Comparison of Epidemiologic and Clinical COVID-19 Profiles in Children in Argentina, During Circulation of Original and Variant (Alpha, Gamma and Lambda) Strains.

BACKGROUND: Information on the impact of the different variants in children in Latin America is scarce. The objective of this study was to describe epidemiologic and clinical features of COVID-19 infection in children under 18 years of age in Argentina, comparing the periods before and after the circulation of new variants. METHODS: Observational, cross-sectional, multicentric, analytical study. All patients under 18 years of age with confirmed SARS-CoV-2 infection admitted at 22 healthcare centers were included. Two study periods were established: Period 1 (EW10-2020 to EW12-2021) for the Wuhan strain; Period 2 (EW13 to EW35 2021) for Alpha, Gamma, Delta and Lambda variants. FINDINGS: A total of 6330 confirmed cases were included. Period 1: 3575 (56.5%), period 2: 2755 (43.5%). During period 2, a lower number of asymptomatic cases was observed, while general, respiratory and neurologic signs and symptoms increased in all age groups. Oxygen therapy requirement was higher during the first period (36.7% vs 19.1%; P < 0.001). No significant differences were observed in the rates of severe or critical cases (6.3% vs 5,4%; P = 0.102), intensive care admission (2.1% vs 2%; P < 0.656) or case fatality (0.3% vs 0.5 %; P < 0.229). MIS-C cases occurred more frequently during the first period (1.9% vs 1.1%; P = 0.009). INTERPRETATION: The clinical spectrum of COVID-19 in Argentina has evolved. With the emergence of new variants, although the number of asymptomatic cases declined, numbers of severe and critical cases, as well as case fatality rates in children, remained unchanged.

Respiratory syncytial virus and influenza surveillance in schoolchildren seen at a children's hospital over 2 months of the second semester of 2021. / Vigilancia de virus sincicial respiratorio e influenza en niños escolarizados asistidos en un hospital pediátrico durante 2 meses del segundo semestre de 2021.

INTRODUCTION: Reporting of respiratory infections reduced during the COVID-19 pandemic. The objective was to estimate the prevalence of respiratory syncytial virus(RSV) and influenza in schoolchildren seen at a children's hospital during the return to school. METHODS: Cross-sectional study of patients aged 3-18 years suspected of COVID-19 with a negative test for SARS-CoV-2 between August and October 2021. Participants were stratified by level of education. PCR was used to detect RSV and influenza. RESULTS: A total of 619 children were included: 234 in pre-school, 224 in primary and 161 in secondary school; 25.5% (158) tested positive for RSV (36.3% in the pre-school level versus 21% in primary and 16% in secondary school). Infection among adolescents was associated with school contact with symptomatic cases (OR 2.5; 95%CI 1-6.80; p = 0.04). No case of influenza was detected. CONCLUSIONS: RSV was isolated in one fourth of the study population, with a higher frequency in pre-school; among adolescents, it was associated with school contact with symptomatic cases. No case of influenza was detected.

Introducción. Durante la pandemia de COVID-19, disminuyeron las notificaciones de infecciones respiratorias. El objetivo fue estimar la prevalencia de virus sincicial respiratorio (VSR) e influenza en niños escolarizados asistidos en un hospital pediátrico durante el retorno a la presencialidad. Métodos. Estudio transversal de casos sospechosos de COVID-19, de 3-18 años, con prueba negativa para SARS-CoV-2, entre agosto y octubre de 2021. Se estratificó por nivel educativo. Se utilizó PCR para detectar VSR e influenza. Resultados. Se incluyeron 619 niños: 234 del nivel inicial, 224 del primario y 161 del secundario; 25,5 % (158) fueron positivos para VSR (36,3 % del nivel inicial versus 21 % del primario y 16 % del secundario); en adolescentes se asoció la infección al contacto escolar con caso sintomático (OR 2,5; IC95%: 1-6,80; p = 0,04). No se aisló virus influenza. Conclusión. VSR se aisló en un cuarto de la población estudiada, con mayor frecuencia en el nivel inicial; en adolescentes, se asoció con contacto escolar sintomático. No se detectaron casos de influenza.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

COVID-19 in Children: Correlation Between Epidemiologic, Clinical Characteristics, and RT-qPCR Cycle Threshold Values.

BACKGROUND: Initially, the impact of SARS-CoV-2 infection on children was unknown. Standard COVID-19 diagnosis is confirmed using real-time qPCR. Cycle threshold (Ct) values of RT-qPCR are inversely proportional to viral load and the test indirectly quantifies viral RNA copy numbers. The objective of this study was to determine the correlation between epidemiology, clinical characteristics, severity of confirmed COVID-19 cases, and Ct values. METHODS: An observational, analytical, cross-sectional study. All children with COVID-19 under 18 years old admitted to the Ricardo Gutiérrez Children's Hospital between March 1, 2020, and February 28, 2021, were included. SARS-CoV-2 infection was confirmed using RT-qPCR. RESULTS: Median age of patients was 7 years. Ct values were estimated in 419 cases, median Ct value was 23.5 [interquartile range (IQR): 18.9-30.9]. Levels were significantly lower in symptomatic than asymptomatic patients (Ct: 22.1; IQR: 18.4-22.1), in children <2 years of age (Ct: 20.6; IQR: 17.3-27.3) and when sample collection was <4 days after symptom onset (Ct: 21.1; IQR: 18.1-27.5). In children >2 years of age, Ct values were significantly lower in symptomatic (Ct: 22.6; IQR: 18.7-29.3) than asymptomatic (Ct: 31.2; IQR: 24.5-33.3) patients. CONCLUSIONS: Children younger than 2 years with COVID-19 have lower values of Ct-as a proxy for higher viral load-than older children. Symptomatic children over 2 years of age had lower Ct values compared with asymptomatic children.

Impact of COVID-19 on the circulation of respiratory viruses in a children's hospital: an expected absence. / Impacto del COVID-19 en la circulación de virus respiratorios en un hospital pediátrico: una ausencia esperada.

INTRODUCTION: Respiratory viruses are the main cause of acute lower respiratory tract infection (ALRTI) in the pediatric population. In March 2020, the World Health Organization declared that the new coronavirus disease 2019 (COVID-19) had reached the pandemic status. Our objective was to describe the impact of COVID-19 pandemic on hospitalizations due to ALRTI at Hospital de Niños Ricardo Gutiérrez (HNRG) and virus circulation. METHODS: Observational, retrospective, and descriptive study of patients hospitalized due to ALRTI comparing 2019 and 2020. RESULTS: In 2020, the rate of hospitalization due to ALRTI decreased by 73%. In 2019, 517 patients with ALRTI were hospitalized; the following viruses were identified in 174: respiratory syncytial virus (RSV) (71.2%), adenovirus (AV) (10.3%), parainfluenza virus (PIV) (9.7%), and influenza virus (FLU) (8.6%). In 2020, 94 patients with ALRTI were hospitalized. Until epidemiological week (EW) 13, cases of ALRTI due to PIV and AV were recorded; in EW 29, there was 1 case of bronchiolitis due to AV and rhinovirus (RV), followed by isolated cases of RV; no ALRTI due to RSV or FLU was recorded. In total, 9 cases of ALRTI due to COVID-19 were recorded: 2 moderate bronchiolitis and 7 focal pneumonia; 1 adolescent with comorbidities died due to COVID-19 pneumonia. In 2020, patients were older and had more comorbidities and prior hospitalizations compared to 2019. Focal pneumonia prevailed. CONCLUSIONS: In 2020, the rate of hospitalization due to ALRTI decreased significantly compared to 2019, with the absence of seasonal respiratory virus circulation in the pediatric population.

Introducción. Los virus respiratorios son la principal causa de infección respiratoria aguda baja (IRAB) en la población pediátrica. En marzo de 2020, la Organización Mundial de la Salud declaró el estado de pandemia de la enfermedad por el nuevo coronavirus 2019 (COVID-19) con un impacto global elevado. El objetivo de este estudio fue describir el impacto de la pandemia de COVID-19 en las internaciones por IRAB en el Hospital de Niños Ricardo Gutiérrez (HNRG) y la circulación viral. Métodos. Estudio observacional, retrospectivo y descriptivo de pacientes internados por IRAB, comparando los años 2019 y 2020. Resultados. En 2020, la tasa de hospitalización por IRAB se redujo un 73 % en el HNRG (575,1/10 000 en 2019 y 155,3/10 000 en 2020). En 2019 se internaron 517 pacientes con IRAB; en 174 se identificaron los virus: sincicial respiratorio (71,2%), adenovirus (AV) (10,3%), parainfluenza (PIF) (9,7 %) e influenza (FLU) (8,6 %). En 2020, se hospitalizaron 94 pacientes con IRAB. Hasta la semana epidemiológica (SE) 13 se registraron casos de IRAB por PIF y AV; en la SE 29 un caso de bronquiolitis por AV y rinovirus (RV), seguido de casos aislados de RV; no hubo IRAB por VSR ni por FLU. Se registraron 9 casos de IRAB por COVID-19: 2 bronquiolitis moderadas y 7 neumonías focales; con un adolescente fallecido por neumonía por COVID-19 con comorbilidades. En 2020, los casos presentaron mayor edad, más comorbilidades e internaciones previas en comparación con el 2019. La neumonía focal fue la presentación clínica predominante. Conclusión. En 2020, la tasa de hospitalización por IRAB se redujo significativamente en comparación con el año anterior, con ausencia de circulación de virus respiratorios estacionales en la población asistida en nuestro centro.

A multicenter study of confirmed COVID-19 cases: preliminary data on 2690 pediatric patients in Argentina during the first year of the pandemic. / Estudio multicéntrico de casos confirmados de COVID-19: datos preliminares de 2690 pacientes pediátricos en Argentina durante el primer año de la pandemia.

INTRODUCTION: The current evidence indicates that the severity of the coronavirus disease 2019 (COVID-19) is lower in the pediatric population but local data are still limited. Objective: To characterize the clinical and epidemiological aspects of COVID-19 infection in patients younger than 18 years in Argentina. POPULATION AND METHODS: Cross-sectional, observational, and analytical study of confirmed COVID-19 patients aged 0-18 years seen between March 2020 and March 2021 at 19 referral children's hospitals of Argentina. A multivariate analysis was done to identify predictors of severe cases. RESULTS: A total of 2690 COVID-19 cases were included: 77.7% lived in the Metropolitan Area of Buenos Aires; 50.1% were males; patients' median age was 5.6 years. Of them, 90% were seen during epidemiological weeks 20-47 of 2020; 60.4% had a history of contact with COVID-19 patients; and 96.6% in their family setting. Also, 51.4% had respiratory symptoms; 61.6%, general symptoms; 18.8%, gastrointestinal symptoms; 17.1%, neurological symptoms; 7.2%, other symptoms; and 21.5% were asymptomatic. In addition, 59.4% of patients were hospitalized and 7.4% had a severe or critical course. A total of 57 patients developed multisystem inflammatory syndrome. A history of asthma, bronchopulmonary dysplasia, congenital heart disease, moderate to severe malnutrition, obesity, chronic neurological disease and/or age younger than 6 months were independent predictors of severity. Living in a vulnerable neighborhood was a protective factor. CONCLUSIONS: More than half of cases referred a history of contact with COVID-19 patients in the family setting. Hospitalization was not based on clinical criteria of severity. Severity was associated with the presence of certain comorbidities.

Introducción. La evidencia actual indica que la gravedad de la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés) es menor en la población pediátrica, los datos locales aún son limitados. OBJETIVO: caracterizar los aspectos clínicos y epidemiológicos de la infección por COVID-19 en menores de 18 años en Argentina. Población y métodos. Estudio transversal, observacional y analítico de casos confirmados de COVID-19 entre 0 y 18 años asistidos entre marzo de 2020 y marzo de 2021 en 19 centros pediátricos de referencia de Argentina. Se realizó un análisis multivariado para identificar las variables predictoras de cuadros graves. RESULTADOS: Se incluyeron 2690 casos de COVID-19: 77,7 % residentes del área metropolitana de Buenos Aires, 50,1 % de sexo masculino, mediana de edad de 5,6 años. El 90 % ocurrió entre las semanas epidemiológicas 2047 del 2020; 60,4 % con antecedente de contacto con personas con COVID-19; y 96,6 % en el entorno familiar. El 51,4 % presentó síntomas respiratorios; 61,6 % síntomas generales; 18,8 % síntomas gastrointestinales; 17,1 % síntomas neurológicos; 7,2 % otros y 21,5 % fueron asintomáticos. El 59,4 % fue hospitalizado; 7,4 % fueron graves o críticos. Se registraron 57 casos de síndrome inflamatorio multisistémico. El antecedente de asma, displasia broncopulmonar, cardiopatía congénita, desnutrición moderada a grave, obesidad, enfermedad neurológica crónica y/o edad menor de 6 meses resultaron predictores independientes de gravedad. Residir en barrios vulnerables resultó protector. CONCLUSIONES: Más de la mitad de los casos refirieron antecedente de contacto con personas con COVID-19 en el entorno familiar. La hospitalización no respondió a criterios clínicos de gravedad. La gravedad se encuentra asociada a la existencia de ciertas comorbilidades.

Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials.

BACKGROUND: Shortages of component two of Sputnik V vaccine (rAd5) are delaying the possibility of achieving full immunisation. The immunogenic response associated with the use of alternative schemes to complete the scheme was not explored. METHODS: We did two non-inferiority randomized clinical trials with outcomes measures blinded to investigators on adults aged 21-65 years, vaccinated with a single dose of rAd26 ≥ 30 days before screening and no history of SARS-CoV-2. Participants were assigned (1:1:1:1:1) to receive either rAd5; ChAdOx1; rAd26; mRNA-1273 or BBIBP-CorV. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-spike IgG concentration at 28 days after the second dose, when comparing rAd26/rAd5 with rAd26/ChAdOx1, rAd26/rAd26, rAd26/mRNAmRNA-1273 and rAd26/BBIBP-CorV. Serum neutralizing capacity was evaluated using wild type SARS-CoV-2 reference strain 2019 B.1. The safety outcome was 28-day rate of serious adverse. The primary analysis included all participants who received ≥ 1 dose. The studies were registered with NCT04962906 and NCT05027672. Both trials were conducted in Buenos Aires, Argentina. FINDINGS: Between July 6 and August 3, 2021, 540 individuals (age 56·7 [SD 7·3]; 243 (45%) women) were randomly assigned to received rAd5 (n=150); ChAdOx1 (n=150); rAd26 (N=87); mRNAmRNA-1273 (n=87) or BBIBP-CorV (n=65). 524 participants completed the study. As compared with rAd26/rAd5 (1·00), the GMR (95%CI) at day 28 was 0·65 (0·51-0·84) among those who received ChAdOx1; 0·47 (0·34-0·66) in rAd5; 3·53 (2·68-4·65) in mRNA-1273 and 0·23 (0·16-0·33) in BBIBP-CorV. The geometric mean (IU/ml) from baseline to day 28 within each group increased significantly with ChAdOx1 (4·08 (3·07-5·43)); rAd26 (2·69 (1·76-4·11)); mRNA-1273 (21·98 (15·45-31·08)) but not in BBIBP-CorV (1·22 (0·80-1·87)). INTERPRETATION: Except for mRNA-1273 which proved superior, in all other alternatives non-inferiority was rejected. Antibody concentration increased in all non-replicating viral vector and RNA platforms. FUNDING: The trials were supported (including funding, material support in the form of vaccines and testing supplies) by the Buenos Aires City Government.

Latin American forum on immunization services during the COVID-19 pandemic.

Introduction: The Latin American Society of Pediatric Infectology (SLIPE for its acronym in Spanish) is working hard to contribute with strategic actions to prevent the recurrence of Vaccine-Preventable Diseases and to prevent the reduction of vaccine coverage in the region of the Americas.Areas covered: On Friday, September 25th, a Latin American forum of experts on immunization services during the COVID-19 pandemic was held through Webex platform. Issues such as: the imminent risk of occurrence and outbreaks of vaccine-preventable diseases, the importance of epidemiological surveillance and the vaccination campaign challenges, in the context of a pandemic were discussed.Expert opinion: Vaccination campaigns should no longer be postponed or delayed; instead, they must be reactivated; governments, scientific societies, and physicians must promote vaccination programs to avoid outbreaks of vaccine-preventable diseases. On the eve of a SARS-CoV-2 vaccine, it is necessary to insist on the availability of sufficient doses to avoid dose shortages in disadvantaged areas of the region.