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1.
Ann Rheum Dis ; 2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1625022

ABSTRACT

OBJECTIVES: SARS-CoV-2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. METHODS: In this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4. RESULTS: Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed. CONCLUSIONS: This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

2.
Proc Natl Acad Sci U S A ; 118(44)2021 11 02.
Article in English | MEDLINE | ID: covidwho-1493344

ABSTRACT

Here, we expressed two neutralizing monoclonal antibodies (Abs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; H4 and B38) in three formats: IgG1, IgA1 monomers (m), and IgA1 dimers (d) in glycoengineered Nicotiana benthamiana plants. All six Ab variants assembled properly and exhibited a largely homogeneous glycosylation profile. Despite modest variation in antigen binding between Ab formats, SARS-CoV-2 neutralization (NT) potency significantly increased in the following manner: IgG1 < IgA1-m < IgA1-d, with an up to 240-fold NT increase of dimers compared to corresponding monomers. Our results underscore that both IgA's structural features and multivalency positively impact NT potency. In addition, they emphasize the versatile use of plants for the rapid expression of complex human proteins.


Subject(s)
Antibodies, Monoclonal/chemistry , COVID-19/virology , Immunoglobulin A/chemistry , Immunoglobulin G/chemistry , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Chlorocebus aethiops , Enzyme-Linked Immunosorbent Assay , Humans , Neutralization Tests , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
3.
Proc Natl Acad Sci U S A ; 118(42)2021 10 01.
Article in English | MEDLINE | ID: covidwho-1447423

ABSTRACT

Monoclonal antibodies (mAbs) that efficiently neutralize SARS-CoV-2 have been developed at an unprecedented speed. Notwithstanding, there is a vague understanding of the various Ab functions induced beyond antigen binding by the heavy-chain constant domain. To explore the diverse roles of Abs in SARS-CoV-2 immunity, we expressed a SARS-CoV-2 spike protein (SP) binding mAb (H4) in the four IgG subclasses present in human serum (IgG1-4) using glyco-engineered Nicotiana benthamiana plants. All four subclasses, carrying the identical antigen-binding site, were fully assembled in planta and exhibited a largely homogeneous xylose- and fucose-free glycosylation profile. The Ab variants ligated to the SP with an up to fivefold increased binding activity of IgG3. Furthermore, all H4 subtypes were able to neutralize SARS-CoV-2. However, H4-IgG3 exhibited an up to 50-fold superior neutralization potency compared with the other subclasses. Our data point to a strong protective effect of IgG3 Abs in SARS-CoV-2 infection and suggest that superior neutralization might be a consequence of cross-linking the SP on the viral surface. This should be considered in therapy and vaccine development. In addition, we underscore the versatile use of plants for the rapid expression of complex proteins in emergency cases.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Monoclonal/biosynthesis , Glycosylation , Humans , Neutralization Tests , Recombinant Proteins/biosynthesis
4.
Ann Rheum Dis ; 80(10): 1345-1350, 2021 10.
Article in English | MEDLINE | ID: covidwho-1394067

ABSTRACT

OBJECTIVES: Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation. METHODS: Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls. RESULTS: All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response. CONCLUSIONS: The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Rituximab/therapeutic use , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , B-Lymphocytes/immunology , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunogenicity, Vaccine/drug effects , Male , Middle Aged , SARS-CoV-2 , T-Lymphocytes/immunology
6.
Allergy ; 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1373783

ABSTRACT

BACKGROUND: The determinants of successful humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of critical importance for the design of effective vaccines and the evaluation of the degree of protective immunity conferred by exposure to the virus. As novel variants emerge, understanding their likelihood of suppression by population antibody repertoires has become increasingly important. METHODS: In this study, we analyzed the SARS-CoV-2 polyclonal antibody response in a large population of clinically well-characterized patients after mild and severe COVID-19 using a panel of microarrayed structurally folded and unfolded SARS-CoV-2 proteins, as well as sequential peptides, spanning the surface spike protein (S) and the receptor-binding domain (RBD) of the virus. RESULTS: S- and RBD-specific antibody responses were dominated by immunoglobulin G (IgG), mainly IgG1 , and directed against structurally folded S and RBD and three distinct peptide epitopes in S2. The virus neutralization activity of patients´ sera was highly correlated with IgG antibodies specific for conformational but not sequential RBD epitopes and their ability to prevent RBD binding to its human receptor angiotensin-converting enzyme 2 (ACE2). Twenty percent of patients selectively lacked RBD-specific IgG. Only immunization with folded, but not with unfolded RBD, induced antibodies against conformational epitopes with high virus-neutralizing activity. Conformational RBD epitopes required for protection do not seem to be altered in the currently emerging virus variants. CONCLUSION: These results are fundamental for estimating the protective activity of antibody responses after natural infection or vaccination and for the design of vaccines, which can induce high levels of SARS-CoV-2-neutralizing antibodies conferring sterilizing immunity.

7.
NPJ Vaccines ; 6(1): 104, 2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1360199

ABSTRACT

COVID-19 vaccines were developed with an unprecedented pace since the beginning of the pandemic. Several of them have reached market authorization and mass production, leading to their global application on a large scale. This enormous progress was achieved with fundamentally different vaccine technologies used in parallel. mRNA, adenoviral vector as well as inactivated whole-virus vaccines are now in widespread use, and a subunit vaccine is in a final stage of authorization. They all rely on the native viral spike protein (S) of SARS-CoV-2 for inducing potently neutralizing antibodies, but the presentation of this key antigen to the immune system differs substantially between the different categories of vaccines. In this article, we review the relevance of structural modifications of S in different vaccines and the different modes of antigen expression after vaccination with genetic adenovirus-vector and mRNA vaccines. Distinguishing characteristics and unknown features are highlighted in the context of protective antibody responses and reactogenicity of vaccines.

9.
BMJ Open ; 11(8): e045225, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338867

ABSTRACT

OBJECTIVES: We explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria. DESIGN: Prospective cohort study. SETTING: A single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein. PARTICIPANTS: All 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020. INTERVENTION: Nasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR). OUTCOME MEASURES: We compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present. RESULTS: Twenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1-4) among early acute, 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified. CONCLUSIONS: RT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Austria , Cohort Studies , Humans , Primary Health Care , Prospective Studies , Sensitivity and Specificity
10.
J Clin Med ; 10(9)2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1335105

ABSTRACT

Despite being located close to the European epicenter of the COVID-19 pandemic in Italy, Austria has managed to control the first wave. In Austria, the largest health insurance fund covers 7 million people and has 12,000 employees, including 3700 healthcare workers (HCW). For patient and staff safety, transmission control measures were implemented and mass testing of employees for SARS-CoV-2 antibodies was conducted. An IgG SARS-CoV-2 rapid test on fingerstick blood was used as a screening test (ST), followed by serologic studies with 3 different immunoassays and confirmatory testing by a neutralization test (NT). Among 7858 employees, 144 had a positive ST and 88 were confirmed by a NT (1.12%, CI: 0.9-1.38%). The positive predictive value (PPV) of the ST was 69.3% (CI: 60.5-77.2). Interestingly, 40% of the NT positive serum samples were tested negative in all 3 immunoassays. Of the total sample, 2242 HCW (28.5%) were identified. Unexpectedly, there was no difference in the prevalence of NT positives in HCW compared to non-HCW (23/2242 vs. 65/5301, p = 0.53). SARS-CoV-2 antibody prevalence was not increased among HCW. Although HCW are at potentially increased risk for SARS-CoV-2 infection, transmission control measures in healthcare facilities appear sufficient to limit transmission of infection.

11.
Ann Rheum Dis ; 80(10): 1345-1350, 2021 10.
Article in English | MEDLINE | ID: covidwho-1319387

ABSTRACT

OBJECTIVES: Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation. METHODS: Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls. RESULTS: All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response. CONCLUSIONS: The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Rituximab/therapeutic use , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , B-Lymphocytes/immunology , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunogenicity, Vaccine/drug effects , Male , Middle Aged , SARS-CoV-2 , T-Lymphocytes/immunology
12.
Sci Rep ; 11(1): 10158, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1226443

ABSTRACT

We analyzed SARS-CoV-2 seroprevalence in a large, well-described representative Viennese cohort after an early governmental lockdown with respect to the occurrence of symptoms and household transmission. Participants of the LEAD Study, a population-based cohort study from Vienna, Austria, were invited along with their household members (April 20th to May20th 2020). Sera were analyzed using anti-SARS-CoV-2 immunoassay including a neutralization test as a confirmatory assay. A total of 12,419 individuals participated (5984 LEAD participants; 6435 household members), 163 (1.31%; 59 LEAD cohort members) of whom were SARS-CoV-2 antibody positive. The estimated number of COVID-19 cases projected from our findings by age and sex for Vienna was 21,504 (1.13%). Cumulative number of positively tested cases in Vienna until May 20th 2020 was 3020, hence 7.1 times (95% confidence interval 5.5-9.1) lower than projected. Relative risk (RR) of seropositivity by age was highest for children aged 6-9 years [RR compared to age group 20-49: 1.21 (CI 0.37-4.01)], lowest for ≥ 65 years [RR 0.47 (CI 0.21-1.03)]. Half of the positive individuals developed no or mild symptoms. In a multivariate analysis, taste and smell disturbances were most strongly related to SARS-CoV-2 positivity. Infection probability within households with one confirmed SARS-CoV-2-specific antibody-positive person was 31%. Although seroprevalence was very low (1.13%) for a central European capital city, due to an early governmental lockdown, SARS-CoV-2 infections were more prevalent than officially reported polymerase chain reaction-positive cases. Of note, seroprevalence was highest in young children. Half of SARS-CoV-2 antibody-positive subjects had no or only mild symptoms. Taste and smell disturbances were most prominent, possibly guiding clinicians in diagnosing SARS-CoV-2 infection.


Subject(s)
COVID-19/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Austria/epidemiology , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Serological Testing , Child , Communicable Disease Control , Female , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Young Adult
13.
Pediatric Allergy and Immunology ; 32(4):762-770, 2021.
Article in English | ProQuest Central | ID: covidwho-1209466

ABSTRACT

BackgroundChildren are discussed as hidden SARS‐CoV‐2 virus reservoir because of predominantly mild or even asymptomatic course of disease. The objective of this cross‐sectional study in May‐July 2020 was to assess the prevalence of SARS‐CoV‐2 antibodies and virus RNA in schoolchildren, consistent with previous infection by contact tracing.MethodsSchool authorities approached parents for voluntary participation. Interested families were contacted by the study team. A nasal and oropharyngeal swab, a blood sample, and a questionnaire were employed. Primary endpoint was the frequency of SARS‐CoV‐2 real‐time PCR (RT‐PCR) and antibody‐positive children. Antibody positivity was assessed by a highly sensitive first‐line ELISA, and a neutralization assay and two other immunoassays as confirmatory assays.ResultsOf 2069 children (median age 13 years, IQR 10‐15), 2 cases (0.1%) tested positive for SARS‐CoV‐2 RNA and 26 cases (1.3%) tested positive for specific antibodies. SARS‐CoV‐2‐specific antibodies exhibited detectable virus‐neutralizing activity in 92% (24 of 26 samples). Seropositivity was associated with a history of mild clinical symptoms in 14 children (53.8%), while 12 children (46.2%) remained asymptomatic. Among 13 seropositive children being tested concomitantly with their siblings, only one pair of siblings was seropositive. Contact tracing revealed adult family members and school teachers as potential index cases.ConclusionIn schoolchildren, the infection rate with SARS‐CoV‐2 is low and associated with a mild or asymptomatic course of disease. Virus spreading seemed to occur more likely in intergenerational contacts than among siblings in the same household. The presence of neutralizing SARS‐CoV‐2 antibodies in children may reflect protective adaptive immunity.

14.
J Clin Microbiol ; 59(5)2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195818

ABSTRACT

In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Three hundred fifty-four blood samples longitudinally obtained from 81 IgG-seroconverting progressed coronavirus disease 2019 (CoVID-19) patients were quantified for spike 1 (S1), S2, and nucleocapsid protein (NCP)-specific IgM, IgA, IgG, and total Ig antibodies using a microarray, 11 different enzyme-linked immunosorbent assays (ELISAs)/chemiluminescence immunoassays (CLIAs), and 1 rapid test by seven manufacturers. The assays' specificity was assessed in 130 non-CoVID-19 pneumonia patients. Using the microarray, NCP-specific IgA and IgG antibodies continuously displayed higher detection rates during acute CoVID-19 than S1- and S2-specific ones. S1-specific IgG antibodies, however, reached higher peak values. Until the 26th day post-symptom onset, all patients developed IgG responses against S1, S2, and NCP. Although detection rates by ELISAs/CLIAs generally resembled those of the microarray, corresponding to the target antigen, sensitivities and specificities varied among all tests. Notably, patients with more severe CoVID-19 displayed higher IgG and IgA levels, but this difference was mainly observed with S1-specific immunoassays. In patients with high SARS-CoV-2 levels in the lower respiratory tract, we observed high detection rates of IgG and total Ig immunoassays with a particular rise of S1-specific IgG antibodies when viral concentrations in the tracheal aspirate subsequently declined over time. In summary, our study demonstrates that differences in sensitivity among commercial immunoassays during acute SARS-CoV-2 infection are only partly related to the target antigen. Importantly, our data indicate that NCP-specific IgA and IgG antibodies are detected earlier, while higher S1-specific IgA antibody levels occur in severely ill patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoassay/methods , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Kinetics , Phosphoproteins/immunology , SARS-CoV-2 , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
15.
Int J Environ Res Public Health ; 18(8)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1186958

ABSTRACT

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure (p = 0.003), positively tested family members (p = 0.04), and travel history (p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose (p = 0.002) and altered taste or smell (p < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.


Subject(s)
COVID-19 , Austria , Health Personnel , Humans , Incidence , Infection Control , Prospective Studies , SARS-CoV-2 , Seroepidemiologic Studies , Tertiary Care Centers
16.
Wien Klin Wochenschr ; 133(7-8): 271-283, 2021 04.
Article in English | MEDLINE | ID: covidwho-1135163
17.
Pediatr Allergy Immunol ; 32(4): 762-770, 2021 05.
Article in English | MEDLINE | ID: covidwho-1054576

ABSTRACT

BACKGROUND: Children are discussed as hidden SARS-CoV-2 virus reservoir because of predominantly mild or even asymptomatic course of disease. The objective of this cross-sectional study in May-July 2020 was to assess the prevalence of SARS-CoV-2 antibodies and virus RNA in schoolchildren, consistent with previous infection by contact tracing. METHODS: School authorities approached parents for voluntary participation. Interested families were contacted by the study team. A nasal and oropharyngeal swab, a blood sample, and a questionnaire were employed. Primary endpoint was the frequency of SARS-CoV-2 real-time PCR (RT-PCR) and antibody-positive children. Antibody positivity was assessed by a highly sensitive first-line ELISA, and a neutralization assay and two other immunoassays as confirmatory assays. RESULTS: Of 2069 children (median age 13 years, IQR 10-15), 2 cases (0.1%) tested positive for SARS-CoV-2 RNA and 26 cases (1.3%) tested positive for specific antibodies. SARS-CoV-2-specific antibodies exhibited detectable virus-neutralizing activity in 92% (24 of 26 samples). Seropositivity was associated with a history of mild clinical symptoms in 14 children (53.8%), while 12 children (46.2%) remained asymptomatic. Among 13 seropositive children being tested concomitantly with their siblings, only one pair of siblings was seropositive. Contact tracing revealed adult family members and school teachers as potential index cases. CONCLUSION: In schoolchildren, the infection rate with SARS-CoV-2 is low and associated with a mild or asymptomatic course of disease. Virus spreading seemed to occur more likely in intergenerational contacts than among siblings in the same household. The presence of neutralizing SARS-CoV-2 antibodies in children may reflect protective adaptive immunity.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , SARS-CoV-2/immunology , Adolescent , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Seroepidemiologic Studies , Young Adult
18.
Wien Klin Wochenschr ; 132(21-22): 635-644, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-996402

ABSTRACT

The recent emergence of a new coronavirus (severe acute respiratory syndrome coronavirus­2, SARS-CoV-2) that is transmitted efficiently among humans and can result in serious disease and/or death has become a global threat to public health and economy. In this article, we describe some of the most important characteristics of this new virus (including gaps in our understanding) and provide a perspective of ongoing activities for developing virus-specific countermeasures, such as vaccines and antiviral drugs.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Humans , SARS-CoV-2
19.
Front Med (Lausanne) ; 7: 592629, 2020.
Article in English | MEDLINE | ID: covidwho-954056

ABSTRACT

Disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from mild illness to severe respiratory disease and death. In this study, we determined the kinetics of viral loads, antibody responses (IgM, IgG, neutralization) and SARS-CoV-2-specific CD4 T cells by quantifying these parameters in 435 serial respiratory and blood samples collected from a cohort of 29 COVID-19 patients with either moderate or severe disease during the whole period of hospitalization or until death. Remarkably, there was no significant difference in the kinetics and plateau levels of neutralizing antibodies among the groups with different disease severity. In contrast, the dynamics of specific CD4 T cell responses differed considerably, but all patients with moderate or severe disease developed robust SARS-CoV-2-specific responses. Of note, none of the patients had detectable cross-reactive CD4 T cells in the first week after symptom onset, which have been described in 20-50% of unexposed individuals. Our data thus provide novel insights into the kinetics of antibody and CD4 T cell responses as well as viral loads that are key to understanding the role of adaptive immunity in combating the virus during acute infection and provide leads for the timing of immune therapies for COVID-19.

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