Sergio Serrano-Villar
@irycis.org
Physician-Scientist. Department of Infectious Diseasees
Hospital Universitario Ramon y Cajal
RESEARCH INTERESTS
Microbiome, inflammation, HIV, cancer, COVID19
Immunopathogenesis, translational studies, clinical trials, epidemiological research.
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Raquel Ron, Elena Moreno, Marta Rosas Cancio-Suárez, and Sergio Serrano-Villar
Ovid Technologies (Wolters Kluwer Health)
Purpose of review Early detection and treatment of human papillomavirus (HPV)-related anal dysplasia in some high-risk groups can help anal cancer prevention, but new tools to improve diagnostic and risk assessment are needed. Here, we aim to discuss the evidence on the role of the microbiome as a potential biomarker for anal high-grade squamous intraepithelial lesions (HSILs) in people with HIV (PWH). Recent findings This review covers relevant studies on the links between the microbiome and HPV infection, cervical dysplasia/cancer, and anal HPV disease. It focuses on anal samples and precancerous lesions. Summary The review highlights the promising potential of the anal microbiome as a novel biomarker for precancerous lesions in people with HIV, while also discussing limitations and future research needs.
Raquel Ron, Javier Martínez-Sanz, Sabina Herrera, Luis Ramos-Ruperto, Alejandro Díez-Vidal, Talía Sainz, Noelia Álvarez-Díaz, Andrea Correa-Pérez, Alfonso Muriel, Jesús López-Alcalde,et al.
Frontiers Media SA
Raquel Ron, Javier Martínez-Sanz, Sabina Herrera, Luis Ramos-Ruperto, Alejandro Díez-Vidal, Talía Sainz, Noelia Álvarez-Díaz, Andrea Correa-Pérez, Alfonso Muriel, Jesús López-Alcalde,et al.
Frontiers Media SA
BackgroundIn people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial.MethodsWe conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, and reporting CD4/CD8 ratio or CD8+ counts. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5. (CRD42020170931).FindingsWe identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher mortality risk (OR 3.65; 95% CI 3.04 - 4.35; I2 = 0.00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term.ConclusionsOur results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0.5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.
Sergio Serrano-Villar, Camilla Tincati, Sajan C. Raju, Johan S. Sáenz, Elena Moreno, Rafael Bargiela, Alfonso Cabello-Ubeda, Elena Sendagorta, Alina Kurz, Jose A. Perez Molina,et al.
Springer Science and Business Media LLC
Oihane E. Albóniga, Elena Moreno, Javier Martínez-Sanz, Pilar Vizcarra, Raquel Ron, Jorge Díaz-Álvarez, Marta Rosas Cancio-Suarez, Matilde Sánchez-Conde, Juan Carlos Galán, Santiago Angulo,et al.
Springer Science and Business Media LLC
Elena Moreno, Javier Martínez-Sanz, Rosa Martín-Mateos, Jorge Díaz-Álvarez, Sergio Serrano-Villar, Diego Burgos-Santamaría, Laura Luna, María Jesús Vivancos, Ana Moreno-Zamora, María Jesús Pérez-Elías,et al.
Springer Science and Business Media LLC
AbstractMetabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.
Oihane E. Albóniga, Elena Moreno, Javier Martínez-Sanz, Pilar Vizcarra, Raquel Ron, Jorge Díaz-Álvarez, Marta Rosas, Matilde Sánchez-Conde, Juan Carlos Galán, Santiago Angulo,et al.
Springer Science and Business Media LLC
AbstractThe mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. To understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. We collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected (‘non-susceptible’) and subjects who became infected during the follow-up (‘susceptible’), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. We show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. This study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.
Erick De La Torre Tarazona, Daniel Jiménez, Daniel Marcos-Mencía, Alejandro Mendieta-Baro, Alejandro Rivera-Delgado, Beatriz Romero-Hernández, Alfonso Muriel, Mario Rodríguez-Domínguez, Sergio Serrano-Villar, and Santiago Moreno
MDPI AG
The susceptibility to SARS-CoV-2 infection and the severity of COVID-19 manifestations vary significantly among individuals, prompting the need for a deeper understanding of the disease. Our objective in this study was to investigate whether previous infections with human common cold coronaviruses (hCCCoV) might impact susceptibility to and the progression of SARS-CoV-2 infections. We assessed the serum antibody levels against SARS-CoV-2 and four hCCCoV (H-CoV-OC43, -NL63, -HKU1, and -229E) in three distinct populations: 95 uninfected individuals (COVID-19-negative), 83 individuals with mild or asymptomatic COVID-19 (COVID-19-mild), and 45 patients who died due to COVID-19 (COVID-19-severe). The first two groups were matched in terms of their exposure to SARS-CoV-2. We did not observe any differences in the mean antibody levels between the COVID-19-mild and the COVID-19-negative participants. However, individuals in the COVID-19-mild group exhibited a higher frequency of antibody levels (sample/control) > 0.5 against H-CoV-HKU1, and >1 against H-CoV-229E and -OC43 (p < 0.05). In terms of severity, we noted significantly elevated H-CoV-NL63 IgG levels in the COVID-19-severe group compared to the other groups (p < 0.01). Our findings suggest a potential mild influence of hCCCoV antibody levels on the susceptibility to SARS-CoV-2 infection and the severity of COVID-19. These observations could aid in the development of strategies for predicting and mitigating the severity of COVID-19.
Javier Martínez-Sanz, Jorge Díaz-Álvarez, Marta Rosas Cancio-Suarez, Raquel Ron, José Antonio Iribarren, Enrique Bernal, Félix Gutiérrez, Andrés Ruiz Sancho, Noemi Cabello, Julián Olalla,et al.
Elsevier BV
José A. Pérez-Molina, Clara Crespillo-Andújar, Elena Trigo, Sandra Chamorro, Marta Arsuaga, Leticia Olavarrieta, Beatriz Navia, Oihane Martín, Begoña Monge-Maillo, Francesca F. Norman,et al.
Public Library of Science (PLoS)
Background The implications of the gut microbial communities in the immune response against parasites and gut motility could explain the differences in clinical manifestations and treatment responses found in patients with chronic Chagas disease. Methodology/Principal findings In this pilot prospective cross-sectional study, we included 80 participants: 29 with indeterminate CD (ICD), 16 with cardiac CD (CCD), 15 with digestive CD (DCD), and 20 controls without CD. Stool was collected at the baseline visit and faecal microbial community structure DNA was analyzed by whole genome sequencing. We also performed a comprehensive dietary analysis. Ninety per cent (72/80) of subjects were of Bolivian origin with a median age of 47 years (IQR 39–54) and 48.3% (29/60) had received benznidazole treatment. There were no substantial differences in dietary habits between patients with CD and controls. We identified that the presence or absence of CD explained 5% of the observed microbiota variability. Subjects with CD exhibited consistent enrichment of Parabacteroides spp, while for Enterococcus hirae, Lactobacillus buchneri and Megamonas spp, the effect was less clear once excluded the outliers values. Sex, type of visceral involvement and previous treatment with benznidazole did not appear to have a confounding effect on gut microbiota structure. We also found that patients with DCD showed consistent Prevotella spp enrichment. Conclusions We found a detectable effect of Chagas disease on overall microbiota structure with several potential disease biomarkers, which warrants further research in this field. The analysis of bacterial diversity could prove to be a viable target to improve the prognosis of this prevalent and neglected disease.
Marta Rosas Cancio-Suárez, Jorge Díaz-Álvarez, Raquel Ron, Javier Martínez-Sanz, Sergio Serrano-Villar, Santiago Moreno, and Matilde Sánchez-Conde
MDPI AG
Pre-exposure prophylaxis (PrEP) is a highly effective HIV-prevention strategy that involves the continuous administration of antiretroviral drugs to HIV-negative individuals with a substantial risk of contracting an HIV infection. The use of PrEP has shown a reduction in the risk of HIV acquisition through sexual intercourse by up to 99%. Despite its effectiveness, PrEP uptake remains low among populations at high risk of HIV infection. This highlights the need for further research in strategies to enhance awareness and uptake of PrEP amongst these specific populations. This article presents a comprehensive overview of the existing literature on the effectiveness of PrEP in reducing HIV transmission rates. Additionally, we examine the obstacles related to PrEP implementation and uptake and put forward potential strategies to raise awareness and improve its use among populations at an increased risk of contracting HIV.
Sergio Serrano-Villar, Camilla Tincati, Sajan C. Raju, Johan S. Sáenz, Elena Moreno, Rafael Bargiela, Alfonso Cabello-Ubeda, Elena Sendagorta, Alina Kurz, Jose A. Perez Molina,et al.
Springer Science and Business Media LLC
Christina K. Psomas, Sergio Serrano-Villar, Benoit Guery, Philippe Halfon, and Giulia Marchetti
Elsevier BV
Oscar M. Moreno-Arrones, Carlota Garcia-Hoz, Rosa del Campo, Garbiñe Roy, David Saceda-Corralo, Juan Jimenez-Cauhe, Manuel Ponce-Alonso, Sergio Serrano-Villar, Pedro Jaen, John Paoli,et al.
S. Karger AG
<b><i>Background:</i></b> Folliculitis decalvans (FD) is a rare primary neutrophilic scarring alopecia whose etiology has not been completely elucidated yet. <b><i>Objective:</i></b> The aim of the study was to determine if the follicular microbiota residing in FD-affected hair follicles had a distinct microbiological signature and if an aberrant immune response was present in the pathogenesis of FD. <b><i>Methods:</i></b> We conducted a cross-sectional study of 10 patients affected by FD. Trichoscopy-guided follicular biopsies were taken from affected and healthy scalp to identify the follicular microbiome using next-generation sequencing. We searched for microbiological biomarkers of FD-affected follicles using the linear discriminant analysis (LDA) effect size (LEfSe) tool. Additionally, peripheral blood mononuclear cells were obtained, and their cytokine production was quantified after incubation with pathogen-associated molecular patterns isolated from patients’ biopsies and compared with healthy controls. <b><i>Results:</i></b> β-diversity analysis showed statistically significant differences regarding bacteria comparing follicular microbiota of healthy and FD-affected hairs. Ruminococcaceae, <i>Agathobacter</i> sp., <i>Tyzzerella</i> sp., and Bacteriodales vadin HA21 family were good predictors of disease status. IL-10, TNF-α, and IL-6 levels were significantly decreased in patients after incubation with various strains of bacteria compared with controls. <b><i>Conclusion:</i></b> FD hair follicles have a specific heterogenous follicular bacterial microbiota signature. Additionally, these patients seem to have an impaired immunological response.
Jose A Perez-Molina, Clara Crespillo-Andújar, Javier Zamora, Borja M Fernández-Félix, Andrea Gaetano-Gil, Juan C López-Bernaldo de Quirós, Sergio Serrano-Villar, Santiago Moreno, Noelia Álvarez-Díaz, and Juan Berenguer
Oxford University Press (OUP)
Abstract We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or &gt;200 CD4/μL) or VL (≤ or &gt;100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45–2.61 and OR, 1.75; 95% CI: 1.30–2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 &lt;200 cells/μL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.
Jose R Castillo-Mancilla, Mary Morrow, Peter W Hunt, Samuel R Schnittman, Andrew N Phillips, Jason V Baker, Jessica E Haberer, Maria Joao Janeiro, Filipa Aragao, Cal Cohen,et al.
Oxford University Press (OUP)
Abstract Background Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (&lt;50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown. Methods We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to &lt;100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up. Results Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6%–37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to &lt;100% for an additional event to occur over 3- and 5-year follow-up, respectively. Conclusions Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (eg, via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated.
Raquel Ron, Elena Moreno, Javier Martínez-Sanz, Fátima Brañas, Talía Sainz, Santiago Moreno, and Sergio Serrano-Villar
Oxford University Press (OUP)
Abstract In the last decade, studies in persons with HIV (PWH) on antiretroviral therapy (ART) have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low CD4/CD8 ratio reflects increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of the CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cutoff points, associated clinical events, effects of treatments, and how the CD4/CD8 ratio could improve decision making in the clinic. Here, we critically review the literature, identify knowledge gaps, and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.
Javier Martínez-Sanz, Sergio Serrano-Villar, Alfonso Muriel, Lucio J García Fraile, Eva Orviz, Álvaro Mena de Cea, Antoni A Campins, and Santiago Moreno
Oxford University Press (OUP)
Abstract Background Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. Methods Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with human immunodeficiency virus (HIV) receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Participants were matched by propensity score. We fitted generalized equation models to assess changes in weight, blood lipids, and hepatic steatosis index, and to compare the incidence of diabetes, hypertension, and lipid-lowering drug use after 144 weeks. Results In total, 1446 participants were matched in each group. Median age was 38 years, 85% were male, mean weight at baseline was 73 kg. Participants who switched to TAF had a mean weight increase of +0.5 kg at 144 weeks over those who maintained TDF, with no difference in the occurrence of overweight or obesity. Individuals who switched to TAF had a significant increase in total cholesterol (+7.9 mg/dL) and triglycerides (+11.2 mg/dL), with no differences in the total cholesterol-high-density lipoprotein (HDL) ratio. However, no increased incidence of diabetes, hypertension, or lipid-lowering drug use was observed after the follow-up period. Conclusions Switching from TDF to TAF is associated with modest weight gain and increases in total cholesterol and triglycerides, without an impact on the incidence of obesity or metabolic-related clinical events, in this Spanish cohort with a majority White male population.
Elena Moreno, Raquel Ron, and Sergio Serrano-Villar
Frontiers Media SA
Although the microbiota has largely been associated with the pathogenesis of viral infections, most studies using omics techniques are correlational and hypothesis-generating. The mechanisms affecting the immune responses to viral infections are still being fully understood. Here we focus on the two most important sexually transmitted persistent viruses, HPV and HIV. Sophisticated omics techniques are boosting our ability to understand microbiota-pathogen-host interactions from a functional perspective by surveying the host and bacterial protein and metabolite production using systems biology approaches. However, while these strategies have allowed describing interaction networks to identify potential novel microbiota-associated biomarkers or therapeutic targets to prevent or treat infectious diseases, the analyses are typically based on highly dimensional datasets —thousands of features in small cohorts of patients—. As a result, we are far from getting to their clinical use. Here we provide a broad overview of how the microbiota influences the immune responses to HIV and HPV disease. Furthermore, we highlight experimental approaches to understand better the microbiota-host-virus interactions that might increase our potential to identify biomarkers and therapeutic agents with clinical applications.
Javier Martínez-Sanz, Alba Talavera-Rodríguez, Jorge Díaz-Álvarez, Marta Rosas Cancio-Suárez, Juan Miguel Rodríguez, Claudio Alba, María Luisa Montes, Rosa Martín-Mateos, Diego Burgos-Santamaría, Santiago Moreno,et al.
Frontiers Media SA
IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection.MethodsWe collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe).ResultsWe included 30 HIV+MASLD+, 30 HIV+MASLD- and 20 HIV-MASLD+ participants. Major butyrate producers, including Faecalibacterium, Ruminococcus, and Lachnospira dominated the microbiota in all three groups. Shannon’s and Simpson’s diversity metrics were higher among MASLD+ individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD-, with MASLD+ participants overlapping regardless of HIV status (ADONIS significance &lt;0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value &lt;0.001; ANOSIM, p value &lt;0.001). MASLD but not HIV determined a different microbiota structure (HIV+MASLD- vs. HIV+MASLD+, q-value = 0.002; HIV-MASLD+ vs. HIV+MASLD+, q-value = 0.930; and HIV-MASLD+ vs. HIV+MASLD-, q-value &lt; 0.001). The most abundant genera in MASLD- were Prevotella, Bacteroides, Dialister, Acidaminococcos, Alloprevotella, and Catenibacterium. In contrast, the most enriched genera in MASLD+ were Ruminococcus, Streptococcus, Holdemanella, Blautia, and Lactobacillus.ConclusionsWe found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.
Marta Rosas Cancio-Suárez, Raquel Ron, Jorge Díaz-Álvarez, Javier Martínez-Sanz, Sergio Serrano-Villar, Santiago Moreno, and Matilde Sánchez-Conde
Frontiers Media SA
Sex-related drug consumption and its health-related consequences have gained relevance in the assessment of patients with sexually transmitted infections (STIs), which pose a significant challenge to public health. We aim to assess the prevalence and characteristics of drug consumption and chemsex practices, describe the associated risk factors among general individuals attending an STI clinic, and evaluate the psychological impact associated with these behaviors. We conducted an online anonymous survey offered to patients with a diagnosis of STI in a tertiary hospital in Spain. Data included sociodemographic characteristics, sexual preferences and behavior, and assessment of drug use, chemsex, and psychological and mental health symptoms. Data from 145 subjects was collected, with a higher proportion of cis-gender men (71%), and a median age of 32 years. 64 participants (44%) reported drug use in the last year, with an observed 33.8% prevalence of chemsex consumption. Drug use and chemsex were more frequent among cis-gender men, Men who have Sex with Men (MSM), people living with HIV (PLHIV), and those reporting previous group sex. Poppers and cannabis were the most frequently reported drugs, with a prevalence close to 20% for cocaine, mephedrone, extasis, and GHB. Consequences related to drug use included unpleasant physical sensations, sexual dysfunction, and impaired sexual experience after reduction or drug discontinuation. The prevalence of drug use and chemsex practices are high among patients evaluated for STIs, especially between men, MSM, and subjects practicing group sex. The study highlights the urgent need for targeted interventions on prevention and reduction of their impact on health and social well-being.
Sergio Serrano-Villar, José Moltó-Marhuenda, Marta Montero-Alonso, Cesar Diaz-Torné, María López-Cavanillas, and Leopoldo Pérez de Isla
Elsevier BV
Elena Moreno, Marius Trøseid, Ivan Vujkovic-Cvijin, Giulia Marchetti, Laura Martín-Pedraza, and Sergio Serrano-Villar
Frontiers Media SA
COPYRIGHT © 2023 Moreno, Trøseid, Vujkovic-Cvijin, Marchetti, Martı́n-Pedraza and Serrano-Villar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 18 April 2023 DOI 10.3389/fimmu.2023.1202222
María Úbeda, María del Carmen Maza, Pilar Delgado, Lydia Horndler, David Abia, Laura García-Bermejo, Sergio Serrano-Villar, Cristina Calvo, Ugo Bastolla, Talia Sainz,et al.
Frontiers Media SA
BackgroundChildren are less susceptible than adults to symptomatic COVID‐19 infection, but very few studies addressed their underlying cause. Moreover, very few studies analyzed why children highly exposed to the virus remain uninfected.MethodsWe analyzed the serum levels of ACE2, angiotensin II, anti-spike and anti-N antibodies, cytokine profiles, and virus neutralization in a cohort of children at high risk of viral exposure, cohabiting with infected close relatives during the lockdown in Spain.ResultsWe analyzed 40 children who were highly exposed to the virus since they lived with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected relatives during the lockdown for several months without taking preventive measures. Of those, 26 reported mild or very mild symptoms. The induced immune response to the virus was analyzed 3 months after the household infection. Surprisingly, only 15 children had IgG anti-S (IgG+) determined by a sensitive method indicative of a past infection. The rest, negative for IgG anti-N or S in various tests, could be further subdivided, according to IgM antibodies, into those having IgM anti-S and IgM anti-N (IgG−IgMhigh) and those having only IgM anti-N (IgG−IgMlow). Interestingly, those two subgroups of children with IgM antibodies have strikingly different patterns of cytokines. The IgMhigh group had significantly higher IFN-α2 and IFN-γ levels as well as IL-10 and GM-CSF than the IgMlow group. In contrast, the IgMlow group had low levels of ACE2 in the serum. Both groups have a weaker but significant capacity to neutralize the virus in the serum than the IgG+ group. Two children were negative in all immunological antibody tests.ConclusionsA significant proportion of children highly exposed to SARS-CoV-2 did not develop a classical adaptive immune response, defined by the production of IgG, despite being in close contact with infected relatives. A large proportion of those children show immunological signs compatible with innate immune responses (as secretion of natural antibodies and cytokines), and others displayed very low levels of the viral receptor ACE2 that may have protected them from the virus spreading in the body despite high and constant viral exposure.
Sergio Serrano-Villar, Calvin Cohen, Jason V. Baker, Maria João Janeiro, Filipa Aragão, Kathleen Melbourne, Jose Luis Gonzalez, Laura Lara, Connie Kim, and Santiago Moreno
Frontiers Media SA
[This corrects the article DOI: 10.3389/fimmu.2022.976564.].