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Background: Coronavirus disease 2019 (COVID-19) infection is a major public health problem in the world and reinfections are becoming more frequent. Our main objective was to describe the epidemiological, clinical, and genomic characteristics of the confirmed cases of reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the capital of Lima and Callao, Peru. Methods: We searched in the Peruvian laboratory information system from April 2020 up to May 2021, looking for cases having 2 positive molecular tests for SARS-CoV-2 with more than 90 days between them. We performed genomic sequencing to the available pairs of samples and described the clinical characteristics, epidemiological impact, and genomic analysis of the confirmed reinfections. Results: There were 1 694 164 people with a positive diagnostic test for SARS-CoV-2 in Lima/Callao during the study period. Of these, 1695 had 2 positive molecular tests with more than 90 days between them. Two hundred eleven had both samples available for genomic analysis according to our selection criteria, and these were retrieved and submitted to sequencing. Thirty cases were confirmed to be SARS-CoV-2 reinfections with 2 different lineages in the 2 episodes. The variant Lambda (C.37) was the most common during the second infection and accounted for 19 (63.3%) of the 30 cases. Conclusions: We report 30 cases of confirmed SARS-CoV-2 reinfections. The Lambda variant was the most common cause of the second infections, in concordance with its predominant circulation during Peru's second wave. This report describes the largest series of confirmed reinfections by SARS-CoV-2 in Latin America.We describe the epidemiological, clinical, and genomic characteristics of the confirmed cases of reinfection by severe acute respiratory syndrome coronavirus 2 in Lima and Callao, durante la segunda ola en Peru. The Lambda variant (C.37) was the most common cause of the second infections.
RESUMO
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major threat to public health. Rapid molecular testing for convenient and timely diagnosis of SARS-CoV-2 infections represents a challenge that could help to control the current pandemic and prevent future outbreaks. We aimed to develop and validate a multiplex and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using lyophilized LAMP reagents for sensitive and rapid detection of SARS-CoV-2. LAMP primers were designed for a set of gene targets identified by a genome-wide comparison of viruses. Primer sets that showed optimal features were combined into a multiplex RT-LAMP assay. Analytical validation included assessment of the limit of detection (LoD), intra- and inter-assay precision, and cross-reaction with other respiratory pathogens. Clinical performance compared to that of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was assessed using 278 clinical RNA samples isolated from swabs collected from individuals tested for COVID-19. The RT-LAMP assay targeting the RNA-dependent RNA polymerase (RdRp), membrane (M), and ORF1ab genes achieved a comparable LoD (0.65 PFU/mL, CT=34.12) to RT-qPCR and was 10-fold more sensitive than RT-qPCR at detecting viral RNA in clinical samples. Cross-reactivity to other respiratory pathogens was not observed. The multiplex RT-LAMP assay demonstrated a strong robustness and acceptable intra- and inter-assay precision (mean coefficient of variation, 4.75% and 8.30%). Diagnostic sensitivity and specificity values were 100.0% (95% CI: 97.4-100.0%) and 98.6% (95% CI: 94.9-99.8%), respectively, showing high consistency (Cohen's kappa, 0.986; 95% CI: 0.966-1.000; p<0.0001) compared to RT-qPCR. The novel one-step multiplex RT-LAMP assay is storable at room temperature and showed similar diagnostic accuracy to conventional RT-qPCR, while being faster (<45 min), simpler, and cheaper. The new assay could allow reliable and early diagnosis of SARS-CoV-2 infections in primary health care. It may aid large-scale testing in resource-limited settings, especially if it is integrated into a point-of-care diagnostic device.
Assuntos
COVID-19 , SARS-CoV-2 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Colorimetria , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , RNA Viral/genética , Transcrição Reversa , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To standardize and validate an in-house RT-LAMP test for the detection of SARS-CoV-2, based on laboratory and field assays using samples from COVID-19 suspected patients. MATERIALS AND METHODS: An in-house SARS-CoV-2 RT-LAMP molecular test was standardized, establishing the detection limit with Vero cells of isolated Peruvian strains of SARS-CoV-2, and the robustness to various concentrations of primers. The laboratory validation was performed with 384 nasal and pharyngeal swab samples (UFH) obtained between March and July 2020. The field validation was performed with 383 UFH obtained from COVID-19 suspected symptomatic cases. All samples were tested by RT-LAMP and RT-qPCR. The RT-qPCR was considered as the reference standard test. The concordance measures and diagnostic performance were calculated. RESULTS: The detection limit was consistent in cases with Ct <30 in both tests, showing efficiency to detect up to 1000 copies/µL of the target gene. Robustness was evidenced with half of the primer concentrations and 20 µL of final volume. Absence of amplification was identified for other HCoVs. Concordance showed a kappa index of 0.88 (95% CI: 0.83-0.93) and 0.89 (95% CI: 0.84 - 0.94) in laboratory and field settings, respectively. The sensitivity value in the laboratory was 87.4% (95% CI: 80.8 - 92.4) and 88.1% in the field (95% CI: 81.6 - 92.9). The specificity value in both settings was 98.8% (95% CI: 96.4-99.7). CONCLUSIONS: The in-house SARS-CoV-2 RT-LAMP test was successfully validated based on its adequate robustness, no cross-reactions, good concordance, and diagnostic performance compared to RT-qPCR.
OBJETIVOS: Estandarizar una prueba RT-LAMP in house para la detección de SARS-CoV-2 y validarla con muestras de laboratorio y de campo en pacientes con sospecha clínica de COVID-19. MATERIALES Y MÉTODOS: Se estandarizó una prueba molecular RT-LAMP in house para la detección de SARS-CoV-2 estableciéndose el límite de detección con células Vero de cepas peruanas aisladas de SARS-CoV-2. Se validó la prueba en laboratorio con 384 muestras de hisopado nasal y faríngeo (HNF) obtenidas entre marzo y julio de 2020. Para la validación de campo se obtuvieron muestras de HNF de 383 casos sintomáticos sospechosos de COVID-19. Todas las muestras fueron evaluadas por RT-LAMP y RT-qPCR. Para la validación de laboratorio y de campo se consideró como estándar de referencia al RT-qPCR, se calcularon medidas de concordancia y rendimiento diagnóstico. RESULTADOS: El límite de detección fue consistente en los casos con umbral de ciclo (Ct) Ct < 30 en ambas pruebas, mostrando eficiencia para detectar hasta 1000 copias/µL del gen diana. Se evidenció robustez con la mitad de las concentraciones de cebadores y 20 µL de volumen final. Se identificó ausencia de amplificación para otros coronavirus humanos. La concordancia en laboratorio obtuvo un Kappa de 0,88 (IC 95%: 0,83-0,93) y en campo fue de 0,89 (IC 95%: 0,84−0,94); la sensibilidad en laboratorio fue de 87,4% (IC 95%: 80,8−92,4) y en campo fue de 88,1% (IC 95%: 81,6−92,9), la especificidad en ambos escenarios fue de 98,8% (IC 95%: 96,4−99,7). CONCLUSIONES: La prueba RT-LAMP in house fue validada por presentar una adecuada robustez, sin reacciones cruzadas, buena concordancia y rendimiento diagnóstico comparado con el RT-qPCR.
Assuntos
COVID-19 , SARS-CoV-2 , Animais , Chlorocebus aethiops , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , RNA Viral , Padrões de Referência , Sensibilidade e Especificidade , Células VeroRESUMO
RESUMEN Objetivos: Estandarizar una prueba RT-LAMP in house para la detección de SARS-CoV-2 y validarla con muestras de laboratorio y de campo en pacientes con sospecha clínica de COVID-19. Materiales y métodos: Se estandarizó una prueba molecular RT-LAMP in house para la detección de SARS-CoV-2 estableciéndose el límite de detección con células Vero de cepas peruanas aisladas de SARS-CoV-2. Se validó la prueba en laboratorio con 384 muestras de hisopado nasal y faríngeo (HNF) obtenidas entre marzo y julio de 2020. Para la validación de campo se obtuvieron muestras de HNF de 383 casos sintomáticos sospechosos de COVID-19. Todas las muestras fueron evaluadas por RT-LAMP y RT-qPCR. Para la validación de laboratorio y de campo se consideró como estándar de referencia al RT-qPCR, se calcularon medidas de concordancia y rendimiento diagnóstico. Resultados: El límite de detección fue consistente en los casos con umbral de ciclo (Ct) Ct < 30 en ambas pruebas, mostrando eficiencia para detectar hasta 1000 copias/µL del gen diana. Se evidenció robustez con la mitad de las concentraciones de cebadores y 20 µL de volumen final. Se identificó ausencia de amplificación para otros coronavirus humanos. La concordancia en laboratorio obtuvo un Kappa de 0,88 (IC 95%: 0,83-0,93) y en campo fue de 0,89 (IC 95%: 0,84−0,94); la sensibilidad en laboratorio fue de 87,4% (IC 95%: 80,8−92,4) y en campo fue de 88,1% (IC 95%: 81,6−92,9), la especificidad en ambos escenarios fue de 98,8% (IC 95%: 96,4−99,7). Conclusiones: La prueba RT-LAMP in house fue validada por presentar una adecuada robustez, sin reacciones cruzadas, buena concordancia y rendimiento diagnóstico comparado con el RT-qPCR.
ABSTRACT Objectives: To standardize and validate an in-house RT-LAMP test for the detection of SARS-CoV-2, based on laboratory and field assays using samples from COVID-19 suspected patients. Materials and methods: An in-house SARS-CoV-2 RT-LAMP molecular test was standardized, establishing the detection limit with Vero cells of isolated Peruvian strains of SARS-CoV-2, and the robustness to various concentrations of primers. The laboratory validation was performed with 384 nasal and pharyngeal swab samples (UFH) obtained between March and July 2020. The field validation was performed with 383 UFH obtained from COVID-19 suspected symptomatic cases. All samples were tested by RT-LAMP and RT-qPCR. The RT-qPCR was considered as the reference standard test. The concordance measures and diagnostic performance were calculated. Results: The detection limit was consistent in cases with Ct <30 in both tests, showing efficiency to detect up to 1000 copies/μL of the target gene. Robustness was evidenced with half of the primer concentrations and 20 μL of final volume. Absence of amplification was identified for other HCoVs. Concordance showed a kappa index of 0.88 (95% CI: 0.83-0.93) and 0.89 (95% CI: 0.84 - 0.94) in laboratory and field settings, respectively. The sensitivity value in the laboratory was 87.4% (95% CI: 80.8 - 92.4) and 88.1% in the field (95% CI: 81.6 - 92.9). The specificity value in both settings was 98.8% (95% CI: 96.4-99.7). Conclusions: The in-house SARS-CoV-2 RT-LAMP test was successfully validated based on its adequate robustness, no cross-reactions, good concordance, and diagnostic performance compared to RT-qPCR.
Assuntos
Padrões de Referência , Técnicas de Diagnóstico Molecular , Diagnóstico , SARS-CoV-2 , Pacientes , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Reações Cruzadas , COVID-19RESUMO
RESUMEN Objetivos: Estandarizar una prueba RT-LAMP in house para la detección de SARS-CoV-2 y validarla con muestras de laboratorio y de campo en pacientes con sospecha clínica de COVID-19. Materiales y métodos: Se estandarizó una prueba molecular RT-LAMP in house para la detección de SARS-CoV-2 estableciéndose el límite de detección con células Vero de cepas peruanas aisladas de SARS-CoV-2. Se validó la prueba en laboratorio con 384 muestras de hisopado nasal y faríngeo (HNF) obtenidas entre marzo y julio de 2020. Para la validación de campo se obtuvieron muestras de HNF de 383 casos sintomáticos sospechosos de COVID-19. Todas las muestras fueron evaluadas por RT-LAMP y RT-qPCR. Para la validación de laboratorio y de campo se consideró como estándar de referencia al RT-qPCR, se calcularon medidas de concordancia y rendimiento diagnóstico. Resultados: El límite de detección fue consistente en los casos con umbral de ciclo (Ct) Ct < 30 en ambas pruebas, mostrando eficiencia para detectar hasta 1000 copias/µL del gen diana. Se evidenció robustez con la mitad de las concentraciones de cebadores y 20 µL de volumen final. Se identificó ausencia de amplificación para otros coronavirus humanos. La concordancia en laboratorio obtuvo un Kappa de 0,88 (IC 95%: 0,83-0,93) y en campo fue de 0,89 (IC 95%: 0,84−0,94); la sensibilidad en laboratorio fue de 87,4% (IC 95%: 80,8−92,4) y en campo fue de 88,1% (IC 95%: 81,6−92,9), la especificidad en ambos escenarios fue de 98,8% (IC 95%: 96,4−99,7). Conclusiones: La prueba RT-LAMP in house fue validada por presentar una adecuada robustez, sin reacciones cruzadas, buena concordancia y rendimiento diagnóstico comparado con el RT-qPCR.
ABSTRACT Objectives: To standardize and validate an in-house RT-LAMP test for the detection of SARS-CoV-2, based on laboratory and field assays using samples from COVID-19 suspected patients. Materials and methods: An in-house SARS-CoV-2 RT-LAMP molecular test was standardized, establishing the detection limit with Vero cells of isolated Peruvian strains of SARS-CoV-2, and the robustness to various concentrations of primers. The laboratory validation was performed with 384 nasal and pharyngeal swab samples (UFH) obtained between March and July 2020. The field validation was performed with 383 UFH obtained from COVID-19 suspected symptomatic cases. All samples were tested by RT-LAMP and RT-qPCR. The RT-qPCR was considered as the reference standard test. The concordance measures and diagnostic performance were calculated. Results: The detection limit was consistent in cases with Ct <30 in both tests, showing efficiency to detect up to 1000 copies/μL of the target gene. Robustness was evidenced with half of the primer concentrations and 20 μL of final volume. Absence of amplification was identified for other HCoVs. Concordance showed a kappa index of 0.88 (95% CI: 0.83-0.93) and 0.89 (95% CI: 0.84 - 0.94) in laboratory and field settings, respectively. The sensitivity value in the laboratory was 87.4% (95% CI: 80.8 - 92.4) and 88.1% in the field (95% CI: 81.6 - 92.9). The specificity value in both settings was 98.8% (95% CI: 96.4-99.7). Conclusions: The in-house SARS-CoV-2 RT-LAMP test was successfully validated based on its adequate robustness, no cross-reactions, good concordance, and diagnostic performance compared to RT-qPCR.
Assuntos
Estudo de Validação , Técnicas de Diagnóstico Molecular , SARS-CoV-2 , Laboratórios , Pacientes , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Reações Cruzadas , Diagnóstico , COVID-19RESUMO
RESUMEN Objetivo: Describir los resultados de los exámenes de laboratorio realizados en muestras biológicas de pacientes con síndrome de Guillain-Barré (SGB), recibidas en el Instituto Nacional de Salud (INS) entre los años 2018 y 2019. Materiales y métodos: Se realizó un estudio observacional en pacientes con SGB notificados en el sistema de vigilancia epidemiológica. Se obtuvieron muestras biológicas analizadas en el INS para investigar arbovirus, virus respiratorios, enterovirus y enterobacterias, entre otros. Resultados: Se recibió un total de 2051 especímenes clínicos de 906 pacientes con SGB. Tres pacientes dieron positivo al dengue y tres pacientes al Zika. En 19 pacientes, el cultivo en heces fue positivo para Campylobacter jejuni. El análisis filogenético de diez cepas de Campylobacter jejuni las clasificó como genotipo ST2993, reportado previamente en China y asociado a un brote de SGB. En 2018, hubo 12 muestras que habían dado positivo al PCR para enterovirus en el líquido cefalorraquídeo, pero ninguna pudo corroborarse con el cultivo respectivo ni con secuenciamiento de genoma completo. Un paciente dio positivo por virus de la influenza A, dos por virus de la influenza B, dos por adenovirus, cinco por virus respiratorio sincicial, y diez por rinovirus. Conclusión: Se han encontrado diversos agentes patógenos en especímenes de pacientes con SGB, sin embargo, la presencia de Campylobacter jejuni genotipo ST2993, un patógeno relacionado a brotes de SGB en varios continentes, sería el probable agente causal. Es necesario confirmar esta hipótesis con estudios analíticos y determinar la cadena de transmisión de este agente para implementar las medidas de prevención y control.
ABSTRACT Objective: To describe the results of laboratory tests performed on biological samples from patients with Guillain-Barré syndrome (GBS) submitted to the Instituto Nacional de Salud (INS) between 2018 and 2019. Materials and methods: We conducted an observational study on patients with GBS, by using data from the epidemiological surveillance system. Biological samples, previously analyzed at the INS, were obtained to study arboviruses, respiratory viruses, enteroviruses and enterobacteria, among others. Results: A total of 2,051 specimens were obtained from 906 patients with GBS. Three patients tested positive for dengue and three for Zika. In 19 patients, the stool culture was positive for Campylobacter jejuni. Phylogenetic analysis of 10 Campylobacter jejuni strains classified them as genotype ST2993, which was previously reported in China and associated to a GBS outbreak. Twelve cerebrospinal fluid samples tested positive for enterovirus by PCR in 2018, but none could be verified by culture or complete genome sequencing during the study. One patient was positive for influenza A, two for influenza B, two for adenovirus, five for respiratory syncytial virus, and ten for rinovirus. Conclusion: Several pathogens were found in samples from patients with GBS. However, we found that the genotype ST2993 of Campylobacter jejuni was the most likely causal agent, a pathogen that is related to GBS outbreaks in different continents. It is necessary to confirm this hypothesis with additional analytical studies and it is important to describe the transmission mechanism of C. jejuni genotype ST2993 in order to implement prevention and control measures.
Assuntos
Humanos , Masculino , Feminino , Pacientes , Vírus , Surtos de Doenças , Síndrome de Guillain-Barré , Campylobacter jejuni , Enterovirus , Monitoramento Epidemiológico , LaboratóriosRESUMO
OBJECTIVE: To describe the results of laboratory tests performed on biological samples from patients with Guillain-Barré syndrome (GBS) submitted to the Instituto Nacional de Salud (INS) between 2018 and 2019. MATERIALS AND METHODS: We conducted an observational study on patients with GBS, by using data from the epidemiological surveillance system. Biological samples, previously analyzed at the INS, were obtained to study arboviruses, respiratory viruses, enteroviruses and enterobacteria, among others. RESULTS: A total of 2,051 specimens were obtained from 906 patients with GBS. Three patients tested positive for dengue and three for Zika. In 19 patients, the stool culture was positive for Campylobacter jejuni. Phylogenetic analysis of 10 Campylobacter jejuni strains classified them as genotype ST2993, which was previously reported in China and associated to a GBS outbreak. Twelve cerebrospinal fluid samples tested positive for enterovirus by PCR in 2018, but none could be verified by culture or complete genome sequencing during the study. One patient was positive for influenza A, two for influenza B, two for adenovirus, five for respiratory syncytial virus, and ten for rinovirus. CONCLUSION: Several pathogens were found in samples from patients with GBS. However, we found that the genotype ST2993 of Campylobacter jejuni was the most likely causal agent, a pathogen that is related to GBS outbreaks in different continents. It is necessary to confirm this hypothesis with additional analytical studies and it is important to describe the transmission mechanism of C. jejuni genotype ST2993 in order to implement prevention and control measures.
OBJETIVO: Describir los resultados de los exámenes de laboratorio realizados en muestras biológicas de pacientes con síndrome de Guillain-Barré (SGB), recibidas en el Instituto Nacional de Salud (INS) entre los años 2018 y 2019. MATERIALES Y MÉTODOS: Se realizó un estudio observacional en pacientes con SGB notificados en el sistema de vigilancia epidemiológica. Se obtuvieron muestras biológicas analizadas en el INS para investigar arbovirus, virus respiratorios, enterovirus y enterobacterias, entre otros. RESULTADOS: Se recibió un total de 2051 especímenes clínicos de 906 pacientes con SGB. Tres pacientes dieron positivo al dengue y tres pacientes al Zika. En 19 pacientes, el cultivo en heces fue positivo para Campylobacter jejuni. El análisis filogenético de diez cepas de Campylobacter jejuni las clasificó como genotipo ST2993, reportado previamente en China y asociado a un brote de SGB. En 2018, hubo 12 muestras que habían dado positivo al PCR para enterovirus en el líquido cefalorraquídeo, pero ninguna pudo corroborarse con el cultivo respectivo ni con secuenciamiento de genoma completo. Un paciente dio positivo por virus de la influenza A, dos por virus de la influenza B, dos por adenovirus, cinco por virus respiratorio sincicial, y diez por rinovirus. CONCLUSIÓN: Se han encontrado diversos agentes patógenos en especímenes de pacientes con SGB, sin embargo, la presencia de Campylobacter jejuni genotipo ST2993, un patógeno relacionado a brotes de SGB en varios continentes, sería el probable agente causal. Es necesario confirmar esta hipótesis con estudios analíticos y determinar la cadena de transmisión de este agente para implementar las medidas de prevención y control.
Assuntos
Síndrome de Guillain-Barré , Campylobacter jejuni/genética , Campylobacter jejuni/isolamento & purificação , Vírus da Dengue/isolamento & purificação , Fezes/microbiologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/microbiologia , Síndrome de Guillain-Barré/terapia , Síndrome de Guillain-Barré/virologia , Humanos , Peru/epidemiologia , Filogenia , Zika virus/isolamento & purificaçãoRESUMO
OBJECTIVES.: To identify the main viral etiological agents in patients with severe acute respiratory infection (SARI) hospitalized in a Pediatric Intensive Care Unit (PICU) and to analyze their clinical characteristics. MATERIALS AND METHODS.: Prospective longitudinal study in children under five years of age hospitalized due to SARI at the PICU of t Instituto Nacional de Salud del Niño (National Children´s Hospital) in Lima, Peru. Real-time direct immunofluorescence and RT-PCR tests were performed for the diagnosis of respiratory viruses on tracheal aspirate or nasopharyngeal swab samples. RESULTS.: We included 117 patients. Median age was four months, 66% had comorbidity and 91% required mechanical ventilation. Respiratory virus monoinfection was identified in 47% and viral co-infection in 2.6%, with the respiratory syncytial virus subtype A (RSV-A) being the most frequent. The median length of hospitalization was 21 days and 20 (17%) patients died. An association was found between a history of chronic lung disease and RSV-A infection (p=0.045), and between Down syndrome and influenza A virus infection (p=0.01). After controlling for potential confounders, congenital heart disease (RR 3.1; 95% CI: 1.3-5.8, p=0.002) and nosocomial infection (RR 2.6; 95% CI: 1.0-5.3, p=0.01) were found to increase the risk of death in patients with SARI. CONCLUSIONS.: RSV-A was the most common viral etiology in children under five hospitalized by SARI at the PICU. No association was found between viral infection and patient survival.
OBJETIVOS.: Identificar los principales agentes etiológicos virales en pacientes con infección respiratoria aguda grave (IRAG) hospitalizados en una Unidad de Cuidados Intensivos Pediátricos (UCIP) y analizar sus características clínicas. MATERIALES Y MÉTODOS.: Estudio longitudinal prospectivo en menores de cinco años hospitalizados por IRAG en la UCIP del Instituto Nacional de Salud del Niño en Lima, Perú. Se realizaron pruebas de inmunofluorescencia directa y RT-PCR en tiempo real para el diagnóstico de virus respiratorios en muestras de aspirado traqueal o hisopado nasofaríngeo. RESULTADOS.: Se incluyeron 117 pacientes. La mediana de edad fue cuatro meses, el 66% presentaron comorbilidad y el 91% requirieron ventilación mecánica. Se identificó monoinfección por virus respiratorios en el 47% y coinfección viral en el 2,6%, siendo el virus sincicial respiratorio subtipo A (VSR-A) el más frecuente. La mediana del tiempo de hospitalización fue de 21 días y 20 (17%) pacientes fallecieron. Se encontró asociación entre el antecedente de enfermedad pulmonar crónica y la infección por el VSR-A (p=0,045) y entre el síndrome de Down y la infección por virus influenza A (p=0,01). Después de controlar por potenciales factores de confusión, se halló que la cardiopatía congénita (RR: 3,1; IC 95%: 1,3-5,8; p=0,002) y la infección nosocomial (RR: 2,6; IC 95%: 1,0-5,3; p=0,01) incrementaron el riesgo de muerte en pacientes con IRAG. CONCLUSIONES.: El VSR-A fue la etiología viral más frecuente en menores de cinco años hospitalizados por IRAG en la UCIP. No se encontró asociación entre la infección viral y la sobrevida del paciente.