Secuelas respiratorias clínicas, funcionales y tomográficas de pacientes hospitalizados por Covid-19 al año del diagnóstico: ESTUDIO SECUELAR-19 / Clinical, functional and tomographic respiratory sequels of patients hospitalized for COVID-19 at one year of diag nosis: SECUELAR-19 TRIAL

Resumen Introducción : Hay información escasa sobre evolución a largo plazo de pacientes hospitalizados por neumo nía COVID-19 moderada (NM) y grave (NG). El objetivo del estudio fue determinar impacto clínico, funcional respiratorio y tomográfico (TACAR) luego del alta a 12 meses del diagnóstico. Métodos : análisis según grupos NM y NG, desatura dores (PD) en prueba de caminata 6 min (PC6M) y patrón tomográfico símil fibrótico (SF). Comparamos resultados a 3 y 12 meses de seguimiento. Resultados : 194 pacientes enrolados, evaluados al año: 103 (53% ): masculinos (62.4%), edad 57.7 ± 10.9 años, comorbilidades (hipertensión arterial 38.8%, dia betes 29.6%, antecedentes respiratorios-AR- 18.4%). Com paramos variables a los 3 y 12 meses (media/DE): CVF 84%(19) a 88(19) (p = 0.01); 27% tuvo CVF<80% al año. En PC6M: 426 metros (108) a 447(92) (p = < 0.01). El 12.8% fue PD al año. NG tuvo mayor SF (40% vs. 27.9% p = 0.021). SF se relacionó con CVF <80% (p = 0.004) en toda la co horte, y NG (p < 0.001). Al año en análisis multivariado se asoció a CVF <80%, AR (OR 4.32, 1.15-16.25), diabetes (OR 2.96, 1.02-8.57) y patrón SF (OR 3.51, 1.25-9.88). PD se asoció a AR (OR 12.2, 2.41-61.85). Discusión : Se observó mejoría en todas las variables al año. Pero al año persisten alteraciones funcionales y tomográficas en <50% de los pacientes. El subgrupo de PD se relacionó a AR. Es importante el seguimiento protocolizado de los pacientes hospitalizados, especial mente los grupos NG, PD y SF.

Abstract Introduction : There is scarce information on longterm evolution of hospitalized patients with moderate (MP) and severe (SP) COVID-19 pneumonia. Objective: to de termine clinical, respiratory function, and tomographic (HRCT) impact after being discharged 12 months after diagnosis. Methods : Analysis according to MP and SP, desatura tor patients (DP) in 6-minute walking test (6MWT) and HRCT fibrotic-like pattern (FLP). Results compared at 3 and 12 months of follow-up. Results : 194 patients enrolled and one year later 103 (53%) were evaluated: gender male (62.4%), age 57.7 ± 10.9 years, comorbidities (arterial hypertension 38.8%, diabetes 29.6%, and respiratory diseases-RD-18.4%). Variables compared 3 months to 12 months (mean/SD): FVC: 84%( 19) to 88%( 19) (p= 0.01). A 27% of patients had FVC<80% at one year. In 6MWT:426 (108) to 447 (92) (p = <0.01). 12.8% are DP in one year. SP had a greater FLP than MP (40% vs. 27.9%, p = 0.021). The FLP group was related to FVC < 80% (p = 0.004) in all patients but only in SP (p < 0.001). After one year, in multivariate analysis, FVC < 80% was associated with RD (OR 4.32, 1.15-16.25), diabetes (OR 2.96, 1.02-8.57) and FLP (OR 3.51, 1.25-9.88). DP were associated with RD (OR 12.2, 2.41-61.85). Discussion : Improvement was observed in all vari ables when comparing 3 to 12 months. However, after one year, functional and tomographic alterations persist in less than 50% of patients. DP subgroup was related to RD. Protocolled follow-up of hospitalized patients is important, especially in SP, DP, and FLP groups.

[Clinical, functional and tomographic respiratory sequels of patients hospitalized for COVID-19 at one year of diagnosis: SECUELAR-19 TRIAL]. / Secuelas respiratorias clínicas, funcionales y tomográficas de pacientes hospitalizados por COVID-19 al año del diagnóstico: ESTUDIO SECUELAR-19.

INTRODUCTION: There is scarce information on longterm evolution of hospitalized patients with moderate (MP) and severe (SP) COVID-19 pneumonia. OBJECTIVE: to determine clinical, respiratory function, and tomographic (HRCT) impact after being discharged 12 months after diagnosis. METHODS: Analysis according to MP and SP, desaturator patients (DP) in 6-minute walking test (6MWT) and HRCT fibrotic-like pattern (FLP). Results compared at 3 and 12 months of follow-up. RESULTS: 194 patients enrolled and one year later 103 (53%) were evaluated: gender male (62.4%), age 57.7 ± 10.9 years, comorbidities (arterial hypertension 38.8%, diabetes 29.6%, and respiratory diseases-RD-18.4%). Variables compared 3 months to 12 months (mean/SD): FVC: 84%( 19) to 88%( 19) (p= 0.01). A 27% of patients had FVC<80% at one year. In 6MWT:426 (108) to 447 (92) (p = <0.01). 12.8% are DP in one year. SP had a greater FLP than MP (40% vs. 27.9%, p = 0.021). The FLP group was related to FVC < 80% (p = 0.004) in all patients but only in SP (p < 0.001). After one year, in multivariate analysis, FVC < 80% was associated with RD (OR 4.32, 1.15-16.25), diabetes (OR 2.96, 1.02-8.57) and FLP (OR 3.51, 1.25-9.88). DP were associated with RD (OR 12.2, 2.41-61.85). DISCUSSION: Improvement was observed in all variables when comparing 3 to 12 months. However, after one year, functional and tomographic alterations persist in less than 50% of patients. DP subgroup was related to RD. Protocolled follow-up of hospitalized patients is important, especially in SP, DP, and FLP groups.

Introducción: Hay información escasa sobre evolución a largo plazo de pacientes hospitalizados por neumonía COVID-19 moderada (NM) y grave (NG). El objetivo del estudio fue determinar impacto clínico, funcional respiratorio y tomográfico (TACAR) luego del alta a 12 meses del diagnóstico. Métodos: análisis según grupos NM y NG, desaturadores (PD) en prueba de caminata 6 min (PC6M) y patrón tomográfico símil fibrótico (SF). Comparamos resultados a 3 y 12 meses de seguimiento. Resultados: 194 pacientes enrolados, evaluados al año: 103 (53% ): masculinos (62.4%), edad 57.7 ± 10.9 años, comorbilidades (hipertensión arterial 38.8%, diabetes 29.6%, antecedentes respiratorios-AR-18.4%). Comparamos variables a los 3 y 12 meses (media/DE): CVF 84%(19) a 88(19) (p = 0.01); 27% tuvo CVF<80% al año. En PC6M: 426 metros (108) a 447(92) (p = < 0.01). El 12.8% fue PD al año. NG tuvo mayor SF (40% vs. 27.9% p = 0.021). SF se relacionó con CVF <80% (p = 0.004) en toda la cohorte, y NG (p < 0.001). Al año en análisis multivariado se asoció a CVF <80%, AR (OR 4.32, 1.15-16.25), diabetes (OR 2.96, 1.02-8.57) y patrón SF (OR 3.51, 1.25-9.88). PD se asoció a AR (OR 12.2, 2.41-61.85). Discusión: Se observó mejoría en todas las variables al año. Pero al año persisten alteraciones funcionales y tomográficas en <50% de los pacientes. El subgrupo de PD se relacionó a AR. Es importante el seguimiento protocolizado de los pacientes hospitalizados, especialmente los grupos NG, PD y SF.

El asma no controlada en la atención primaria: implementación y uso práctico de ReferID / Uncontrolled Asthma in Primary Care: Implementation and Practical Use of ReferID

Introducción: la evidencia de vida real muestra deficiencias en alcanzar los objetivos de control del asma, con elevado consumo de agonistas beta-2 de acción corta (SA-BA) y sobreuso de corticoides sistémicos (CS). Métodos: estudio observacional, des-criptivo, aplicando la herramienta ReferID con 4 preguntas para identificar pacientes con asma no controlada y/o en riesgo de crisis severas: en los últimos 12 meses [1] ¿Re-cibió ≥2 ciclos de CS y/o los usó como mantenimiento?; [2] ¿Tuvo ≥2 visitas a emergen-cias por asma?; [3] ¿Estuvo intubado o en Unidad de Cuidados Intensivos (UCI) por as-ma?; [4] ¿Cuántos inhaladores de SABA ha utilizado? Una respuesta afirmativa a las preguntas 1, 2 o 3, o usar ≥3 envases de SABA, sugieren riesgo de ataque grave, nece-sidad de CS y/o riesgo vital. En estos pacientes se recomienda evaluación por especia-listas. Resultados: participaron 441 pacientes de 7 instituciones del Área Metropolita-na de Buenos Aires. Al 60,1% (intervalo de confianza del 95% [IC95]:55,5%-64,7%) se le recomendó evaluación por especialista. El 33,8% (IC95:29,39%-38,21%) recibió ≥2 ciclos de CS y/o los usaba como mantenimiento. El 36,1% (IC95:31,62%-40,58%) asis-tió ≥2 veces a emergencias. El 41,5% (IC95:30,06%-38,94%) usó ≥3 envases de SABA. El 8,8% (IC95:6,16%-11,44%) tenía historia de intubación o UCI. El 37,2% se atendió en instituciones públicas, con indicadores de gravedad significativamente mayores que en las privadas. Conclusiones: ReferID es una herramienta simple que ayuda a identificar a pacientes en riesgo de crisis severa y/o que pudieran tener diagnóstico de asma gra-ve; y que se beneficiarían de una evaluación por un especialista. AU

Introduction: real-life evidence shows deficiencies in achieving asthma control goals, with high use of short-acting beta-2 agonists (SABA) and overuse of systemic cortico-steroids (SC). Methods: observational, descriptive study, applying the ReferID tool with 4 questions to identify patients with uncontrolled asthma and/or at risk of severe crisis: in the last 12 months [1] Have you received ≥2 cycles of CS and/or used them as main-tenance therapy?; [2] Have you had ≥2 emergency visits for asthma?; [3] Have you ever been intubated or admitted to the Intensive Care Unit (ICU) for asthma?; [4] How many SABA inhalers have you used? An affirmative answer to questions 1, 2 or 3, or using ≥3 canisters of SABA, suggests risk of severe attack, need for CS and/or life-threatening risk. In these patients, evaluation by specialists is recommended. Results: 441 patients from 7 institutions in the Metropolitan Area of Buenos Aires were enrolled. An evalu-ation by specialists was recommended for 60.1% (95% confidence interval [95%CI]: 55.5%-64.7%); 33.8% (95%CI:29.39%-38.21%) received ≥2 cycles of CS and/or used them as maintenance; 36.1% (95%CI:31.62%-40.58%) attended ≥2 times to the emer-gency department; 41.5% (95%CI:30.06%-38.94%) used ≥3 containers of SABA; 8.8% (95%CI:6.16%-11.44%) had a history of intubation or ICU admission; 37.2% were as-sisted in public institutions, with significantly higher severity indicators than in private ones. Conclusions: Refer ID is a simple, useful tool to quickly identify asthma patients who are at risk of severe exacerbations and/or may have a diagnosis of severe asthma and would benefit from evaluation by a specialist. AU

[Clinical, functional and tomographic respiratory sequels of patients hospitalized for COVID-19 at six month of diagnosis: SECUELAR-19 trial]. / Secuelas respiratorias clínicas, funcionales y tomográficas de pacientes hospitalizados por COVID-19 a seis meses del diagnóstico: estudio SECUELAR-19.

INTRODUCTION: There is scarce information about middle-term evolution of hospitalized patients who suffer from pneumonia caused by COVID-19. The objective of this study is to determine the clinical, respiratory, tomographic and functional impact on COVID-19 patients with moderate (MP) to severe (SP) pneumonia after six months of acute infection. METHODS: Analysis was carried out by MP and SP groups, desaturators during the 6-minute-walking test and the presence of fibrotic like pattern on HRCT. Outcomes at 3 and 6 months were compared. RESULTS: The analysis included 129 patients, between 57 ± 11 years old. Frequent comorbidities were: arterial hypertension 38.1%, diabetes 30.4%, respiratory 18.6%). Comparing 3 and 6 months, improvement in quality of life was observed in MP and SP. The DP walked less meters in the MWT, worsened life quality and more fibrotic like pattern. The fibrotic pattern was related to the fall of CVF < 80% on MP and SP (p = 0.048 and p = 0.007), and with DP (p = 0.002). On multivariated analysis, the fibrotic like pattern was associated to the reduction of CVF with OR = 4.44 (1.94-10.18, p <0.01) and desaturation OR = 5.01(1.63-15.42, p < 0.01). On this cohort it was observed more functional and tomographic compromise on the DP The fibrotic like pattern was related to worse functional evolution and oximetry. DISCUSSION: Follow-up after discharge of COVID-19 patients with SP, DP or fibrotic changes in HCRT is underlined.

Introducción: Hay información escasa sobre la evolución de los enfermos hospitalizados por neumonía por COVID-19 a mediano plazo. El objetivo de este estudio fue determinar en pacientes con neumonía moderada (NM) o grave (NG) por COVID-19, el impacto clínico, funcional respiratorio y tomográfico a los 6 meses. Métodos: Se realizó análisis según grupos de NM y NG, desaturadores (PD) en la prueba de caminata de 6 minutos y presencia del patrón tomográfico de alta resolución (TACAR) símil fibrótico. Se compararon los resultados a los 3 y 6 meses. Resultados: Se incluyeron 129 pacientes, edad 57 ± 11 años, comorbilidades frecuentes (hipertensión arterial 38.1%, diabetes 30.4% y respiratorias 18.6%). Al comparar 3 y 6 meses se observó mejoría de la calidad de vida en NM y NG. Los PD presentaron menor metraje caminado, peor calidad de vida y mayor presencia de patrón símil fibrótico. Este patrón se relacionó con la caída de la FVC 80% en NM y NG (p = 0.048 y p = 0.007), y con PD (p = 0.002). En el análisis multivariado, el patrón símil fibrótico s e asoció a la reducción de la CVF con OR = 4.44 (1.94-10.18, p <0.01) y a la desaturación, OR = 5.01 (1.63-15.42, p <0.01). En esta cohorte se observó mayor compromiso funcional y tomográfico en los PD. El patrón símil fibrótico se relacionó con peor evolución funcional y oximétrica. Discusión: Es importante el seguimiento de los pacientes con NG, los PD y los que presentan patrón fibrótico al alta de neumonía por COVID-19.

Secuelas respiratorias clínicas, funcionales y tomográficas de pacientes hospitalizados por COVID-19 a seis meses del diagnóstico: estudio SECUELAR-19 / Clinical, functional and tomographic respiratory sequels of patients hospitalized for COVID-19 at six month of diagnosis: SECUELAR-19 trial

Resumen Introducción: Hay información escasa sobre la evolución de los enfermos hospitalizados por neumonía por COVID-19 a mediano plazo. El objetivo de este estudio fue determinar en pacientes con neumonía moderada (NM) o grave (NG) por COVID-19, el impacto clínico, funcional respiratorio y tomográfico a los 6 meses. Métodos: Se realizó análisis según grupos de NM y NG, desaturadores (PD) en la prueba de cami nata de 6 minutos y presencia del patrón tomográfico de alta resolución (TACAR) símil fibrótico. Se compararon los resultados a los 3 y 6 meses. Resultados: Se incluyeron 129 pacientes, edad 57±11 años, comorbilidades frecuentes (hipertensión arterial 38.1%, diabetes 30.4% y respiratorias 18.6%). Al comparar 3 y 6 meses se ob servó mejoría de la calidad de vida en NM y NG. Los PD presentaron menor metraje caminado, peor calidad de vida y mayor presencia de patrón símil fibrótico. Este patrón se relacionó con la caída de la FVC 80% en NM y NG (p = 0.048 y p = 0.007), y con PD (p = 0.002). En el análisis multivariado, el patrón símil fibrótico s e asoció a la reducción de la CVF con OR = 4.44 (1.94-10.18, p<0.01) y a la desaturación, OR = 5.01 (1.63-15.42, p<0.01). En esta cohorte se observó mayor compromiso funcional y tomográfico en los PD. El patrón símil fibrótico se relacionó con peor evolución funcional y oximétrica. Discusión: Es importante el seguimiento de los pacientes con NG, los PD y los que presentan patrón fibrótico al alta de neumonía por COVID-19.

Abstract Introduction: There is scarce information about middle-term evolution of hospitalized patients who suffer from pneumonia caused by COVID-19. The objective of this study is to determine the clinical, respiratory, tomographic and functional impact on COVID-19 patients with moderate (MP) to severe (SP) pneumonia after six months of acute infection. Methods: Analysis was carried out by MP and SP groups, desaturators during the 6-minute-walking test and the presence of fibrotic like pattern on HRCT. Outcomes at 3 and 6 months were compared. Results: The analysis included 129 patients, between 57 ± 11 years old. Frequent comorbidities were: arterial hypertension 38.1%, diabetes 30.4%, respiratory 18.6%). Comparing 3 and 6 months, improvement in quality of life was observed in MP and SP. The DP walked less meters in the MWT, worsened life quality and more fibrotic like pattern. The fibrotic pattern was related to the fall of CVF < 80% on MP and SP (p = 0.048 and p = 0.007), and with DP (p = 0.002). On multivariated analysis, the fibrotic like pattern was associated to the reduction of CVF with OR = 4.44 (1.94-10.18, p<0.01) and desaturation OR = 5.01(1.63-15.42, p < 0.01). On this cohort it was observed more functional and tomographic compromise on the DP The fibrotic like pattern was related to worse functional evolution and oximetry. Discussion: Follow-up after discharge of COVID-19 patients with SP, DP or fibrotic changes in HCRT is underlined.

Lung function and organ dysfunctions in 178 patients requiring mechanical ventilation during the 2009 influenza A (H1N1) pandemic.

INTRODUCTION: Most cases of the 2009 influenza A (H1N1) infection are self-limited, but occasionally the disease evolves to a severe condition needing hospitalization. Here we describe the evolution of the respiratory compromise, ventilatory management and laboratory variables of patients with diffuse viral pneumonitis caused by pandemic 2009 influenza A (H1N1) admitted to the ICU. METHOD: This was a multicenter, prospective inception cohort study including adult patients with acute respiratory failure requiring mechanical ventilation (MV) admitted to 20 ICUs in Argentina between June and September of 2009 during the influenza A (H1N1) pandemic. In a standard case-report form, we collected epidemiological characteristics, results of real-time reverse-transcriptase--polymerase-chain-reaction viral diagnostic tests, oxygenation variables, acid-base status, respiratory mechanics, ventilation management and laboratory tests. Variables were recorded on ICU admission and at days 3, 7 and 10. RESULTS: During the study period 178 patients with diffuse viral pneumonitis requiring MV were admitted. They were 44 ± 15 years of age, with Acute Physiology And Chronic Health Evaluation II (APACHE II) scores of 18 ± 7, and most frequent comorbidities were obesity (26%), previous respiratory disease (24%) and immunosuppression (16%). Non-invasive ventilation (NIV) was applied in 49 (28%) patients on admission, but 94% were later intubated.Acute respiratory distress syndrome (ARDS) was present throughout the entire ICU stay in the whole group (mean PaO2/FIO2 170 ± 25). Tidal-volumes used were 7.8 to 8.1 ml/kg (ideal body weight), plateau pressures always remained < 30 cmH2O, without differences between survivors and non-survivors; and mean positive end-expiratory pressure (PEEP) levels used were between 8 to 12 cm H2O. Rescue therapies, like recruitment maneuvers (8 to 35%), prone positioning (12 to 24%) and tracheal gas insufflation (3%) were frequently applied. At all time points, pH, platelet count, lactate dehydrogenase assay (LDH) and Sequential Organ Failure Assessment (SOFA) differed significantly between survivors and non-survivors. Lack of recovery of platelet count and persistence of leukocytosis were characteristic of non-survivors. Mortality was high (46%); and length of MV was 10 (6 to 17) days. CONCLUSIONS: These patients had severe, hypoxemic respiratory failure compatible with ARDS that persisted over time, frequently requiring rescue therapies to support oxygenation. NIV use is not warranted, given its high failure rate. Death and evolution to prolonged mechanical ventilation were common outcomes. Persistence of thrombocytopenia, acidosis and leukocytosis, and high LDH levels found in non-survivors during the course of the disease might be novel prognostic findings.