COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

INTRODUCTION: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. METHODS: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. RESULTS: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). CONCLUSIONS: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. Methods: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48 h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. Results: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p < 0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p < 0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p < 0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). Conclusions: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Introducción: Nuestro trabajo describe la frecuencia de sobreinfecciones en pacientes con COVID-19 en UCI e identifica factores de riesgo asociados con su aparición. Secundariamente, evaluamos la estancia en UCI, mortalidad intrahospitalaria y analizamos un subgrupo de infecciones causadas por microorganismos multirresistentes (MDR). Métodos: Estudio realizado entre marzo y junio de 2020. Definimos como sobreinfección a aquellas que aparecieron ≥48 h del ingreso. Incluimos las causadas por bacterias y hongos y evaluamos la infección respiratoria asociada a la ventilación mecánica (IRAVM), bacteriemia primaria, bacteriemia secundaria e infección del tracto urinario. Se realizó un análisis multivariante de los factores de riesgo. Resultados: Incluimos 213 pacientes, documentándose 174 episodios de sobreinfección en 95 casos (44,6%): IRAVM 78 episodios, bacteriemia primaria 66, bacteriemia secundaria 9 e ITU 21. Los MDR causaron el 29,3% de los episodios. La mediana de tiempo hasta el primer episodio fue de 18 días, siendo mayor en las causadas por MDR vs. no MDR (28 vs. 16, p < 0,01). El análisis multivariante identificó la administración de corticoides (OR 4,9 IC 95% 1,4-16,9), tocilizumab (OR 2,4 IC 95% 1,1-5,9) y antibióticos de amplio espectro (OR 2,5 IC 95% 1,2-5,1) como factores de riesgo asociados. Los pacientes con sobreinfección presentaron una estancia en UCI más prolongada (35 vs. 12 días, p < 0,01) pero no mayor mortalidad intrahospitalaria (45,3% vs. 39,7%, p 0,13). Conclusiones: Las sobreinfecciones en los pacientes con COVID-19 aparecen tardíamente. La administración de corticoides, tocilizumab y antibióticos de amplio espectro se asocia con su aparición.

Mortalidad y función renal a largo plazo en pacientes ingresados en la UCI por COVID-19 con fracaso renal agudo, terapia continua de reemplazo renal y ventilación mecánica invasiva / Mortality and renal long-term outcome of critically ill COVID-19 patients with acute kidney failure, continuous renal replacement therapy and invasive mechanical ventilation

Introducción: La interacción de COVID-19, ventilación mecánica invasiva (VMI) y fracaso renal agudo (FRA) con necesidad de terapia continua de reemplazo renal (TCRR) es conocida, pero hay pocos datos publicados sobre el pronóstico a largo plazo de este tipo de FRA.MétodosEste estudio analiza los resultados a largo plazo de 30 pacientes ingresados en la UCI por neumonía por COVID-19, con VMI y FRA con TCRR en el pico de máxima incidencia. Comparamos las características basales, la evolución clínica y bioquímica y los diferentes filtros usados en la TCRR para identificar los factores de riesgo asociados a la muerte intrahospitalaria. Se analizaron el filtrado glomerular estimado (FGe), la proteinuria y la hematuria a los 6meses de seguimiento de los supervivientes.ResultadosDe los 30 pacientes, 19 fallecieron y 11 fueron dados de alta. Los pacientes con peor función renal tuvieron mayor mortalidad (p=0,009). Los filtros usados con capacidad adsortiva no ofrecieron beneficios en cuanto a la supervivencia. De los 11 supervivientes, ninguno requirió terapia renal sustitutiva (TRS) una vez superada la infección, pero tuvieron una pérdida importante y mantenida en el tiempo de función renal (FGe de 44ml/min/1,73 m2).ConclusiónLa mortalidad en pacientes con neumonía por COVID-19 que requieren VMI y TCRR es extremadamente elevada (63%). Los filtros con capacidad adsortiva no modificaron la supervivencia. La función renal basal fue un factor predictor de mortalidad. En este tipo de FRA el deterioro de la función renal no se recupera, objetivándose una reducción importante del FGe a los 6 meses. (AU)

Background: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation.MethodsIn this retrospective observational study we analyzed the long-term clinical course and outcomes of 30 critically ill patients hospitalized with COVID-19 during the peak of highest incidence in the first wave, with acute respiratory distress syndrome (ARDS) and AKI that required CRRT. Baseline features, clinical course, laboratory data, therapies and filters used in CRRT were compared between survivors and non-survivors to identify risk factors associated with in-hospital death. Renal parameters: glomerular filtration rate, proteinuria and microhematuria were collected at 6months after discharge.Results19 patients (63%) died and 11 were discharged. Mean time to death was 48days (7-206) after admission. Patients with worse baseline renal function had higher mortality (P=.009). Patients were treated with CRRT for an average of 18.4days. Filters with adsorptive capacity (43%) did not offer survival benefits. Regarding long-term renal outcomes, survivor patients did not receive any additional dialysis, but 9 out of 11 patients had an important loss of renal function (median of eGF of 44 (13-76)ml/min/1.73m2) after 6months.ConclusionMortality among critically ill hospitalized patients diagnosed with COVID-19 on CRRT is extremely high (63%). Baseline renal function is a predictor factor of mortality. Filters with adsorption capacity did not modify survival. None survivor patients required long-term dialysis, but an important loss of renal function occurred after AKI episode related to COVID-19 infection. (AU)

Mortality and renal long-term outcome of critically ill COVID-19 patients with acute kidney failure, continuous renal replacement therapy and invasive mechanical ventilation.

Background: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation. Methods: In this retrospective observational study we analyzed the long-term clinical course and outcomes of 30 critically ill patients hospitalized with COVID-19 during the peak of highest incidence in the first wave, with acute respiratory distress syndrome (ARDS) and AKI that required CRRT. Baseline features, clinical course, laboratory data, therapies and filters used in CRRT were compared between survivors and non-survivors to identify risk factors associated with in-hospital death. Renal parameters: glomerular filtration rate, proteinuria and microhematuria were collected at 6 months after discharge. Results: 19 patients (63%) died and 11 were discharged. Mean time to death was 48 days (7-206) after admission. Patients with worse baseline renal function had higher mortality (P = 0.009). Patients were treated with CRRT for an average of 18.4 days. Filters with adsorptive capacity (43%) did not offer survival benefits. Regarding long-term renal outcomes, survivor patients did not receive any additional dialysis, but 9 out of 11 patients had an important loss of renal function (median of eGF of 44 (13-76) ml/min/1.73 m2) after 6 months. Conclusion: Mortality among critically ill hospitalized patients diagnosed with COVID-19 on CRRT is extremely high (63%). Baseline renal function is a predictor factor of mortality. Filters with adsorption capacity did not modify survival. None survivor patients required long-term dialysis, but an important loss of renal function occurred after AKI episode related to COVID-19 infection.

Introducción: La interacciónde COVID-19, ventilación mecánica invasiva (VMI) y fracaso renal agudo (FRA) con necesidad de terapia continua de reemplazo renal (TCRR) es conocida, pero hay pocos datos publicados sobre el pronóstico a largo plazo de este tipo de FRA. Métodos: Este estudio analiza los resultados a largo plazo de 30 pacientes ingresados en la UCI por neumonía por COVID-19, con VMI y FRA con TCRR en el pico de máxima incidencia. Comparamos las características basales, la evolución clínica y bioquímica y los diferentes filtros usados en la TCRR para identificar los factores de riesgo asociados a la muerte intrahospitalaria. Se analizaron el filtrado glomerular estimado (FGe), la proteinuria y la hematuria a los 6 meses de seguimiento de los supervivientes. Resultados: De los 30 pacientes, 19 fallecieron y 11 fueron dados de alta. Los pacientes con peor función renal tuvieron mayor mortalidad (p = 0,009). Los filtros usados con capacidad adsortiva no ofrecieron beneficios en cuanto a la supervivencia. De los 11 supervivientes, ninguno requirió terapia renal sustitutiva (TRS) una vez superada la infección, pero tuvieron una pérdida importante y mantenida en el tiempo de función renal (FGe de 44 ml/min/1,73 m2). Conclusión: La mortalidad en pacientes con neumonía por COVID-19 que requieren VMI y TCRR es extremadamente elevada (63%). Los filtros con capacidad adsortiva no modificaron la supervivencia. La función renal basal fue un factor predictor de mortalidad. En este tipo de FRA el deterioro de la función renal no se recupera, objetivándose una reducción importante del FGe a los 6 meses.

Mortality and renal long-term outcome of critically ill COVID-19 patients with acute kidney failure, continuous renal replacement therapy and invasive mechanical ventilation. / Mortalidad y función renal a largo plazo en pacientes ingresados en la UCI por COVID-19 con fracaso renal agudo, terapia continua de reemplazo renal y ventilación mecánica invasiva.

BACKGROUND: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation. METHODS: In this retrospective observational study we analyzed the long-term clinical course and outcomes of 30 critically ill patients hospitalized with COVID-19 during the peak of highest incidence in the first wave, with acute respiratory distress syndrome (ARDS) and AKI that required CRRT. Baseline features, clinical course, laboratory data, therapies and filters used in CRRT were compared between survivors and non-survivors to identify risk factors associated with in-hospital death. Renal parameters: glomerular filtration rate, proteinuria and microhematuria were collected at 6months after discharge. RESULTS: 19 patients (63%) died and 11 were discharged. Mean time to death was 48days (7-206) after admission. Patients with worse baseline renal function had higher mortality (P=.009). Patients were treated with CRRT for an average of 18.4days. Filters with adsorptive capacity (43%) did not offer survival benefits. Regarding long-term renal outcomes, survivor patients did not receive any additional dialysis, but 9 out of 11 patients had an important loss of renal function (median of eGF of 44 (13-76)ml/min/1.73m2) after 6months. CONCLUSION: Mortality among critically ill hospitalized patients diagnosed with COVID-19 on CRRT is extremely high (63%). Baseline renal function is a predictor factor of mortality. Filters with adsorption capacity did not modify survival. None survivor patients required long-term dialysis, but an important loss of renal function occurred after AKI episode related to COVID-19 infection.

Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

Long-term survival of mechanically ventilated patients with severe COVID-19: an observational cohort study.

BACKGROUND: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality. METHODS: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality. RESULTS: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56-62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033-1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011-1.044), diabetes (OR 1.546, 95% CI 1.085-2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001-1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124-3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358-0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205-3.460). CONCLUSION: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).

Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. METHODS: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan-Meier and Cox regression analysis. RESULTS: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis (p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11-1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99-1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. CONCLUSION: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

BACKGROUND: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. METHODS: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. RESULTS: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). CONCLUSIONS: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.

Linfoma no hodgkin: reporte de un caso / Non-Hodgkin’s lymphoma

Aunque su etiología aun no está claramente definida, los linfomas son proliferaciones malignas del sistema linfoide y se clasifican según su histología, como tipos hodgkin y no hodgkin. Los linfomas no hodgkin (LNH) comprenden todos los que no muestran en su constitución la célula de Red – Stemberg; son muy heterogéneos, no todos se localizan en ganglios linfáticos (como ejemplo de forma extraganglionar podemos citar los que se presentan asociados a la presencia de H. pylori en la mucosa del estómago), la mayoría con origen en los linfocitos B y tiene marcadores de superficie característicos de la propia membrana celular. La edad más común de presentación es aproximadamente la quinta década de vida y en adelante, actualmente los LNH se los puede dividir en dos grupos de acuerdo a su conducta clínica: indolentes y agresivos, aunque hay otras clasificaciones (Rappaport, REAL, Kiel, Working F., etc.) El diagnóstico definitivo lo da la biopsia apoyado en estudios de imágenes. Presentamos el caso de una paciente de sexo femenino, 60 años de edad, que consulta por adenopatía inguinal unilateral derecha, leve edema y dolor en miembro inferior derecho, con moderada pérdida de peso.

Although its etiology is not yet clearly defined, lymphomas are malignant proliferations of the lymphatic system and are classified according to their histology as Hodgkin and non Hodgkin types. The Non-Hodgkin’s lymphomas (NHL) constitute all the ones whose composition does not show the Red-Stemberg cell. They are heterogenic, and not all of them are localized in lymph nodes (as a sample of extraganglionar shape we can mention the ones that are associated to the presence of Helicobacter Pylori in the stomach mucous), most of them originated in the lymphocyte B, which have surface indicators typical of the cellular membrane. In some cases they appear at the age of 50 on, nowadays the NHL can be divided into two groups according to their clinical behavior: indolent and aggressive, although there are other classifications (Rappaport, REAL, Kiel, Working F, etc) the definite diagnosis is given by the biopsy and image diagnosis. Here the case of a 60 year-old female patient whose consultation is for right inguinal adenopathy, slight edema and pain in right leg and moderate weight loss.