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  1. Article: SARS-CoV-2 outbreak in a nursing home after vaccination with BNT162b2: A role for the quantification of circulating antibodies

    Càmara, Jordi / González-Díaz, Aida / Barrabeig, Irene / Fernández-Huerta, Miguel / Calatayud, Laura / Niubó, Jordi / Martí, Sara / Ángeles Domínguez, Mª / Ardanuy, Carmen

    Vaccine. 2022 Mar. 10,

    2022  

    Abstract: We describe an outbreak of SARS-CoV-2 (B.1.351) in a nursing home. At the outbreak onset 96% of residents and 76% of HCW had received two doses of BNT162b2. Twenty-eight residents (28/53) and six HCW (6/33) were infected. Infected residents had lower ... ...

    Abstract We describe an outbreak of SARS-CoV-2 (B.1.351) in a nursing home. At the outbreak onset 96% of residents and 76% of HCW had received two doses of BNT162b2. Twenty-eight residents (28/53) and six HCW (6/33) were infected. Infected residents had lower levels of anti-S antibodies compared to those who were not infected (157 vs 552 U/mL). Among 50 residents with available serological status, nineteen (19/25) with serum concentration < 300 U/mL and seven (7/25) with concentration > 300 U/mL acquired SARS-CoV-2 (RR 2.7 [95 %CI 1.4–5.3]). The quantification of circulating antibodies could be useful in detecting people with an impaired immune response who are at high risk of acquiring and spreading SARS-CoV-2.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; blood serum ; immune response ; risk ; vaccination ; vaccines
    Language English
    Dates of publication 2022-0310
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2022.03.026
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  2. Article ; Online: Decay of HIV RNA in Seminal Plasma and Rectal Fluid in Treatment-Naive Adults Starting Antiretroviral Therapy With Dolutegravir Plus Lamivudine or Bictegravir/Emtricitabine/Tenofovir Alafenamide.

    Scévola, Sofía / Niubó, Jordi / Domingo, Pere / Verdejo, Guillermo / Curran, Adrian / Diaz-Brito, Vicens / Peñafiel, Judith / Tiraboschi, Juan / Morenilla, Sandra / Garcia, Benito / Soriano, Irene / Podzamczer, Daniel / Imaz, Arkaitz

    The Journal of infectious diseases

    2023  Volume 228, Issue 7, Page(s) 919–925

    Abstract: Background: Decay of HIV in seminal plasma (SP) and rectal fluid (RF) has not yet been described for the antiretroviral combination of dolutegravir (DTG) + lamivudine (3TC).: Methods: In this randomized multicenter pilot trial, males who were ... ...

    Abstract Background: Decay of HIV in seminal plasma (SP) and rectal fluid (RF) has not yet been described for the antiretroviral combination of dolutegravir (DTG) + lamivudine (3TC).
    Methods: In this randomized multicenter pilot trial, males who were antiretroviral naive were randomized (2:1) to DTG + 3TC or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). HIV-1 RNA was measured in blood plasma (BP), SP, and RF at baseline; days 3, 7, 14, and 28; and weeks 12 and 24.
    Results: Of 25 individuals enrolled, 24 completed the study (DTG + 3TC, n = 16; BIC/FTC/TAF, n = 8). No significant differences were observed between groups for median decline in HIV-1 RNA from baseline at each time point or median time to achieve HIV-1 RNA <20 copies/mL in BP and SP and <20 copies/swab in RF. HIV-1 RNA decay patterns were compared in individuals receiving DTG + 3TC. Despite significantly higher percentages for changes from baseline in BP, median (IQR) times to HIV-1 RNA suppression were shorter in SP (7 days; 0-8.75) and RF (10.5 days; 3-17.5) than in BP (28 days; 14-84; P < .001).
    Conclusions: Comparable HIV-1 RNA decay in BP, SP, and RF was observed between DTG + 3TC and BIC/FTC/TAF. As shown with triple-drug integrase inhibitor-based regimens, rapid HIV-1 RNA suppression in SP and RF is achieved with DTG + 3TC, despite decay patterns differing from those of BP.
    Clinical trials registration: EudraCT 2019-004109-28.
    MeSH term(s) Male ; Adult ; Humans ; Lamivudine/therapeutic use ; Semen ; HIV Infections/drug therapy ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Pyridones/therapeutic use ; Anti-Retroviral Agents/therapeutic use ; Drug Combinations ; RNA, Viral ; Emtricitabine/therapeutic use ; Anti-HIV Agents/therapeutic use
    Chemical Substances tenofovir alafenamide (EL9943AG5J) ; Lamivudine (2T8Q726O95) ; bictegravir (8GB79LOJ07) ; dolutegravir (DKO1W9H7M1) ; Heterocyclic Compounds, 3-Ring ; Pyridones ; Anti-Retroviral Agents ; Drug Combinations ; RNA, Viral ; Emtricitabine (G70B4ETF4S) ; Anti-HIV Agents
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad304
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  3. Article ; Online: Development and validation of equilibrium dialysis UHPLC-MS/MS measurement procedures for total and unbound concentrations of bictegravir, dolutegravir, darunavir and doravirine in human plasma. Application to patients with HIV.

    Rigo-Bonnin, Raúl / García-Tejada, Laura / Mas-Bosch, Virgínia / Imaz, Arkaitz / Manuel Tiraboschi, Juan / Scévola, Sofía / Niubó, Jordi / Navarro-Alcaraz, Antonio / Podzamczer, Daniel

    Clinica chimica acta; international journal of clinical chemistry

    2023  Volume 552, Page(s) 117678

    Abstract: Background: Fixed-dose combinations of antiretroviral drugs are commonly used to treat HIV infection and therapeutic monitoring is not part of routine clinical practice. However, drug concentrations monitoring might have role in different clinical ... ...

    Abstract Background: Fixed-dose combinations of antiretroviral drugs are commonly used to treat HIV infection and therapeutic monitoring is not part of routine clinical practice. However, drug concentrations monitoring might have role in different clinical scenarios as well as for research purposes. This study aimed to develop and validate UHPLC-MS/MS procedures for measuring total and unbound concentrations of bictegravir, dolutegravir, darunavir and doravirine in human plasma.
    Material and methods: Equilibrium dialysis preceded sample preparation (based on protein precipitation) for measuring unbound antiretroviral concentrations. Chromatographic separations were achieved on an Acquity®-UPLC® HSS™-T3 column (50 mm × 2.1 mm; 1.8 µm) using a non-linear water/acetonitrile gradient containing 0.1 % formic acid at a 0.5 mL/min flow rate. Antiretrovirals were detected by tandem mass spectrometry in positive electrospray ionisation and multiple reaction monitoring modes.
    Results: No significant interferences or carry-over were observed. Imprecisions, absolute relative biases, normalised matrix effects and recoveries were ≤15.0 %, ≤11.1 %, (94.7-104.1)% and (96.7-105.5)%, respectively. Non-linear measuring intervals were observed between (25-10,000) µg/L for total/plasma dialysate concentrations and linearity schemes (1.00-100) µg/L for buffer dialysate concentrations.
    Conclusions: The UHPLC-MS/MS procedures developed could be used for research purposes and therapeutic drug monitoring of antiretrovirals in routine clinical practice.
    MeSH term(s) Humans ; Tandem Mass Spectrometry/methods ; Darunavir ; Chromatography, High Pressure Liquid/methods ; HIV Infections/drug therapy ; Renal Dialysis ; Dialysis Solutions
    Chemical Substances doravirine (913P6LK81M) ; Darunavir (YO603Y8113) ; dolutegravir (DKO1W9H7M1) ; bictegravir (8GB79LOJ07) ; Dialysis Solutions
    Language English
    Publishing date 2023-11-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2023.117678
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  4. Article ; Online: Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing.

    Fernández-Huerta, Miguel / Salmerón, Paula / Hernández-Hermida, Yolanda / Andrés, Cristina / Niubó, Jordi / Calatayud, Laura / Domínguez, M Ángeles / Pumarola, Tomàs / Ardanuy, Carmen / Antón, Andrés / Càmara, Jordi

    Enfermedades infecciosas y microbiologia clinica (English ed.)

    2023  Volume 41, Issue 8, Page(s) 462–467

    Abstract: Introduction: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR ... ...

    Abstract Introduction: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay Allplex™ SARS-CoV-2 for the qualitative detection of SARS-CoV-2 RNA.
    Methods: Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d'Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed.
    Results: Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis.
    Conclusion: In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions.
    Language English
    Publishing date 2023-04-17
    Publishing country Spain
    Document type Journal Article
    ISSN 2529-993X
    ISSN (online) 2529-993X
    DOI 10.1016/j.eimce.2022.01.007
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  5. Article ; Online: Successful treatment of hepatitis C virus infection combining daclatasvir and simeprevir in a heart transplant recipient with decompensated cirrhosis.

    Casanovas, Teresa / Roca, Josep / Niubó, Jordi

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2016  Volume 35, Issue 7, Page(s) 949–951

    MeSH term(s) Antiviral Agents/therapeutic use ; Drug Therapy, Combination ; Heart Transplantation ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepatitis C/virology ; Humans ; Imidazoles/therapeutic use ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/drug therapy ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; Simeprevir/therapeutic use
    Chemical Substances Antiviral Agents ; BMS-790052 ; Imidazoles ; Simeprevir (9WS5RD66HZ)
    Language English
    Publishing date 2016-05-17
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2016.05.005
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  6. Article: Prevalence of Hepatitis C Virus Infection, Genotypes and Subtypes in Migrants from Pakistan in Barcelona, Spain.

    Dopico, Eva / Rodriguez-Frias, Francisco / Ubillos, Itziar / Rando-Segura, Ariadna / Garcia-Cehic, Damir / Gregori, Josep / Rando-Matos, Yolanda / Solsona, Luis / Niubó, Jordi / Esteban, Juan Ignacio / Costa, Josep / Martínez, Miguel J / Quer, Josep

    Infection and drug resistance

    2022  Volume 15, Page(s) 4637–4644

    Abstract: Background: Hepatitis C virus (HCV) is a major cause of chronic liver infection with 71 million people infected worldwide. Pakistan has the second highest prevalence of HCV infection and more than half (52%) of Pakistani living in Spain reside in ... ...

    Abstract Background: Hepatitis C virus (HCV) is a major cause of chronic liver infection with 71 million people infected worldwide. Pakistan has the second highest prevalence of HCV infection and more than half (52%) of Pakistani living in Spain reside in Barcelona. The aim of this study was to analyse the seroprevalence and viraemic rate and determine the genotypes and subtypes of HCV among Pakistanis living in the southern metropolitan area of Barcelona.
    Methods: We included all Pakistani patients seeking primary healthcare in the southern metropolitan area of Barcelona from August 2011 to July 2014. Serum samples were screened for HCV antibodies. HCV viral load was determined by reverse transcription polymerase chain reaction and genotypes and subtypes were performed using Versant HCV Genotype and/or deep-sequencing. Screening for hepatitis B virus (HBV) was also carried out.
    Results: Among 5877 Pakistani patients, 565 (9.61%) were screened for anti-HCV antibodies, with 68 (12.04%) being positive. The viral load was determined in 65, with 31 presenting active infection and the viraemic rate was 47.69% (95% confidence interval 36.02-59.62). HCV genotyping and subtyping were performed in 24 individuals. Most infections corresponded to HCV genotype 3 (91.67%), and high resolution HCV subtyping was performed in 18 samples, 16 of which presented subtype 3a. One subject presented HBV coinfection with undetectable HBV DNA. During the study period, we identified a possible case of HCV vertical transmission followed by spontaneous viraemia clearance in a chronically infected mother with a C/T IL28B genetic polymorphism.
    Conclusion: These results suggest that general HCV screening protocols in patients from high prevalence countries, such as Pakistan, would be helpful to identify and treat active HCV infections. This could avoid further transmission and contribute to building targeted health policies for micro-elimination of HCV infection in specific communities.
    Language English
    Publishing date 2022-08-18
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494856-1
    ISSN 1178-6973
    ISSN 1178-6973
    DOI 10.2147/IDR.S367715
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  7. Article ; Online: [No title information]

    Fernández-Huerta, Miguel / Salmerón, Paula / Hernández-Hermida, Yolanda / Andrés, Cristina / Niubó, Jordi / Calatayud, Laura / Angeles Domínguez, M / Pumarola, Tomàs / Ardanuy, Carmen / Antón, Andrés / Càmara, Jordi

    Enfermedades infecciosas y microbiologia clinica

    2022  

    Abstract: Introduction: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR ... ...

    Title translation Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing.
    Abstract Introduction: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay Allplex
    Methods: Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d'Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed.
    Results: Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis.
    Conclusion: In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions.
    Language Spanish
    Publishing date 2022-02-14
    Publishing country Spain
    Document type English Abstract ; Journal Article
    ZDB-ID 1070941-1
    ISSN 1578-1852 ; 0213-005X
    ISSN (online) 1578-1852
    ISSN 0213-005X
    DOI 10.1016/j.eimc.2022.01.014
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  8. Article ; Online: Doravirine Concentrations and Human Immunodeficiency Virus Type 1 RNA in the Genital Fluids of Virologically Suppressed Adults Switching to Doravirine Plus Emtricitabine/Tenofovir Alafenamide.

    Scévola, Sofía / Imaz, Arkaitz / Cottrell, Mackenzie L / Niubo, Jordi / Van Horne, Brian / Tiraboschi, Juan / Saumoy, Maria / Morenilla, Sandra / Soriano, Irene / Kashuba, Angela D M / Podzamczer, Daniel

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2022  Volume 75, Issue 11, Page(s) 2012–2015

    Abstract: Doravirine (DOR) concentrations and HIV-1 RNA were evaluated in genital fluids from adults with HIV on stable therapy who switched to DOR + FTC/TAF. High protein-unbound DOR concentrations were observed in both seminal plasma and cervicovaginal fluid. ... ...

    Abstract Doravirine (DOR) concentrations and HIV-1 RNA were evaluated in genital fluids from adults with HIV on stable therapy who switched to DOR + FTC/TAF. High protein-unbound DOR concentrations were observed in both seminal plasma and cervicovaginal fluid. DOR + FTC/TAF maintained viral suppression in genital fluids in all but 1 participant.
    MeSH term(s) Adult ; Humans ; HIV-1/genetics ; Anti-HIV Agents/therapeutic use ; HIV Infections/drug therapy ; Emtricitabine/therapeutic use ; RNA/therapeutic use ; Genitalia
    Chemical Substances tenofovir alafenamide (EL9943AG5J) ; doravirine (913P6LK81M) ; Anti-HIV Agents ; emtricitabine tenofovir alafenamide ; Emtricitabine (G70B4ETF4S) ; RNA (63231-63-0)
    Language English
    Publishing date 2022-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciac410
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  9. Article ; Online: No Changes in Human Immunodeficiency Virus (HIV) Suppression and Inflammatory Markers in Cerebrospinal Fluid in Patients Randomly Switched to Dolutegravir Plus Lamivudine (Spanish HIV/AIDS Research Network, PreEC/RIS 62).

    Tiraboschi, Juan M / Rojas, Jhon / Zetterberg, Henrik / Blennow, Kaj / Niubo, Jordi / Gostner, Johanna / Navarro-Alcaraz, Antonio / Piatti, Camila / Fuchs, Dietmar / Gisslén, Magnus / Rigo-Bonnin, Raul / Martinez, Esteban / Podzamczer, Daniel

    The Journal of infectious diseases

    2022  Volume 223, Issue 11, Page(s) 1928–1933

    Abstract: A major concern of human immunodeficiency virus (HIV) dual therapy is a potentially lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury, and inflammatory biomarkers and dolutegravir ( ... ...

    Abstract A major concern of human immunodeficiency virus (HIV) dual therapy is a potentially lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury, and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG plus lamivudine (3TC). All participants maintained viral suppression in plasma and CSF at week 48. We observed no increase in CSF markers of inflammation or neuronal injury. Median (interquartile range) total and unbound DTG in CSF were 7.3 (5.9-8.4) and 1.7 (1.2-1.9) ng/mL, respectively. DTG+3TC may maintain viral control without changes in inflammatory/injury markers within the CNS reservoir.
    MeSH term(s) Anti-HIV Agents/therapeutic use ; Biomarkers/cerebrospinal fluid ; Drug Substitution ; HIV Infections/drug therapy ; HIV-1 ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Humans ; Lamivudine/therapeutic use ; Oxazines/therapeutic use ; Piperazines/therapeutic use ; Pyridones/therapeutic use ; Viral Load
    Chemical Substances Anti-HIV Agents ; Biomarkers ; Heterocyclic Compounds, 3-Ring ; Oxazines ; Piperazines ; Pyridones ; Lamivudine (2T8Q726O95) ; dolutegravir (DKO1W9H7M1)
    Language English
    Publishing date 2022-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiaa645
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  10. Article ; Online: SARS-CoV-2 outbreak in a nursing home after vaccination with BNT162b2: A role for the quantification of circulating antibodies.

    Càmara, Jordi / González-Díaz, Aida / Barrabeig, Irene / Fernández-Huerta, Miguel / Calatayud, Laura / Niubó, Jordi / Martí, Sara / Ángeles Domínguez, Ma / Ardanuy, Carmen

    Vaccine

    2022  Volume 40, Issue 18, Page(s) 2531–2534

    Abstract: We describe an outbreak of SARS-CoV-2 (B.1.351) in a nursing home. At the outbreak onset 96% of residents and 76% of HCW had received two doses of BNT162b2. Twenty-eight residents (28/53) and six HCW (6/33) were infected. Infected residents had lower ... ...

    Abstract We describe an outbreak of SARS-CoV-2 (B.1.351) in a nursing home. At the outbreak onset 96% of residents and 76% of HCW had received two doses of BNT162b2. Twenty-eight residents (28/53) and six HCW (6/33) were infected. Infected residents had lower levels of anti-S antibodies compared to those who were not infected (157 vs 552 U/mL). Among 50 residents with available serological status, nineteen (19/25) with serum concentration < 300 U/mL and seven (7/25) with concentration > 300 U/mL acquired SARS-CoV-2 (RR 2.7 [95 %CI 1.4-5.3]). The quantification of circulating antibodies could be useful in detecting people with an impaired immune response who are at high risk of acquiring and spreading SARS-CoV-2.
    MeSH term(s) Antibodies, Viral ; BNT162 Vaccine ; COVID-19/epidemiology ; COVID-19/prevention & control ; Humans ; Nursing Homes ; SARS-CoV-2 ; Vaccination
    Chemical Substances Antibodies, Viral ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2022-03-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2022.03.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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