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BACKGROUND: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. METHODS: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov ( NCT04651790 ). FINDINGS: The recruitment of participants occurred between November 27 (th) , 2020, until January 9 (th) , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. INTERPRETATION: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens. FUNDING: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Introducción. El linfoma extranodal nasal de células T/natural killer (ENKL) es un linfoma no Hodgkin altamente agresivo y de etiología desconocida. Sus manifestaciones clínicas suelen ser obstrucción nasal, epistaxis y signos inflamatorios; sin embargo, el diagnóstico puede llegar a ser difícil, requiriendo histopatología e inmunohistoquímica para su detección. Como tratamiento se han propuesto radioterapia y quimioterapia, según el estadio de la enfermedad. Presentación del caso. Paciente masculino de 44 años de edad, previamente sano, quien asistió al servicio de consulta externa por cuadro clínico de 2 meses de evolución consistente en síntomas de obstrucción y secreción nasal, edema y eritema facial. Se realizó diagnóstico inicial de celulitis facial, pero dado que no hubo mejoría con el tratamiento antibiótico, el sujeto fue remitido al servicio de urgencias de una institución de mayor complejidad, donde se le practicaron imágenes complementarias que mostraron una masa en la cavidad nasal derecha; mediante análisis histopatológico se estableció que se trataba de un ENKL, por lo que se indicó radioterapia; sin embargo, a consecuencia del estadio avanzado de dicha patología, el paciente falleció. Conclusión. El diagnóstico oportuno de ENKL es crucial para mejorar la expectativa de vida de quienes lo padecen; sin embargo, puede representar un reto clínico debido a su presentación inespecífica.

BackgroundThe ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.MethodsThis is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790).FindingsThe recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity.InterpretationImmunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens.FundingMinistry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Human respiratory syncytial virus (hRSV) is the primary viral cause of respiratory diseases, leading to bronchiolitis and pneumonia in vulnerable populations. The only current treatment against this virus is palliative, and no efficient and specific vaccine against this pathogen is available.The authors describe the disease symptoms caused by hRSV, the economic and social impact of this infection worldwide, and how this infection can be modulated using pharmacological treatments, preventing and limiting its dissemination. The authors discuss the use of antibodies as prophylactic tools -such as palivizumab- and the use of nonspecific drugs to decrease the symptoms associated with the infection -such as bronchodilators, corticoids, and antivirals. They also discuss current vaccine candidates, new prophylactic treatments, and new antivirals options, which are currently being tested.Today, many researchers are focused on developing different strategies to modulate the symptoms induced by hRSV. However, to achieve this, understanding how current treatments are working and their shortcomings needs to be further elucidated.

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

Neurobehavioral alterations and cognitive impairment are common phenomena that represent neuropsychiatric disorders and can be triggered by an exacerbated immune response against pathogens, brain injury, or autoimmune diseases. Pro-inflammatory molecules, such as cytokines and chemokines, are produced in the brain by resident cells, mainly by microglia and astrocytes. Brain infiltrating immune cells constitutes another source of these molecules, contributing to an impaired neurological synapse function, affecting typical neurobehavioral and cognitive performance. Currently, there is increasing evidence supporting the notion that behavioral alterations and cognitive impairment can be associated with respiratory viral infections, such as human respiratory syncytial virus, influenza, and SARS-COV-2, which are responsible for endemic, epidemic, or pandemic outbreak mainly in the winter season. This article will review the brain′s pro-inflammatory response due to infection by three highly contagious respiratory viruses that are the leading cause of acute respiratory illness, morbidity, and mobility in infants, immunocompromised and elderly population. How these respiratory viral pathogens induce increased secretion of pro-inflammatory molecules and their relationship with the alterations at a behavioral and cognitive level will be discussed.

Indexación Scopus The World Health Organization (WHO) announced in March a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This new infectious disease was named Coronavirus Disease 19 (COVID-19), and at October 2020, more than 39,000,000 cases of SARS-CoV-2 have been detected worldwide leading to near 1,100,000 deaths. Clinically, COVID-19 is characterized by clinical manifestations, such as fever, dry cough, headache, and in more severe cases, respiratory distress. Moreover, neurological-, cardiac-, and renal-related symptoms have also been described. Clinical evidence suggests that migration of immune cells to the affected organs can produce an exacerbated release of proinflammatory mediators that contribute to disease and render the immune response as a major player during the development of the COVID-19 disease. Due to the current sanitary situation, the development of vaccines is imperative. Up to the date, 42 prototypes are being tested in humans in different clinical stages, with 10 vaccine candidates undergoing evaluation in phase III clinical trials. In the same way, the search for an effective treatment to approach the most severe cases is also in constant advancement. Several potential therapies have been tested since COVID-19 was described, including antivirals, antiparasitic and immune modulators. Recently, clinical trials with hydroxychloroquine—a promising drug in the beginning—were suspended. In addition, the Food and Drug Administration (FDA) approved convalescent serum administration as a treatment for SARS-CoV-2 patients. Moreover, monoclonal antibody therapy is also under development to neutralize the virus and prevent infection. In this article, we describe the clinical manifestations and the immunological information available about COVID-19 disease. Furthermore, we discuss current therapies under study and the development of vaccines to prevent this disease. © Copyright © 2020 Canedo-Marroquín, Saavedra, Andrade, Berrios, Rodríguez-Guilarte, Opazo, Riedel and Kalergis. https://www.frontiersin.org/articles/10.3389/fimmu.2020.569760/full

Mucormycosis is a life-threatening disease, were rhinocerebral infection is most commonly seen in the clinical setting. Chronic mucormycosis is a rare presentation that exhibits a challenging diagnosis. We describe the case of a 47 year old diabetic man with complains of left zygomatic arch swelling of 3 months evolution. He had received previous antibiotic treatment without improvement. Biopsy of maxillary sinus revealed the presence of non-septated, 90° angle branched hyphae compatible with zygomicetes. The patient was treated with surgical debridement and amphotericin B until there was no evidence of fungi in the tissue by biopsy. We reviewed chronic rhino-orbito-cerebral mucormycosis from 1964–2014 and 22 cases were found, being this the second case of chronic mucormycosis reported in Mexico. A quarter of the cases were seen in immunocompetent hosts. As only 20% of the causal agent can be isolated by culture, the diagnosis is mainly made by biopsy. Besides treatment with amphotericin B, posaconazole as alternative, and control of the underlying comorbidities, surgical debridement represents the corner stone therapy. We recommend at least 36 month follow-up, due to the 13% risk of recurrence. A chronic presentation has a general survival rate of approximately 83%., Highlights • We describe the case of a chronic rhino-orbito-cerebral mucormycosis. • Chronic mucormycosis has low rate of frequency and is difficult to diagnose. • A quarter of chronic rhino-orbito-cerebral mucormycosis cases are in immunocompetents. • Surgical debridement is the corner stone of mucormycosis treatment. • Survival rate in chronic mucormycosis cases (83%) is higher than acute cases (10–35%).

espanolEl signo de Chilaiditi es un hallazgo radiografico infrecuente que consiste en la interposicion de un asa intestinal entre el higado y el diafragma. No existe etiologia claramente establecida; sin embargo, se han planteado varias hipotesis que explican su presencia, entre ellos la hiperlaxitud de los ligamentos suspensorios del higado, el aumento de la presion intraabdominal y la redundancia colonica. Al asociarse este hallazgo con sintomas gastrointestinales o respiratorios se denomina sindrome de Chilaiditi, y su tratamiento principalmente es sintomatico, en casos excepcionales requiere abordaje quirurgico. Este signo se encuentra usualmente de manera incidental y se ha visto una relacion con enfermedad respiratoria cronica; pudiendo afectar su curso clinico, motivando a profundizar en el estudio integral. Se presenta el caso de un paciente adulto mayor, en seguimiento medico por enfermedad pulmonar obstructiva cronica, cuya radiografia de torax evidencia la interposicion de un asa intestinal entre la cupula diafragmatica derecha y el higado. MED.UIS. 2018;31(3):57-61. EnglishThe Chilaiditi sign is a rare radiographic finding, which consists in the interposition of an intestinal handle between the liver and the diaphragm. There is no clear etiology established, however, several hypotheses have been proposed to explain its presence, includingthe hyper-laxity of the liver suspensory ligaments, an increase on the intra-abdominal pressure and colonic redundancy. When this finding is associated with gastrointestinal or respiratory symptoms is called “Chilaiditi syndrome”, and its treatment is mainly symptomatic;in exceptional cases a surgical approach is required. The Chilaiditi sign is usually an incidental finding, and a connection with chronic respiratory disease has been seen, and it could affect this pathology’s clinical course, being this a motivation to deepen in an integral study. We present a case of an elder patient, being followed due to chronic obstructive pulmonary disease, whose chest X-ray shows interposition of an intestinal handle between the right diaphragmatic dome and the liver. MED.UIS. 2018;31(3):57-61.

Alteplase is the only approved drug for the treatment of acute ischemic stroke, but it is offered to a minority of patients, not only because of the short therapeutic window but also because of the numerous contraindications associated with thrombolysis, such as thrombocytopenia. There is some controversy on the true risk associated with thrombolysis in patients with thrombocytopenia. Here we report the case of a young patient, who developed an in-hospital acute ischemic stroke involving a large territory of the right middle cerebral artery, who was successfully treated with intravenous alteplase, despite having thrombocytopenia and prolonged prothrombin times due to systemic lupus erythematosus and antiphospholipid syndrome. This case exemplifies the need to reassess contraindications for thrombolysis, many based on expert opinion and not clinical evidence, especially in complex clinical situations.