ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is usually mild and self-limited in children. However, a few Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections in children may progress to severe disease with respiratory distress or can result in a multisystem inflammatory syndrome (MIS-C) associated with COVID-19. The immune mechanisms for these differential clinical outcomes are largely unknown. METHODS: A prospective cohort study was performed to analyze the laboratory parameters, antibody response, immune phenotypes and cytokine profiles of 51 children with different clinical presentations of COVID-19. RESULTS: We found that the absolute lymphocyte counts gradually decreased with disease severity. Furthermore, SARS-CoV-2 IgG levels in the acute phase and convalescence were not significantly different in patients with different disease severity. A decrease in CD3 + , CD4 + and CD8 + T cells was observed as disease severity increased. Both CD4 + and CD8 + T cells were activated in children with COVID-19, but no difference in the percentage of HLADR + -expressing cells was detected across the severity groups. In contrast, MIS-C patients exhibited augmented exhausted effector memory CD8 + T cells. Interestingly, the cytokine profile in sera of moderate/severe and MIS-C patients revealed an increase in anti-inflammatory IL-1RA and a suppression of tumor necrosis factor-α, RANTES, eotaxin and PDGF-BB. MIS-C patients also exhibited augmented IL-1ß. CONCLUSIONS: We report distinct immune profiles dependent on severity in pediatric COVID-19 patients. Further investigation in a larger population will help unravel the immune mechanisms underlying pediatric COVID-19.
Subject(s)
COVID-19 , Cytokines , Becaplermin , COVID-19/complications , COVID-19/immunology , Chemokine CCL5 , Cytokines/immunology , Humans , Immunoglobulin G , Interleukin 1 Receptor Antagonist Protein , Phenotype , Prospective Studies , RNA, Viral , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: 25-hydroxyvitamin D (VD) effects on lung function and immune-modulation might affect respiratory syncytial virus (RSV) infection outcomes. We aimed to assess VD levels on admission and their association with life-threatening RSV disease (LTD). METHODS: A prospective cohort study was conducted during 2017-2019. Previously healthy infants aged <12 months, hospitalized with a first episode of RSV infection, were enrolled. LTD was defined by need for intensive care and ventilatory support. Serum VD levels <20 ng/mL were categorized as deficient, and 20-29.9 ng/mL as insufficient. RESULTS: Of 125 patients studied, 73 (58%) were male. Median age was 4 months. Twenty-two patients developed LTD. No differences in viral load were seen between cases with LTD and controls (P = .94). Patients who developed LTD had significantly lower VD levels: median 18.4 ng/mL (IQR, 15.1-26.9 ng/mL) versus 31.7 ng/mL (IQR, 23.6-42.0 ng/mL), P < .001; 59% of infants with LTD had VD deficiency compared with 12% in those with better outcome. Multivariable regression analysis confirmed VD deficiency as a risk factor (odds ratio, 11.83; 95% confidence interval, 3.89-35.9; P < .001). CONCLUSIONS: These findings provide additional evidence for the development of strategies to prevent severe RSV infections.
Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Female , Humans , Infant , Male , Prospective Studies , Respiratory Syncytial Viruses , Severity of Illness Index , Vitamin DABSTRACT
BACKGROUND: Genetic background may be an important host determinant of respiratory syncytial virus (RSV) disease severity, but full characterization of susceptibility genes remains unclear. This study aimed to assess the presence of specific single-nucleotide polymorphisms (SNPs) in selected genes codifying for different components of the antiviral innate immune response, to determine their role for developing RSV life-threatening disease (LTD). METHODS: Prospective cohort study including previously healthy full-term infants hospitalized with a first RSV infection during 2017-2018. RSV detection, quantification and subgroup determination, and genotyping for SNPs in Toll-like receptor 4 (TLR4 rs4986790, rs4986791), Toll-like receptor 8 (TLR8 rs3761624), macrophage receptor with collagenous structure(MARCO rs1318645) and myxovirus resistance 1(MX1 rs469390) were performed by real-time polymerase chain reaction in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit requiring ventilatory support. RESULTS: Seventy-five patients were studied, 15 (20%) developed LTD. Infants with concurrent SNPs in MX1 and TLR8, MARCO and TLR8 or MARCO, MX1 and TLR8 had an increased risk of developing LTD. Multivariable logistic regression analysis confirmed this significant association (odds ratio [OR] = 3.75, P = 0.046; OR = 3.92, P = 0.040; OR = 5.56, P = 0.010, respectively). No differences were seen in viral load of patients with LTD compared with those with better outcome (P = 0.737). In addition, no differences in viral load were seen in patients with the described high-risk SNPs compared with those without these polymorphisms. CONCLUSIONS: Life-threatening RSV infection in previously healthy infants was significantly associated with the presence of combined SNPs in MARCO, MX1 and TLR8.
Subject(s)
Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Respiratory Syncytial Virus Infections/genetics , Child, Hospitalized , Female , Humans , Immunity, Innate , Infant , Male , Myxovirus Resistance Proteins/genetics , Prospective Studies , Receptors, Immunologic/genetics , Respiratory Syncytial Virus Infections/immunology , Toll-Like Receptor 4/genetics , Toll-Like Receptor 8/genetics , Viral LoadABSTRACT
La tuberculosis extrapulmonar representa el 1520 % de todas las formas de presentación. La tuberculosis ganglionar periférica es la segunda forma extrapulmonar más frecuente en niños de Argentina, luego de la pleural. En el Servicio de Tisiología del Hospital de Niños "Dr. Ricardo Gutiérrez", se analizaron en forma retrospectiva 92 casos de tuberculosis ganglionar periférica asistidos entre agosto, 2000-septiembre, 2015. La edad media fue 8,7 ± 5 años. Las adenopatías fueron periféricas únicas (31,5 %), periféricas múltiples (20,6 %) y periféricas asociadas a profundas (47,8 %). Predominó la localización cervical (80 %). El 80 % recibió antibioticoterapia previa, sin respuesta. El 56 % tenía foco de contagio conocido; 69 %, prueba cutánea de tuberculina positiva y 54 %, radiografía de tórax patológica. Todos iniciaron tratamiento antifímico por clínica compatible, exposición y/o prueba cutánea de tuberculina positiva, antes de la confirmación microbiológica o histológica. La evolución fue curación (81,5 %), derivación cercana al domicilio (8,7 %), abandono (8,7 %). Un paciente falleció.
Extrapulmonary tuberculosis accounts for 15-20 % of all clinical presentations of tuberculosis. Peripheral tuberculous lymphadenitis is the second most common presentation of extrapulmonary tuberculosis in children, after pleural tuberculosis, in Argentina. We analyzed 92 patients with peripheral tuberculous lymphadenitis seen at the Department of Tisiology of Hospital de Niños "Dr. Ricardo Gutiérrez" between August 2000 and September 2015. The patients' mean age was 8.7 ± 5 years. Nodal sites corresponded to single peripheral (31.5 %), multiple peripheral (20.6 %), and peripheral associated with deep nodes (47.8 %). Cervical lymph nodes were the most common site of involvement (80 %). In 80 % of patients previous antibiotic therapy had been administered, without response. The tuberculosis source was known in 56 %; 69 % had a positive tuberculin skin test; and 54 %, a pathological chest X-ray. Tuberculosis treatment was started on all patients based on clinical criteria, exposure and/or positive tuberculin skin test, prior to microbiological or histological confirmation. The clinical course was either healing (81.5 %), referral to a facility near home (8.7 %) or dropout (8.7 %). One patient died.
Subject(s)
Humans , Child , Pediatrics , Tuberculosis , Tuberculosis, Lymph Node , Lymphadenopathy , MycobacteriumABSTRACT
Extrapulmonary tuberculosis accounts for 15-20 % of all clinical presentations of tuberculosis. Peripheral tuberculous lymphadenitis is the second most common presentation of extrapulmonary tuberculosis in children, after pleural tuberculosis, in Argentina. We analyzed 92 patients with peripheral tuberculous lymphadenitis seen at the Department of Tisiology of Hospital de Niños "Dr. Ricardo Gutiérrez" between August 2000 and September 2015. The patients' mean age was 8.7 ± 5 years. Nodal sites corresponded to single peripheral (31.5 %), multiple peripheral (20.6 %), and peripheral associated with deep nodes (47.8 %). Cervical lymph nodes were the most common site of involvement (80 %). In 80 % of patients previous antibiotic therapy had been administered, without response. The tuberculosis source was known in 56 %; 69 % had a positive tuberculin skin test; and 54 %, a pathological chest X-ray. Tuberculosis treatment was started on all patients based on clinical criteria, exposure and/or positive tuberculin skin test, prior to microbiological or histological confirmation. The clinical course was either healing (81.5 %), referral to a facility near home (8.7 %) or dropout (8.7 %). One patient died.
La tuberculosis extrapulmonar representa el 1520 % de todas las formas de presentación. La tuberculosis ganglionar periférica es la segunda forma extrapulmonar más frecuente en niños de Argentina, luego de la pleural. En el Servicio de Tisiología del Hospital de Niños "Dr. Ricardo Gutiérrez", se analizaron en forma retrospectiva 92 casos de tuberculosis ganglionar periférica asistidos entre agosto, 2000-septiembre, 2015. La edad media fue 8,7 ± 5 años. Las adenopatías fueron periféricas únicas (31,5 %), periféricas múltiples (20,6 %) y periféricas asociadas a profundas (47,8 %). Predominó la localización cervical (80 %). El 80 % recibió antibioticoterapia previa, sin respuesta. El 56 % tenía foco de contagio conocido; 69 %, prueba cutánea de tuberculina positiva y 54 %, radiografía de tórax patológica. Todos iniciaron tratamiento antifímico por clínica compatible, exposición y/o prueba cutánea de tuberculina positiva, antes de la confirmación microbiológica o histológica. La evolución fue curación (81,5 %), derivación cercana al domicilio (8,7 %), abandono (8,7 %). Un paciente falleció.
