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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.
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Anticuerpos Neutralizantes , Vacunas contra la COVID-19 , COVID-19 , Animales , Humanos , Ratones , Anticuerpos Antivirales , Linfocitos T CD8-positivos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Vacunas ViralesRESUMEN
BackgroundIn Sweden, information on seroprevalence of tick-borne encephalitis virus (TBEV) in the population, including vaccination coverage and infection, is scattered. This is largely due to the absence of a national tick-borne encephalitis (TBE) vaccination registry, scarcity of previous serological studies and use of serological methods not distinguishing between antibodies induced by vaccination and infection. Furthermore, the number of notified TBE cases in Sweden has continued to increase in recent years despite increased vaccination.AimThe aim was to estimate the TBEV seroprevalence in Sweden.MethodsIn 2018 and 2019, 2,700 serum samples from blood donors in nine Swedish regions were analysed using a serological method that can distinguish antibodies induced by vaccination from antibodies elicited by infection. The regions were chosen to reflect differences in notified TBE incidence.ResultsThe overall seroprevalence varied from 9.7% (95% confidence interval (CI): 6.6-13.6%) to 64.0% (95% CI: 58.3-69.4%) between regions. The proportion of vaccinated individuals ranged from 8.7% (95% CI: 5.8-12.6) to 57.0% (95% CI: 51.2-62.6) and of infected from 1.0% (95% CI: 0.2-3.0) to 7.0% (95% CI: 4.5-10.7). Thus, more than 160,000 and 1,600,000 individuals could have been infected by TBEV and vaccinated against TBE, respectively. The mean manifestation index was 3.1%.ConclusionA difference was observed between low- and high-incidence TBE regions, on the overall TBEV seroprevalence and when separated into vaccinated and infected individuals. The estimated incidence and manifestation index argue that a large proportion of TBEV infections are not diagnosed.
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Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas , Infecciones por Flavivirus , Humanos , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/prevención & control , Suecia/epidemiología , Cobertura de Vacunación , Estudios Seroepidemiológicos , Vacunación , Anticuerpos AntiviralesRESUMEN
Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.
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BACKGROUND: Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection. METHODS: In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARS-CoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659). FINDINGS: The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication. INTERPRETATION: The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies. FUNDING: The present studies were supported by grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and Karolinska Institutet.
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COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Estudios de Seguimiento , Huésped Inmunocomprometido , Estudios Prospectivos , ARN Mensajero , VacunaciónAsunto(s)
COVID-19 , Leucemia Linfocítica Crónica de Células B , Humanos , COVID-19/prevención & control , ARN Mensajero , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/genética , SARS-CoV-2 , Huésped Inmunocomprometido , Vacunación , Anticuerpos AntiviralesRESUMEN
Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Linfocitos T CD8-positivos , COVID-19/prevención & control , Humanos , Inmunidad Humoral , ARN Mensajero/genética , Síndrome , Vacunación , Proteínas del Envoltorio ViralRESUMEN
Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50-99% likelihood, and 4.0% (n = 203) to have a 10-49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
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Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021-000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1 .
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Vacuna BNT162/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , Huésped Inmunocomprometido/inmunología , Células Asesinas Naturales/inmunología , SARS-CoV-2/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Vacuna BNT162/administración & dosificación , COVID-19/epidemiología , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Citometría de Flujo , Humanos , Células Asesinas Naturales/metabolismo , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Subfamília C de Receptores Similares a Lectina de Células NK/metabolismo , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pandemias/prevención & control , SARS-CoV-2/fisiología , Vacunación/métodos , Vacunación/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: We compared the accuracy of preoperative transvaginal ultrasound (TVUS) versus magnetic resonance imaging (MRI) for the assessment of myometrial invasion (MI) in patients with endometrial cancer (EC), while definitive histopathological diagnosis served as a reference method. PATIENTS AND METHODS: Study performed at a single tertiary centre from 2019 to 2021, included women with a histopathological proven EC, hospitalized for scheduled surgery. TVUS and MRI were performed prior to surgical staging for assessment MI, which was estimated using two objective TVUS methods (Gordon's and Karlsson's) and MRI. Patients were divided into two groups, after surgery and histopathological assessment of MI: superficial (≤ 50%) and deep (> 50%). RESULTS: Sixty patients were eligible for the study. According to the reference method, there were 34 (56.7%) cases in the study with MI < 50%, and 26 (43.3%) with MI > 50%. Both objective TVUS methods and MRI showed no statistical significant differences in overall diagnostic performance for the preoperative assessment of MI. The concordance coefficient between both TVUS methods, MRI and histopathology was statistically significant (p < 0.001). Gordon's method calculating MI reached a positive predictive value (PPV) of 83%, negative predictive value (NPV) of 83%, 77% sensitivity, 88% specificity, and 83% overall accuracy. Karlsson's method reached PPV of 82%, NPV of 79%, 69% sensitivity, 88% specificity, and 80% overall accuracy. Accordingly, MRI calculating MI reached PPV of 83%, NPV of 97%, 97% sensitivity, 85% specificity, and 90% overall accuracy. CONCLUSIONS: We found that objective TVUS assessment of myometrial invasion was performed with a diagnostic accuracy comparable to that of MRI in women with endometrial cancer.
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Neoplasias Endometriales , Miometrio , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Miometrio/diagnóstico por imagen , Miometrio/patología , Miometrio/cirugía , Invasividad Neoplásica/diagnóstico por imagen , Invasividad Neoplásica/patología , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Immunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves oral cavity, a primary site of infection, is presently unknown. METHODS: Immunocompromised patients (n = 404) and healthy controls (n = 82) participated in a prospective clinical trial (NCT04780659) encompassing two doses of the mRNA BNT162b2 vaccine. Primary immunodeficiency (PID), secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL) patients were included. Salivary and serum immunoglobulin G (IgG) reactivities to SARS-CoV-2 spike were measured by multiplex bead-based assays and Elecsys anti-SARS-CoV-2 S assay. FINDINGS: IgG responses to SARS-CoV-2 spike antigens in saliva in HIV and HSCT/CAR-T groups were comparable to those of healthy controls after vaccination. The PID, SOT, and CLL patients had weaker responses, influenced mainly by disease parameters or immunosuppressants. Salivary responses correlated remarkably well with specific IgG titers and the neutralizing capacity in serum. Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded area under the curve (AUC) = 0.95 and positive predictive value (PPV) = 90.7% for the entire cohort after vaccination. CONCLUSIONS: Saliva conveys vaccine responses induced by mRNA BNT162b2. The predictive power of salivary spike IgG makes it highly suitable for screening vulnerable groups for revaccination. FUNDING: Knut and Alice Wallenberg Foundation, Erling Perssons family foundation, Region Stockholm, Swedish Research Council, Karolinska Institutet, Swedish Blood Cancer Foundation, PID patient organization of Sweden, Nordstjernan AB, Center for Medical Innovation (CIMED), Swedish Medical Research Council, and Stockholm County Council (ALF).
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COVID-19 , Leucemia Linfocítica Crónica de Células B , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Huésped Inmunocomprometido , Inmunoglobulina A Secretora , Inmunoglobulina G , Estudios Prospectivos , ARN Mensajero , SARS-CoV-2 , Saliva , Seroconversión , Glicoproteína de la Espiga del CoronavirusRESUMEN
Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.
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Vacuna BNT162 , COVID-19 , Humanos , Anticuerpos Antivirales , Formación de Anticuerpos , Vacuna BNT162/inmunología , COVID-19/prevención & control , Infecciones por VIH , Inmunoglobulina A Secretora , Saliva/inmunologíaRESUMEN
Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study.
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Infecciones por Virus ADN/diagnóstico , Leucemia/virología , Metagenómica/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Torque teno virus/genética , Preescolar , Infecciones por Virus ADN/inmunología , ADN Viral/sangre , Humanos , Leucemia/sangre , Leucemia/patología , Límite de Detección , Torque teno virus/aislamiento & purificación , Receptores de Trasplantes , Replicación ViralRESUMEN
We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1-13 of the pandemic. Sixty patients (median age 71 y, range 43-97) were identified. Median CIRS was eight (4-20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1-6 vs 7-13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , COVID-19/complicaciones , Leucemia Linfocítica Crónica de Células B/inmunología , SARS-CoV-2/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/transmisión , COVID-19/virología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/terapia , Leucemia Linfocítica Crónica de Células B/virología , Masculino , Persona de Mediana Edad , Pronóstico , SARS-CoV-2/aislamiento & purificaciónRESUMEN
BACKGROUND: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. METHODS: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. FINDINGS: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. INTERPRETATION: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. FUNDING: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.
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Vacuna BNT162/efectos adversos , Vacuna BNT162/inmunología , Huésped Inmunocomprometido/inmunología , Inmunogenicidad Vacunal/inmunología , SARS-CoV-2/inmunología , Adenina/efectos adversos , Adenina/análogos & derivados , Adenina/uso terapéutico , Anticuerpos Antivirales/sangre , COVID-19/prevención & control , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunoterapia Adoptiva , Leucemia Linfocítica Crónica de Células B , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Trasplante de Órganos , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Enfermedades de Inmunodeficiencia Primaria/inmunología , Estudios Prospectivos , Seroconversión , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación/efectos adversos , Eficacia de las VacunasRESUMEN
OBJECTIVE: The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. METHODS: More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. RESULTS: Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. CONCLUSION: These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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BACKGROUND: Declining humoral immunity in coronavirus disease 2019 (COVID-19) patients and possible reinfection have raised concern. Mucosal immunity, particularly salivary antibodies, may be short lived although long-term studies are lacking. METHODS: Using a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (nâ =â 74, cohort 1), undiagnosed individuals with self-reported questionnaires (nâ =â 147, cohort 2), and individuals sampled prepandemic (nâ =â 35, cohort 3). RESULTS: Salivary IgG antibody responses in cohort 1 (mainly mild COVID-19) were detectable up to 9 months postrecovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in blood and saliva in most patients. Salivary IgA was rarely detected at this time point. In cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19-like symptoms. Salivary IgG tolerated temperature and detergent pretreatments. CONCLUSIONS: Unlike SARS-CoV-2 salivary IgA that appeared short lived, specific saliva IgG appeared stable even after mild COVID-19, as for blood serology. This noninvasive saliva-based SARS-CoV-2 antibody test with home self-collection may be a complementary alternative to conventional blood serology.
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Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Inmunoglobulina G/inmunología , SARS-CoV-2/inmunología , Saliva/inmunología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.
Asunto(s)
Prueba Serológica para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/sangre , COVID-19/inmunología , Prueba Serológica para COVID-19/economía , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Sensibilidad y Especificidad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: The aim of this study is to compare the antenatal care, body weight, and weight gain in pregnancy between the adolescent and adult pregnancies and, thus, examine the impact of adolescence on the studied parameters. METHODS: This prospective study includes 300 pregnant women who were the patients of University Clinical Center Tuzla, Clinic for Gynecology and Obstetrics from January 2011 to December 2014. The women were divided into two groups: an experimental group consisted of 150 adolescent pregnant women aged 13-19 years and a control group consisted of 150 adult pregnant women aged 20-35 years. The following parameters were analyzed: age of pregnant women, number of antenatal controls in pregnancy, prepregnancy body weight, weight gain in pregnancy, parity, and obstetric history data. RESULTS: A significantly higher number of adolescent pregnant women belongs to a subgroup from one to two examinations during pregnancy (P < 0.000013) and to subgroups from three to five examinations (P < 0.000001). A significantly smaller number of adolescent pregnant women performed their first antenatal control in the first 2 lunar months (P < 0.01). A subgroup with optimal body weight (from 51 to 69 kg) are the most prevalent among adolescent pregnant women (P < 0.000001). A significantly larger number of adolescent pregnant women had an optimal weight gain of 7.8 to 12.99 kg (P < 0.001). CONCLUSIONS: The adolescent pregnant women have suboptimal antenatal care, which could lead to adverse maternal and birth outcomes, but have optimal body weight and weight gain during pregnancy.