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1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2147739

ABSTRACT

Introduction Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 domain 1 spike-protein (S) specific antibodies (Abs) in buccal and nasal mucosal surfaces of vaccinees. Methods To this end, we analyzed 69 individuals who received their first vaccine dose between February and July 2021. Vaccines administered were BNT162b2, mRNA-1273 or ChAdOx1-nCoV-19. Detection of IgG and IgA Abs was performed using commercial ELISA kits for both blood and swab samples after protocol modification for the latter. Results Anti-spike IgG and IgA Abs in the buccal and/or nasal swabs were detectable in >81% of the study subjects after the second dose. The IgG measurements in buccal swabs appeared to correlate in a more consistent way with the respective measurements in blood with a correlation coefficient of r=0.74. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Optimal selection of the assay cut-off for the IgG antibody detection in buccal swabs conferred a sensitivity of 91.8% and a specificity of 100%. Last, individuals vaccinated with mRNA-based vaccines exhibited higher antibody levels in both blood and mucosal surfaces compared to those receiving ChAdOx1-nCoV-19 confirming previously reported results. Conclusion In conclusion, our findings show a differential prevalence of anti-S Abs on mucosal surfaces after vaccination for SARS-CoV-2, while they also set the basis for potential future use of IgG antibody detection in buccal swabs for extended immunity screening in large populations.

2.
Nat Commun ; 13(1): 7315, 2022 Nov 28.
Article in English | MEDLINE | ID: covidwho-2133436

ABSTRACT

The COVID-19 course and immunity differ in children and adults. We analyzed immune response dynamics in 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial response is plasmablast-driven in children. Four months after infection, children show an enhanced specific antibody response and lower but detectable spike 1 protein (S1)-specific B and T cell responses than their parents. While specific antibodies decline, neutralizing antibody activity and breadth increase in both groups. The frequencies of S1-specific B and T cell responses remain stable. However, in children, one year after infection, an increase in the S1-specific IgA class switch and the expression of CD27 on S1-specific B cells and T cell maturation are observed. These results, together with the enhanced neutralizing potential and breadth of the specific antibodies, suggest a progressive maturation of the S1-specific immune response. Hence, the immune response in children persists over 12 months but dynamically changes in quality, with progressive neutralizing, breadth, and memory maturation. This implies a benefit for booster vaccination in children to consolidate memory formation.


Subject(s)
COVID-19 , Adult , Child , Humans , SARS-CoV-2 , Antibody Formation , Antibodies, Neutralizing , Immunization, Secondary
3.
J Clin Invest ; 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2098125

ABSTRACT

BACKGROUND: Results of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP. METHODS: Of 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP-donors (n=113) with asymptomatic to moderate COVID-19 were included as a reference group. RESULTS: The median follow-up of patients was 396 days, the estimated 1-year survival was 78.7% in the CCP and 60.2% in the control group (p=0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared to the control group (91.5% versus 60.2%; p=0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase of neutralizing antibodies after vaccination between CCP and the control group. CONCLUSION: The trial demonstrated a trend towards better outcome in the CCP group without reaching statistical significance. A pre-defined subgroup analysis showed a significant better outcome (long-term survival; time to discharge from ICU and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared to the control group. A substantial long-term disease burden remains after severe COVID-19. TRIAL REGISTRATION: EudraCT number 2020-001310-38FUNDING. Bundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802/ZMI1-2521COR802.

4.
Transpl Int ; 35: 10677, 2022.
Article in English | MEDLINE | ID: covidwho-2080318

ABSTRACT

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12-18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 ("Comirnaty"; Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD+27+ memory cells in patients. Whereas spike specific CD4+ T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults.


Subject(s)
COVID-19 , Kidney Transplantation , Adolescent , Adult , Antibodies, Viral , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/adverse effects , COVID-19/prevention & control , Humans , Immunity, Humoral , Kidney Transplantation/adverse effects , RNA, Viral , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
5.
Front Immunol ; 13: 1008438, 2022.
Article in English | MEDLINE | ID: covidwho-2080155

ABSTRACT

Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. Results: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. Conclusion: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.


Subject(s)
COVID-19 , Cytokines , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-17 , Chemokine CCL3 , Tumor Necrosis Factor-alpha , Interleukin-6 , Interleukin-4 , Capsid , COVID-19/therapy , Becaplermin , Chemokine CXCL10 , Interleukin-2 , Interleukin-8 , Interleukin-9 , Granulocyte Colony-Stimulating Factor
6.
Front Immunol ; 13: 943476, 2022.
Article in English | MEDLINE | ID: covidwho-2005870

ABSTRACT

Background: Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy volunteers (HC), but limited data is available about response longevity upon rituximab treatment. Methods: We evaluated humoral and cellular responses upon 3rd vaccination in seven patients with rheumatoid arthritis (RA) who initially mounted anti-spike SARS-CoV-2 IgG antibodies after primary 2x vaccination and got re-exposed to rituximab (RTX) 1-2 months after the second vaccination. Ten patients with RA on other therapies and ten HC represented the control groups. As control for known long-lived induced immunity, we analyzed humoral and cellular tetanus toxoid (TT) immune responses in steady-state. Results: After 3rd vaccination, 5/7 seroconverted RTX patients revealed lower anti-SARS-CoV-2 IgG levels but similar neutralizing capacity compared with HC. Antibody levels after 3rd vaccination correlated with values after 2nd vaccination. Despite significant reduction of circulating total and antigen-specific B cells in RTX re-exposed patients, we observed the induction of IgG+ MBCs upon 3rd vaccination. Notably, only RTX treated patients revealed a high amount of IgA+ MBCs before and IgA+ plasmablasts after 3rd vaccination. IgA+ B cells were not part of the steady state TT+ B cell pool. TNF-secretion and generation of effector memory CD4 spike-specific T cells were significantly boosted upon 3rd vaccination. Summary: On the basis of pre-existing affinity matured MBCs within primary immunisation, RTX re-exposed patients revealed a persistent but atypical GC immune response accompanied by boosted spike-specific memory CD4 T cells upon SARS-CoV-2 recall vaccination.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Antibodies, Viral , COVID-19 Vaccines , Germinal Center , Humans , Immunoglobulin A , Immunoglobulin G , Rituximab , SARS-CoV-2 , Vaccination
7.
Transplant international : official journal of the European Society for Organ Transplantation ; 35, 2022.
Article in English | EuropePMC | ID: covidwho-1999389

ABSTRACT

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12–18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 (“Comirnaty”;Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD+27+ memory cells in patients. Whereas spike specific CD4+ T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults. Graphical

8.
Front Immunol ; 13: 920210, 2022.
Article in English | MEDLINE | ID: covidwho-1924111

ABSTRACT

In this prospective observational cohort study we analyzed cellular and serological immune response parameters against SARS-CoV-2 and current variants of concern (VOC) in 147 COVID-19-convalescent and 39 COVID-19-naïve individuals before and after BNT162b2 booster vaccination. No significant differences regarding immunological response parameters were observed between younger and older individuals. Booster vaccination induced full recovery of both cellular and serological response parameters including IFN-γ secretion and anti-spike antibody titers with strong neutralization capacities against wild type SARS-COV-2 and Delta. Surprisingly, even serological neutralization capacity against Omicron was detectable one month after second vaccination and four months before it had been first observed in South Africa. As a result, more than 90% of convalescent individuals exhibited detectable and 75% strong Omicron neutralization capacity after booster vaccination, compared with 72% and 46% of COVID-19-naïve individuals. Our results support the notion that broad and cross-reactive immune memory against SARS-CoV-2 including currently known VOCs can be established by booster vaccination with spike-based mRNA vaccines like BNT162b2, particularly in COVID-19-convalescent individuals of all ages. Nevertheless, especially in COVID-19-naïve individuals future variants escaping the memory immune response may require vaccine approaches such as inactivated whole virus vaccines, which include all antigenic components of the virus.


Subject(s)
COVID-19 , Viral Vaccines , BNT162 Vaccine , COVID-19/prevention & control , Humans , Prospective Studies , SARS-CoV-2 , Vaccination , Vaccines, Inactivated
9.
Front Immunol ; 13: 822885, 2022.
Article in English | MEDLINE | ID: covidwho-1834400

ABSTRACT

Background: Vaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and cellular responses upon vaccination. The ability to predict vaccination responses is essential to guide adequate safety and optimal protection in these patients. Methods: B- and T- cell data before vaccination were evaluated for characteristics predicting vaccine responses in altogether 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. Eleven patients with rheumatoid arthritis (RA) on other therapies, 11 kidney transplant recipients (KTR) on regular immunosuppression and 15 healthy controls (HC) served as controls. A multidimensional analysis of B cell subsets via UMAP algorithm and a correlation matrix were performed in order to identify predictive markers of response in patients under RTX therapy. Results: Significant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were identified at baseline. In this context, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) were naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells. Moreover, there was a positive correlation between neutralizing antibodies and B cells expressing HLA-DR and CXCR5 as well as an inverse correlation with CD95 expression and CD21low expression by B cells among vaccination responders. Summary: Substantial repopulation of the naïve B cell compartment after RTX therapy appeared to be essential for an adequate vaccination response, which seem to require the additional capability of antigen presentation and germinal center formation. Moreover, expression of exhaustion markers represent negative predictors of vaccination responses.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Humans , Immunoglobulin G , Rituximab/therapeutic use , SARS-CoV-2 , Vaccination/methods
10.
JCI Insight ; 7(9)2022 05 09.
Article in English | MEDLINE | ID: covidwho-1765224

ABSTRACT

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.


Subject(s)
Antimetabolites , COVID-19 Vaccines , COVID-19 , Kidney Transplantation , Antibodies, Viral , Antimetabolites/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Immunity, Cellular , Immunity, Humoral , Immunosuppressive Agents/therapeutic use , SARS-CoV-2 , Transplant Recipients , Vaccination
11.
Nat Commun ; 13(1): 128, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1616978

ABSTRACT

The quality and persistence of children's humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Antigens, Viral/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Child , Child, Preschool , Cross Reactions/immunology , Female , Humans , Infant , Male , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods
12.
Arthritis Rheumatol ; 74(6): 934-947, 2022 06.
Article in English | MEDLINE | ID: covidwho-1589171

ABSTRACT

OBJECTIVE: Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy are at higher risk of poor COVID-19 outcomes and show substantially impaired humoral immune response to anti-SARS-CoV-2 vaccine. However, the complex relationship between antigen-specific B cells and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown. METHODS: Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 patients with rheumatoid arthritis (RA) or antineutrophil cytoplasmic antibody-associated vasculitis receiving RTX, 12 patients with RA receiving other therapies, and 30 healthy controls after SARS-CoV-2 vaccination with either messenger RNA or vector-based vaccines. RESULTS: A minimum of 10 B cells per microliter (0.4% of lymphocytes) in the peripheral circulation appeared to be required for RTX-treated patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX-treated patients who lacked IgG seroconversion showed reduced receptor-binding domain-positive B cells (P = 0.0005), a lower frequency of Tfh-like cells (P = 0.0481), as well as fewer activated CD4 (P = 0.0036) and CD8 T cells (P = 0.0308) compared to RTX-treated patients who achieved IgG seroconversion. Functionally relevant B cell depletion resulted in impaired interferon-γ secretion by spike-specific CD4 T cells (P = 0.0112, r = 0.5342). In contrast, antigen-specific CD8 T cells were reduced in both RA patients and RTX-treated patients, independently of IgG formation. CONCLUSION: In RTX-treated patients, a minimum of 10 B cells per microliter in the peripheral circulation is a candidate biomarker for a high likelihood of an appropriate cellular and humoral response after SARS-CoV-2 vaccination. Mechanistically, the data emphasize the crucial role of costimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B cell and plasma cell differentiation.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Antibodies, Viral , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Cell Count , Humans , Immunity, Humoral , Immunoglobulin G , Rituximab/therapeutic use , SARS-CoV-2 , Vaccination/methods
13.
EBioMedicine ; 75: 103761, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1587930

ABSTRACT

BACKGROUND: Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. METHODS: To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). FINDINGS: Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4+ and CD8+ T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. INTERPRETATION: In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern. FUNDING: This project has received funding from the European Union's Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute (RKI), the Baden-Württemberg Stiftung, the county of Lower Saxony, the Ministry for Science, Research and the Arts of Baden-Württemberg, Germany, and the National Institutes of Health.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/prevention & control , Immunity, Cellular/drug effects , Immunization, Secondary , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , COVID-19/epidemiology , COVID-19/immunology , Female , Humans , Male , Middle Aged , Prevalence
14.
J Am Soc Nephrol ; 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1566580

ABSTRACT

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

15.
EJHaem ; 3(1): 72-79, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1540110

ABSTRACT

Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires tests to monitor antibody formation and prevalence. We detected SARS-CoV-2 antibodies using red cells coated by Kode technology with short peptides derived from the SARS-CoV-2 spike protein (SP). Such modified red cells, called C19-kodecytes, can be used as reagent cells in any manual or automated column agglutination assay. We investigated the presence of SARS-CoV-2 antibodies in 130 samples from COVID-19 convalescent plasma donors using standard manual technique, two FDA-authorized enzyme-linked immunosorbent assay (ELISA) assays and a virus neutralisation assay. The sensitivity of the C19-kodecyte assay was 88%, comparable to the anti-SP and anti-nucleocapsid protein (NCP) ELISAs (86% and 83%) and the virus neutralisation assay (88%). The specificity of the C19-kodecyte assay was 90% (anti-SP 100% and anti-NCP 97%). Likewise, 231 samples from 73 vaccinated individuals were tested with an automated analyser, and we monitored the appearance and persistence of SARS-CoV-2 antibodies. The C19-kodecyte assay is a robust tool for SARS-CoV-2 antibody detection. Automated blood group analyser use enables large-scale SARS-CoV-2 antibody testing for vaccination monitoring in population surveys.

16.
Eur J Immunol ; 52(1): 138-148, 2022 01.
Article in English | MEDLINE | ID: covidwho-1479399

ABSTRACT

The interferon pathway, a key antiviral defense mechanism, is being considered as a therapeutic target in COVID-19. Both, substitution of interferon and JAK/STAT inhibition to limit cytokine storms have been proposed. However, little is known about possible abnormalities in STAT signaling in immune cells during SARS-CoV-2 infection. We investigated downstream targets of interferon signaling, including STAT1, STAT2, pSTAT1 and 2, and IRF1, 7 and 9 by flow cytometry in 30 patients with COVID-19, 17 with mild, and 13 with severe infection. We report upregulation of STAT1 and IRF9 in mild and severe COVID-19 cases, which correlated with the IFN-signature assessed by Siglec-1 (CD169) expression on peripheral monocytes. Interestingly, Siglec-1 and STAT1 in CD14+ monocytes and plasmablasts showed lower expression among severe cases compared to mild cases. Contrary to the baseline STAT1 expression, the phosphorylation of STAT1 was enhanced in severe COVID-19 cases, indicating a dysbalanced JAK/STAT signaling that fails to induce transcription of interferon stimulated response elements (ISRE). This abnormality persisted after IFN-α and IFN-γ stimulation of PBMCs from patients with severe COVID-19. Data suggest impaired STAT1 transcriptional upregulation among severely infected patients may represent a potential predictive biomarker and would allow stratification of patients for certain interferon-pathway targeted treatments.


Subject(s)
COVID-19/immunology , Monocytes/immunology , SARS-CoV-2/immunology , STAT1 Transcription Factor/immunology , Signal Transduction/immunology , Up-Regulation/immunology , Adult , Aged , Female , Humans , Interferon Regulatory Factors/immunology , Male , Middle Aged , Patient Acuity , Phosphorylation/immunology
17.
Front Immunol ; 12: 743422, 2021.
Article in English | MEDLINE | ID: covidwho-1472388

ABSTRACT

Elderly residents of long-term care facilities (LTCFs) have long been underrepresented in studies on vaccine efficacy, particularly in light of currently emerging variants of concern (VOCs). In this prospective observational cohort study, we analyzed serological immune responses in 190 individuals before, 3 weeks after 1st and 3 weeks after 2nd vaccination with BNT162b2. Unvaccinated COVID-19-convalescent subjects served as reference. End points comprised serum anti-spike IgG and IgA titers as well as neutralization capacities against unmutated and mutated SARS-CoV-2 receptor binding domains including B.1.1.7, B.1.351 and P.1. We found that antibody titers and neutralization capacities up to 3 weeks after 2nd vaccination with BNT162b2 were significantly higher in COVID-19-convalescent as compared to COVID-19-naive vaccinees. Moreover, pre-vaccination anti-NCP IgG titers, but not age or gender, had a high impact on the strength and kinetics of post-vaccination neutralization capacity development. Most importantly, BNT162b2-induced neutralization capacity was cross-reactive with VOCs. In contrast to unvaccinated convalescents, vaccinated convalescent individuals of all ages acquired strong neutralizing capacities against current VOCs. The present study suggests that COVID-19-convalescent individuals with a broad age range between 18 and 98 years benefit from BNT162b2 vaccination by developing strong and broad neutralizing immune responses against SARS-CoV-2 including current VOCs.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , Convalescence , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Long-Term Care , Middle Aged , Prospective Studies , Vaccination , Young Adult
18.
J Clin Invest ; 131(20)2021 10 15.
Article in English | MEDLINE | ID: covidwho-1470551

ABSTRACT

BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.


Subject(s)
COVID-19/therapy , SARS-CoV-2 , Aged , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/administration & dosage , Antibodies, Viral/therapeutic use , COVID-19/immunology , COVID-19/physiopathology , Combined Modality Therapy , Cross-Over Studies , Female , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Treatment Outcome
19.
Transfusionsmedizin ; 11(03):182-187, 2021.
Article in English | Web of Science | ID: covidwho-1390252

ABSTRACT

The following article provides an overview of commercially available test systems for screening blood samples for various antibodies against SARS-CoV-2. It also discusses possible applications of such testing, ranging from seroprevalence and longitudinal studies to screening of potential convalescent plasma donors and monitoring of the humoral immune response after vaccination against SARS-CoV-2.

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