Respiratory syncytial virus: A new era / Virus respiratorio sincitial: un nuevo tiempo

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain. (AU)

El Virus Respiratorio Sincitial (VRS), es un problema de salud pública de primera magnitud que en años recientes ha experimentado cambios muy importantes. En primer lugar, se ha producido una mayor facilidad diagnóstica con pruebas confirmatorias altamente fiables y rápidamente disponibles. Esto ha permitido conocer mejor su epidemiología y VRS ha pasado de ser una enfermedad de la edad pediátrica, grave sólo en lactantes y niños inmunodeprimidos, a ser una enfermedad común en personas de toda edad, particularmente importante en pacientes de edades avanzadas o con enfermedades que inmunodeprimen. Los avances terapéuticos y profilácticos, recientes, tanto con anticuerpos monoclonales de larga duración como con vacunas, constituyen otro motivo de satisfacción. Por estos motivos, el Comité de COVID y de patógenos emergentes del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) ha considerado pertinente revisar este tema, a la luz de los nuevos conocimientos y de los nuevos recursos para afrontar esta infección. Hemos formulado una serie de preguntas que creemos de interés no sólo para los colegiados si no para cualquier persona no experta en este tema, con una vista particular en la situación de la infección por VRS en España. (AU)

COVID -19: On the threshold of the fifth year. The situation in Spain / COVID-19: A las puertas del quinto año

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection. (AU)

Pese a haber salido de la situación de pandemia, la incidencia de episodios de COVID-19 ha aumentado recientemente en España, incluidos los casos pediátricos y los ingresos en Unidades de Cuidados Intensivos. Circulan entre nosotros diversas variantes recombinantes, particularmente la XBB surgidas de dos sublinajes Omicron BA.2 con mutaciones en los genes que codifican las proteínas de la espícula y que pudieran aumentar la unión al receptor ACE2 y ser más propensas al escape inmune. Frente a ellas, 3 empresas farmacéuticas han elaborado vacunas adaptadas al sublinaje XBB.1.5 que ya se encuentran disponibles para su administración en nuestro medio con riesgos que no deben ser diferentes a los de las vacunas mRNA previas y con relaciones beneficio/riesgos claramente favorables. Deben aplicarse a pacientes con potencial de mala evolución de COVID-19 y a los colectivos que tienen una particular relación de proximidad con ellos. Su aplicación debe ser entendida no sólo desde una perspectiva de conveniencia individual sino desde la de la responsabilidad colectiva. Lo más conveniente parece hacer una inmunización simultánea de COVID-19 y gripe en nuestro medio. En el aspecto terapéutico hay poco que esperar ahora mismo de los antisueros pero siguen estando disponibles e indicados los fármacos antivirales ya conocidos aunque su eficacia tendrá que reevaluarse por su impacto en poblaciones mayoritariamente inmunizadas y con pronóstico mejor que las de tiempos pasados. A nuestro juicio, es necesario seguir haciendo un uso razonable y puntual de mascarillas y otros medios no farmacológicos de protección. (AU)

Tuberculosis in Spain: An opinion paper / Tuberculosis en España: Un documento de opinión

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Il lustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapul monary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observa tion in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal impli cations of this disease are not a minor issue and our situation in this regard has been reviewed (AU)

El presente documento es el resultado de las deliberacio nes del Comité sobre Patógenos Emergentes y COVID-19 del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) en re lación a la situación actual de la tuberculosis, particularmente en España. Hemos revisado aspectos tales como la evolución de su incidencia, las poblaciones actualmente más expuestas y los circuitos sanitarios para la atención a estos pacientes en España. Se ha discutido también la tuberculosis latente, la rea lidad de la enfermedad extrapulmonar en el siglo XXI y los me dios de que en la práctica diaria se dispone para el diagnóstico tanto de las formas latentes como de las activas. La aportación de la biología molecular que ha cambiado la perspectiva de es ta enfermedad ha constituido otro de los temas de debate. El documento trata de poner en perspectiva tanto los fármacos clásicos y sus cifras de resistencia como la disponibilidad e in dicaciones de los nuevos. Junto a esto, se ha discutido la rea lidad de la observación directa en la administración de fárma cos antituberculosos. Toda esta revolución está posibilitando el acortamiento del tiempo de tratamiento de la tuberculosis tema que ha sido igualmente revisado. Si todo se hace bien, el riesgo de recaída de la tuberculosis es pequeño pero existen te. Por otra parte, muchas situaciones especiales han merecido discusión en este documento como por ejemplo la tuberculosis en edad pediátrica y la tuberculosis como causa de preocupa ción en cirugía y cuidados intensivos. Se ha discutido tanto la situación de la vacuna BCG y sus indicaciones presentes, co mo el futuro de nuevas vacunas que permitan alcanzar el viejo sueño de erradicar esta enfermedad. Finalmente, las implica ciones éticas y medicolegales que esta enfermedad plantea no son un tema menor y se ha revisado nuestra situación en este particular (AU)

Sexually transmitted infections in Spain: Current status / Infecciones de transmisión sexual en España: Situación actual

Sexually Transmitted Infections (STI) are a major public health problem. The problems inherent to their diagnosis, treatment and prevention have to do not only with their nature, but also with organizational issues and overlapping competencies of the different health authorities in Spain. The real situation of STI in Spain, at present, is poorly known. For this reason, the Scientific Committee on COVID and Emerging Pathogens of the Illustrious Official College of Physicians of Madrid (ICOMEM) has formulated a series of questions on this subject which were distributed, not only among the members of the Committee, but also among experts outside it. The central health authorities provide very high and increasing figures for gonococcal infection, syphilis, Chlamydia trachomatis infection and lymphogranuloma venereum (LGV). Both HIV infection and Monkeypox are two important STI caused by viruses in our environment, to which it should be added, mainly, Herpes simplex virus (HSV) and Human papillomavirus (HPV) infections. Emerging microorganisms such as Mycoplasma genitalium pose not only pathogenic challenges but also therapeutic problems, as in the case of N. gonohrroeae. The pathways that patients with suspected STI follow until they are adequately diagnosed and treated are not well known in Spain. Experts understand that this problem is fundamentally managed in public health institutions, and that Primary Care and Hospital Emergency Services, together with some institutions that deal monographically with this problem, are the recipients of most of these patients (AU)

Las Infecciones de Transmisión Sexual (ITS) constituyen un problema de Salud Pública de primera magnitud. Los prob lemas inherentes a su diagnóstico, tratamiento y prevención tienen que ver no solo con la naturaleza de las mismas, sino también con problemas de organización y de solapamiento de competencias de las distintas autoridades sanitarias. La situación real de las ITS en España no se conoce bien en el momento actual. Por este motivo, el Comité Científico sobre COVID y Patógenos emergentes del Ilustre Colegio Ofi cial de Médicos de Madrid (ICOMEM) se ha formulado una se rie de preguntas sobre este tema que ha distribuido, no sólo entre los miembros del Comité, sino también entre expertos ajenos al mismo. Las autoridades ministeriales aportan cifras muy elevadas y crecientes de infección gonocócica, sífilis, in fección por Chlamydia trachomatis y Linfogranuloma venéreo. Tanto la infección por VIH como Monkeypox son en nuestro medio dos importantes ITS causadas por virus a las que deben añadirse, principalmente, las infecciones por el Virus herpes simplex (VHS) y el Virus del Papiloma Humano (HPV). Emer gen patógenos como Mycoplasma genitalium que plantean no sólo retos patogénicos si no también problemas terapéuticos, como ocurre en el caso de N. gonohrroeae. Los caminos que siguen los pacientes con sospecha de ITS hasta su adecuado diagnóstico y tratamiento no se conocen bien en España. Los expertos entienden que este problema es fundamentalmente manejado en instituciones sanitarias de titularidad pública, y que los servicios de Atención Primaria y de Urgencias Hospitalarias, junto con algunas instituciones monográficamente destinadas a este problema, son los re ceptores de la mayor parte de estas enfermedades. Una de las dificultades más serias de las ITS estriba en la disponibilidad de las pruebas microbiológicas necesarias para su diagnóstico, particularmente en esta época de externalización de servicios de Microbiología (AU)

Advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in Spain. How and when is it justified to maintain it? / Ventajas e inconvenientes de mantener la obligatoriedad del uso de las mascarillas en centros sanitarios y sociosanitarios en España. ¿Cómo y cuándo está justificado mantenerla?

We address the advantages and disadvantages of main taining the mandatory use of masks in health centers and nursing homes in the current epidemiological situation in Spain and after the declaration of the World Health Organiza tion on May 5, 2023 of the end of COVID-19 as public health emergency. We advocate for prudence and flexibility, respect ing the individual decision to wear a mask and emphasizing the need for its use when symptoms suggestive of a respira tory infection appear, in situations of special vulnerability (such as immunosuppression), or when caring for patients with those infections. At present, given the observed low risk of se vere COVID-19 and the low transmission of other respiratory infections, we believe that it is disproportionate to maintain the mandatory use of masks in a general way in health centers and nursing homes. However, this could change depending on the results of epidemiological surveillance and it would be necessary to reconsider returning to the obligation in periods with a high incidence of respiratory infections (AU)

Abordamos las ventajas e inconvenientes de mantener la obligatoriedad del uso de las mascarillas en centros sani tarios y sociosanitarios en la situación epidemiológica actual de España y tras la declaración de la Organización Mundial de la Salud el 5 de mayo de 2023 del fin de la COVID-19 como emergencia de salud pública. Propugnamos prudencia y flexi bilidad, respetando la decisión individual de usar mascarilla y enfatizando la necesidad de su uso ante la aparición de sín tomas sugestivos de infección respiratoria, en situaciones de especial vulnerabilidad (como inmunodepresión) o al attender pacientes con dichas infecciones. En la actualidad, dado el ba jo riesgo observado de COVID-19 grave y la baja transmisión de otras infecciones respiratorias, creemos que es despropor cionado mantener el uso obligatorio de mascarillas de forma generalizada en centros sanitarios y sociosanitarios. No obs tante, esto podría cambiar en función de los resultados de la vigilancia epidemiológica y habría que reconsiderar volver a la obligatoriedad en periodos con alta incidencia de infecciones respiratorias (AU)

Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper / Situación del herpes zóster y de las vacunas contra el mismo en 2023: Un documento de opinión

Herpes zoster infection (HZ) is an important public health problem due to its high incidence and frequent complications, especially post-herpetic neuropathy . The incidence of HZ increases with age and is more frequent in immunocompromised patients. It is estimated that at least 60,000 people develop HZ each year in Spain.The usual forms of HZ are so clinically characteristic that they do not usually require microbiological confirmation, which is reserved for cases without cutaneous manifestations or with atypical presentation.There are currently two vaccines approved by the regulatory agencies and marketed in Spain to prevent the onset of HZ and its complications. The first (Zostavax®) was marketed by the company MSD and licensed in Europe in 2006 and is a live attenuated virus vaccine that is administered in a single dose, while the second (Shingrix®) is a recombinant vaccine, marketed in 2017 and requires two doses. While the former cannot be administered to immunocompromised persons, the latter can be prescribed to any group of adults.The criteria for the indication and financing of these vaccines have not been uniform in the various autonomous communities of Spain.These and other aspects of HZ have been discussed by a group of experts from the Illustrious Official College of Physicians of Madrid (ICOMEM) whose criteria and opinions are included in this paper. (AU)

La infección por herpes zoster (HZ) es un importante problema de salud pública, por su elevada incidencia y frecuentes complicaciones; en especial la neuropatía post herpética. La incidencia de HZ aumenta con la edad y es más frecuente en inmunodeprimidos. Se calcula que, al menos, 60.000 personas desarrollan HZ cada año en España. Las formas habituales de HZ son tan características clínicamente que no suelen requerir confirmación microbiológica que se reserva para casos sin manifestaciones cutáneas o con manifestaciones atípicas En la actualidad, existen en España dos vacunas aprobadas por las agencias reguladoras y comercializadas para prevenir la aparición de HZ y sus complicaciones. La primera (Zostavax®) fue comercializada por la compañía MSD y autorizada en Europa en 2006 y es una vacuna de virus vivos atenuados que se administra en dosis única, mientras que la segunda (Shingrix®) es una vacuna recombinante, comercializada en 2017 y requiere dos dosis. Mientras la primera no puede ser administrada a inmunodeprimidos, la segunda puede administrarse a cualquier grupo de personas. Los criterios de indicación y de financiación de estas vacunas no han sido uniformes en las diversas comunidades autónomas de España. Estos y otros aspectos sobre HZ han sido discutidos por un grupo de expertos del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) cuyo criterio y opinión recogemos en este trabajo. (AU)

Acute Epstein-Barr virus infection: Diagnostic challenge in young children, risk factors for hospitalisation and cytomegalovirus co-detection.

AIM: Acute Epstein-Barr virus (aEBV) and cytomegalovirus (CMV) infections frequently have similar manifestations. We aim to evaluate the characteristics of aEBV infection, risk factors for hospitalisation and differences according to CMV IgM detection (EBV-CMV co-detection) in children. METHODS: Retrospective, single-centre study including patients <16 years diagnosed with aEBV infection (positive anti-EBV IgM/Paul-Bunnell test and acute symptomatology). EBV-CMV co-detection was defined as positive CMV IgM. Factors associated with age, hospitalisation and EBV-CMV co-detection were analysed in a multivariate analysis. RESULTS: A total of 149 patients were included (median age 4.6 years). Most frequent manifestations were fever (77%), cervical lymphadenopathy (64%) and elevated liver enzymes (54%). Younger children had lower rate of positive Paul-Bunnell test (35% vs. 87%; p < 0.01), but higher rate of EBV-CMV co-detection (54% vs. 29%; p = 0.03). These children tended to have less typical symptoms of infectious mononucleosis and higher hospitalisation rate. The overall antibiotic prescription was 49%. Hospitalisation (27 children; 18%) was independently associated with prior antibiotic therapy and anaemia. Sixty-two cases (42%) had EBV-CMV co-detection, which was independently associated with elevated liver enzymes and younger age. CONCLUSION: In this study, younger children with aEBV infection presented more frequently with atypical clinical symptoms, had higher EBV-CMV co-detection rates and were more often hospitalised. Hospitalisation was associated with prior antibiotic prescription.

COVID in Pediatric Age: an opinion paper / COVID en la edad pediátrica: un documento de opinión

The incidence of COVID in pediatrics was underestimated during the first months of the pandemic due to the oligosymptomatic nature of the infection in many children and thescarcity of diagnostic tests applied to this population. It is nowaccepted that children are infected and transmit the diseasein the same way as adults. On the contrary, children have lesssevere and less lethal COVID, probably due to a lower maturityof the child’s immune system, a lower number of ACE2 receptors and the lower presence of comorbidities in this populationgroup.The development of a multisystemic inflammatory syndrome after SARS-CoV-2 infection in children, despite its rarity, is a very serious condition that frequently requires intensivecare. Other less severe post-COVID manifestations have beendescribed in children but are not yet well defined.COVID has had and continues to have a significant psychological impact on the children themselves, on their caregiversand on the exacerbation of pre-existing psychiatric conditions.We apply adult therapeutic principles to children but withvery low levels of evidence. Information on the tolerability of the available medications in this population group is stillscarce. The mortality of COVID in children is very low and generally affects children with significant comorbidities.There are, at present, three vaccines licensed for pediatricuse which are compatible with all other vaccines applicable tochildren.In these circumstances, there has been much speculationabout the indication for vaccination in the pediatric age group,but given its good tolerance, there are clinical and ethical reasons that, in our opinion, justify it. (AU)

La incidencia de COVID en pediatría ha estado infraestimada durante los primeros meses de la pandemia por el carácter oligosintomático de la infección en muchos niños y porla escasez de pruebas diagnósticas aplicadas a esta población.Hoy se admite que los niños se infectan y transmiten la enfermedad igual que los adultos. Por el contrario, los niños tienencuadros clínicos menos graves y letales lo cuál parece relacionado con una menor madurez del sistema inmune del niño,una menor cantidad de receptores ACE2 y la menor presenciade comorbilidades en este grupo de población.El desarrollo de un síndrome inflamatorio multisistémicotras la infección por SARS-CoV-2 en niños, pese a su rareza, esun cuadro muy grave que frecuentemente requiere cuidadosintensivos. Se han descrito otros cuadros post-COVID en niños,menos graves, pero todavía no muy bien definidos.La COVID-19 ha tenido y tiene un importante impacto psicológico en los propios niños, en sus cuidadores y en la exacerbación de cuadros psiquiátricos pre-existentes.Aplicamos a los niños los principios terapéuticos de losadultos pero con niveles muy bajos de evidencia y la toleranciade los medicamentos disponibles en este grupo de poblaciónes todavía mal conocida. La mortalidad de la COVID en niñoses muy baja e incide generalmente en niños con importantescomorbilidades.Hay, en el momento presente, tres vacunas autorizadaspara el uso pediátrico y las vacunas frente a SARS-CoV-2 soncompatibles con el resto de las vacunas aplicables a niños.En estas circunstancias se ha especulado mucho sobre laindicación de vacunación en la edad pediátrica pero dada subuena tolerancia, existen, en nuestra opinión, razones clínicasy éticas que la justifican. (AU)

Booster or additional vaccination doses in patients vaccinated against COVID-19 / Dosis vacunales de recuerdo o adicionales en pacientes vacunados frente a COVID-19

Several health organizations, mainly in Western countries, have recently authorized the use of a booster dose of the COVID-19 vaccine for patients previously vaccinated with mRNA vaccines, with criteria that do not always coincide. The COVID Scientific Committee of the Illustrious College of Physicians of Madrid (ICOMEM) has received and asked several questions about this situation, to which the group has tried to give answers, after deliberation and consensus. The efficacy of the vaccines administered so far is beyond doubt and they have managed to reduce, fundamentally, the severe forms of the disease. The duration of this protection is not well known, is different in different individuals and for different variants of the virus and is not easily predictable with laboratory tests. Data on the real impact of a supplementary or “booster” dose in the scientific literature are scarce for the moment and its application in large populations such as those in the state of Israel may be associated with a decrease in the risk of new and severe episodes in the short observation period available. We also lack sufficient data on the safety and potential adverse effects of these supplementary doses and we do not know the ideal time to administer them in different situations.In this state of affairs, it seems prudent to administer supplemental doses to those exposed to a higher risk, such as immunocompromised individuals and the elderly. On the other hand, we consider that this is not the time to accelerate, on the spur of the moment, a massive administration of a third dose to other population groups that are less exposed and at lower risk, without waiting for adequate scientific information, which will undoubtedly arrive gradually. We do not believe that this position is incompatible with the practical and ethical warnings made by the World Health Organization in this respect. (AU)

Varias organizaciones sanitarias, fundamentalmente de países occidentales, han autorizado recientemente el uso de una dosis de refuerzo de la vacuna frente al COVID-19 para pacientes previamente vacunados con vacunas mRNA, con criterios no siempre coincidentes. El Comité Científico de COVID, del Ilustre Colegio de Médicos de Madrid (ICOMEM) ha recibido y se ha formulado diversas preguntas sobre esta situación, a la que el grupo ha tratado de dar respuestas, tras deliberación y consenso. La eficacia de las vacunas administradas hasta el momento está fuera de toda duda y han logrado disminuir, fundamentalmente, las formas graves de enfermedad. La duración de esa protección no se conoce bien, es diferente en distintos individuos y para distintas variantes del virus y no es fácilmente predecible con pruebas de laboratorio. Los datos sobre el impacto real de una dosis complementaria o “booster” en la literatura científica son escasos por el momento y su aplicación en grandes poblaciones como las del estado de Israel pueden asociarse a una disminución del riesgo de nuevos episodios y episodios graves en el corto periodo de observación disponible. Carecemos también de datos suficientes sobre la seguridad y potenciales efectos adversos de estas dosis complementarias e ignoramos el momento idóneo de administrarlas en distintas situaciones. En este estado de cosas, parece prudente administrar dosis complementarias a aquellos expuestos a un mayor riesgo, como pueden ser los individuos inmunodeprimidos y las personas mayores. Por el contrario, consideramos que no es este el momento de acelerar improvisadamente una administración masiva de una tercera dosis a otros grupos de población menos expuesta y de menor riesgo, sin esperar la adecuada información científica, que sin duda irá llegando paulatinamente. No creemos que esta posición, sea incompatible con las advertencias prácticas y éticas que realiza la Organización Mundial de la Salud a este respecto. (AU)

Pharmacological treatment of COVID-19: an opinion paper / Tratamiento farmacológico del COVID-19: un documento de opinión

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation. (AU)

La precocidad y la eficacia de las vacunas desarrolladas hasta ahora frente al COVID-19, ha sido el avance más significativo y salvador frente a la pandemia. El desarrollo vacunal no ha impedido, durante todo el periodo de la pandemia, la búsqueda constante de remedios terapéuticos, tanto entre los medicamentos ya existentes y con indicaciones diversas, como en el desarrollo de nuevos fármacos. Sobre estos nuevos fármacos, sobre las novedades en la inmunoterapia y sobre lo aprendido de los moduladores de la respuesta inmune ya conocidos y que se han mostrado eficaces frente al virus, el Comité Científico del COVID-19 del Ilustre Colegio de Médicos de Madrid ha querido ofrecer una aproximación precoz, simplificada y critica que pueda ayudar a comprender la situación actual. (AU)

Persistence and viability of SARS-CoV-2 in primary infection and reinfections / Persistencia y viabilidad de SARS-CoV-2 en la primoinfección y reinfecciones

Since the beginning of the SARS-CoV-2 epidemic, virus isolation in the infected patient was only possible for a short period of time and it was striking that this occurred constantly and did not provide guidance on the clinical course. This fact led to confusion about the efficacy of some of the drugs initially used, which seemed to have a high efficiency in viral clearance and proved ineffective in modifying the course of the disease. The immune response also did not prove to be definitive in terms of evolution, although most of the patients with very mild disease had a weak or no antibody response,and the opposite was true for the most severe patients.With whatever the antibody response, few cases have been re-infected after a first infection and generally, those that have, have not reproduced a spectrum of disease similar to the first infection. Among those re-infected, a large number have been asymptomatic or with very few symptoms, others have had a moderate picture and very few have had a poor evolution.Despite this dynamic of rapid viral clearance, laboratory tests were still able to generate positive results in the recovery of genomic sequences and this occurred in patients who were already symptom-free, in others who were still ill and in those who were very seriously ill. There was also no good correlate.For this reason and with the perspective of this year and the half of pandemic, we compiled what the literature leaves us in these aspects and anticipating that, as always in biology, there are cases that jump the limits of the general behavior of the dynamics of infection in general. (AU)

Desde el inicio de la epidemia por SARS-CoV-2, el aislamiento del virus en el paciente infectado era posible solo durante un periodo corto de tiempo y llamaba la atención que esto ocurría de una manera constante y no orientaba sobre la evolución clínica. Este hecho, indujo a confusión sobre la eficacia de algunos de los fármacos utilizados inicialmente que parecían tener una gran eficiencia en el aclarado viral y que resultaron ineficaces para modificar el curso de la enfermedad. La respuesta inmune tampoco se mostraba definitiva para aventurar la evolución aunque la mayoría de los pacientes que tenían una enfermedad muy leve, tenían una débil o nula respuesta de anticuerpos y en los más graves pasaba lo contrario.Con cualquiera que haya sido la respuesta de anticuerpos, pocos casos han vuelto a infectarse tras una primo-infección y generalmente, los que lo han hecho, no han reproducido un espectro de enfermedad similar a la primera infección. Entre los re-infectados, gran parte han sido asintomáticos o con muy pocos síntomas, otros han tenido un cuadro moderado y muy pocos han tenido mala evolución.Pese a esa dinámica de rápido aclaramiento viral, las pruebas de laboratorio podían seguir siendo capaces de generar positivos en la recuperación de secuencias genómicas y esto ocurría en pacientes libres ya de síntomas, en otros que seguían enfermos y en los muy graves. Tampoco había un buen correlato.Por eso y con la perspectiva de este año y medio de pandemia recopilamos lo que nos deja la literatura en estos aspectos adelantando que, como siempre en biología, existen casos que saltan los límites del comportamiento general de la dinámica de la infección en general. (AU)

Actions and attitudes on the immunized patients against SARS-CoV-2 / Acciones y actitudes ante el paciente inmunizado contra el SARS-CoV-2

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows:The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons.Vaccinated subjects who have contact with a SARSCoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances.Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. (AU)

El acceso a las vacunas frente a COVID-19 de millones de seres humanos y su alto nivel de protección frente a la enfermedad, tanto en sus formas leves como graves, junto a una verosímil disminución de la transmisión de la infección desde pacientes vacunados, ha motivado una serie de preguntas de los colegiados y de la sociedad. El Comité Científico del ICOMEM sobre esta materia ha tratado de responder a dichas preguntas tras discusión y consenso entre sus miembros. Las respuestas principales pueden resumirse así: La aparición de nuevas infecciones por SARS-CoV-2 tanto en vacunados como en previamente infectados, es muy escasa, en el tiempo de observación del que ya disponemos. Cuando ocurren infecciones de brecha, suelen ser asintomáticas o paucisintomáticas y, en principio, tendrían una menor capacidad de trasmisión a otras personas.Los sujetos vacunados que tienen contacto con un paciente infectado por SARS-CoV-2 pueden evitar la cuarentena, mientras se encuentren asintomáticos, si bien esta decisión depende de la edad, la profesión, las variantes circulantes, el grado de contacto y el tiempo pasado desde la vacunación. En países con una alta proporción de la población vacunada se sugiere ya la posibilidad de que las personas plenamente vacunadas prescindan del uso de las mascarillas y el distanciamiento social en la mayoría de las circunstancias.Se desaconseja la utilización de pruebas diagnósticas de manera sistemática para evaluar la respuesta inmune o el grado de protección frente a la reinfección tras la infección natural o la vacunación, dado que en este momento se ignoran sus consecuencias prácticas. La información existente hasta este momento, impide hacer cualquier precisión frente a una posible necesidad de revacunación futura. (AU)

Longitudinal plasma cytokine concentrations and recurrent wheezing after RSV bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in young children has been associated with increased risk for developing recurrent wheezing, but the underlying mechanisms, are not completely defined. We hypothesized that RSV induces a disregulated immune response defined by a distinct cytokine profile in infants at increased risk for developing recurrent wheezing. METHODS: Previously healthy infants less than 12 months of age hospitalized with a first episode of RSV bronchiolitis were enrolled and blood samples and clinical and epidemiological data collected. A group of healthy non-infected controls were enrolled in parallel. Children were followed longitudinally and subsequent blood samples collected in RSV-infected infants at one month and at one year after hospital discharge to measure longitudinal plasma concentrations of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17 and IL1-ß. Risk of post-RSV wheezing was assessed by Poisson modelling. RESULTS: From October 2008 to March 2012 we enrolled 37 infants hospitalized with RSV bronchiolitis and 9 healthy age-matched controls. Within the RSV cohort, 17 (46%) children developed recurrent wheezing within the following 12 months. Plasma cytokine profiles measured during the acute infection were similar in children who developed recurrent wheezing versus those who did not, but lower in healthy controls vs RSV infants who subsequently developed wheezing. At one month and 12 months post-acute RSV infection, infants who developed recurrent wheezing had higher IFN-γ plasma concentrations versus those with no-wheezing (p < 0.05). Moreover, IFN-γ concentrations were identified as independent predictor of post-RSV wheezing. CONCLUSIONS: Children with RSV-associated recurrent wheezing had persistently elevated plasma concentrations of IFN-γ for a year after acute infection, suggesting that this cytokine could be used as a biomarker for risk of recurrent wheezing and possibly plays a role in the pathogenesis of this condition.

[Patient care, right to information and consent for minors in situations of parental conflict. Clinical guidelines in the context of Spanish legislation]. / Atención a menores con progenitores en conflicto en materia de información y consentimiento relativos a la salud de los hijos. Protocolo asistencial en el contexto de la legislación vigente.

Among the main social and legislative changes as regards family matters that have taken place in Spain in the last few years, are included: (i) the gradual increase in legal disputes between parents, and (ii) the introduction of Law 26/2015 on Child Protection, which modified Law 41/2002 on the Freedom of the Patient. These searched for a balance between the rights of minors and the powers of the parents, particularly when the former had not reached 16 years or had sufficient maturity or, having reached it, the decision puts their life or health at severe risk. Likewise, it has led to a jurisprudence that determines that, for any minor, there are particularly sensitive, "special" or "important" health care actions, such as psychotherapy or surgical treatments, which require, with exceptions, the consent of both parents for it to be carried out. All this, however, subject to the discretion of the doctor responsible, who must always look after the best interests of the minor. For this reason, healthcare for minors, occasionally, lead to complex conflicts as regards information and consent by the parents, particularly when they do not agree. A review is presented on the current legislative framework and the main legal concepts that regulate the healthcare of minors as regards information and consent relative to health, as well a healthcare protocol for the care of minors in situations of conflict between parents, developed in the Gregorio Marañón Hospital of Madrid, and endorsed by the Official Medical Collegiate of Madrid.

Neurologic Complications in Children Hospitalized With Influenza Infections: Prevalence, Risk Factors and Impact on Disease Severity.

BACKGROUND: Influenza infection is a common cause of respiratory disease and hospitalization in children. Neurologic manifestations of the infection have been increasingly reported and may have an impact on the severity of the disease. The aim of this study is to describe neurologic events in pediatric patients hospitalized with influenza and identify associated risk factors. METHODS: Retrospective cohort study which included all hospitalized patients with microbiologic confirmation of influenza disease over 4 epidemic seasons, focusing on neurologic complications. Demographic, laboratory and clinical data, as well as past history, were recorded. Descriptive and analytic statistical study was performed using SPSS and R statistical software. RESULTS: Two hundred forty-five patients were included. Median age was 21 months (interquartile range, 6-57) and 47.8% had a previous underlying condition. Oseltamivir was administered to 86% of patients, median hospitalization was 4 days (interquartile range, 3-6), and pediatric intensive care unit admission rate 8.9%. Twenty-nine patients (11.8%) developed neurologic events, febrile seizures being the most frequent, followed by nonfebrile seizures and encephalopathy. Status epilepticus occurred in 4 children, and 69.6% of seizures recurred. Patients with a previous underlying condition were at greater risk of developing a neurologic complication [odds ratio (OR), 4.55; confidence interval (CI), 95% 1.23-16.81). Male sex (OR, 3.21; CI 95%, 1.22-8.33), influenza B virus (OR, 2.82; CI 95%, 1.14-7.14) and neurologic events (OR, 3.34; CI 95%, 1.10-10.19) were found to be risk factors for pediatric intensive care unit admission. CONCLUSIONS: A significant proportion of influenza-related hospitalized patients develop neurologic complications, especially seizures which may be prolonged or recurrent. Previous underlying conditions pose the greatest risk to neurologic events, which increase disease severity.

Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia.

BACKGROUND: Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. METHODS: Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV. RESULTS: There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08). CONCLUSIONS: A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.

Enfermedad invasiva por Streptococcus pyogenes: cambios en la incidencia y factores pronósticos / Invasive disease due to Streptococcus pyogenes: Changes in incidence and prognostic factors

Introducción: La enfermedad invasiva por Streptococcus del grupo A (EISGA) es una infección grave en niños, habiéndose comunicado un aumento de incidencia en los últimos años. Objetivo: Evaluar las características y evolución de la EISGA en niños y determinar cambios en la incidencia o gravedad. Material y métodos: Estudio retrospectivo de niños ≤ 16 años evaluados en un hospital terciario pediátrico de Madrid y diagnosticados de EISGA (junio 2005-julio 2013). Se analizó la epidemiología, clínica, microbiología y tratamiento, evaluándose cambios a lo largo del periodo estudiado y parámetros asociados a gravedad. Resultados: Se incluyeron 55 niños con EISGA; 33 (60%) mujeres, con una mediana de 48,5 (20,5-88,9) meses. Los síndromes clínicos más frecuentes fueron celulitis/absceso subcutáneo (21,8%), absceso ORL (20%), neumonía (16,4%), infección osteoarticular (16,4%) y mastoiditis (12,7%). La incidencia de EISGA (casos/105 urgencias/año) aumentó de 5,6 (4,2-7,2) entre junio 2005-mayo 2009 a 18,9 (15,1-26) entre junio 2009-mayo 2013; p = 0,057. El 63,6% (n = 35) y el 18,2% (n = 10) de los pacientes precisaron cirugía e ingreso en UCIP, respectivamente. Los niños en UCIP fueron más pequeños (26,5 vs. 52,6 meses; p = 0,116), presentaron proteína C reactiva más elevada (24,5 vs. 10,7 mg/dl; p < 0,001) y mayor frecuencia de neumonía (60 vs. 7%; p < 0,001). En el análisis multivariante solo la proteína C reactiva fue factor de riesgo de ingreso en UCIP (OR: 1,14 [1,004-1,286]; p = 0,04). No hubo secuelas. Conclusiones: Se objetivó un aumento de la incidencia de EISGA en niños en nuestro medio, siendo la menor edad, la presencia de neumonía y la proteína C reactiva elevada los parámetros asociados a gravedad en esta serie

Introduction: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years. Objective: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity. Material and methods: A retrospective study was conducted on children ≤ 16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity. Results: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/105 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P = .057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P = .116), had a higher C-reactive protein (24.5 vs 10.7 mg/dl, P < .001) and higher frequency of pneumonia (60 vs 7%, P < .001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P = .04). There were no sequelae. Conclusions: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series

Enfermedad meningocócica invasiva en niños y adultos en un hospital terciario: epidemiología reciente y factores pronósticos / Invasive meningococcal disease in children and adults in a tertiary level hospital. Recent epidemiology and prognostic factors

Introducción: La enfermedad meningocócica invasiva (EMI) supone una causa importante de morbimortalidad en niños y adultos. Objetivo principal: describir las características clínicas y epidemiológicas de los pacientes con EMI. Objetivos secundarios: describir las diferencias entre niños y adultos, factores pronósticos y cambios epidemiológicos en los últimos 14 años. Métodos: Estudio retrospectivo realizado en un hospital terciario. Se incluyeron los pacientes diagnosticados de EMI entre 2004 y 2017, recogiéndose datos epidemiológicos, clínicos y microbiológicos. Resultados: Fueron diagnosticados 84 pacientes con EMI, 50 (59,5%) niños. Edad mediana en niños 2 años (RIC: 0,7-7,5) y adultos 41,2 años (RIC: 26,4-69,3). Bacteriemia en 47 casos (56%), meningitis en 24 (28,6%) y ambas en 13 (15,5%). Predominio del serogrupo B (MenB), en el 40,5%, seguido del serogrupo C (MenC), en el 15,5%, con mayor proporción de MenC en adultos (26,5 vs. 8%; p = 0,022). Disminución en la incidencia de 2004-2010 a 2011-2017, pasando de 3,14 a 1,33 casos/100.000 urgencias en el centro de estudio (p < 0,001). El 84% de los niños había recibido ≥ 1 dosis de vacuna frente a MenC, ninguno frente a MenB. Mayor proporción de ingreso en UCI en niños (78 vs. 44,1%; p = 0,001). Tendencia a mayor letalidad en adultos (11,8 vs. 2%; p = 0,153). La intubación y la trombocitopenia fueron factores de riesgo independientes de desenlace adverso, y la leucopenia y el exantema purpúrico de gravedad. Conclusiones: Se objetivó un descenso en la incidencia de EMI, siendo MenB el mayoritario. El mayor porcentaje de MenC en adultos probablemente esté relacionado con una menor cobertura vacunal. La trombocitopenia, la leucopenia y el exantema purpúrico fueron factores de riesgo relacionados con peor pronóstico

Introduction: Invasive meningococcal disease (IMD) has a high morbidity and mortality in children and adults. The aim of this study was to describe the clinical and epidemiological characteristics of patients with IMD, to compare them among children and adults, and to determine prognostic factors and changes in epidemiology during a 14-year period. Methods: A retrospective study was conducted on patients admitted to a third level hospital with IMD between 2004 and 2017. An analysis was made of the clinical, epidemiological and microbiological data. Results: A total of 84 patients were diagnosed with IMD, of which 50 (59.5%) were children. Median age was 2 years (IQR 0.7-7.5) for children and 41.2 years (IQR 26.4-69.3) for adults. Diagnosis was bacteraemia in 47 patients (56%), meningitis in 24 (28.6%), and both in 13 (15.5%). Serogroup B (MenB) was the most common cause of IMD (40.5%), followed by serogroup C (MenC) in 15.5%, which was more common among adults (26.5% vs 8%, P = .022). Incidence rate decreased between 2004-2010 and 2011-2017, from 3.14 to 1.33 cases/100.000 emergencies attended in the study hospital (P < .001). Eighty-four percent of children had received ≥ 1 dose of vaccine against MenC, with none against MenB. Children had higher proportion of ICU admissions (78% vs 44.1%, P = .001). Mortality was slightly higher in adults (11.8% vs 2.0%, P = .153). Adverse outcomes (sequelae or mortality) were independently associated with intubation and thrombocytopenia, while disease severity with leukopenia and purpuric rash. Conclusions: IMD incidence has decreased in our setting, with MenB being the most common serogroup. The higher prevalence of MenC in adults was probably related to lower vaccination coverage. According to this study, thrombocytopenia, leukopenia, and purpuric rash were parameters associated with worse outcome

[Invasive disease due to Streptococcus pyogenes: Changes in incidence and prognostic factors]. / Enfermedad invasiva por Streptococcus pyogenes: cambios en la incidencia y factores pronósticos.

INTRODUCTION: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years. OBJECTIVE: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity. MATERIAL AND METHODS: A retrospective study was conducted on children≤16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity. RESULTS: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/105 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P=.057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P=.116), had a higher C-reactive protein (24.5 vs 10.7mg/dl, P<.001) and higher frequency of pneumonia (60 vs 7%, P<.001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P=.04). There were no sequelae. CONCLUSIONS: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series.

Impact of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children under 15 years old in Madrid, Spain, 2007 to 2016: The HERACLES clinical surveillance study.

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Using the data from the HERACLES clinical surveillance study (2007-2016), we describe the population impact of the 13-valent pneumococcal conjugate vaccine (PVC13) on invasive pneumococcal disease (IPD) in children <15 years of age in the Community of Madrid, Spain. After six years of the inclusion of PCV13 in the vaccination calendar (2010-2016), and despite changes in the Regional Immunization Programme that limited its availability, the net benefit incidence rate (IR) of IPD fell by 70.1% (IRR 0.3 [95% CI: 0.22-0.4]; p ≤ 0.001), mainly due to a significant reduction (91%) in the PCV13 serotypes (IRR 0.09 [95% CI: 0.05-0.16], p ≤ 0.001). Furthermore, no significant changes were detected in the IR of IPD caused by non-PCV13 serotypes. The IRs of the aggressive, resistant and most prevalent serotype in the analysed population, the 19A serotype, dramatically decreased from the beginning to the end of the study (98%) [IRR 0.03 (95% CI: 0.00-0.19), p ≤ 0.001], to its almost total disappearance. Remarkably, this reduction led to a pronounced decline in the percentage of cefotaxime-resistant isolates and the incidence of meningitis cases. Assessment of the clinical impact revealed a reduction in the number of all clinical presentations of IPD, confirming the effectiveness of the PCV13. Finally, PCV13 detected by PCR is predicted to have a stronger impact than the one based on culture methods, which can overlook more than 20% of cases of IPD, mainly pleural empyemas.