RESUMEN
Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT provide the first line of defense against EHV-1 and are crucial for orchestrating immunity. To define host-pathogen interactions, we characterized B-cell responses, antibody isotype functions, and EHV-1 replication of susceptible (non-immune) and clinically protected (immune) horses after experimental EHV-1 infection. Nasal secretion and nasal wash samples were collected and used for the isolation of DNA, RNA, and mucosal antibodies. Shedding of infectious virus, EHV-1 copy numbers, viral RNA expression, and host B-cell activation in the URT were compared based on host immune status. Mucosal EHV-1-specific antibody responses were associated with EHV-1 shedding and viral RNA transcription. Finally, mucosal immunoglobulin G (IgG) and IgA isotypes were purified and tested for neutralizing capabilities. IgG1 and IgG4/7 neutralized EHV-1, while IgG3/5, IgG6, and IgA did not. Immune horses secreted high amounts of mucosal EHV-1-specific IgG4/7 antibodies and quickly upregulated B-cell pathway genes, while EHV-1 was undetected by virus isolation and PCR. RNA transcription analysis reinforced incomplete viral replication in immune horses. In contrast, complete viral replication with high viral copy numbers and shedding of infectious viruses was characteristic for non-immune horses, together with low or absent EHV-1-specific neutralizing antibodies during viral replication. These data confirm that pre-existing mucosal IgG1 and IgG4/7 and rapid B-cell activation upon EHV-1 infection are essential for virus neutralization, regulation of viral replication, and mucosal immunity against EHV-1.IMPORTANCEEquine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion storms, and neurologic outbreaks known as equine herpes myeloencephalopathy (EHM). EHV-1 is transmitted with respiratory secretions by nose-to-nose contact or via fomites. The virus initially infects the epithelium of the upper respiratory tract (URT). Host-pathogen interactions and mucosal immunity at the viral entry site provide the first line of defense against the EHV-1. Robust mucosal immunity can be essential in protecting against EHV-1 and to reduce EHM outbreaks. It has previously been shown that immune horses do not establish cell-associated viremia, the prerequisite for EHM. Here, we demonstrate how mucosal antibodies can prevent the replication of EHV-1 at the epithelium of the URT and, thereby, the progression of the virus to the peripheral blood. The findings improve the mechanistic understanding of mucosal immunity against EHV-1 and can support the development of enhanced diagnostic tools, vaccines against EHM, and the management of EHV-1 outbreaks.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Inmunoglobulina G , Replicación Viral , Animales , Herpesvirus Équido 1/inmunología , Caballos , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/inmunología , Inmunoglobulina G/inmunología , Inmunidad Mucosa , Esparcimiento de Virus/inmunología , Linfocitos B/inmunología , Linfocitos B/virología , Interacciones Huésped-Patógeno/inmunologíaRESUMEN
The application of recombinant herpesvirus of turkey, expressing the H9 hemagglutinin gene from low pathogenic avian influenza virus (LPAIV) H9N2 and the avian orthoavulavirus-1 (AOAV-1) (commonly known as Newcastle Disease virus (NDV)) fusion protein (F) as an rHVT-H9-F vaccine, is an alternative to currently used classical vaccines. This study investigated H9- and ND-specific humoral and mucosal responses, H9-specific cell-mediated immunity, and protection conferred by the rHVT-H9-F vaccine in specific pathogen-free (SPF) chickens. Vaccination elicited systemic NDV F- and AIV H9-specific antibody response but also local antibodies in eye wash fluid and oropharyngeal swabs. The ex vivo H9-specific stimulation of splenic and pulmonary T cells in the vaccinated group demonstrated the ability of vaccination to induce systemic and local cellular responses. The clinical protection against a challenge using a LPAIV H9N2 strain of the G1 lineage isolated in Morocco in 2016 was associated with a shorter duration of shedding along with reduced viral genome load in the upper respiratory tract and reduced cloacal shedding compared to unvaccinated controls.
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Anticuerpos Antivirales , Pollos , Subtipo H9N2 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Esparcimiento de Virus , Animales , Subtipo H9N2 del Virus de la Influenza A/inmunología , Subtipo H9N2 del Virus de la Influenza A/genética , Pollos/inmunología , Gripe Aviar/prevención & control , Gripe Aviar/inmunología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Esparcimiento de Virus/inmunología , Organismos Libres de Patógenos Específicos , Virus de la Enfermedad de Newcastle/inmunología , Virus de la Enfermedad de Newcastle/genética , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/virología , Inmunidad Celular , Herpesvirus Meleágrido 1/inmunología , Herpesvirus Meleágrido 1/genética , Vacunación/métodos , Inmunidad Humoral , Vectores Genéticos/inmunología , Inmunogenicidad Vacunal , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genéticaRESUMEN
The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of interindividual variability. We identified 6 distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate, and clearance rate, by clustering data from 768 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1,510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection as well as by an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during Omicron infection, following vaccination, and following reinfection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.
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COVID-19 , SARS-CoV-2 , Carga Viral , Esparcimiento de Virus , COVID-19/inmunología , COVID-19/virología , Humanos , SARS-CoV-2/inmunología , Esparcimiento de Virus/inmunología , Cinética , Masculino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Reinfección/inmunología , Reinfección/virología , Adulto , Femenino , Modelos TeóricosRESUMEN
OBJECTIVES: To monitor the early emergence of genetic mutations related to reduced susceptibility to monoclonal anti-body (mAb)-based treatment in immunocompromised patients with long-term viral excretion using whole-genome sequencing at a tertiary university hospital in Barcelona, Spain. METHODS: Serial severe acute respiratory syndrome coronavirus 2-positive samples (mid-December 2021-mid-March 2022) from eight immunosuppressed, fully vaccinated patients (for solid-organ transplantation or haematologic malignancies) with long-term viral excretion despite undergoing mAb therapy (sotrovimab) for coronavirus disease 2019 were selected. Whole-genome sequencing was performed following the ARTIC, version 4.1, protocol on the MiSeq platform. Mutations in the coding sequence of the spike protein with a frequency of ≥5% were studied. RESULTS: A total of 37 samples from the studied cases were analysed. All the cases, except one, were confirmed to have the Omicron variant BA.1; one had Delta (AY.100). Thirty-four different mutations were detected within the receptor-binding domain of the spike protein in 62.5% of patients, eight of which were not lineage related and located in the sotrovimab target epitope (P337L, E340D, E340R, E340K, E340V, E340Q, R346T and K356T). Except for P337L, all changes showed a significant increase in frequency or fixation after the administration of sotrovimab. Some of them have been associated with either reduced susceptibility to mAb therapy, such as those at position 340, or the acquisition of a new glycosylation site (346 and 356 positions). CONCLUSIONS: This study highlights the importance of monitoring for early in vivo selection of mutations associated with reduced susceptibility to mAb therapy, especially in immunocompromised patients receiving anti-viral drugs, whose immune response is not able to control viral replication, resulting in long-term viral shedding, and those receiving selective evolution pressure. Virologic surveillance of genetically resistant viruses to available anti-viral therapies is considered a priority for both patients and the community.
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COVID-19 , Farmacorresistencia Viral , Huésped Inmunocomprometido , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Esparcimiento de Virus , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/genética , COVID-19/inmunología , Mutación , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Farmacorresistencia Viral/genética , Huésped Inmunocomprometido/inmunología , Esparcimiento de Virus/genética , Esparcimiento de Virus/inmunologíaRESUMEN
While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1-2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.
Asunto(s)
Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Modelos Animales de Enfermedad , SARS-CoV-2/inmunología , Esparcimiento de Virus/inmunología , Factores de Edad , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , COVID-19/genética , COVID-19/transmisión , Chlorocebus aethiops , Femenino , Hurones , Perfilación de la Expresión Génica/métodos , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Células Vero , VirulenciaRESUMEN
Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.
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COVID-19/inmunología , COVID-19/terapia , Plasma/inmunología , Enfermedades de Inmunodeficiencia Primaria/inmunología , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Niño , Femenino , Humanos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , Esparcimiento de Virus/inmunología , Adulto Joven , Sueroterapia para COVID-19RESUMEN
Bovine papillomaviruses types 1 and 2 (BPV1, BPV2) commonly induce skin tumours termed sarcoids in horses and other equids. Sarcoids seriously compromise the health and welfare of affected individuals due to their propensity to resist treatment and reoccur in a more severe form. We have developed influenza (Flu) A and B virus vectors that harbour a truncated NS1 gene (iNS) assuring interferon induction and co-express shuffled BPV1 E6 and E7 antigens for sarcoid immunotherapy. In a safety trial involving 12 healthy horses, intradermal administration of iNSA/E6E7equ and iNSB/E6E7equ was well tolerated, with the only transient side effect being mild fever in four horses. Repeated screening of secretions and faeces by RT-PCR and plaque assay revealed no virus shedding, thus also confirming biological safety. In a patient trial involving 29 horses bearing BPV1-induced single or multiple sarcoids, at least one lesion per horse was intratumourally injected and then boosted with iNSA/E6E7equ and/or iNSB/E6E7equ. The treatment induced a systemic antitumour response as reflected by the synchronous regression of injected and non-injected lesions. Irrespective of vaccination schemes, complete tumour regression was achieved in 10/29 horses. In 10/29 horses, regression is still ongoing (May 2021). Intriguingly, scrapings collected from former tumour sites in two patients tested negative by BPV1 PCR. Nine severely affected individuals with a history of unsuccessful therapeutic attempts did not (6/29) or only transiently (3/29) respond to the treatment. INSA/E6E7equ and iNSB/E6E7equ proved safe and effective in significantly reducing the tumour burden even in severe cases.
Asunto(s)
Papillomavirus Bovino 1/inmunología , Neoplasias/inmunología , Neoplasias/virología , Sarcoidosis/patología , Sarcoidosis/virología , Animales , Chlorocebus aethiops , Vectores de Enfermedades , Femenino , Caballos , Humanos , Gripe Humana/inmunología , Masculino , Orthomyxoviridae/inmunología , Vacunación/métodos , Células Vero , Esparcimiento de Virus/inmunologíaRESUMEN
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and life. A useful pathological animal model accurately reflecting human pathology is needed to overcome the COVID-19 crisis. In the present study, COVID-19 cynomolgus monkey models including monkeys with underlying diseases causing severe pathogenicity such as metabolic disease and elderly monkeys were examined. Cynomolgus macaques with various clinical conditions were intranasally and/or intratracheally inoculated with SARS-CoV-2. Infection with SARS-CoV-2 was found in mucosal swab samples, and a higher level and longer period of viral RNA was detected in elderly monkeys than in young monkeys. Pneumonia was confirmed in all of the monkeys by computed tomography images. When monkeys were readministrated SARS-CoV-2 at 56 d or later after initial infection all of the animals showed inflammatory responses without virus detection in swab samples. Surprisingly, in elderly monkeys reinfection showed transient severe pneumonia with increased levels of various serum cytokines and chemokines compared with those in primary infection. The results of this study indicated that the COVID-19 cynomolgus monkey model reflects the pathophysiology of humans and would be useful for elucidating the pathophysiology and developing therapeutic agents and vaccines.
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COVID-19/inmunología , Modelos Animales de Enfermedad , Macaca fascicularis/inmunología , Enfermedades de los Primates/inmunología , SARS-CoV-2/inmunología , Animales , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/virología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Pulmón/diagnóstico por imagen , Pulmón/inmunología , Pulmón/virología , Macaca fascicularis/virología , Masculino , Enfermedades de los Primates/virología , SARS-CoV-2/fisiología , Tomografía Computarizada por Rayos X/métodos , Esparcimiento de Virus/inmunología , Esparcimiento de Virus/fisiologíaRESUMEN
Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.
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COVID-19/inmunología , COVID-19/prevención & control , Interacciones Huésped-Patógeno/inmunología , Huésped Inmunocomprometido , Trasplante de Órganos , SARS-CoV-2/inmunología , Receptores de Trasplantes , COVID-19/complicaciones , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Terapia Combinada , Síndrome de Liberación de Citoquinas/etiología , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Inmunidad Celular , Inmunidad Humoral , Trasplante de Órganos/efectos adversos , Vacunación , Esparcimiento de Virus/inmunologíaRESUMEN
We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.
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COVID-19/complicaciones , COVID-19/inmunología , SARS-CoV-2/inmunología , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Esparcimiento de Virus/inmunología , Síndrome Post Agudo de COVID-19RESUMEN
Two separate introductions of human seasonal N2 neuraminidase genes were sustained in U.S. swine since 1998 (N2-98) and 2002 (N2-02). Herein, we characterized the antigenic evolution of the N2 of swine influenza A virus (IAV) across 2 decades following each introduction. The N2-98 and N2-02 expanded in genetic diversity, with two statistically supported monophyletic clades within each lineage. To assess antigenic drift in swine N2 following the human-to-swine spillover events, we generated a panel of swine N2 antisera against representative N2 and quantified the antigenic distance between wild-type viruses using enzyme-linked lectin assay and antigenic cartography. The antigenic distance between swine and human N2 was smallest between human N2 circulating at the time of each introduction and the archetypal swine N2. However, sustained circulation and evolution in swine of the two N2 lineages resulted in significant antigenic drift, and the N2-98 and N2-02 swine N2 lineages were antigenically distinct. Although intralineage antigenic diversity was observed, the magnitude of antigenic drift did not consistently correlate with the observed genetic differences. These data represent the first quantification of the antigenic diversity of neuraminidase of IAV in swine and demonstrated significant antigenic drift from contemporary human seasonal strains as well as antigenic variation among N2 detected in swine. These data suggest that antigenic mismatch may occur between circulating swine IAV and vaccine strains. Consequently, consideration of the diversity of N2 in swine IAV for vaccine selection may likely result in more effective control and aid public health initiatives for pandemic preparedness. IMPORTANCE Antibodies inhibiting the neuraminidase (NA) of IAV reduce clinical disease, virus shedding, and transmission, particularly in the absence of neutralizing immunity against hemagglutinin. To understand antibody recognition of the genetically diverse NA in U.S. swine IAV, we characterized the antigenic diversity of N2 from swine and humans. N2 detected in swine IAV were derived from two distinct human-to-swine spillovers that persisted, are antigenically distinct, and underwent antigenic drift. These findings highlight the need for continued surveillance and vaccine development in swine with increased focus on the NA. Additionally, human seasonal N2 isolated after 2005 were poorly inhibited by representative swine N2 antisera, suggesting a lack of cross-reactive NA antibody-mediated immunity between contemporary swine and human N2. Bidirectional transmission between humans and swine represents a One Health challenge, and determining the correlates of immunity to emerging IAV strains is critical to mitigating zoonotic and reverse-zoonotic transmission.
Asunto(s)
Epítopos/inmunología , Virus de la Influenza A/genética , Neuraminidasa/genética , Animales , Variación Antigénica/genética , Antígenos Virales/inmunología , Reacciones Cruzadas/inmunología , Epítopos/genética , Evolución Molecular , Variación Genética/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Subtipo H3N2 del Virus de la Influenza A/genética , Virus de la Influenza A/patogenicidad , Gripe Humana/genética , Neuraminidasa/inmunología , Neuraminidasa/metabolismo , Infecciones por Orthomyxoviridae/inmunología , Estaciones del Año , Porcinos , Enfermedades de los Porcinos/virología , Estados Unidos , Esparcimiento de Virus/inmunologíaRESUMEN
Objectives: The epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been researched. However, the prevalence of repositivity by real-time PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods: A retrospective study was conducted involving 599 discharged patients with COVID-19 in a single medical centre. The clinical features of patients during their hospitalization and 14-day post-discharge quarantine were collected. Results: A total of 122 patients (20.4%) out of 599 patients retested positive after discharge. Specifically, 94 (15.7%) retested positive within 24 h of discharge, and another 28 patients (4.7%) were repositive on day 7 after discharge, although none showed any clinical symptomatic recurrence. Both repositives and nonrepositives have similar patterns of IgG and IgM. Notably, the length of hospitalization of non-repositive patients was longer than that of 24-h repositive patients and 7-day repositive patients. In addition, the length of hospitalization of 24-h repositive patients was shorter than that of 7-day repositive patients, indicating that the length of hospitalization was also a determinant of viral shedding. Conclusion: Our study provides further information for improving the management of recovered and discharged patients, and further studies should be performed to elucidate the infectiveness of individuals with prolonged or RNA repositivity.
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Cuidados Posteriores/estadística & datos numéricos , Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , COVID-19/diagnóstico , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/sangre , COVID-19/epidemiología , COVID-19/terapia , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Alta del Paciente , ARN Viral/aislamiento & purificación , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/estadística & datos numéricos , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Esparcimiento de Virus/inmunología , Adulto JovenAsunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Programas de Inmunización , Internacionalidad , Investigadores , SARS-CoV-2/inmunología , Vacunología , Adolescente , Anciano , Anciano de 80 o más Años , Envejecimiento/inmunología , COVID-19/mortalidad , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/provisión & distribución , Portador Sano/inmunología , Portador Sano/prevención & control , Niño , Transmisión de Enfermedad Infecciosa/prevención & control , Femenino , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Inmunidad Colectiva/inmunología , Inmunización Secundaria , Persona de Mediana Edad , Seguridad del Paciente , Qatar/epidemiología , Reinfección/inmunología , Reinfección/prevención & control , Reinfección/virología , Investigadores/educación , Seychelles/epidemiología , Sudáfrica/epidemiología , Factores de Tiempo , Reino Unido/epidemiología , Estados Unidos/epidemiología , Vacunología/educación , Vacunología/tendencias , Carga Viral , Esparcimiento de Virus/inmunología , Organización Mundial de la Salud/organización & administraciónRESUMEN
Con el propósito de ampliar el conocimiento epidemiológico sobre la circulación del SARS-CoV-2 en la ciudad de Ushuaia durante el brote ocurrido de marzo a mayo de 2020, nos planteamos realizar un estudio observacional, de corte transversal, de mayo a julio, buscando la respuesta serológica al contacto con el virus en trabajadores esenciales municipales. N=1305. Los datos fueron ingresados a una plataforma con ingreso restringido, para luego cruzar las variables obtenidas en formato Excel. La mayoría de las personas estudiadas fueron de género masculino, con una media de edad de 38,5 años. El 20% de las personas con IgG+ tuvieron nexo epidemiológico. La prevalencia fue del 2,75%. Quienes presentaron IgM+ fueron descartados por otro método, considerándose falsos positivos. La idea y realización en forma precoz del estudio fue útil para evaluar la diseminación viral asintomática en el personal municipal afectado a tareas esenciales y tomar decisiones en las primeras etapas de la pandemia. No se encontraron diferencias significativas en los grupos más expuestos. Se observaron casos de transmisión asintomática intrafamiliar. Estas pruebas serológicas no tienen fines diagnósticos ni confieren un pasaporte inmunitario. Pudimos establecer la confiabilidad de la técnica utilizada, fundamentalmente en relación a la IgG. El método se optimizó. Consideramos que las políticas públicas basadas en evidencias científicas permiten tomar mejores decisiones en beneficio de la comunidad. Creemos que el presente estudio aporta al estado de comprensión en la materia. Cada reporte puede ser de utilidad para el conocimiento de la diseminación viral
With the purpose of expanding epidemiological knowledge about the circulation of SARS-CoV-2 in the city of Ushuaia during the outbreak that occurred from March to May of this current, we plan to carry out an observational, cross-sectional study from May to July, seeking the serological response to contact with the virus in essential municipal workers. N = 1316. The data were entered into a platform with restricted entry, to later cross the variables obtained in Excel format. Most of the people studied were male, with a mean age of 38 years. 20% of the people with IgG + had an epidemiological link. The prevalence was 2.88%. Those who presented IgM+ were discarded by another method, being considered false positives. The early idea and implementation of the study was useful to evaluate asymptomatic viral shedding in municipal personnel affected by essential tasks and to make decisions in the early stages of the pandemic. No significant differences were found in the most exposed groups. Cases of asymptomatic interfamily transmission were observed. These serological tests do not have diagnostic purposes nor do they confer an immune passport. We were able to establish the reliability of the technique used, mainly in relation to IgG. The method was optimized. We believe that public policies based on scientific evidence allow us to make better decisions for the benefit of the community. We believe that the present study contributes to the state of understanding in the matter. Each report can be useful for understanding viral shedding.
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Humanos , Adulto , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Estudios Transversales , Personal de Salud , Esparcimiento de Virus/inmunología , Administración Municipal , Prueba Serológica para COVID-19 , COVID-19/epidemiologíaAsunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , COVID-19/virología , Citotoxicidad Inmunológica , SARS-CoV-2/clasificación , SARS-CoV-2/inmunología , Linfocitos T/inmunología , Anticuerpos Neutralizantes/análisis , Anticuerpos Neutralizantes/inmunología , COVID-19/prevención & control , Industria Farmacéutica , Humanos , Memoria Inmunológica , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Incertidumbre , Esparcimiento de Virus/inmunologíaRESUMEN
Importance: Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective: The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants: The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures: Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results: The cohort included 3â¯257â¯478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2â¯876â¯773 (88.3%) had a negative index antibody result, and 378â¯606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance: In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.
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Prueba de Ácido Nucleico para COVID-19 , Prueba Serológica para COVID-19 , COVID-19 , Susceptibilidad a Enfermedades , SARS-CoV-2 , Adulto , Factores de Edad , Anticuerpos Antivirales/aislamiento & purificación , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , Prueba de Ácido Nucleico para COVID-19/métodos , Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , Prueba Serológica para COVID-19/métodos , Prueba Serológica para COVID-19/estadística & datos numéricos , Correlación de Datos , Susceptibilidad a Enfermedades/diagnóstico , Susceptibilidad a Enfermedades/epidemiología , Susceptibilidad a Enfermedades/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Estudios Seroepidemiológicos , Evaluación de Síntomas/métodos , Evaluación de Síntomas/estadística & datos numéricos , Estados Unidos/epidemiología , Esparcimiento de Virus/inmunologíaRESUMEN
Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.
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Ebolavirus/inmunología , Insuficiencia Respiratoria/virología , Enfermedades de los Porcinos/virología , Animales , Anticuerpos Antivirales/inmunología , Causalidad , Virus ADN/patogenicidad , Brotes de Enfermedades/prevención & control , Ebolavirus/metabolismo , Ebolavirus/patogenicidad , Filipinas/epidemiología , Insuficiencia Respiratoria/veterinaria , Sus scrofa/virología , Porcinos/virología , Enfermedades de los Porcinos/epidemiología , Esparcimiento de Virus/inmunologíaRESUMEN
There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.
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COVID-19/inmunología , Modelos Animales de Enfermedad , Hurones/inmunología , SARS-CoV-2/inmunología , Animales , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Pulmón/inmunología , Pulmón/patología , ARN Viral/aislamiento & purificación , SARS-CoV-2/genética , Replicación Viral/efectos de los fármacos , Replicación Viral/inmunología , Esparcimiento de Virus/efectos de los fármacos , Esparcimiento de Virus/inmunologíaRESUMEN
BACKGROUND: The viral persistence in patients with Coronavirus Disease 2019 (COVID-19) remains to be investigated. METHODS: We investigated the viral loads, therapies, clinical features, and immune responses in a 70-year patient tested positive for SARS-CoV-2 for 3 months. FINDINGS: The patient exhibited the highest prevalence of abnormal indices of clinical features and immune responses at the first admission, including fever (38.3 â), decreased lymphocytes (0.83 × 109/L) and serum potassium (3.1 mmol/L), as well as elevated serum creatinine (115 µmol/L), urea (8.6 mmol/L), and C-reactive protein (80 mg/L). By contrast, at the second and the third admission, these indices were all normal. Through three admissions, IL-2 increased from 0.14 pg/mL, 0.69 pg/mL, to 0.91 pg/mL, while IL-6 decreased from 11.78 pg/mL, 1.52 pg/mL, to 0.69 pg/mL, so did IL-10 from 5.13 pg/mL, 1.85 pg/mL, to 1.75 pg/mL. The steady declining trend was also found in TNF-α (1.49, 1.15, and 0.85 pg/mL) and IFN-γ (0.64, 0.42, and 0.27 pg/mL). The threshold cycle values of RT-PCR were 26.1, 30.5, and 23.5 for ORFlab gene, and 26.2, 30.6, and 22.7 for N gene, showing the patient had higher viral loads at the first and the third admission than during the middle term of the disease. The patient also showed substantially improved acute exudative lesions on the chest CT scanning images. CONCLUSIONS: The patient displayed declining immune responses in spite of the viral shedding for 3 months. We inferred the declining immune responses might result from the segregation of the virus from the immune system.
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COVID-19/inmunología , Fiebre/inmunología , Linfopenia/inmunología , SARS-CoV-2/patogenicidad , Esparcimiento de Virus/inmunología , Anciano , Antivirales/uso terapéutico , Biomarcadores/sangre , Proteína C-Reactiva/inmunología , Proteína C-Reactiva/metabolismo , COVID-19/diagnóstico por imagen , COVID-19/patología , COVID-19/virología , Prueba de COVID-19/métodos , Creatinina/sangre , Creatinina/inmunología , Fiebre/diagnóstico por imagen , Fiebre/patología , Fiebre/virología , Hospitalización , Humanos , Inmunidad , Interferón gamma/sangre , Interferón gamma/inmunología , Interleucina-10/sangre , Interleucina-10/inmunología , Interleucina-2/sangre , Interleucina-2/inmunología , Interleucina-6/sangre , Interleucina-6/inmunología , Linfopenia/diagnóstico por imagen , Linfopenia/patología , Linfopenia/virología , Masculino , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Tomografía Computarizada por Rayos X , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunología , Carga Viral/efectos de los fármacosRESUMEN
In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24-59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7. Several interferon-stimulated genes are differentially expressed in children with pre-LAIV asymptomatic respiratory viral infections and negatively correlated with LAIV VLs. Upregulation of genes enriched in macrophages, neutrophils, and eosinophils is associated with lower VLs and found more commonly in children with asymptomatic viral infections. Variability in pre-infection mucosal interferon gene expression in children may impact the course of subsequent influenza infections. This variability may be due to frequent respiratory viral infections, demonstrating the potential importance of mucosal virus-virus interactions in children.