Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.

Background: After primary vaccination schemes with rAd26-rAd5 (Sputnik V), ChAdOx1 nCoV-19, BBIBP-CorV or heterologous combinations, the effectiveness of homologous or heterologous boosters (Sputnik V, ChAdOx, Pfizer-BioNTech, Moderna) against SARS-CoV-2 infections, hospitalisations and deaths has been scarcely studied. Methods: Test-negative, case-control study, conducted in Argentina during omicron BA.1 predominance, in adults ≥50 years old tested for SARS-CoV-2 who had received two or three doses of COVID-19 vaccines. Outcomes were COVID-associated infections, hospitalisations and deaths after administering mRNA and vectored boosters, < or ≥60 days from the last dose. Findings: Of 422,124 individuals tested for SARS-CoV-2, 221,993 (52.5%) tested positive; 190,884 (45.2%) and 231,260 (54.8%) had received 2-dose and 3-dose vaccination schemes, respectively. The 3-dose scheme reduced infections, hospitalisations and death (OR 0.81 [0.80-0.83]; 0.28 [0.25-0.32] and 0.25 [0.22-0.28] respectively), but protection dropped after 60 days to 1.04 [1.01-1.06]; 0.52 [0.44-0.61] and 0.38 [0.33-0.45]). Compared with 2-dose-schemes, homologous boosters after primary schemes with vectored-vaccines provided lower protection against infections < and ≥60 days (0.94 [0.92-0.97] and 1.05 [1.01-1.09], respectively) but protected against hospitalisations (0.30 [0.26-0.35]) and deaths (0.29 [0.25-0.33]), decreasing after 60 days (0.59 [0.47-0.74] and 0.51 [0.41-0.64], respectively). Heterologous boosters protected against infections (0.70 [0.68-0.71]) but decreased after 60 days (1.01 [0.98-1.04]) and against hospitalisations and deaths (0.26 [0.22-0.31] and 0.22 [0.18-0.25], respectively), which also decreased after 60 days (0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Heterologous boosters protected against infections when applied <60 days (0.70 [0.68-0.71], p < 0.001), against hospitalisations when applied ≥60 days (0.43 [0.35-0.53], p < 0.01), and against deaths < and ≥60 days (0.22 [0.18-0.25], p < 0.01 and 0.33 [0.26-0.41], p < 0.001). Interpretation: During omicron predominance, heterologous boosters such as viral vectored and mRNA vaccines, following Sputnik V, ChAdOx1, Sinopharm or heterologous primary schemes might provide better protection against death; this effect might last longer in individuals aged ≥50 than homologous boosters. Funding: None.

Efectividad de refuerzos homólogos y heterólogos luego de esquemas primarios con Sputnik V, Astra-Zeneca y Sinopharm durante el período omicron en adultos mayores de 50 años en la provincia de Buenos Aires / Effectiveness of homologous and heterologous boosters after primary regimens with Sputnik V, AstraZeneca, and Sinopharm during the omicron variant period in adults over 50 years old in the province of Buenos Aires

Objetivo: Evaluar la efectividad de esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o combinaciones heterólogas seguidos de refuerzos a vector viral (Sputnik V, Astra-Zeneca) o ARNm (Pfizer-BioNTech, Moderna) frente a infecciones, hospitalizaciones y muertes por SARS-CoV-2. Material y métodos: Estudio de casos y controles con test negativo realizado en la provincia de Buenos Aires, durante el predominio de ómicron BA.1, que incluyó individuos ≥ 50 años con test positivo para SARS-CoV-2 que habían recibido 2 o 3 dosis de vacunas. Se registraron infecciones, hospitalizaciones y muertes después de administrar refuerzos con Sputnik V, Astra-Zeneca o ARNm. Resultados: De 422 124 personas analizadas para SARS-Cov-2, 221 993 (52.5%) presentaron test positivos; 190 884 (45.2%) y 231.260 (54.8%) recibieron esquemas de vacunación de 2 y 3 dosis, respectivamente. Los esquemas primarios con Astra-Zeneca, Sputnik V o vector viral, combinados con un refuerzo a vector viral, mostraron protección contra infecciones (OR: 0.94 [0.92 a 0.97]), hospitalizaciones (OR: 0.30 [0.26 a 0.35]) y muertes (OR: 0.29 [0.25 a 0.33]. Los esquemas primarios con Astra-Zeneca y Sputnik V más refuerzo de ARNm, o con Sinopharm más refuerzo de ARNm o vector viral otorgaron protección adicional contra infecciones (OR: 0.70 [0.68 a 0.71]). Hubo un efecto protector frente a hospitalizaciones y muertes (OR: 0.26 [0.22 a 0.31] y 0.22 [0.18 a 0.25]) en todos los casos. Conclusiones: Durante el predominio de ómicron, los refuerzos heterólogos con vacunas a vector viral y de ARNm, posteriores a los esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o heterólogos, podrían proporcionar mejor protección y mayor duración del efecto contra la muerte en personas mayores de 50 años, en comparación con refuerzos homólogos

Objective: To evaluate the effectiveness of primary vaccination regimens involving Sputnik V, Astra-Zeneca, Sinopharm, or heterologous combinations followed by viral vector boosters (Sputnik V, As-traZeneca) or mRNA boosters (Pfizer-BioNTech, Moderna) against infections, hospitalizations and deaths caused by SARS-CoV-2. Material and methods: Case-control studies with negative tests conducted in the Buenos Aires province during the Omicron BA.1 predominance. The study included patients ≥ 50 years of age, who tested positive for SARS-CoV-2 and had received two or three doses of vaccines. Infections, hospitalizations, and deaths were registered following the administration of Sputnik V, AstraZeneca, or mRNA boosters. Findings: Out of 422 124 people tested for SARS-Cov-2, 221 993 (52.5%) had positive test results; 190,884 (45.2%) and 231 260 (54.8%) received two-dose and three-dose vaccination schemes, respectively. Primary regimens with AstraZeneca, Sputnik V, or viral vector, combined with a viral vector booster demonstrated protection against infections (OR 0.94 [0.92 to 0.97]), hospitalizations (OR 0.30 [0.26 to 0.35]) and deaths (OR 0.29 [0.25 to 0.33]. Primary regimens with AstraZeneca and Sputnik V combined with mRNA boosters, as well as pri-mary schemes with Sinopharm combined with mRNA or viral vectored boosters showed additional protection against infections (OR 0.70 [0.68 to 0.71]). There was a protective effect against hospi-talizations and deaths (OR 0.26 [0.22-0.31] and 0.22 [0.18 -0.25]) in all cases. Conclusions: During Omicron predominance, heterologous boosters with viral-vector and mRNA vaccines, administered after Sputnik V, AstraZeneca, Sinopharm, or heterologous primary regimens, could provide enhanced protection and prolonged effectiveness against mortality in individuals aged ≥ 50, compared to ho-mologous boosters

Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires / Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study

Resumen Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes >18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró adminis tración temprana o tardía a la infusión de TCZ ≤ ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no inva siva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Abstract Introduction: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. Methods: Multicenter, retrospective cohort study in cluding patients>18 years hospitalized between 7/1/2021- 8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. Results: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Com pared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). Discussion: This study supports the early use of TCZ in patients with severe or critical COVID-19.

[Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study]. / Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires.

INTRODUCTION: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. METHODS: Multicenter, retrospective cohort study including patients >18 years hospitalized between 7/1/2021-8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were 28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. RESULTS: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Compared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). DISCUSSION: This study supports the early use of TCZ in patients with severe or critical COVID-19.

Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes > 18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró administración temprana o tardía a la infusión de TCZ = ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no invasiva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Factores de riesgo de focos secundarios de infección en niños con bacteriemia por Staphylococcus aureus adquirida en la comunidad. Estudio de cohorte 2010-2016 / Risk factors for the appearance of secondary foci of infection in children with community-acquired Staphylococcus aureus bacteraemia. Cohort study 2010-2016

INTRODUCCIÓN: La bacteriemia por Staphylococcus aureus (SA) adquirida en la comunidad representa una causa frecuente de ingreso en niños. La aparición de focos secundarios (FS) condiciona una mayor morbimortalidad. OBJETIVOS: Identificar factores de riesgo de aparición de FS de infección en niños con bacteriemia por SA de la comunidad. MATERIAL Y MÉTODOS: Cohorte prospectiva. Desde enero de 2010 a diciembre de 2016 se incluyeron todos los niños (de 30 días a 16 años), hospitalizados en un hospital pediátrico de derivación por infecciones adquiridas en la comunidad, con aislamiento de SA en hemocultivos. Se compararon características microbiológicas, demográficas y clínicas según presentaran o no FS de infección tras 72 h de hospitalización. RESULTADOS: Se incluyeron 283 niños, el 65% varones (n = 184), con una mediana de edad de 60 meses (RIC: 30-132). El 17% (n = 48) tenían alguna enfermedad de base y el 97% (n = 275) un foco clínico de infección, siendo los más frecuentes: osteoarticular el 55% (n = 156) y abscesos de partes blandas el 27% (n = 79). El 65% (n = 185) eran SA resistentes a meticilina. Presentaron FS el 16% de los pacientes (n = 44): neumonía el 73% (n = 32), osteoarticular el 11% (n = 5), partes blandas el 11% (n = 5) y sistema nervioso central el 5% (n = 2). En el análisis multivariado fueron predictores de FS la persistencia de hemocultivos positivos tras el quinto día (OR: 2,40; IC95%: 1,07-5,37; p < 0,001) y la sepsis (OR: 17,23; IC95%: 5,21-56,9; p < 0,001). No hubo asociación con la sensibilidad a la meticilina. CONCLUSIONES: En esta cohorte predominaron las infecciones por SA resistente a la meticilina. La aparición de FS se asoció con la persistencia de la bacteriemia después del quinto día y la sepsis al ingreso

INTRODUCTION: Community-acquired Staphylococcus aureus (SA) bacteraemia is a common cause of hospitalisation in children. The occurrence of secondary foci (SF) of SA infection is associated with higher morbidity and mortality. OBJECTIVES: To identify risk factors for SF of infection in children with community-acquired SA bacteraemia. MATERIAL AND METHODS: Prospective cohort. All children aged from 30 days to 16 years admitted to a paediatric referral hospital between January 2010 and December 2016 for community-acquired infections, with SA isolated in blood cultures, were included. Microbiological, demographic and clinical characteristics were compared, with or without SF infection after 72 hours of hospitalisation. RESULTS: A total of 283 patients were included, 65% male (n = 184), with a median age of 60 months (IQR: 30-132). Seventeen per cent (n = 48) had at least one underlying disease and 97% (n = 275) had some clinical focus of infection, the most common being: osteoarticular 55% (n = 156) and soft tissue abscesses 27% (n = 79). A total of 65% (n = 185) were resistant to methicillin. A SF of infection was found in 16% of patients (n = 44). The SF identified were pneumonia 73% (n=32), osteoarticular 11% (n = 5), soft tissue 11% (n = 5) and central nervous system 5% (n=2). In the multivariate analysis, the persistence of positive blood cultures after the fifth day (OR: 2.40, 95%CI: 1.07-5.37, P < 0.001) and sepsis (OR: 17.23, 95%CI 5.21-56.9, P < 0.001) were predictors of SF. There was no association with methicillin sensitivity. CONCLUSIONS: In this cohort, methicillin-resistant SA infections predominated. The occurrence of SF of infection was associated with the persistence of bacteraemia after the fifth day and sepsis on admission

Risk factors for the appearance of secondary foci of infection in children with community-acquired Staphylococcus aureus bacteraemia. Cohort study 2010-2016. / Factores de riesgo de focos secundarios de infección en niños con bacteriemia por Staphylococcus aureus adquirida en la comunidad. Estudio de cohorte 2010-2016.

INTRODUCTION: Community-acquired Staphylococcus aureus (SA) bacteraemia is a common cause of hospitalisation in children. The occurrence of secondary foci (SF) of SA infection is associated with higher morbidity and mortality. OBJECTIVES: To identify risk factors for SF of infection in children with community-acquired SA bacteraemia. MATERIAL AND METHODS: Prospective cohort. All children aged from 30 days to 16 years admitted to a paediatric referral hospital between January 2010 and December 2016 for community-acquired infections, with SA isolated in blood cultures, were included. Microbiological, demographic and clinical characteristics were compared, with or without SF infection after 72hours of hospitalisation. RESULTS: A total of 283 patients were included, 65% male (n=184), with a median age of 60 months (IQR: 30-132). Seventeen per cent (n=48) had at least one underlying disease and 97% (n=275) had some clinical focus of infection, the most common being: osteoarticular 55% (n=156) and soft tissue abscesses 27% (n=79). A total of 65% (n=185) were resistant to methicillin. A SF of infection was found in 16% of patients (n=44). The SF identified were pneumonia 73% (n=32), osteoarticular 11% (n=5), soft tissue 11% (n=5) and central nervous system 5% (n=2). In the multivariate analysis, the persistence of positive blood cultures after the fifth day (OR: 2.40, 95%CI: 1.07-5.37, P<0.001) and sepsis (OR: 17.23, 95%CI 5.21-56.9, P<0.001) were predictors of SF. There was no association with methicillin sensitivity. CONCLUSIONS: In this cohort, methicillin-resistant SA infections predominated. The occurrence of SF of infection was associated with the persistence of bacteraemia after the fifth day and sepsis on admission.

Absceso cerebral en niños: experiencia en diez años en un hospital pediátrico de alta complejidad / Brain abscess in children: ten years of experience in a third level pediatric hospital

El absceso cerebral es una infección focal, que se presenta con una frecuencia de 0,3-1,3 casos cada 100000 personas/año.¹ Se describe la epidemiología, clínica y microbiología de 38 niños con diagnóstico de absceso cerebral internados entre el 1/4/2005 y el 31/12/2015 en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" de la Ciudad de Buenos Aires. Veinticuatro pacientes fueron varones. La mediana de edad fue de 132 meses. Se detectaron factores predisponentes en 25 niños. La mediana de evolución entre el inicio de los síntomas y la consulta fue de 7 días. Hubo 27 casos con lesiones únicas. Se realizó un drenaje quirúrgico en 34 pacientes. Las bacterias más frecuentes fueron anaerobios, Streptococcus viridans y Staphylococcus aureus. La mediana de tratamiento antibiótico fue de 56 días y la mediana de internación fue de 43 días. La letalidad fue del 3%.

Brain abscess is a focal infection that occurs with a frequency of 0.3-1.3 cases per 100,000 people/year. We describe the epidemiology, clinical and microbiology characteristics of 38 children diagnosed with brain abscess hospitalized between 4/1/2005 and 12/31/2015 at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" in Buenos Aires City. Twenty-four patients were male. The median age was 132 months. Predisposing factors were detected in 25 children. The median evolution from onset of symptoms to the visit was 7 days. There were 27 cases with single lesions. Surgical drainage was performed in 34 patients. The most frequent bacteria were anaerobes, Streptococcus viridans and Staphylococcus aureus. The median of antibiotic treatment was 56 days and the median of hospitalization was 43 days. The lethality was 3%.

[Brain abscess in children: ten years of experience in a third level pediatric hospital]. / Absceso cerebral en niños: experiencia en diez años en un hospital pediátrico de alta complejidad.

Brain abscess is a focal infection that occurs with a frequency of 0.3-1.3 cases per 100,000 people/year. We describe the epidemiology, clinical and microbiology characteristics of 38 children diagnosed with brain abscess hospitalized between 4/1/2005 and 12/31/2015 at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" in Buenos Aires City. Twenty-four patients were male. The median age was 132 months. Predisposing factors were detected in 25 children. The median evolution from onset of symptoms to the visit was 7 days. There were 27 cases with single lesions. Surgical drainage was performed in 34 patients. The most frequent bacteria were anaerobes, Streptococcus viridans and Staphylococcus aureus. The median of antibiotic treatment was 56 days and the median of hospitalization was 43 days. The lethality was 3%.

El absceso cerebral es una infección focal, que se presenta con una frecuencia de 0,3-1,3 casos cada 100 000 personas/año.1 Se describe la epidemiología, clínica y microbiología de 38 niños con diagnóstico de absceso cerebral internados entre el 1/4/2005 y el 31/12/2015 en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" de la Ciudad de Buenos Aires. Veinticuatro pacientes fueron varones. La mediana de edad fue de 132 meses. Se detectaron factores predisponentes en 25 niños. La mediana de evolución entre el inicio de los síntomas y la consulta fue de 7 días. Hubo 27 casos con lesiones únicas. Se realizó un drenaje quirúrgico en 34 pacientes. Las bacterias más frecuentes fueron anaerobios, Streptococcus viridans y Staphylococcus aureus. La mediana de tratamiento antibiótico fue de 56 días y la mediana de internación fue de 43 días. La letalidad fue del 3%.