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1.
N Engl J Med ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34614326

RESUMO

BACKGROUND: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. METHODS: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. RESULTS: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). CONCLUSIONS: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34565682

RESUMO

BACKGROUND: The repeated waves of the COVID-19 pandemic have highlighted the necessity to optimize vaccine responses in immunocompromised populations. We investigated the safety and immunogenicity of a third, booster, dose of the Pfizer BNT162b2 vaccine in heart transplant (HT) patients. METHODS: The cohort comprised 96 adult HT patients who received a third homologous dose of the BNT162b2 vaccine 168 days after the second dose. The vaccine-induced antibody responses of both receptor-binding domain (RBD) IgG and neutralizing antibodies were assessed in all patients, with a positive antibody response being defined as the presence of either IgG anti-RBD or neutralizing antibodies. For a subset of patients, T cell response was also studied. RESULTS: The third dose was associated with a low rate of adverse events, mostly mild pain at the injection site. No serious adverse events were recorded, and there were no episodes of rejection. At 18 days following the third dose of the vaccine, the positive antibody response increased from 23% to 67%, with a corresponding increase in neutralizing capacity. The third dose elicited SARS-CoV-2 neutralization titers >9-fold and IgG anti-RBD antibodies >3-fold of the range achieved after the two primary doses. Mycophenolate use, lower eGFR and higher C-reactive protein were independently associated with a reduced likelihood of generating an immune response. Importantly, a specific T-cell response following the third dose was evident in the majority of transplant recipients. CONCLUSIONS: An homologous third booster dose of the BNT162b2 vaccine gave overall consistent tolerability and a good safety profile, while eliciting humoral and cellular immune responses.

3.
Eur J Cancer ; 157: 124-131, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508994

RESUMO

AIM: Patients with cancer are at an increased risk for severe coronavirus disease of 2019, thus data on the safety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted this prospective study of patients with cancer vaccinated with BNT162b2 and monitored for antibody response and safety. The aim was to evaluate the rate of seropositivity and define predictors for non-reactive immune response. Furthermore, we evaluated the frequency and the severity of adverse events. METHODS: The study included patients with solid tumours undergoing anticancer treatment and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralising antibodies were measured 2-4 weeks after each vaccine dose. RESULTS: The analysis included 129 patients, of which 70.5% patients were metastatic. Patients were treated with chemotherapy (55%), immunotherapy (34.1%), biological agents (24.8%), hormonal treatment (8.5%) and radiotherapy (4.6%), that were given either alone or in combinations. The seropositivity rate among patients with cancer and controls was 32.4% versus 59.8% (p < 0.0001) after the first dose and 84.1% versus 98.9% (p < 0.0001) after the second dose, respectively. Median RBD-IgG titre was lower among patients than controls (p < 0.0001). Patients who were seronegative after the second dose had significantly more comorbidities than that with patients with seropositivity (77.8% vs 41.1%, respectively, p = 0.0042). CONCLUSION: Adequate antibody response after BNT162b2 vaccination was achieved after two doses but not after one dose, in patients with cancer vaccinated during anticancer therapy.

4.
Am J Obstet Gynecol MFM ; : 100492, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547533

RESUMO

BACKGROUND: The exclusion of pregnant women from COVID-19 mRNA vaccine trials raised hesitancy regarding the benefit of vaccination of pregnant women, hence little is known about the vaccine's efficacy in this population. OBJECTIVE: To determine the maternal-neonatal transplacental transfer of SARS CoV-2 antibodies among vaccinated parturient women. A control group of COVID 19 recovered patients was included in order to compare IgG levels between vaccinated and recovered patients. STUDY DESIGN: A prospective cohort study in a single tertiary medical center in Israel between February and March 2021; parturient women who had been vaccinated with BNT162B2 mRNA vaccine during pregnancy were included and compared to COVID-19 recovered parturient women. SARS CoV-2 IgG antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast-milk samples. The primary outcome was to determine whether neonatal cord and dried blood spot samples were positive for SARS CoV-2 antibodies and to evaluate transfer ratio defined as cord blood IgG divided by maternal IgG levels. RESULTS: The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 disease during pregnancy. All maternal blood sera samples and 98.3% of cord blood sera samples were positive for SARS Cov-2 IgG with median concentrations of 26.1 (IQR 22.0;39.7) and 20.2 (IQR 12.7;29.0) respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS CoV-2 IgG with median concentrations of 11.0 (IQR 7.2;12.8) and 4.9 (IQR 3.8;6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS Cov-2 IgG and cord blood (R=0.483, p=0.0001), neonatal blood spot (R=0.515, p=0.004), and breast milk levels (R=0.396, p=0.005) of SARS CoV-2 IgG. The median placental transfer ratio of SARS-COV-2 IgG was 0.77. Comparison of vaccinated with recovered COVID-19 patients revealed significantly higher SARS CoV-2 IgG levels in maternal serum and cord blood among vaccinated women (p<0.0001). CONCLUSION(S): Our study demonstrated efficient transfer of SARS CoV-2 IgG across the placenta from women vaccinated with BNT162b2 mRNA vaccine during pregnancy to their neonates with positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34438069

RESUMO

OBJECTIVES: The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with human immunodeficiency virus type 1 (PLWH) are unknown. We aimed to assess the immunogenicity and safety of this vaccine in PLWH. METHODS: In this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health-care workers (HCWs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored. RESULTS: At a median of 18 days (interquartile range 14-21 days) after the second dose, anti-RBD-IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD-IgG at a median of 26 days (interquartile range 24-27 days) after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCWs, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue and headache. AIDS-related adverse events were not reported. Human immunodeficiency virus load increased in 3/143 (2%) patients from <40 copies/mL to ≤100 copies/mL. CD4+ T-cell count decreased from a geometric mean of 700 cells/µL (95% CI 648-757 cells/µL) to 633.8 cells/µL (95% CI 588-683 cells/µL) (p < 0.01). CONCLUSIONS: BNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on antiretroviral therapy with unsuppressed CD4 count and suppressed viral load.

6.
Epidemiol Infect ; 149: e153, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34372950

RESUMO

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , Surtos de Doenças , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Fatores Etários , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , Criança , Pré-Escolar , Surtos de Doenças/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Coletiva/imunologia , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Características de Residência/estatística & dados numéricos , Estudos Soroepidemiológicos , Fatores de Tempo , Adulto Jovem
7.
Vaccines (Basel) ; 9(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34452062

RESUMO

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

8.
Eur J Clin Microbiol Infect Dis ; 40(10): 2199-2206, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34342767

RESUMO

BACKGROUND: The current practice of COVID-19 diagnosis worldwide is the use of oro-nasopharyngeal (ONP) swabs. Our study aim was to explore mouthwash (MW) as an alternative diagnostic method, in light of the disadvantages of ONP swabs. METHODS: COVID-19 outpatients molecular-confirmed by ONP swab were repeatedly examined with ONP swab and MW with normal saline (0.9%). Other types of fluids were compared to normal saline. The Cq values obtained with each method were compared. RESULTS: Among 137 pairs of ONP swabs and MW samples, 84.6% (116/137) of ONP swabs were positive by at least one of the genes (N, E, R). However MW detected 70.8% (97/137) of samples as positive, which means 83.6% (97/116) out of positive ONP swabs, missing mainly Cq value > 30. In both methods, the N gene was the most sensitive one. Therefore, MW samples targeting N gene, which was positive in 95/137 (69.3%), are comparable to ONP swabs targeting E and R genes which gave equal results-95/137 (69.3%) and 90/137 (65.7%), respectively. Comparing saline MW to distilled water gave equal results, while commercial mouth-rinsing solutions were less sensitive. CONCLUSIONS: MW with normal saline, especially when tested by N gene, can effectively detect COVID-19 patients. Furthermore, this method was not inferior when compared to R and E genes of ONP swabs, which are common targets in many laboratories around the world.


Assuntos
COVID-19/diagnóstico , Antissépticos Bucais/análise , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Adulto , Idoso , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/genética , Saliva/química , Adulto Jovem
10.
Lancet Respir Med ; 9(9): 999-1009, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34224675

RESUMO

BACKGROUND: Concurrent with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. METHODS: We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1-2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4-5 (ie, 1-2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. FINDINGS: Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19-0·31) and immunosuppressed individuals (0·21, 0·14-0·31) compared with individuals aged 18·00-45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80-0·89), older age (ie, ≥66 years; 0·64, 0·58-0·71), immunosuppression (0·44, 0·33-0·58), and other specific comorbidities: diabetes (0·88, 0·79-0·98), hypertension (0·90, 0·82-0·98), heart disease (0·86, 0·75-1·00), and autoimmune diseases (0·82, 0·73-0·92). INTERPRETATION: BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. FUNDING: Sheba Medical Center, Israel Ministry of Health.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Seguimentos , Humanos , Imunidade Humoral , Imunogenicidade da Vacina , Israel/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Estudos Prospectivos , SARS-CoV-2/imunologia , Vacinação/métodos , Vacinação/estatística & dados numéricos , Adulto Jovem
11.
N Engl J Med ; 385(16): 1474-1484, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34320281

RESUMO

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

12.
Haematologica ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320789

RESUMO

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. We investigated the safety and efficacy of BNT162b2 mRNA Covid-19 vaccine in patients with CLL from nine medical centers in Israel, In total 400 patients were included, of which 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, antibody response was detected in 43% of the cohort. In treatment- naïve patients 61% responded to the vaccine, while only 18%, 37% and 5% of patients with CLL ongoing, previously treated with BTKi, or recent anti CD20 antibody developed responses respectively. 62% and 14% of patients treated with BCL2 monotherapy or combined with anti CD20 developed immune response respectively. Neutralizing antibodies demonstrated high concordance with positive serologic response to spike (S) protein. Based on our results a simple scoring model including recent treatment with anti-CD20, age younger than 70 years, treatment naïve status, and normal IGG, IGA, IGM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the vaccine was found to be safe in patients with CLL, but its efficacy is limited particularly in treated patients.

13.
Transplantation ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34310101

RESUMO

Background: Data about SARS-CoV-2 vaccines efficacy in renal transplant recipients (RTR) is lacking. Methods: To reveal predictors for humoral response to BNT162b2 vaccine among RTR, patients were divided to positive (N=42) and negative (N=78) response groups based on receptor-binding domain (RBD) IgG >= 1.1 and neutralizing antibodies (NA) >= 16 dilution versus RBD IgG < 1.1 or NA < 16 respectively. NA were detected using a SARS-CoV-2 pseudo-virus. Results: NA were detected in only 42/120 (35%) of RTR vs. 197/202 (97.5%) immunocompetent controls (p < 0.001). NA geometric mean titers (GMTs) in RTR were significantly lower vs. the control group [83.7 (95% CI 50.5-138.8) vs. 482 (95% CI 411-566), p < 0.001]. In a multivariable analysis, mycophenolic acid (MPA) dose and hemoglobin (Hb) level were found to be independent predictors for antibody response in RTR. A positive response rate of 27% vs. 63% was observed in patients on and off MPA, respectively. An increase in MPA dose by 1 mg/kg weight reduced the odds for a positive response by 17% (OR 0.83, 95% CI 0.75-0.92, p<0.001). GMTs for RBD IgG were significantly reduced as MPA daily dose increased. Hb blood level < 13 g/dL reduced the antibody response by 63% (p=0.04). Pain at the injection site after the second vaccine dose was significantly higher in the responders vs. nonresponders (20.5% vs. 5.5%, p=0.01). Conclusions: Only 35% of RTR develop NA to the BNT162b2 mRNA vaccine. MPA is a major suppressor of antibody response in RTR.

14.
Euro Surveill ; 26(26)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34212838

RESUMO

SARS-CoV-2 Delta (B.1.617.2) variant of concern (VOC) and other VOCs are spreading in Europe. Micro-neutralisation assays with sera obtained after Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in 36 healthcare workers (31 female) demonstrated significant fold change reduction in neutralising titres compared with the original virus: Gamma (P.1) 2.3, Beta (B.1.351) 10.4, Delta 2.1 and 2.6. The reduction of the Alpha (B.1.1.7) variant was not significant. Despite being lower, remaining neutralisation capacity conferred by Comirnaty against Delta and other VOCs is probably protective.


Assuntos
COVID-19 , SARS-CoV-2 , Vacinas contra COVID-19 , Europa (Continente) , Feminino , Pessoal de Saúde , Humanos , Israel , Vacinação
15.
J Heart Lung Transplant ; 40(8): 759-762, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34034958

RESUMO

BACKGROUND: Data on the safety and efficacy of SARS-CoV-2 vaccines in immunocompromised populations are sparse. METHODS: We conducted a prospective study of 77 heart transplant (HT) recipients vaccinated with two doses of BNT162b2 vaccine and monitored for adverse events following both doses, the receptor-binding domain (RBD) IgG response, and neutralizing antibodies. RESULTS: BNT162b2 vaccination was associated with a low rate of adverse events, characterized mostly by pain at the injection site. By a mean 41 days post second dose there were no clinical episodes of rejection, as suggested by a troponin leak or allograft dysfunction. At a mean 21 days following the second dose, IgG anti-RBD antibodies were detectable in 14 (18%) HT recipients. Immune sera neutralized SARS-CoV-2 pseudo-virus in 8 (57%) of those with IgG anti-RBD antibodies. Immunosuppressive regimen containing mycophenolic acid was associated with lower odds of an antibody response (OR = 0.12, p = 0.042). CONCLUSIONS: Whether a longer time-frame for observation of an antibody response is required after vaccination in immunosuppressed individuals remains unknown.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Transplante de Coração , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/virologia , Idoso , Formação de Anticorpos , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Imunossupressão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Eur J Epidemiol ; 36(7): 727-734, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33884542

RESUMO

The first local spread of COVID-19 in Israel was detected in March 2020. Due to the diversity in clinical presentations of COVID-19, diagnosis by RT-PCR alone might miss patients with mild or no symptoms. Serology testing may better evaluate the actual magnitude of the spread of infection in the population. This is the first nationwide seroprevalence study conducted in Israel. It is one of the most widespread to be conducted thus far, and the largest per-country population size. The survey was conducted between June 28 and September 14, 2020 and included 54,357 patients who arrived at the Health Maintenance Organizations to undergo a blood test for any reason. A patient was considered seropositive after two consecutive positive results with two different kits (Abbott and DiaSorin).The overall seroprevalence was 3.8% (95%CI 3.7-4.0), males higher than females [4.9% (95%CI 4.6-5.2) vs. 3.1% (95%CI 2.9-3.3) respectively]. Adolescents had the highest prevalence [7.8% (95%CI 7.0-8.6)] compared to other age groups. Participants who had undergone RT-PCR testing had a tenfold higher risk to be seropositive. The prevalence-to-incidence ratio was 4.5-15.7. Serology testing is an important complimentary tool for assessing the actual magnitude of infection and thus essential for implementing policy measures to control the pandemic. A positive serology test result was recently accepted in Israel as being sufficient to define recovery, with possible far-reaching consequences, such as the deploying of employees to ensure the maintenance of a functional economy.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19 , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19/métodos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Soroepidemiológicos , Adulto Jovem
18.
Lancet Infect Dis ; 21(4): 529-536, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33212068

RESUMO

BACKGROUND: The tetravalent dengue vaccine (CYD-TDV) has been shown to provide protection against dengue disease over 5-year follow-up in participants with previous dengue infection, but increased the risk of dengue hospitalisation and severe dengue during long-term follow-up in those without previous dengue infection. WHO recommended pre-vaccination screening to identify those with previous dengue infection (ie, dengue seropositive) who would benefit from vaccination. We re-evaluated CYD-TDV efficacy in those identified as dengue seropositive using five commercially available immunoassays, and assessed immunoassay performance. METHODS: We included participants in the immunogenicity subsets of the phase 3 CYD14 (NCT01373281) and CYD15 (NCT01374516) CYD-TDV efficacy trials, which enrolled children aged 2-16 years in 2011-12 in five countries in the Asia-Pacific region (CYD14) and five Latin American countries (CYD15). Participants assessed had received at least one injection of study drug (CYD-TDV or placebo) and had baseline samples available. We tested baseline samples by IgG-based immunoassays to classify baseline dengue serostatus, using two ELISAs (EUROIMMUN and Panbio) and three rapid diagnostic tests (RDTs; TELL ME FAST, SD BIOLINE, and OnSite). Vaccine efficacy in preventing symptomatic, hospitalised, and severe virologically confirmed dengue was determined for participants who tested positive by each immunoassay. The specificity and sensitivity of each immunoassay was determined as percentage negative and positive agreement compared with the reference algorithm, which used dengue plaque reduction neutralisation test with 50% and 90% cutoffs and non-structural protein 1 IgG ELISA results to assign baseline serostatus. FINDINGS: Samples were available for 3967 participants, 2735 (69·0%) of whom were classified as seropositive by the reference algorithm. Vaccine efficacy against symptomatic virologically confirmed dengue in immunoassay-positive participants was high across all five immunoassays (EUROIMMUN ELISA 88·2% [95% CI 77·3 to 93·9], Panbio ELISA 87·6% [76·7 to 93·4], TELL ME FAST RDT 88·8% [67·0 to 96·2], SD BIOLINE RDT 82·8% [66·9 to 91·1], and OnSite RDT 89·7% [64·6 to 97·0]), as was vaccine efficacy against hospitalised virologically confirmed dengue (EUROIMMUN-ELISA 72·8% [38·9 to 87·9], Panbio ELISA 77·5% [52·8 to 89·3], TELL ME FAST RDT 92·4% [37·8 to 99·1], SD BIOLINE RDT 87·2% [54·5 to 96·4], and OnSite RDT 73·7% [-5·1 to 93·4]) and severe virologically confirmed dengue (EUROIMMUN ELISA 86·9% [-16·8 to 98·5], Panbio ELISA 91·3% [27·6 to 99·0], TELL ME FAST RDT 100·0% [not estimable to 100·0%], SD BIOLINE RDT 89·4% [9·6 to 98·8], and OnSite RDT 73·4% [-193·7 to 97·6]). The immunoassays exhibited high specificity (≥98·8% for all immunoassays apart from SD BIOLINE RDT) but variable sensitivities, with higher sensitivities observed for the ELISAs (EUROIMMUN 89·2% [87·9 to 90·3] and Panbio 92·5 [91·4 to 93·5]) than the RDTs (TELL ME FAST 52·5% [50·6 to 54·4], SD BIOLINE 71·1% [69·3 to 72·8], and OnSite 47·6% [45·7 to 49·5]). INTERPRETATION: Our findings suggest that these immunoassays could be used for pre-vaccination screening for CYD-TDV as tools to assist risk stratification until more sensitive and convenient tests become available. FUNDING: Sanofi Pasteur.


Assuntos
Vacinas contra Dengue/efeitos adversos , Vírus da Dengue/imunologia , Dengue/diagnóstico , Imunoensaio/instrumentação , Programas de Rastreamento/instrumentação , Adolescente , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Criança , Pré-Escolar , Ensaios Clínicos Fase III como Assunto , Dengue/imunologia , Dengue/prevenção & controle , Dengue/virologia , Vacinas contra Dengue/administração & dosagem , Feminino , Humanos , Imunoensaio/estatística & dados numéricos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Testes de Neutralização/instrumentação , Testes de Neutralização/estatística & dados numéricos , Seleção de Pacientes , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Reprodutibilidade dos Testes , Estudos Retrospectivos
19.
Clin Microbiol Infect ; 27(3): 474.e1-474.e3, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309698

RESUMO

OBJECTIVE: The role of school closure in mitigating coronavirus disease 2019 (COVID-19) transmission has been questioned. In our medical centre, during a 9-week national lockdown, an alternative school was opened for health-care workers' (HCW) children with a small number of children per class and strict symptom surveillance. After lockdown was lifted we screened children and their parents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology. METHODS: We conducted a cross-sectional study of HCW parents and their children after one teacher contracted COVID-19 following exposure at home and 53 children were exposed, isolated and tested by RT-PCR. We compared families with children attending the alternative school with families whose children who remained at home during the 9-week lockdown. Epidemiological and medical data were collected using a short questionnaire; nasopharyngeal and oropharyngeal swabs were obtained and tested for SARS-CoV-2 by RT-PCR, and blood was collected for SARS-CoV-2 IgA and IgG titres. RESULTS: A total of 435 children attended the Sheba alternative school. Among the 53 children exposed to the infected teacher, none tested positive by RT-PCR. Of these, 18 children-parent pairs were tested for serology and all were negative. A total of 106/435 (24%) children and their 78 parents were recruited for the cross-sectional study; 70 attended the Sheba school and 36 did not. Approximately 16% of children in either group reported symptoms (11/70 in the school group and 6/36 in the 'stay home' group), but SARS-CoV-2 was not detected by PCR in any, and previous exposure, as determined by serological tests, was low and not significantly different between the groups. CONCLUSION: In an alternative school for children of HCWs, active during COVID-19 national outbreak, we found no evidence of increased infection compared with children that stayed home.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Instituições Acadêmicas/estatística & dados numéricos , Adulto , COVID-19/diagnóstico , Criança , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Israel/epidemiologia , Masculino , Pais , Prevalência , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Centros de Atenção Terciária
20.
EClinicalMedicine ; 29: 100651, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33235985

RESUMO

Background: An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. Methods: Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and an in-house RBD ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed. Findings: Immunoassays sensitivities between 81.5%-89.4% and specificities between 97.7%-100% resulted in a profound impact on the expected Positive Predictive Value (PPV) in low (<15%) prevalence scenarios. No meaningful increase was detected in the false positive rate in children compared to adults. A positive correlation between disease severity and antibody titers, and no decrease in antibody titers in the first 8 weeks after PCR positivity was observed. We identified a subgroup of symptomatic SARS-CoV-2 positive patients (~5% of patients), who remained seronegative across a wide range of antigens, isotypes, and technologies. Interpretation: The commercially available automated immunoassays exhibit significant differences in performance and expected PPV in low prevalence scenarios. The low false-positivity rate in under 20's suggests that cross-reactive immunity from previous CoV strains is unlikely to explain the milder disease course in children. Finding no decrease in antibody titers in the first 8 weeks is in contrast to some reports of short half-life for SARS-CoV-2 antibodies. The ~5% who were seronegative non-responders, using multiple assays in a population-wide manner, represents the proportion of patients that may be at risk for re-infection. Funding: Israel Ministry of Health.

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