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To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection.
Hugo Fernández-Bellon; Jordi Rodon; Leira Fernández-Bastit; Vanessa Almagro; Pilar Padilla-Solé; Cristina Lorca-Oró; Rosa Valle; Núria Roca; Santina Grazioli; Tiziana Trogu; Albert Bensaid; Jorge Carrillo; Nuria Izquierdo-Useros; Julià Blanco; Mariona Parera; Marc Noguera-Julián; Bonaventura Clotet; Ana Moreno; Joaquim Segalés; Júlia Vergara-Alert. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Viruses 2021, 13, 1683 .
AMA StyleHugo Fernández-Bellon, Jordi Rodon, Leira Fernández-Bastit, Vanessa Almagro, Pilar Padilla-Solé, Cristina Lorca-Oró, Rosa Valle, Núria Roca, Santina Grazioli, Tiziana Trogu, Albert Bensaid, Jorge Carrillo, Nuria Izquierdo-Useros, Julià Blanco, Mariona Parera, Marc Noguera-Julián, Bonaventura Clotet, Ana Moreno, Joaquim Segalés, Júlia Vergara-Alert. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Viruses. 2021; 13 (9):1683.
Chicago/Turabian StyleHugo Fernández-Bellon; Jordi Rodon; Leira Fernández-Bastit; Vanessa Almagro; Pilar Padilla-Solé; Cristina Lorca-Oró; Rosa Valle; Núria Roca; Santina Grazioli; Tiziana Trogu; Albert Bensaid; Jorge Carrillo; Nuria Izquierdo-Useros; Julià Blanco; Mariona Parera; Marc Noguera-Julián; Bonaventura Clotet; Ana Moreno; Joaquim Segalés; Júlia Vergara-Alert. 2021. "Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses." Viruses 13, no. 9: 1683.
Background Understanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic. Methods A prospective cohort of 332 COVID-19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models. Findings Long-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while outpatient responses were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection, although viral variants, mainly B.1.351, reduced the efficacy of neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of B.1.351 variant compared to outpatients. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses. Conclusions Neutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses, counteracting the significant resistance to neutralization of new viral variants. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.
Edwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Ferran Tarrés-Freixas; Raquel Ortiz; Carla Rovirosa; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Marc Noguera-Julian; Jorge Carrillo; Roger Paredes; Lourdes Mateu; Anna Chamorro; Ruth Toledo; Marta Massanella; Bonaventura Clotet; Julià Blanco. Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection. 2021, 1 .
AMA StyleEdwards Pradenas, Benjamin Trinité, Víctor Urrea, Silvia Marfil, Ferran Tarrés-Freixas, Raquel Ortiz, Carla Rovirosa, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Alfonso Valencia, Nuria Izquierdo-Useros, Marc Noguera-Julian, Jorge Carrillo, Roger Paredes, Lourdes Mateu, Anna Chamorro, Ruth Toledo, Marta Massanella, Bonaventura Clotet, Julià Blanco. Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection. . 2021; ():1.
Chicago/Turabian StyleEdwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Ferran Tarrés-Freixas; Raquel Ortiz; Carla Rovirosa; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Marc Noguera-Julian; Jorge Carrillo; Roger Paredes; Lourdes Mateu; Anna Chamorro; Ruth Toledo; Marta Massanella; Bonaventura Clotet; Julià Blanco. 2021. "Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection." , no. : 1.
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Natalia Ortega; Marta Ribes; Marta Vidal; Rocío Rubio; Ruth Aguilar; Sarah Williams; Diana Barrios; Selena Alonso; Pablo Hernández-Luis; Robert A. Mitchell; Chenjerai Jairoce; Angeline Cruz; Alfons Jimenez; Rebeca Santano; Susana Méndez; Montserrat Lamoglia; Neus Rosell; Anna Llupià; Laura Puyol; Jordi Chi; Natalia Rodrigo Melero; Daniel Parras; Pau Serra; Edwards Pradenas; Benjamin Trinité; Julià Blanco; Alfredo Mayor; Sonia Barroso; Pilar Varela; Anna Vilella; Antoni Trilla; Pere Santamaria; Carlo Carolis; Marta Tortajada; Luis Izquierdo; Ana Angulo; Pablo Engel; Alberto L. García-Basteiro; Gemma Moncunill; Carlota Dobaño. Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses. Nature Communications 2021, 12, 1 .
AMA StyleNatalia Ortega, Marta Ribes, Marta Vidal, Rocío Rubio, Ruth Aguilar, Sarah Williams, Diana Barrios, Selena Alonso, Pablo Hernández-Luis, Robert A. Mitchell, Chenjerai Jairoce, Angeline Cruz, Alfons Jimenez, Rebeca Santano, Susana Méndez, Montserrat Lamoglia, Neus Rosell, Anna Llupià, Laura Puyol, Jordi Chi, Natalia Rodrigo Melero, Daniel Parras, Pau Serra, Edwards Pradenas, Benjamin Trinité, Julià Blanco, Alfredo Mayor, Sonia Barroso, Pilar Varela, Anna Vilella, Antoni Trilla, Pere Santamaria, Carlo Carolis, Marta Tortajada, Luis Izquierdo, Ana Angulo, Pablo Engel, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño. Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses. Nature Communications. 2021; 12 ():1.
Chicago/Turabian StyleNatalia Ortega; Marta Ribes; Marta Vidal; Rocío Rubio; Ruth Aguilar; Sarah Williams; Diana Barrios; Selena Alonso; Pablo Hernández-Luis; Robert A. Mitchell; Chenjerai Jairoce; Angeline Cruz; Alfons Jimenez; Rebeca Santano; Susana Méndez; Montserrat Lamoglia; Neus Rosell; Anna Llupià; Laura Puyol; Jordi Chi; Natalia Rodrigo Melero; Daniel Parras; Pau Serra; Edwards Pradenas; Benjamin Trinité; Julià Blanco; Alfredo Mayor; Sonia Barroso; Pilar Varela; Anna Vilella; Antoni Trilla; Pere Santamaria; Carlo Carolis; Marta Tortajada; Luis Izquierdo; Ana Angulo; Pablo Engel; Alberto L. García-Basteiro; Gemma Moncunill; Carlota Dobaño. 2021. "Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses." Nature Communications 12, no. : 1.
The understanding of HIV-1 pathogenesis and clinical progression is incomplete because of the variable contribution of host, immune and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has concentrated many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller’s individuals contemporary to LTNPs or recent, named Old and Modern progressors. We analyzed the Env expression, the fusion and cell-to-cell transfer capacities as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4 and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs presenting poor viral functions and shorter sequences were associated with viremic control and the non-progressor clinical phenotype, whereas functional Envs were associated with the lack of virological control and progressor clinical phenotypes. These correlations support the central role of Env genotypic and phenotypic characteristics in the in vivo HIV-1 infection and pathogenesis. IMPORTANCE The role of the virus in the pathogenesis of HIV-1 infection has not been investigated in isolates from individuals with different progression rates. In this work, we studied the properties of the envelope glycoprotein complex (Env) in individuals with different progression rates to elucidate its role in pathogenesis. We estimated the Env expression, the CD4 binding, the fusion and cell-to-cell viral transfer capacities that affect the infectivity of the viral Envs in recombinant viruses. The Envs from individuals which control viral replication and lack clinical progression (LTNP-ECs and vLTNPs) showed lower functional capacities than from subjects with clinical progression (Old and Modern). The functional increase of the Envs characteristics was associated with an increase in viral infectivity and in increased length of variable loops and the number of glycosylation sites of the Env (gp120/SU). These results support the concept that viral characteristics contribute to viral infection and pathogenesis.
Silvia Pérez-Yanes; Maria Pernas; Silvia Marfil; Romina Cabrera-Rodríguez; Raquel Ortiz; Carla Rovirosa; Judith Estévez-Herrera; Isabel Olivares; Concepción Casado; Cecilio Lopez-Galindez; Julià Blanco; Agustin Valenzuela-Fernández. The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis. 2021, 1 .
AMA StyleSilvia Pérez-Yanes, Maria Pernas, Silvia Marfil, Romina Cabrera-Rodríguez, Raquel Ortiz, Carla Rovirosa, Judith Estévez-Herrera, Isabel Olivares, Concepción Casado, Cecilio Lopez-Galindez, Julià Blanco, Agustin Valenzuela-Fernández. The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis. . 2021; ():1.
Chicago/Turabian StyleSilvia Pérez-Yanes; Maria Pernas; Silvia Marfil; Romina Cabrera-Rodríguez; Raquel Ortiz; Carla Rovirosa; Judith Estévez-Herrera; Isabel Olivares; Concepción Casado; Cecilio Lopez-Galindez; Julià Blanco; Agustin Valenzuela-Fernández. 2021. "The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis." , no. : 1.
With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.
Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Ruth Toledo; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulàlia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals. Viruses 2021, 13, 1135 .
AMA StyleBenjamin Trinité, Edwards Pradenas, Silvia Marfil, Carla Rovirosa, Víctor Urrea, Ferran Tarrés-Freixas, Raquel Ortiz, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Rosalba Lepore, Nuria Izquierdo-Useros, Glòria Trujillo, Jaume Trapé, Carolina González-Fernández, Antonia Flor, Rafel Pérez-Vidal, Ruth Toledo, Anna Chamorro, Roger Paredes, Ignacio Blanco, Eulàlia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals. Viruses. 2021; 13 (6):1135.
Chicago/Turabian StyleBenjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Ruth Toledo; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulàlia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2021. "Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals." Viruses 13, no. 6: 1135.
To assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7. Funding This study was funded by Grifols, the Departament de Salut of the Generalitat de Catalunya, the Spanish Health Institute Carlos III, CERCA Programme/Generalitat de Catalunya, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos.
Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulalia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals. 2021, 1 .
AMA StyleBenjamin Trinité, Edwards Pradenas, Silvia Marfil, Carla Rovirosa, Víctor Urrea, Ferran Tarrés-Freixas, Raquel Ortiz, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Rosalba Lepore, Nuria Izquierdo-Useros, Glòria Trujillo, Jaume Trapé, Carolina González-Fernández, Antonia Flor, Rafel Pérez-Vidal, Anna Chamorro, Roger Paredes, Ignacio Blanco, Eulalia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals. . 2021; ():1.
Chicago/Turabian StyleBenjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulalia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2021. "Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals." , no. : 1.
Unraveling long-term kinetics of antibodies to SARS-CoV-2 and the factors influencing its course, like prior antibody levels to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity and effective surveillance strategies. Antibody levels against six SARS-CoV-2 and four HCoV antigens were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry in a cohort of health care workers followed-up for 6 months. Seroprevalence increased over time from 13.5% (month 0) and 15.6% (month 1), to 16.4% (month 6). Levels of antibodies were stable over time, except IgG against nucleocapsid antigen and IgM levels that waned. After the peak response, anti-spike antibody levels increased from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. The neutralizing capacity of antibodies was maintained. Pre-existing antibodies to alpha-HCoV were lower in individuals who subsequently seroconverted for SARS-CoV-2. IgG and IgA to HCoV were significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Natalia Ortega; Marta Ribes; Marta Vidal; Rocio Rubio; Ruth Aguilar; Sarah Williams; Diana Barrios; Selena Alonso; Pablo Hernandez-Luis; Robert Andrew Mitchell; Chenjerai Jairoce; Angeline Marie Cruz; Alfons Jimenez; Rebeca Santano; Susana Mendez; Montserrat Lamoglia; Neus Rosell; Anna Llupia; Laura Puyol; Jordi Chi; Natalia Rodrigo; Daniel Parras; Pau Serra; Edwards Pradenas; Benjamin Trinite; Julia Blanco; Alfredo Mayor; Sonia Barroso; Pilar Varela; Anna Vilella; Antoni Trilla; Pere Santamaria; Carlo Carolis; Marta Tortajada; Luis Izquierdo; Ana Angulo; Pablo Engel; Alberto L. García-Basteiro; Gemma Moncunill; Carlota Dobano. Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19. 2021, 1 .
AMA StyleNatalia Ortega, Marta Ribes, Marta Vidal, Rocio Rubio, Ruth Aguilar, Sarah Williams, Diana Barrios, Selena Alonso, Pablo Hernandez-Luis, Robert Andrew Mitchell, Chenjerai Jairoce, Angeline Marie Cruz, Alfons Jimenez, Rebeca Santano, Susana Mendez, Montserrat Lamoglia, Neus Rosell, Anna Llupia, Laura Puyol, Jordi Chi, Natalia Rodrigo, Daniel Parras, Pau Serra, Edwards Pradenas, Benjamin Trinite, Julia Blanco, Alfredo Mayor, Sonia Barroso, Pilar Varela, Anna Vilella, Antoni Trilla, Pere Santamaria, Carlo Carolis, Marta Tortajada, Luis Izquierdo, Ana Angulo, Pablo Engel, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobano. Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19. . 2021; ():1.
Chicago/Turabian StyleNatalia Ortega; Marta Ribes; Marta Vidal; Rocio Rubio; Ruth Aguilar; Sarah Williams; Diana Barrios; Selena Alonso; Pablo Hernandez-Luis; Robert Andrew Mitchell; Chenjerai Jairoce; Angeline Marie Cruz; Alfons Jimenez; Rebeca Santano; Susana Mendez; Montserrat Lamoglia; Neus Rosell; Anna Llupia; Laura Puyol; Jordi Chi; Natalia Rodrigo; Daniel Parras; Pau Serra; Edwards Pradenas; Benjamin Trinite; Julia Blanco; Alfredo Mayor; Sonia Barroso; Pilar Varela; Anna Vilella; Antoni Trilla; Pere Santamaria; Carlo Carolis; Marta Tortajada; Luis Izquierdo; Ana Angulo; Pablo Engel; Alberto L. García-Basteiro; Gemma Moncunill; Carlota Dobano. 2021. "Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19." , no. : 1.
Summary Background Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes. Methods We conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. IgG antibody titer was evaluated by ELISA against the S2 subunit, the receptor binding domain (RBD), and the nucleoprotein (NP). Statistical analyses were carried out using mixed-effects models. Findings We found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity, which persisted 6 months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a 2-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at 6 months remained higher among hospitalized individuals compared to mild symptomatic. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of anti-RBD, S2, or NP antibody titers, all of them showing a constant decline over the follow-up period. Conclusions Our results reinforce the hypothesis that the quality of the neutralizing immune response against SARS-CoV-2 evolves over the post-convalescent stage. Funding This study was funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (grant nos. SLD016 to J.B. and SLD015 to J.C.), the Spanish Health Institute Carlos III (grant nos. PI17/01518 and PI18/01332 to J.C.), CERCA Programme/Generalitat de Catalunya 2017 SGR 252, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat, and Correos. The funders had no role in the study design, the data collection and analysis, the decision to publish, or the preparation of the manuscript. E.P. was supported by a doctoral grant from the National Agency for Research and Development of Chile (ANID; 72180406). C.A.-N. was supported by a doctoral grant from Generalitat de Catalunya and Fons Social Europeu (FI). S.P.-Y. was supported by Fundación Canaria Doctor Manuel Morales and Universidad de La Laguna.
Edwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Carlos Ávila-Nieto; María Luisa Rodríguez de la Concepción; Ferran Tarrés-Freixas; Silvia Pérez-Yanes; Carla Rovirosa; Erola Ainsua-Enrich; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Roger Paredes; Lourdes Mateu; Anna Chamorro; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes. Med 2021, 2, 313 -320.e4.
AMA StyleEdwards Pradenas, Benjamin Trinité, Víctor Urrea, Silvia Marfil, Carlos Ávila-Nieto, María Luisa Rodríguez de la Concepción, Ferran Tarrés-Freixas, Silvia Pérez-Yanes, Carla Rovirosa, Erola Ainsua-Enrich, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Alfonso Valencia, Nuria Izquierdo-Useros, Roger Paredes, Lourdes Mateu, Anna Chamorro, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes. Med. 2021; 2 (3):313-320.e4.
Chicago/Turabian StyleEdwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Carlos Ávila-Nieto; María Luisa Rodríguez de la Concepción; Ferran Tarrés-Freixas; Silvia Pérez-Yanes; Carla Rovirosa; Erola Ainsua-Enrich; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Roger Paredes; Lourdes Mateu; Anna Chamorro; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2021. "Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes." Med 2, no. 3: 313-320.e4.
The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection.
Benjamin Trinité; Ferran Tarrés-Freixas; Jordi Rodon; Edwards Pradenas; Víctor Urrea; Silvia Marfil; María Luisa Rodríguez de la Concepción; Carlos Ávila-Nieto; Carmen Aguilar-Gurrieri; Ana Barajas; Raquel Ortiz; Roger Paredes; Lourdes Mateu; Alfonso Valencia; Víctor Guallar; Lidia Ruiz; Eulàlia Grau; Marta Massanella; Jordi Puig; Anna Chamorro; Nuria Izquierdo-Useros; Joaquim Segalés; Bonaventura Clotet; Jorge Carrillo; Júlia Vergara-Alert; Julià Blanco. SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity. Scientific Reports 2021, 11, 1 -10.
AMA StyleBenjamin Trinité, Ferran Tarrés-Freixas, Jordi Rodon, Edwards Pradenas, Víctor Urrea, Silvia Marfil, María Luisa Rodríguez de la Concepción, Carlos Ávila-Nieto, Carmen Aguilar-Gurrieri, Ana Barajas, Raquel Ortiz, Roger Paredes, Lourdes Mateu, Alfonso Valencia, Víctor Guallar, Lidia Ruiz, Eulàlia Grau, Marta Massanella, Jordi Puig, Anna Chamorro, Nuria Izquierdo-Useros, Joaquim Segalés, Bonaventura Clotet, Jorge Carrillo, Júlia Vergara-Alert, Julià Blanco. SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity. Scientific Reports. 2021; 11 (1):1-10.
Chicago/Turabian StyleBenjamin Trinité; Ferran Tarrés-Freixas; Jordi Rodon; Edwards Pradenas; Víctor Urrea; Silvia Marfil; María Luisa Rodríguez de la Concepción; Carlos Ávila-Nieto; Carmen Aguilar-Gurrieri; Ana Barajas; Raquel Ortiz; Roger Paredes; Lourdes Mateu; Alfonso Valencia; Víctor Guallar; Lidia Ruiz; Eulàlia Grau; Marta Massanella; Jordi Puig; Anna Chamorro; Nuria Izquierdo-Useros; Joaquim Segalés; Bonaventura Clotet; Jorge Carrillo; Júlia Vergara-Alert; Julià Blanco. 2021. "SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity." Scientific Reports 11, no. 1: 1-10.
Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.
Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Jorge Carrillo; Julià Blanco; Bonaventura Clotet; Nuria Izquierdo-Useros. SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus. Membranes 2021, 11, 64 .
AMA StyleJordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Jorge Carrillo, Julià Blanco, Bonaventura Clotet, Nuria Izquierdo-Useros. SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus. Membranes. 2021; 11 (1):64.
Chicago/Turabian StyleJordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Jorge Carrillo; Julià Blanco; Bonaventura Clotet; Nuria Izquierdo-Useros. 2021. "SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus." Membranes 11, no. 1: 64.
Primary HIV infection (PHI) and subsequent chronic infection alter B-cell compartment. However, longitudinal analysis defining the dynamics of B-cell alterations are still limited. We longitudinally studied B-cell subsets in individuals followed for 1 year after PHI (n = 40). Treated and untreated chronic HIV infected (n = 56) and HIV-uninfected individuals (n = 58) were recruited as reference groups at the Manhiça District in Mozambique. B cells were analyzed by multicolor flow-cytometry. Anti-HIV humoral response and plasma cytokines were assessed by ELISA or Luminex-based technology. A generalized activation of B cells induced by HIV occurs early after infection and is characterized by increases in Activated and Tissue-like memory cells, decreases in IgM-IgD- (switched) and IgM-only B cells. These alterations remain mostly stable until chronic infection and are reverted in part by ART. In contrast, other parameters followed particular dynamics: PD-1 expression in memory cells decreases progressively during the first year of infection, Transitional B cells expand at month 3–4 after infection, and Marginal zone-like B cells show a late depletion. Plasmablasts expand 2 months after infection linked to plasma viral load and anti-p24 IgG3 responses. Most of well-defined changes induced by HIV in B-cell activation and memory subsets are readily observed after PHI, lasting until ART initiation. However, subsequent changes occur after sustained viral infection. These data indicate that HIV infection impacts B cells in several waves over time, and highlight that early treatment would result in beneficial effects on the B-cell compartment.
Montse Jiménez; Lucía Pastor; Victor Urrea; María Luisa Rodríguez de la Concepción; Erica Parker; Laura Fuente-Soro; Chenjerai Jairoce; Inacio Mandomando; Jorge Carrillo; Denise Naniche; Julià Blanco. A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults. Frontiers in Immunology 2021, 11, 1 .
AMA StyleMontse Jiménez, Lucía Pastor, Victor Urrea, María Luisa Rodríguez de la Concepción, Erica Parker, Laura Fuente-Soro, Chenjerai Jairoce, Inacio Mandomando, Jorge Carrillo, Denise Naniche, Julià Blanco. A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults. Frontiers in Immunology. 2021; 11 ():1.
Chicago/Turabian StyleMontse Jiménez; Lucía Pastor; Victor Urrea; María Luisa Rodríguez de la Concepción; Erica Parker; Laura Fuente-Soro; Chenjerai Jairoce; Inacio Mandomando; Jorge Carrillo; Denise Naniche; Julià Blanco. 2021. "A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults." Frontiers in Immunology 11, no. : 1.
Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, thus losing sight of the temporal pattern of these changes1–6. In this longitudinal analysis, conducted on a prospective cohort of COVID-19 patients followed up to 242 days, we found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity that persisted six months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a two-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at six months remained higher among hospitalized individuals. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of antibody titers change, reinforcing the hypothesis that the quality of immune response evolves over the post-convalescent stage4,5.
Edwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Carlos Ávila-Nieto; María Luisa Rodríguez De La Concepción; Ferran Tarrés-Freixas; Silvia Pérez-Yanes; Carla Rovirosa; Erola Ainsua-Enrich; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Roger Paredes; Lourdes Mateu; Anna Chamorro; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Stable neutralizing antibody levels six months after mild and severe COVID-19 episode. 2020, 1 .
AMA StyleEdwards Pradenas, Benjamin Trinité, Víctor Urrea, Silvia Marfil, Carlos Ávila-Nieto, María Luisa Rodríguez De La Concepción, Ferran Tarrés-Freixas, Silvia Pérez-Yanes, Carla Rovirosa, Erola Ainsua-Enrich, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Alfonso Valencia, Nuria Izquierdo-Useros, Roger Paredes, Lourdes Mateu, Anna Chamorro, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Stable neutralizing antibody levels six months after mild and severe COVID-19 episode. . 2020; ():1.
Chicago/Turabian StyleEdwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Carlos Ávila-Nieto; María Luisa Rodríguez De La Concepción; Ferran Tarrés-Freixas; Silvia Pérez-Yanes; Carla Rovirosa; Erola Ainsua-Enrich; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Roger Paredes; Lourdes Mateu; Anna Chamorro; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2020. "Stable neutralizing antibody levels six months after mild and severe COVID-19 episode." , no. : 1.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmune disorder characterized by numerous symptoms of unknown etiology. The ME/CFS immune markers reported so far have failed to generate a clinical consensus, perhaps partly due to the limitations of biospecimen biobanking. To address this issue, we performed a comparative analysis of the impact of long-term biobanking on previously identified immune markers and also explored additional potential immune markers linked to infection in ME/CFS. A correlation analysis of marker cryostability across immune cell subsets based on flow cytometry immunophenotyping of fresh blood and frozen PBMC samples collected from individuals with ME/CFS (n = 18) and matched healthy controls (n = 18) was performed. The functionality of biobanked samples was assessed on the basis of cytokine production assay after stimulation of frozen PBMCs. T cell markers defining Treg subsets and the expression of surface glycoprotein CD56 in T cells and the frequency of the effector CD8 T cells, together with CD57 expression in NK cells, appeared unaltered by biobanking. By contrast, NK cell markers CD25 and CD69 were notably increased, and NKp46 expression markedly reduced, by long-term cryopreservation and thawing. Further exploration of Treg and NK cell subsets failed to identify significant differences between ME/CFS patients and healthy controls in terms of biobanked PBMCs. Our findings show that some of the previously identified immune markers in T and NK cell subsets become unstable after cell biobanking, thus limiting their use in further immunophenotyping studies for ME/CFS. These data are potentially relevant for future multisite intervention studies and cooperative projects for biomarker discovery using ME/CFS biobanked samples. Further studies are needed to develop novel tools for the assessment of biomarker stability in cryopreserved immune cells from people with ME/CFS.
Elisabet Gómez-Mora; Jorge Carrillo; Víctor Urrea; Josepa Rigau; José Alegre; Cecilia Cabrera; Elisa Oltra; Jesús Castro-Marrero; Julià Blanco. Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Biomarker Discovery. Frontiers in Immunology 2020, 11, 1 .
AMA StyleElisabet Gómez-Mora, Jorge Carrillo, Víctor Urrea, Josepa Rigau, José Alegre, Cecilia Cabrera, Elisa Oltra, Jesús Castro-Marrero, Julià Blanco. Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Biomarker Discovery. Frontiers in Immunology. 2020; 11 ():1.
Chicago/Turabian StyleElisabet Gómez-Mora; Jorge Carrillo; Víctor Urrea; Josepa Rigau; José Alegre; Cecilia Cabrera; Elisa Oltra; Jesús Castro-Marrero; Julià Blanco. 2020. "Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Biomarker Discovery." Frontiers in Immunology 11, no. : 1.
The magnitude and the quality of humoral responses against SARS-CoV-2 have been associated with clinical outcome. Although the elicitation of humoral responses against different viral proteins is rapid and occurs in most infected individuals, its magnitude is highly variable among them and positively correlates with COVID-19 disease severity. This rapid response is characterized by the almost concomitant appearance of virus-specific IgG, IgA and IgM antibodies that contain neutralizing antibodies directed against different epitopes of the Spike glycoprotein. Of particularly interest, the antibodies against domain of the Spike that interacts with the cellular receptor ACE2, known as the receptor binding domain (RBD), are present in most infected individuals and are block viral entry and infectivity. Such neutralizing antibodies protect different animal species when administered before virus exposure; therefore, its elicitation is the main target of current vaccine approaches and their clinical use as recombinant monoclonal antibodies (mAbs) is being explored. Yet, little information exists on the duration of humoral responses during natural infection. This is a key issue that will impact the management of the pandemic and determine the utility of seroconversion studies and the level of herd immunity. Certainly, several cases of reinfection have been reported, suggesting that immunity could be transient, as reported for other coronaviruses. In summary, although the kinetics of the generation of antibodies against SASR-CoV-2 and their protective activity have been clearly defined, their role in COVID-19 pathogenesis and the length of these responses are still open questions.
Jorge Carrillo; Nuria Izquierdo-Useros; Carlos Ávila-Nieto; Edwards Pradenas; Bonaventura Clotet; Julià Blanco. Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Biochemical and Biophysical Research Communications 2020, 538, 187 -191.
AMA StyleJorge Carrillo, Nuria Izquierdo-Useros, Carlos Ávila-Nieto, Edwards Pradenas, Bonaventura Clotet, Julià Blanco. Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Biochemical and Biophysical Research Communications. 2020; 538 ():187-191.
Chicago/Turabian StyleJorge Carrillo; Nuria Izquierdo-Useros; Carlos Ávila-Nieto; Edwards Pradenas; Bonaventura Clotet; Julià Blanco. 2020. "Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity." Biochemical and Biophysical Research Communications 538, no. : 187-191.
Human Immunodeficiency Virus 1 (HIV-1) evades adaptive immunity by means of its extremely high mutation rate, which allows the HIV envelope glycoprotein to continuously escape from the action of antibodies. However, some broadly neutralizing antibodies (bNAbs) targeting specific viral regions show the ability to block the infectivity of a large number of viral variants. The discovery of these antibodies opens new avenues in anti-HIV therapy; however, they are still suboptimal tools as their amplitude of action ranges between 50% and 90% of viral variants. In this context, being able to discriminate between sensitive and resistant strains to an antibody would be of great interest for the design of optimal clinical antibody treatments and to engineer potent bNAbs for clinical use. Here, we describe a hierarchical procedure to predict the antibody neutralization efficacy of multiple viral isolates to three well-known anti-CD4bs bNAbs: VRC01, NIH45-46 and 3BNC117. Our method consists of simulating the three-dimensional binding process between the gp120 and the antibody by using Protein Energy Landscape Exploration (PELE), a Monte Carlo stochastic approach. Our results clearly indicate that the binding profiles of sensitive and resistant strains to a bNAb behave differently, showing the latter’s weaker binding profiles, that can be exploited for predicting antibody neutralization efficacy in hypermutated HIV-1 strains.
Pep Amengual-Rigo; Jorge Carrillo; Julià Blanco; Victor Guallar. Predicting Antibody Neutralization Efficacy in Hypermutated Epitopes Using Monte Carlo Simulations. Polymers 2020, 12, 2392 .
AMA StylePep Amengual-Rigo, Jorge Carrillo, Julià Blanco, Victor Guallar. Predicting Antibody Neutralization Efficacy in Hypermutated Epitopes Using Monte Carlo Simulations. Polymers. 2020; 12 (10):2392.
Chicago/Turabian StylePep Amengual-Rigo; Jorge Carrillo; Julià Blanco; Victor Guallar. 2020. "Predicting Antibody Neutralization Efficacy in Hypermutated Epitopes Using Monte Carlo Simulations." Polymers 12, no. 10: 2392.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs of the cat prompted humanitarian euthanasia and a detailed postmortem investigation to assess whether a COVID-19−like disease was causing the condition. Necropsy results showed the animal suffered from feline hypertrophic cardiomyopathy and severe pulmonary edema and thrombosis. SARS-CoV-2 RNA was only detected in nasal swab, nasal turbinates, and mesenteric lymph node, but no evidence of histopathological lesions compatible with a viral infection were detected. The cat seroconverted against SARS-CoV-2, further evidencing a productive infection in this animal. We conclude that the animal had a subclinical SARS-CoV-2 infection concomitant to an unrelated cardiomyopathy that led to euthanasia.
Joaquim Segalés; Mariona Puig; Jordi Rodon; Carlos Avila-Nieto; Jorge Carrillo; Guillermo Cantero; Maria Teresa Terrón; Sílvia Cruz; Mariona Parera; Marc Noguera-Julián; Nuria Izquierdo-Useros; Víctor Guallar; Enric Vidal; Alfonso Valencia; Ignacio Blanco; Julià Blanco; Bonaventura Clotet; Júlia Vergara-Alert. Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain. Proceedings of the National Academy of Sciences 2020, 117, 24790 -24793.
AMA StyleJoaquim Segalés, Mariona Puig, Jordi Rodon, Carlos Avila-Nieto, Jorge Carrillo, Guillermo Cantero, Maria Teresa Terrón, Sílvia Cruz, Mariona Parera, Marc Noguera-Julián, Nuria Izquierdo-Useros, Víctor Guallar, Enric Vidal, Alfonso Valencia, Ignacio Blanco, Julià Blanco, Bonaventura Clotet, Júlia Vergara-Alert. Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain. Proceedings of the National Academy of Sciences. 2020; 117 (40):24790-24793.
Chicago/Turabian StyleJoaquim Segalés; Mariona Puig; Jordi Rodon; Carlos Avila-Nieto; Jorge Carrillo; Guillermo Cantero; Maria Teresa Terrón; Sílvia Cruz; Mariona Parera; Marc Noguera-Julián; Nuria Izquierdo-Useros; Víctor Guallar; Enric Vidal; Alfonso Valencia; Ignacio Blanco; Julià Blanco; Bonaventura Clotet; Júlia Vergara-Alert. 2020. "Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain." Proceedings of the National Academy of Sciences 117, no. 40: 24790-24793.
GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure. The infection with the human immunodeficiency virus (HIV), as for other viral infections, induce global DNA Methylation changes in the host genome. Herein, we identified for first time the methylation impact on host genome in untreated HIV-1 infection with different degrees of in vivo virus control. Specifically, we observed that individuals with a better HIV-1 control showed a hypermethylation of genes associated with antiviral and interferon pathways and the hypomethylation of genes associated with the differentiation process of T follicular helper cells. Interestingly, these epigenetic imprints in host genome were strongly correlated with virus content and HIV-specific T cell responses. Therefore, we propose DNA Methylation as the regulation mechanism of host genes involved in immune HIV-1 control that could interfere in the efficacy of cure strategies. We also highlight the importance of DNA Methylation to regulate immune responses not only in HIV-1 but also in chronic infections or other pathologic situations associated with a sustained activation of the immune system.
Bruna Oriol-Tordera; Maria Berdasco; Anuska Llano; Beatriz Mothe; Cristina Gálvez; Javier Martinez-Picado; Jorge Carrillo; Julià Blanco; Clara Duran-Castells; Carmela Ganoza; Jorge Sanchez; Bonaventura Clotet; Maria Luz Calle; Alex Sánchez-Pla; Manel Esteller; Christian Brander; Marta Ruiz-Riol. Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control. PLOS Pathogens 2020, 16, e1008678 .
AMA StyleBruna Oriol-Tordera, Maria Berdasco, Anuska Llano, Beatriz Mothe, Cristina Gálvez, Javier Martinez-Picado, Jorge Carrillo, Julià Blanco, Clara Duran-Castells, Carmela Ganoza, Jorge Sanchez, Bonaventura Clotet, Maria Luz Calle, Alex Sánchez-Pla, Manel Esteller, Christian Brander, Marta Ruiz-Riol. Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control. PLOS Pathogens. 2020; 16 (8):e1008678.
Chicago/Turabian StyleBruna Oriol-Tordera; Maria Berdasco; Anuska Llano; Beatriz Mothe; Cristina Gálvez; Javier Martinez-Picado; Jorge Carrillo; Julià Blanco; Clara Duran-Castells; Carmela Ganoza; Jorge Sanchez; Bonaventura Clotet; Maria Luz Calle; Alex Sánchez-Pla; Manel Esteller; Christian Brander; Marta Ruiz-Riol. 2020. "Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control." PLOS Pathogens 16, no. 8: e1008678.
Progresses in human immunodeficiency virus type 1 (HIV-1) therapy have converted the once fatal infection into a chronic condition, yet the search for a widely applicable strategy to cure remains elusive. Individuals with HIV-1 infection have chronic antigenic immune stimulation and inflammation, even with low plasma HIV-1 RNA levels and preserved CD4+ counts, which contributes to increased incidence of non–AIDS-defining cancers,1 such that non–small cell lung cancer (NSCLC) is now the leading cause of cancer deaths in individuals receiving effective combination antiretroviral therapy (cART).2 During infection, HIV-1 is reverse transcribed and integrated as a provirus into the host genome. Although the vast majority of infected cells die with cART, a small percentage survive and harbor as integrated proviruses that comprise the latent reservoir.3
Maria Gonzalez-Cao; Teresa Morán; Judith Dalmau; Javier Garcia-Corbacho; Jillian W. P. Bracht; Reyes Bernabe; Oscar Juan; Javier De Castro; Remei Blanco; Ana Drozdowskyj; Jordi Argilaguet; Andreas Meyerhans; Julià Blanco; Julia G. Prado; Jorge Carrillo; Bonaventura Clotet; Bartomeu Massuti; Mariano Provencio; Miguel A. Molina-Vila; Clara Mayo De Las Casa; Monica Garzon; Peng Cao; Chung-Ying Huang; Javier Martinez-Picado; Rafael Rosell. Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection. JAMA Oncology 2020, 6, 1063 -1067.
AMA StyleMaria Gonzalez-Cao, Teresa Morán, Judith Dalmau, Javier Garcia-Corbacho, Jillian W. P. Bracht, Reyes Bernabe, Oscar Juan, Javier De Castro, Remei Blanco, Ana Drozdowskyj, Jordi Argilaguet, Andreas Meyerhans, Julià Blanco, Julia G. Prado, Jorge Carrillo, Bonaventura Clotet, Bartomeu Massuti, Mariano Provencio, Miguel A. Molina-Vila, Clara Mayo De Las Casa, Monica Garzon, Peng Cao, Chung-Ying Huang, Javier Martinez-Picado, Rafael Rosell. Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection. JAMA Oncology. 2020; 6 (7):1063-1067.
Chicago/Turabian StyleMaria Gonzalez-Cao; Teresa Morán; Judith Dalmau; Javier Garcia-Corbacho; Jillian W. P. Bracht; Reyes Bernabe; Oscar Juan; Javier De Castro; Remei Blanco; Ana Drozdowskyj; Jordi Argilaguet; Andreas Meyerhans; Julià Blanco; Julia G. Prado; Jorge Carrillo; Bonaventura Clotet; Bartomeu Massuti; Mariano Provencio; Miguel A. Molina-Vila; Clara Mayo De Las Casa; Monica Garzon; Peng Cao; Chung-Ying Huang; Javier Martinez-Picado; Rafael Rosell. 2020. "Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection." JAMA Oncology 6, no. 7: 1063-1067.
Background The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells and are under clinical trial development. However, the optimisation and standardisation of neoantigen identification, as well as its delivery as immunotherapy are needed to increase tumour-specific T-cell responses and, thus, the clinical efficacy of current cancer immunotherapies. Methods In this recommendation article, launched by the European Society for Medical Oncology (ESMO), we outline and discuss the available framework for neoantigen prediction and present a systematic review of the current scientific evidence. Results A number of computational pipelines for neoantigen prediction are available. Most of them provide peptide major histocompatibility complex (MHC) binding affinity predictions, but more recent approaches incorporate additional features like variant allele fraction, gene expression, and clonality of mutations. Neoantigens can be predicted in all cancer types with high and low tumour mutation burden, in part by exploiting tumour-specific aberrations derived from mutational frameshifts, splice variants, gene fusions, endogenous retroelements and other tumour-specific processes that could yield more potently immunogenic tumour neoantigens. Ongoing clinical trials will highlight those cancer types and combinations of immune therapies that would derive the most benefit from neoantigen-based immunotherapies. Conclusions Improved identification, selection and prioritisation of tumour-specific neoantigens are needed to increase the scope of benefit from cancer vaccines and adoptive T-cell therapies. Novel pipelines are being developed to resolve the challenges posed by high-throughput sequencing and to predict immunogenic neoantigens.
L. De Mattos-Arruda; M. Vazquez; F. Finotello; R. Lepore; E. Porta; J. Hundal; P. Amengual-Rigo; C.K.Y. Ng; A. Valencia; J. Carrillo; T.A. Chan; V. Guallar; N. McGranahan; J. Blanco; M. Griffith. Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group. Annals of Oncology 2020, 31, 978 -990.
AMA StyleL. De Mattos-Arruda, M. Vazquez, F. Finotello, R. Lepore, E. Porta, J. Hundal, P. Amengual-Rigo, C.K.Y. Ng, A. Valencia, J. Carrillo, T.A. Chan, V. Guallar, N. McGranahan, J. Blanco, M. Griffith. Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group. Annals of Oncology. 2020; 31 (8):978-990.
Chicago/Turabian StyleL. De Mattos-Arruda; M. Vazquez; F. Finotello; R. Lepore; E. Porta; J. Hundal; P. Amengual-Rigo; C.K.Y. Ng; A. Valencia; J. Carrillo; T.A. Chan; V. Guallar; N. McGranahan; J. Blanco; M. Griffith. 2020. "Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group." Annals of Oncology 31, no. 8: 978-990.
Background Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV+ individuals could naturally also harbour low viral reservoirs. Methods We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with 50 HIV-DNA copies/106 PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers. Findings We found that 9.3% of the individuals screened had <50 HIV-DNA copies/106 PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8+ TTM and TEMRA in the absence of cART, and higher CD8+ TN after 18 months on therapy. Interpretation Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8+ T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies. Funding MSD Spain
Cristina Gálvez; Victor Urrea; Judith Dalmau; Montse Jimenez; Bonaventura Clotet; Valérie Monceaux; Nicolas Huot; Lorna Leal; Victoria González-Soler; Maria González-Cao; Michaela Müller-Trutwin; Asier Sáez-Cirión; Felipe García; Julià Blanco; Javier Martinez-Picado; Maria Salgado. Extremely low viral reservoir in treated chronically HIV-1-infected individuals. EBioMedicine 2020, 57, 102830 .
AMA StyleCristina Gálvez, Victor Urrea, Judith Dalmau, Montse Jimenez, Bonaventura Clotet, Valérie Monceaux, Nicolas Huot, Lorna Leal, Victoria González-Soler, Maria González-Cao, Michaela Müller-Trutwin, Asier Sáez-Cirión, Felipe García, Julià Blanco, Javier Martinez-Picado, Maria Salgado. Extremely low viral reservoir in treated chronically HIV-1-infected individuals. EBioMedicine. 2020; 57 ():102830.
Chicago/Turabian StyleCristina Gálvez; Victor Urrea; Judith Dalmau; Montse Jimenez; Bonaventura Clotet; Valérie Monceaux; Nicolas Huot; Lorna Leal; Victoria González-Soler; Maria González-Cao; Michaela Müller-Trutwin; Asier Sáez-Cirión; Felipe García; Julià Blanco; Javier Martinez-Picado; Maria Salgado. 2020. "Extremely low viral reservoir in treated chronically HIV-1-infected individuals." EBioMedicine 57, no. : 102830.