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1.
Nat Immunol ; 23(6): 940-946, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35534723

RESUMEN

As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1-66.7) to 96.3% (95% CI, 94.2-98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.


Asunto(s)
COVID-19 , Vacunas , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunogenicidad Vacunal , Inmunoglobulina G , Estudios Prospectivos , SARS-CoV-2
2.
Emerg Infect Dis ; 30(5): 1050-1052, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38666742

RESUMEN

Although a vaccine against SARS-CoV-2 Omicron-XBB.1.5 variant is available worldwide and recent infection is protective, the lack of recorded infection data highlights the need to assess variant-specific antibody neutralization levels. We analyzed IgG levels against receptor-binding domain-specific SARS-CoV-2 ancestral strain as a correlate for high neutralizing titers against XBB variants.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/prevención & control , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Israel/epidemiología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas contra la COVID-19/inmunología , Masculino , Adulto , Persona de Mediana Edad , Femenino , Anciano , Pruebas de Neutralización
3.
N Engl J Med ; 385(24): e84, 2021 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-34614326

RESUMEN

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.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Vacuna BNT162/inmunología , COVID-19/inmunología , Personal de Salud , Inmunogenicidad Vacunal , Inmunoglobulina G/sangre , Adulto , Factores de Edad , Anciano , Anticuerpos Antivirales/sangre , Índice de Masa Corporal , COVID-19/prevención & control , Estudios de Cohortes , Femenino , Humanos , Inmunización Secundaria , Huésped Inmunocomprometido , Israel , Modelos Lineales , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores de Tiempo , Eficacia de las Vacunas
4.
N Engl J Med ; 385(16): 1474-1484, 2021 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-34320281

RESUMEN

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.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19/epidemiología , Personal de Salud/estadística & datos numéricos , Adulto , Enfermedades Asintomáticas , Vacuna BNT162 , COVID-19/diagnóstico , COVID-19/prevención & control , Prueba de Ácido Nucleico para COVID-19 , Estudios de Casos y Controles , Femenino , Humanos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Insuficiencia del Tratamiento
5.
Euro Surveill ; 29(16)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38639095

RESUMEN

Between late 2023 and early 2024, two measles outbreaks occurred in Israel, each caused by importation of measles virus strains of respective B3 and D8 genotypes. In this study, we validate transmission pathways uncovered by epidemiological investigations using a rapid molecular approach, based on complete measles virus genomes. The presented findings support this rapid molecular approach in complementing conventional contact tracing and highlight its potential for informing public health interventions.


Asunto(s)
Sarampión , Humanos , Epidemiología Molecular , Israel/epidemiología , Filogenia , Análisis de Secuencia de ADN , Sarampión/diagnóstico , Sarampión/epidemiología , Virus del Sarampión/genética , Brotes de Enfermedades , Genotipo
6.
Clin Infect Dis ; 76(7): 1315-1317, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36366729

RESUMEN

The correlation between anti-severe acute respiratory syndrome coronavirus 2 antibody levels and infection was reported. Here, we estimated the role of pre-fourth dose levels using data from 1098 healthcare workers. The risk of infection was reduced by 46% (95% confidence interval, 29%-59%) for each 10-fold increase in prebooster levels. Prebooster antibody levels could be used to optimally time boosters.


Asunto(s)
COVID-19 , Humanos , Vacunación , Inmunización Secundaria , Anticuerpos Antivirales , Personal de Salud
7.
Eur J Haematol ; 110(1): 99-108, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36208015

RESUMEN

We assessed the humoral and cellular response to the fourth BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL. A total of 67 patients with CLL and 85 age matched controls tested for serologic response and pseudo-neutralization assay. We also tested the functional T-cell response by interferon gamma (IFNγ) to spike protein in 26 patients. Two weeks after the fourth vaccine antibody serologic response was evident in 37 (55.2%) patients with CLL, 20 /22 (91%) of treatment naïve, and 9/32 (28%) patients with ongoing therapy, compared with 100% serologic response in age matched controls. The antibody titer increased by 10-fold in patients with CLL, however, still 88-folds lower than age matched controls. Predictors of better chances of post fourth vaccination serologic response were previous positive serologies after second, third, and pre-fourth vaccination, neutralizing assay, and treatment naïve patients. T-cell response improved from 42.3% before the fourth vaccine to 84.6% 2 weeks afterwards. During the time period of 3 months after the fourth vaccination, 14 patients (21%) developed COVID-19 infection, all recovered uneventfully. Our data demonstrate that fourth SARS-CoV-2 vaccination improves serologic response in patients with CLL to a lesser extent than healthy controls and induces functional T-cell response.


Asunto(s)
COVID-19 , Leucemia Linfocítica Crónica de Células B , Humanos , Vacunas contra la COVID-19 , ARN Mensajero , Vacuna BNT162 , Leucemia Linfocítica Crónica de Células B/terapia , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Antivirales
8.
J Infect Dis ; 225(5): 785-792, 2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-34850049

RESUMEN

BACKGROUND: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. METHODS: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys. RESULTS: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. CONCLUSIONS: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.


Asunto(s)
Vacuna BNT162/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacuna BNT162/administración & dosificación , Vacuna BNT162/efectos adversos , COVID-19/epidemiología , COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Femenino , Personal de Salud , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , ARN Mensajero , SARS-CoV-2
9.
Clin Infect Dis ; 2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35271690

RESUMEN

Approximately 1-8% of individuals do not develop antibodies following SARS-CoV-2 infection (sero-negatives). One BNT162b2 dose resulted in potent humoral response in 14 sero-negatives and 15 sero-positives, significantly higher than the response of 15 naïve-individuals, to two doses suggesting that COVID-19 provoked a memory response in individuals without detectable antibodies.

10.
J Hepatol ; 77(3): 702-709, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35452692

RESUMEN

BACKGROUND & AIMS: Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine. METHODS: Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored. RESULTS: The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue). CONCLUSION: After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses. LAY SUMMARY: The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.


Asunto(s)
COVID-19 , Trasplante de Hígado , Anciano , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Femenino , Humanos , Inmunidad Celular , Inmunoglobulina G , Masculino , Receptores de Trasplantes , Vacunas Sintéticas , Vacunas de ARNm
11.
Liver Transpl ; 28(2): 215-223, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34767690

RESUMEN

The BNT162b2 messenger RNA (mRNA) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be safe and effective in immunocompetent patients. The safety and efficacy of this vaccine in liver transplantation (LT) recipients is still under evaluation. The objective of this study was to assess the safety and efficacy of the BNT162b2 vaccine among transplant recipients. The immune responses of 76 LT recipients receiving 2 doses of the vaccine were compared with those of 174 age-matched immunocompetent controls. Postvaccination immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 and neutralizing antibodies (NA) to the BNT162b2 mRNA vaccine were determined at least 14 days after the second dose of the vaccine. IgG antibody titers ≥1.1 were defined as positive antibodies. Adverse effects were monitored during the study period. Following administration of the second dose, transplant recipients showed reduced immune responses compared with controls (72% versus 94.2%; P < 0.001). At a median time of 38 days after the second vaccination, the geometric mean of RBD IgG and NA titers were 2.1 (95% confidence interval [CI], 1.6-2.6) and 150 (95% CI, 96-234) among transplant recipients and 4.6 (95% CI, 4.1-5.1) and 429 (95% CI, 350-528) in the control group, respectively (P < 0.001). Antibody responses were lower in transplant recipients who were receiving combined immunosuppression therapy and in those with impaired renal function. Among the LT recipients with negative antibody responses, 1 became infected with SARS-CoV-2, but no recipients with positive antibody responses became infected. Overall, most (n = 39 [51%]) adverse effects self-reported by transplant recipients were mild and occurred more often in women than in men. Compared with patients who were immunocompetent, LT recipients had lower immune responses. The durability of immune responses to the BNT162b2 vaccine among LT recipients requires further investigation.


Asunto(s)
COVID-19 , Trasplante de Hígado , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , Femenino , Humanos , Trasplante de Hígado/efectos adversos , Masculino , ARN Mensajero/genética , SARS-CoV-2 , Receptores de Trasplantes , Vacunas Sintéticas , Vacunas de ARNm
12.
J Med Virol ; 94(8): 4012-4014, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35352372

RESUMEN

Lymphocytic choriomeningitis virus (LCMV) is an often-overlooked cause for viral meningitis but can have severe consequences in certain clinical situations. We present the first documented infection by LCMV in Israel. The epidemiology of LCMV is evolving with a potential for a worldwide endemicity due to the widespread presence of the natural host. Increased awareness and testing are required to identify this virus and screening of certain populations (e.g., organ donors) should be considered.


Asunto(s)
Coriomeningitis Linfocítica , Virus de la Coriomeningitis Linfocítica , Humanos , Israel/epidemiología , Coriomeningitis Linfocítica/diagnóstico
13.
Haematologica ; 107(3): 625-634, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34320789

RESUMEN

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, BNT162b2, an mRNA COVID-19 vaccine with a high efficacy of 95% in immunocompetent individuals, was introduced. We investigated the safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with CLL from nine medical centers in Israel, Overall 400 patients were included, of whom 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, an antibody response was detected in 43% of the cohort. Among these CLL patients, 61% of the treatment-na ve patients responded to the vaccine, while responses developed in only 18% of those with ongoing disease, 37% of those previously treated with a BTK inhibitor and 5% of those recently given an anti-CD20 antibody. Among patients treated with BCL2 as monotherapy or in combination with anti-CD20, 62% and 14%, respectively, developed an immune response. There was a high concordance between neutralizing antibodies and positive serological response to spike protein. Based on our findings we developed a simple seven-factor score including timing of any treatment with anti-CD20, age, treatment status, and 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 BNT162b2 mRNA COVID-19 vaccine was found to be safe in patients with CLL, but its efficacy is limited, particularly in treated patients.


Asunto(s)
COVID-19 , Leucemia Linfocítica Crónica de Células B , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , ARN Mensajero/genética , SARS-CoV-2
14.
Transpl Int ; 35: 10239, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35387393

RESUMEN

Background: An impaired humoral response to full dose of BNT162b2 vaccine was observed in renal transplant recipients (RTR). Methods: To reveal predictors for humoral response to third vaccine, patients were stratified to positive (N = 85) and negative (N = 14) 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: Response rate increased from 32.3% (32/99) before the third dose to 85.9% (85/99) post-third vaccine with a significant rise in geometric mean titers (GMTs) for RBD IgG and NA [0.79 (95% CI 0.65-0.96) vs. 3.08 (95% CI 2.76-3.45), p < 0.001 and 17.46 (95% CI 12.38-24.62) vs. 362.2 (95% CI 220.7-594.6), p < 0.001 respective. 80.6% (54/67) seroconverted and 96.9% (31/32) remained positive following the vaccine with a significant increase in GMTs for RBD IgG and NA. Age, ESRD secondary to diabetic nephropathy (DN) and renal allograft function were independent predictors for antibody response in RTR. Mycophenolic acid (MPA) use and dose had no impact on humoral response following the third booster. AEs were recorded for 70.1% of RTR population. Systemic AEs were more common in recipients with a positive humoral response as opposed to non-responders (45.2% versus 15.4% respectively, p = 0.04). Conclusion: 85.9% of RTR develop NA to BNT162b2 third vaccine, found effective in both negative and positive responders prior to the vaccine. Antigenic re-exposure overcame the suppressive effect of MPA on antibody response in RTR.


Asunto(s)
COVID-19 , Trasplante de Riñón , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , Humanos , Inmunoglobulina G , Ácido Micofenólico , SARS-CoV-2 , Receptores de Trasplantes
15.
Euro Surveill ; 27(39)2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36177870

RESUMEN

We assess the immunogenicity and efficacy of Spikevax and Comirnaty as fourth dose COVID-19 vaccines. Six months post-fourth-dose, IgG levels were higher than pre-fourth dose at 1.58-fold (95% CI: 1.27-1.97) in Spikevax and 1.16-fold (95% CI: 0.98-1.37) in Comirnaty vaccinees. Nearly 60% (159/274) of vaccinees contracted SARS-CoV-2. Infection hazard ratios (HRs) for Spikevax (0.82; 95% CI: 0.62-1.09) and Comirnaty (0.86; 95% CI: 0.65-1.13) vaccinees were similar, as were substantial-disease HRs, i.e. 0.28 (95% CI: 0.13-0.62) and 0.51 (95% CI: 0.27-0.96), respectively.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , COVID-19/prevención & control , Estudios de Seguimiento , Humanos , Inmunoglobulina G , Israel/epidemiología , ARN Mensajero , SARS-CoV-2/genética
16.
Clin Infect Dis ; 73(7): e2444-e2449, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32797228

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. METHODS: We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. RESULTS: Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E-5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E-4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. CONCLUSIONS: Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.


Asunto(s)
COVID-19 , Virus del Dengue , Anticuerpos Antivirales , Reacciones Cruzadas , Humanos , SARS-CoV-2
17.
Eur J Clin Microbiol Infect Dis ; 40(10): 2199-2206, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34342767

RESUMEN

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.


Asunto(s)
COVID-19/diagnóstico , Antisépticos Bucales/análisis , SARS-CoV-2/aislamiento & purificación , Saliva/virología , Adulto , Anciano , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/genética , Saliva/química , Adulto Joven
18.
Epidemiol Infect ; 149: e153, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-34372950

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/inmunología , COVID-19/epidemiología , Brotes de Enfermedades , Inmunoglobulina G/inmunología , SARS-CoV-2/inmunología , Adolescente , Adulto , Factores de Edad , Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , Niño , Preescolar , Brotes de Enfermedades/estadística & datos numéricos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Colectiva/inmunología , Lactante , Recién Nacido , Israel/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Características de la Residencia/estadística & datos numéricos , Estudios Seroepidemiológicos , Factores de Tiempo , Adulto Joven
19.
Eur J Epidemiol ; 36(7): 727-734, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33884542

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Prueba Serológica para COVID-19 , COVID-19/epidemiología , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/diagnóstico , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Prueba Serológica para COVID-19/métodos , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Israel/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Seroepidemiológicos , Adulto Joven
20.
Euro Surveill ; 26(48)2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34857069

RESUMEN

Until recently, children and adolescents were not eligible for COVID-19 vaccination. They may have been a considerable source of SARS-CoV-2 spread. We evaluated SARS-CoV-2 IgG antibody seroprevalence in Israeli children aged 0-15 years from January 2020 to March 2021. Seropositivity was 1.8-5.5 times higher than COVID-19 incidence rates based on PCR testing. We found that SARS-CoV-2 infection among children is more prevalent than previously thought and emphasise the importance of seroprevalence studies to accurately estimate exposure.


Asunto(s)
COVID-19 , Adolescente , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Niño , Humanos , Israel/epidemiología , SARS-CoV-2 , Estudios Seroepidemiológicos
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