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1.
Nature ; 595(7869): 713-717, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34192736

RESUMEN

After the first wave of SARS-CoV-2 infections in spring 2020, Europe experienced a resurgence of the virus starting in late summer 2020 that was deadlier and more difficult to contain1. Relaxed intervention measures and summer travel have been implicated as drivers of the second wave2. Here we build a phylogeographical model to evaluate how newly introduced lineages, as opposed to the rekindling of persistent lineages, contributed to the resurgence of COVID-19 in Europe. We inform this model using genomic, mobility and epidemiological data from 10 European countries and estimate that in many countries more than half of the lineages circulating in late summer resulted from new introductions since 15 June 2020. The success in onward transmission of newly introduced lineages was negatively associated with the local incidence of COVID-19 during this period. The pervasive spread of variants in summer 2020 highlights the threat of viral dissemination when restrictions are lifted, and this needs to be carefully considered in strategies to control the current spread of variants that are more transmissible and/or evade immunity. Our findings indicate that more effective and coordinated measures are required to contain the spread through cross-border travel even as vaccination is reducing disease burden.


Asunto(s)
COVID-19/transmisión , COVID-19/virología , SARS-CoV-2/aislamiento & purificación , COVID-19/epidemiología , COVID-19/prevención & control , Europa (Continente)/epidemiología , Genoma Viral/genética , Humanos , Incidencia , Locomoción , Filogenia , Filogeografía , SARS-CoV-2/clasificación , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Factores de Tiempo , Viaje/estadística & datos numéricos
2.
PLoS Pathog ; 20(1): e1011880, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38271294

RESUMEN

BACKGROUND: West Nile virus (WNV) outbreaks in birds, humans, and livestock have occurred in multiple areas in Europe and have had a significant impact on animal and human health. The patterns of emergence and spread of WNV in Europe are very different from those in the US and understanding these are important for guiding preparedness activities. METHODS: We mapped the evolution and spread history of WNV in Europe by incorporating viral genome sequences and epidemiological data into phylodynamic models. Spatially explicit phylogeographic models were developed to explore the possible contribution of different drivers to viral dispersal direction and velocity. A "skygrid-GLM" approach was used to identify how changes in environments would predict viral genetic diversity variations over time. FINDINGS: Among the six lineages found in Europe, WNV-2a (a sub-lineage of WNV-2) has been predominant (accounting for 73% of all sequences obtained in Europe that have been shared in the public domain) and has spread to at least 14 countries. In the past two decades, WNV-2a has evolved into two major co-circulating clusters, both originating from Central Europe, but with distinct dynamic history and transmission patterns. WNV-2a spreads at a high dispersal velocity (88km/yr-215 km/yr) which is correlated to bird movements. Notably, amongst multiple drivers that could affect the spread of WNV, factors related to land use were found to strongly influence the spread of WNV. Specifically, the intensity of agricultural activities (defined by factors related to crops and livestock production, such as coverage of cropland, pasture, cultivated and managed vegetation, livestock density) were positively associated with both spread direction and velocity. In addition, WNV spread direction was associated with high coverage of wetlands and migratory bird flyways. CONCLUSION: Our results suggest that-in addition to ecological conditions favouring bird- and mosquito- presence-agricultural land use may be a significant driver of WNV emergence and spread. Our study also identified significant gaps in data and the need to strengthen virological surveillance in countries of Central Europe from where WNV outbreaks are likely seeded. Enhanced monitoring for early detection of further dispersal could be targeted to areas with high agricultural activities and habitats of migratory birds.


Asunto(s)
Fiebre del Nilo Occidental , Virus del Nilo Occidental , Animales , Humanos , Virus del Nilo Occidental/genética , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/veterinaria , Filogeografía , Europa (Continente)/epidemiología , Brotes de Enfermedades
3.
EMBO J ; 40(5): e105912, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33283287

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which may result in acute respiratory distress syndrome (ARDS), multiorgan failure, and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air-liquid interface culture system which was characterized by confocal and electron microscopy and single-cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing fetal lung bud tip organoids. These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive alveolar type II-like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda 1 reduced viral replication. Hence, these cultures represent an experimental model for SARS-CoV-2 infection and can be applied for drug screens.


Asunto(s)
Células Epiteliales Alveolares/metabolismo , COVID-19/metabolismo , Modelos Biológicos , Organoides/metabolismo , SARS-CoV-2/fisiología , Replicación Viral , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/virología , Animales , COVID-19/virología , Chlorocebus aethiops , Regulación de la Expresión Génica , Humanos , Interferón Tipo I/biosíntesis , Interferones/biosíntesis , Organoides/patología , Organoides/virología , Células Vero , Interferón lambda
4.
N Engl J Med ; 386(10): 951-963, 2022 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-35045226

RESUMEN

BACKGROUND: The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019. However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-specific antibody levels than those induced by messenger RNA (mRNA)-based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear. METHODS: In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting. RESULTS: Homologous or heterologous booster vaccination resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration. CONCLUSIONS: The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936.).


Asunto(s)
Ad26COVS1/inmunología , Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , Inmunización Secundaria , Inmunogenicidad Vacunal , Inmunoglobulina G/sangre , Vacuna nCoV-2019 mRNA-1273/inmunología , Adulto , Anticuerpos Neutralizantes/sangre , Vacuna BNT162/inmunología , Femenino , Humanos , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Método Simple Ciego , Linfocitos T/inmunología
5.
Nature ; 575(7781): 130-136, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31695207

RESUMEN

With rapidly changing ecology, urbanization, climate change, increased travel and fragile public health systems, epidemics will become more frequent, more complex and harder to prevent and contain. Here we argue that our concept of epidemics must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery. This is an opportunity to combine knowledge and skills from all over the world-especially at-risk and affected communities. Many disciplines need to be integrated, including not only epidemiology but also social sciences, research and development, diplomacy, logistics and crisis management. This requires a new approach to training tomorrow's leaders in epidemic prevention and response.


Asunto(s)
Infecciones/epidemiología , Salud Pública/tendencias , Ciencia/tendencias , Métodos Epidemiológicos , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Control de Infecciones , Infecciones/diagnóstico , Infecciones/microbiología , Infecciones/virología , Salud Pública/historia , Ciencia/historia
6.
Proc Natl Acad Sci U S A ; 119(42): e2202871119, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36215506

RESUMEN

COVID-19 is the latest zoonotic RNA virus epidemic of concern. Learning how it began and spread will help to determine how to reduce the risk of future events. We review major RNA virus outbreaks since 1967 to identify common features and opportunities to prevent emergence, including ancestral viral origins in birds, bats, and other mammals; animal reservoirs and intermediate hosts; and pathways for zoonotic spillover and community spread, leading to local, regional, or international outbreaks. The increasing scientific evidence concerning the origins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is most consistent with a zoonotic origin and a spillover pathway from wildlife to people via wildlife farming and the wildlife trade. We apply what we know about these outbreaks to identify relevant, feasible, and implementable interventions. We identify three primary targets for pandemic prevention and preparedness: first, smart surveillance coupled with epidemiological risk assessment across wildlife-livestock-human (One Health) spillover interfaces; second, research to enhance pandemic preparedness and expedite development of vaccines and therapeutics; and third, strategies to reduce underlying drivers of spillover risk and spread and reduce the influence of misinformation. For all three, continued efforts to improve and integrate biosafety and biosecurity with the implementation of a One Health approach are essential. We discuss new models to address the challenges of creating an inclusive and effective governance structure, with the necessary stable funding for cross-disciplinary collaborative research. Finally, we offer recommendations for feasible actions to close the knowledge gaps across the One Health continuum and improve preparedness and response in the future.


Asunto(s)
COVID-19 , Quirópteros , Salud Única , Animales , Animales Salvajes , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Zoonosis/epidemiología , Zoonosis/prevención & control
7.
Clin Infect Dis ; 78(6): 1514-1521, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38445721

RESUMEN

BACKGROUND: Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants. METHODS: In this multicenter prospective cohort study, we enrolled B-cell- and/or T-cell-deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered. RESULTS: Two hundred and forty five patients infected with the Delta (50%) or Omicron BA.1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7-22); however, it took >30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57-69; P < .001). Spike mutations were observed in 1 of 42 (2.4%) patients after treatment with 2 active mAbs, in 5 of 34 (14.7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant). CONCLUSIONS: Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Huésped Inmunocomprometido , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Anticuerpos Monoclonales/uso terapéutico , COVID-19/inmunología , COVID-19/virología , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Adulto , Resultado del Tratamiento , Mutación
8.
J Virol ; 97(3): e0009923, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36856426

RESUMEN

The emergence of several bat coronavirus-related disease outbreaks in human and domestic animals has fueled surveillance of coronaviruses in bats worldwide. However, little is known about how these viruses interact with their natural hosts. We demonstrate a Betacoronavirus (subgenus Merbecovirus), PN-ßCoV, in the intestine of its natural host, Nathusius's Pipistrelle Bat (Pipistrellus nathusii), by combining molecular and microscopy techniques. Eighty-eight P. nathusii bat carcasses were tested for PN-ßCoV RNA by RT-qPCR, of which 25 bats (28%) tested positive. PN-ßCoV RNA was more often detected in samples of the intestinal tract than in other sample types. In addition, viral RNA loads were higher in intestinal samples compared to other sample types, both on average and in each individual bat. In one bat, we demonstrated Merbecovirus antigen and PN-ßCoV RNA expression in intestinal epithelium and the underlying connective tissue using immunohistochemistry and in situ hybridization, respectively. These results indicate that PN-ßCoV has a tropism for the intestinal epithelium of its natural host, Nathusius's Pipistrelle Bat, and imply that the fecal-oral route is a possible route of transmission. IMPORTANCE Virtually all mammal species circulate coronaviruses. Most of these viruses will infect one host species; however, coronaviruses are known to include species that can infect multiple hosts, for example the well-known virus that caused a pandemic, SARS-CoV-2. Chiroptera (bats) include over 1,400 different species, which are expected to harbor a great variety of coronaviruses. However, we know very little about how any of these coronaviruses interact with their bat hosts; for example, we do not know their modes of transmissions, or which cells they infect. Thus, we have a limited understanding of coronavirus infections in this important host group. The significance of our study is that we learned that a bat coronavirus that occurs in a common bat species in Europe has a tropism for the intestines. This implies the fecal-oral route is a likely transmission route.


Asunto(s)
COVID-19 , Quirópteros , Coronaviridae , Coronavirus del Síndrome Respiratorio de Oriente Medio , Animales , Humanos , Filogenia , SARS-CoV-2 , Intestinos , Tropismo , ARN
9.
J Med Virol ; 96(1): e29397, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38235923

RESUMEN

Mpox is an emerging zoonotic disease which has now spread to over 113 countries as of August 2023, with over 89,500 confirmed human cases. The Netherlands had one of the highest incidence rates in Europe during the peak of the outbreak. In this study, we generated 158 near-complete mpox virus (MPXV) genomes (12.4% of nationwide cases) that were collected throughout the Netherlands from the start of the outbreak in May 2022 to August 2023 to track viral evolution and investigate outbreak dynamics. We detected 14 different viral lineages, suggesting multiple introductions followed by rapid initial spread within the country. The estimated evolutionary rate was relatively high compared to previously described in orthopoxvirus literature, with an estimated 11.58 mutations per year. Genomic rearrangement events occurred at a rate of 0.63% and featured a large deletion event. In addition, based on phylogenetics, we identified multiple potential transmission clusters which could be supported by direct source- and contact tracing data. This led to the identification of at least two main transmission locations at the beginning of the outbreak. We conclude that whole genome sequencing of MPXV is essential to enhance our understanding of outbreak dynamics and evolution of a relatively understudied and emerging zoonotic pathogen.


Asunto(s)
Genómica , Monkeypox virus , Humanos , Países Bajos/epidemiología , Brotes de Enfermedades , Europa (Continente)
10.
BMC Infect Dis ; 24(1): 185, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347527

RESUMEN

BACKGROUND: Timely access to outbreak related data, particularly in the early events of a spillover, is important to support evidence based control measures in response to outbreaks of zoonotic Emerging Infectious Diseases (EID). Yet, this is impeded by several barriers that need to be understood to promote timely sharing of data. Using the MERS epidemic as a model for a zoonotic EID outbreak, this study sought to provide an in-depth understanding of data sharing practices. METHODS: Semi-structured interviews with 25 experts were conducted, along with Focus Group Discussions with 15 additional experts. A root-cause analysis was performed to examine the causal relationships between barriers. Enablers were mapped to the root-cause analysis to understand their influence on the barriers. Finally, root causes were placed in context of core dilemmas identified from the qualitative analysis. FINDINGS: Eight barriers to data sharing were identified, related to collaboration, technical preparedness, regulations, and (conflict of) interests, and placed in the context of six dilemmas inherent to the multi-stakeholder collaboration required for a zoonotic outbreak response. Fourteen identified enablers showed the willingness of stakeholders to overcome or circumvent these barriers, but also indicated the inherent trial and error nature of implementing such enablers. INTERPRETATION: Addressing the barriers requires solutions that must consider the complexity and interconnectedness of the root causes underlying them, and should consider the distinct scopes and interests of the different stakeholders. Insights provided by this study can be used to encourage data sharing practices for future outbreaks FUNDING: Wellcome Trust and UK Aid; EU-H2020 Societal Challenges (grant agreement no. 643476), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.201S.044).


Asunto(s)
Enfermedades Transmisibles Emergentes , Epidemias , Animales , Humanos , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/prevención & control , Brotes de Enfermedades/prevención & control , Zoonosis/epidemiología , Difusión de la Información
11.
BMC Public Health ; 24(1): 1781, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965485

RESUMEN

BACKGROUND: Recently, Europe has seen an emergence of mosquito-borne viruses (MBVs). Understanding citizens' perceptions of and behaviours towards mosquitoes and MBVs is crucial to reduce disease risk. We investigated and compared perceptions, knowledge, and determinants of citizens' behavioural intentions related to mosquitoes and MBVs in the Netherlands and Spain, to help improve public health interventions. METHODS: Using the validated MosquitoWise survey, data was collected through participant panels in Spain (N = 475) and the Netherlands (N = 438). Health Belief Model scores measuring behavioural intent, knowledge, and information scores were calculated. Confidence Interval-Based Estimation of Relevance was used, together with potential for change indexes, to identify promising determinants for improving prevention measure use. RESULTS: Spanish participants' responses showed slightly higher intent to use prevention measures compared to those of Dutch participants (29.1 and 28.2, respectively, p 0.03). Most participants in Spain (92.2%) and the Netherlands (91.8%) indicated they used at least one prevention measure, but differences were observed in which types they used. More Spanish participants indicated to have received information on mosquitoes and MBVs compared to Dutch participants. Spanish participants preferred health professional information sources, while Dutch participants favoured government websites. Determinants for intent to use prevention measures included "Knowledge", "Reminders to Use Prevention Measures", and "Information" in the Netherlands and Spain. Determinants for repellent use included "Perceived Benefits" and "Cues to Action", with "Perceived Benefits" having a high potential for behavioural change in both countries. "Self-Efficacy" and "Knowledge" were determinants in both countries for breeding site removal. CONCLUSION: This study found differences in knowledge between the Netherlands and Spain but similarities in determinants for intent to use prevention measures, intent to use repellents and intent to remove mosquito breeding sites. Identified determinants can be the focus for future public health interventions to reduce MBV risks.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Países Bajos , Humanos , España , Estudios Transversales , Adulto , Femenino , Masculino , Persona de Mediana Edad , Animales , Adulto Joven , Culicidae , Mosquitos Vectores , Control de Mosquitos/métodos , Adolescente , Intención , Encuestas y Cuestionarios , Anciano
12.
Euro Surveill ; 29(17)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38666400

RESUMEN

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.


Asunto(s)
Brotes de Enfermedades , Homosexualidad Masculina , Humanos , Masculino , Países Bajos/epidemiología , Estudios Seroepidemiológicos , Estudios Transversales , Homosexualidad Masculina/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Vaccinia/epidemiología , Anticuerpos Antivirales/sangre , Vacunación/estadística & datos numéricos , Adulto Joven , Modelos Teóricos , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G/sangre
13.
Euro Surveill ; 29(11)2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38487886

RESUMEN

Since the beginning of 2023, the number of people with suspected monkeypox virus (MPXV) infection have sharply increased in the Democratic Republic of the Congo (DRC). We report near-to-complete MPXV genome sequences derived from six cases from the South Kivu province. Phylogenetic analyses reveal that the MPXV affecting the cases belongs to a novel Clade I sub-lineage. The outbreak strain genome lacks the target sequence of the probe and primers of a commonly used Clade I-specific real-time PCR.


Asunto(s)
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Mpox/diagnóstico , Mpox/epidemiología , República Democrática del Congo/epidemiología , Filogenia , Brotes de Enfermedades
14.
J Infect Dis ; 228(5): 586-590, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-36857443

RESUMEN

Modified vaccinia virus Ankara (MVA) is used as a vaccine against monkeypox virus and as a viral vaccine vector. MVA-MERS-S is a vaccine candidate against Middle East respiratory syndrome (MERS)-associated coronavirus. Here, we report that cross-reactive monkeypox virus neutralizing antibodies were detectable in only a single study participant after the first dose of MVA-MERS-S vaccine, in 3 of 10 after the second dose, and in 10 of 10 after the third dose.


Asunto(s)
Infecciones por Coronavirus , Coronavirus del Síndrome Respiratorio de Oriente Medio , Vacunas Virales , Humanos , Anticuerpos ampliamente neutralizantes , Glicoproteína de la Espiga del Coronavirus , Monkeypox virus , Anticuerpos Antivirales , Virus Vaccinia/genética , Infecciones por Coronavirus/prevención & control , Anticuerpos Neutralizantes
15.
J Cell Physiol ; 238(2): 379-392, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36538650

RESUMEN

Arboviruses target bone forming osteoblasts and perturb bone remodeling via paracrine factors. We previously reported that Zika virus (ZIKV) infection of early-stage human mesenchymal stromal cells (MSCs) inhibited the osteogenic lineage commitment of MSCs. To understand the physiological interplay between bone development and ZIKV pathogenesis, we employed a primary in vitro model to examine the biological responses of MSCs to ZIKV infection at different stages of osteogenesis. Precommitted MSCs were infected at the late stage of osteogenic stimulation (Day 7) with ZIKV (multiplicity of infection of 5). We observe that MSCs infected at the late stage of differentiation are highly susceptible to ZIKV infection similar to previous observations with early stage infected MSCs (Day 0). However, in contrast to ZIKV infection at the early stage of differentiation, infection at a later stage significantly elevates the key osteogenic markers and calcium content. Comparative RNA sequencing (RNA-seq) of early and late stage infected MSCs reveals that ZIKV infection alters the mRNA transcriptome during osteogenic induction of MSCs (1251 genes). ZIKV infection provokes a robust antiviral response at both stages of osteogenic differentiation as reflected by the upregulation of interferon responsive genes (n > 140). ZIKV infection enhances the expression of immune-related genes in early stage MSCs while increasing cell cycle genes in late stage MSCs. Remarkably, ZIKA infection in early stage MSCs also activates lipid metabolism-related pathways. In conclusion, ZIKV infection has differentiation stage-dependent effects on MSCs and this mechanistic understanding may permit the development of new therapeutic or preventative measures for bone-related effects of ZIKV infection.


Asunto(s)
Células Madre Mesenquimatosas , Infección por el Virus Zika , Virus Zika , Humanos , Osteogénesis , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Células Cultivadas
16.
Clin Infect Dis ; 76(3): e507-e509, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35867699

RESUMEN

Viral evolution was evaluated in 47 immunocompromised patients treated with sotrovimab. Sequencing of SARS-CoV-2 following therapy was successful in 16. Mutations associated with sotrovimab resistance were documented in 6; viral replication continued after 30 days in 5. Combination antibody therapy may be required to avoid acquired resistance in immunocompromised patients.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Huésped Inmunocomprometido
17.
Clin Infect Dis ; 76(3): e188-e199, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35796536

RESUMEN

BACKGROUND: The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTRs) and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls. METHODS: A total of 152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73 m2), 145 participants on dialysis, 267 KTRs, and 181 controls were included. SARS-CoV-2 Spike S1 specific IgG antibodies were measured using fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta, and Omicron (BA.1) variants by plaque reduction, and T-cell responses by interferon-γ release assay. RESULTS: At 6 months after vaccination, S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTRs. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variants was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected at 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTRs. T-cell responses at 6 months were significantly lower than responses at 28 days. CONCLUSIONS: Although seropositivity rates at 6 months were comparable to rates at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTRs. CLINICAL TRIALS REGISTRATION: NCT04741386.


Asunto(s)
COVID-19 , Trasplante de Riñón , Insuficiencia Renal Crónica , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Inmunoglobulina G , Diálisis Renal , Insuficiencia Renal Crónica/terapia , SARS-CoV-2 , Linfocitos T , Vacunación
18.
Clin Infect Dis ; 76(3): e533-e536, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35723273

RESUMEN

The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous boosters after Ad26.COV2.S-priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed.


Asunto(s)
Ad26COVS1 , COVID-19 , Humanos , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Personal de Salud , Inmunidad
19.
Euro Surveill ; 28(28)2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37440347

RESUMEN

In November 2021, seven western lowland gorillas and four Asiatic lions were diagnosed with COVID-19 at Rotterdam Zoo. An outbreak investigation was undertaken to determine the source and extent of the outbreak and to identify possible transmission routes. Interviews were conducted with staff to identify human and animal contacts and cases, compliance with personal protective equipment (PPE) and potential transmission routes. Human and animal contacts and other animal species suspected to be susceptible to SARS-CoV-2 were tested for SARS-CoV-2 RNA. Positive samples were subjected to sequencing. All the gorillas and lions that could be tested (3/7 and 2/4, respectively) were RT-PCR positive between 12 November and 10 December 2021. No other animal species were SARS-CoV-2 RNA positive. Forty direct and indirect human contacts were identified. Two direct contacts tested RT-PCR positive 10 days after the first COVID-19 symptoms in animals. The zookeepers' viral genome sequences clustered with those of gorillas and lions. Personal protective equipment compliance was suboptimal at instances. Findings confirm transmission of SARS-CoV-2 among animals and between humans and animals but source and directionality could not be established. Zookeepers were the most likely source and should have periodic PPE training. Sick animals should promptly be tested and isolated/quarantined.


Asunto(s)
COVID-19 , Leones , Salud Única , Animales , Humanos , SARS-CoV-2/genética , COVID-19/veterinaria , Gorilla gorilla , ARN Viral/genética , Países Bajos/epidemiología
20.
Euro Surveill ; 28(31)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37535471

RESUMEN

In June 2023, a fatal disease outbreak in cats occurred in Poland. Most cases tested in Poland (29 of 47) were positive for highly pathogenic avian influenza (HPAI) A (H5N1) virus. Genetic analyses revealed clade 2.3.4.4b with point mutations indicative of initial mammalian hosts adaptations. Cat viral sequences were highly similar (n = 21), suggesting a potential common infection source. To investigate possible infection routes, our group tested food samples from affected households. HPAI H5N1 virus was detected in one poultry meat sample.


Asunto(s)
Subtipo H5N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Animales , Gatos , Subtipo H5N1 del Virus de la Influenza A/genética , Gripe Aviar/epidemiología , Polonia/epidemiología , Aves , Filogenia , Mamíferos
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