine responses both in the B and T cell compartment. In vaccine recipients with prior COVID-19, the first vaccine dose induced high antibody concentrations comparable to seronegative vaccine recipients after two injections. This translated into more efficient neutralisation of virus particles, even more pronounced than expected from the RBD ELISA results. Furthermore, T cell responses were stronger in convalescents and particularly strong against the SARS-CoV-2 nucleocapsid protein. INTERPRETATION: Herein, we corroborate recent findings suggesting that in convalescents a single vaccine dose is sufficient to boost adequate in vitro neutralisation of SARS-CoV-2 and therefore may be sufficient to induce adequate protection against severe COVID-19. New spike mutated virus variants render the highly conserved nucleocapsid protein - eliciting strong SARS-CoV-2 specific T cell immunity - an interesting additional vaccine target. FUNDING: Christian Doppler Research Association, Johannes Kepler University Linz.


Subject(s)
B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Enzyme-Linked Immunosorbent Assay/methods , Female , Health Personnel , Humans , Immunity, Humoral/immunology , Male , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods
8.
EBioMedicine ; 70: 103534, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1356204

ABSTRACT

Background In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria triggered the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a previous study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April, representing an exceptionally high level of local seropositivity in Europe. We performed a follow-up study in Ischgl, which is the first to show persistence of immunity and protection against SARS-CoV-2 and some of its variants at a community level. Methods Of the 1259 adults that participated in the baseline study, 801 have been included in the follow-up in November 2020. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 and its variants in Ischgl was compared to the incidence in similar municipalities in Tyrol until April 2021. Findings For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9-54.9) to 45.4% (95% CI 42.0-49.0). Median antibody concentrations dropped considerably (5.345, 95% CI 4.833 - 6.123 to 2.298, 95% CI 2.141 - 2.527) but antibody avidity increased (17.02, 95% CI 16.49 - 17.94 to 42.46, 95% CI 41.06 - 46.26). Only one person had lost detectable antibodies and T cell responses. In parallel to this persistent immunity, we observed that Ischgl was relatively spared, compared to similar municipalities, from the prominent second COVID-19 wave that hit Austria in November 2020. In addition, we used sequencing data to show that the local immunity acquired from wild-type infections also helped to curb infections from variants of SARS-CoV-2 which spread in Austria since January 2021. Interpretation The relatively high level of seroprevalence (40-45%) in Ischgl persisted and might have been associated with the observed protection of Ischgl residents against virus infection during the second COVID-19 wave as well as against variant spread in 2021. Funding Funding was provided by the government of Tyrol and the FWF Austrian Science Fund.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Austria , COVID-19/virology , Cross-Sectional Studies , Europe , Female , Follow-Up Studies , Humans , Male , Seroepidemiologic Studies
9.
Rev Med Virol ; : e2272, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1287398

ABSTRACT

SARS-CoV-2 continues to leave its toll on global health and the economy. Management of the pandemic will rely heavily on the degree of adaptive immunity persistence following natural SARS-CoV-2 infection. Along with the progression of the pandemic, more literature on the persistence of the SARS-CoV-2-specific antibody response is becoming available. Here, we summarize findings on the persistence of the humoral, including neutralizing antibody, response at three to eight months post SARS-CoV-2 infection in non-pregnant adults. While the comparability of the literature is limited, findings on the detectability of immunoglobulin G class of antibodies (IgG) were most consistent and were reported in most studies to last for six to eight months. Studies investigating the response of immunoglobins M and A (IgM, IgA) were limited and reported mixed results, in particular, for IgM. The majority of studies observed neutralizing antibodies at all time points tested, which in some studies lasted up to eight months. The presence of neutralizing antibodies has been linked to protection from re-infection, suggesting long-term immunity to SARS-CoV-2. These neutralizing capacities may be challenged by emerging virus variants, but mucosal antibodies as well as memory B and T cells may optimize future immune responses. Thus, further longitudinal investigation of PCR-confirmed seropositive individuals using sensitive assays is warranted to elucidate the nature and duration of a more long-term humoral response.

10.
Vaccines (Basel) ; 9(6)2021 Jun 07.
Article in English | MEDLINE | ID: covidwho-1259645

ABSTRACT

Serological assays that simultaneously detect antibodies to multiple targets of SARS-CoV-2 and to other structurally related coronaviruses provide a holistic picture of antibody response patterns. Well-validated multiplex immunoassays are scarce. Here, we evaluated the performance of an 11-plex serological assay capable of detecting antibodies directed to four antigenic targets of SARS-CoV-2 and to S1 proteins of other human pathogenic coronaviruses. We used 620 well-characterized sera (n = 458 seropositive and n = 110 seronegative for SARS-CoV-2 in the pre-SARS-CoV-2 era and n = 52 seronegative for SARS-CoV-2 in the era of SARS-CoV-2) as positive and negative standards. We calculated the sensitivity, specificity, as well as positive and negative predictive values, including a 95% confidence interval. The difference in mean fluorescence intensity (95% CI) was used to assess a potential cross-reaction between antibodies to SARS-CoV-2 and the other coronaviruses. The sensitivity (95% CI) of detecting anti-SARS-CoV-2 antibodies to four antigenic targets ranged from 83.4% (76.7-86.7) to 93.7% (91.0-95.7) and the specificity from 98.2% (93.6-99.8) to 100% (96.7-100). We observed no obvious cross-reaction between anti-SARS-CoV-2 antibodies and antibodies to the other coronaviruses except for SARS-CoV-1. The high sensitivity and specificity warrant a reliable utilization of the assay in population-based seroprevalence surveys or vaccine efficacy studies.

11.
J Infect Dis ; 224(5): 764-770, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1258782

ABSTRACT

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5-1.5 months (baseline) and 7-8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/immunology , Austria , Cohort Studies , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Young Adult
12.
Br J Sports Med ; 55(1): 62-66, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060118

ABSTRACT

OBJECTIVES: To evaluate the restart of the German Bundesliga (football (soccer)) during the COVID-19 pandemic from a medical perspective. METHODS: Participants were male professional football players from the two highest German leagues and the officials working closely with them. Our report covers nine match days spread over 9 weeks (May to July 2020). Daily symptom monitoring, PCR testing for SARS-CoV-2 RNA twice weekly, and antibody tests (on two occasions-early during the phase in May 2020 and in the week of the last match) were conducted. Target variables were: (1) onset of typical COVID-19 symptoms, (2) positive PCR results, and (3) IgG seroconversion against SARS-CoV-2. All detected seroconversions were controlled by neutralisation tests. FINDINGS: Suspicious symptoms were reported for one player; an immediate additional PCR test as well as all subsequent diagnostic and antibody tests proved negative for coronavirus. Of 1702 regularly tested individuals (1079 players, 623 officials members), 8 players and 4 officials tested positive during one of the first rounds of PCR testing prior to the onset of team training, 2 players during the third round. No further positive results occurred during the remainder of the season. 694 players and 291 officials provided two serum samples for antibody testing. Nine players converted from negative/borderline to positive (without symptoms); two players who initially tested positive tested negative at the end of the season. 22 players remained seropositive throughout the season. None of the seroconversions was confirmed in the neutralisation test. CONCLUSION: Professional football training and matches can be carried out safely during the COVID-19 pandemic. This requires strict hygiene measures including regular PCR testing.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Return to Sport , SARS-CoV-2 , Soccer/statistics & numerical data , Adult , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing/statistics & numerical data , Cohort Studies , Germany/epidemiology , Humans , Immunoglobulin G/blood , Male , Neutralization Tests , Prospective Studies , SARS-CoV-2/immunology , Safety , Symptom Assessment/methods
13.
Vaccines (Basel) ; 9(1)2020 Dec 28.
Article in English | MEDLINE | ID: covidwho-1024667

ABSTRACT

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

14.
Vaccines ; 9(1):13, 2021.
Article in English | ScienceDirect | ID: covidwho-984743

ABSTRACT

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

15.
Wien Klin Wochenschr ; 133(7-8): 351-358, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-973557

ABSTRACT

BACKGROUND: As coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 evolved only recently, the persistency of the anti-viral antibody response remains to be determined. METHODS: We prospectively followed 29 coronavirus disease 2019 cases, mean age 44 ± 13.2 years. Except for one participant with a pre-existing diagnosis of rheumatoid arthritis, all other participants were previously healthy. We determined anti-viral binding antibodies at 2-10 weeks, 3 months, and 6 months after disease onset as well as neutralizing antibodies at 6 months. Two binding antibody assays were used, targeting the S1 subunit of the spike protein, and the receptor binding domain. RESULTS: All participants fully recovered spontaneously except for one who had persisting hyposmia. Antibodies to the receptor binding domain persisted for 6 months in all cases with a slight increase of titers, whereas antibodies to S1 dropped below the cut-off point in 2 participants and showed a minimal decrease on average, mainly at month 3 of follow-up in males; however, neutralizing antibodies were detected in all samples at 6 months of follow-up. CONCLUSION: There is a stable and persisting antibody response against acute respiratory syndrome coronavirus 2 at 6 months after infection. Neutralizing antibodies confirm virus specificity. As the number of coronavirus disease 2019 convalescent cases is increasing sharply, antibody testing should be implemented to identify immunized individuals. This information can be helpful in various settings of professional and private life.


Subject(s)
COVID-19 , Coronavirus Infections , Adult , Antibodies, Neutralizing , Antibodies, Viral , Humans , Male , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
16.
Clin Microbiol Infect ; 27(3): 473.e1-473.e4, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-956996

ABSTRACT

OBJECTIVES: Elite professional football players and staff are a unique group that might give insight into the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Germany and thus can serve as a model for geographical distribution and an estimation of undetected infections. METHODS: In this prospective cohort study seroprevalence was determined twice in May and June 2020 in players and staff from the German Bundesliga. As screening assays, a commercial ELISA (Euroimmun) and a chemiluminescent immunoassay (CLIA) (Roche) were used, and an in-house neutralization assay (NT) was used as reference standard. Participants were tested twice weekly using PCR from nasopharyngeal and/or oropharyngeal swabs. RESULTS: Seroprevalence (NT used as confirmation) in 2164 samples from 1184 players and staff was rather similar in May (23/1157, 1.99%) and June (21/1007, 2.09%). All participants were PCR-negative during the study period. Significant regional differences in seroprevalence were not observed. When comparing seroprevalence with the cumulative incidence of infections derived from the German notification system (subgroup matching to cohort; men, age 20-69 years), IgG was found eight to ten times more frequently, pointing to a high rate of undetected infection. ELISA and CLIA correlated only moderately (κ 0.52). CONCLUSIONS: Seroprevalence with a high-quality diagnostic in Germany seemed to be around 2%. The number of undetected infections seems to be eight to ten times higher than in notification data. The quality of antibody assays is rather variable, thus results should ideally be confirmed at least by a second assay to prove IgG positivity.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19/epidemiology , Football/statistics & numerical data , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/blood , COVID-19/diagnosis , Germany/epidemiology , Humans , Immunoassay/methods , Incidence , Male , Middle Aged , Polymerase Chain Reaction , Prevalence , Prospective Studies , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Young Adult
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