“Valoración multidisciplinar de las secuelas al mes del alta hospitalaria por neumonía grave COVID 19, ¿existen diferencias en función de la terapia respiratoria empleada durante su ingreso en Cuidados Intensivos?” "Multidisciplinary Approach of the sequelae one month after hospital discharge in patients with severe bilateral COVID-19 pneumonia, are there differences depending on the respiratory therapy used during admission to Intensive Care?”

Objetivo: Describir las secuelas al mes del alta hospitalaria en pacientes que precisaron ingreso en Cuidados Intensivos por neumonía grave COVID 19 y analizar las diferencias entre los que recibieron terapia exclusivamente con oxigenoterapia con alto flujo con respecto a los que precisaron ventilación mecánica invasiva. Diseño: Estudio de cohorte, prospectivo y observacional Ámbito: Consulta multidisciplinar post cuidados intensivos Pacientes o participantes: Pacientes que superaron el ingreso en la unidad de cuidados intensivos (UCI) por neumonía grave COVID 19 desde abril 2020 hasta octubre 2021 Intervenciones: Inclusión en el programa multidisciplinar post UCI Variables de interés principales: Secuelas motoras, sensitivas, psicológicas/psiquiátricas, respiratorias y nutricionales tras el ingreso hospitalario. Resultados: Se incluyeron 104 pacientes. 48 pacientes recibieron oxigenoterapia nasal de alto flujo (ONAF) y 56 ventilación mecánica invasiva (VMI). Las principales secuelas encontradas fueron la neuropatía distal (33,9% VMI vs 10,4% ONAF);plexopatía braquial (10,7% VMI vs 0% ONAF);disminución de fuerza de agarre: mano derecha 20,67kg (+/- 8,27) en VMI vs 31,8 kg (+/- 11,59) en ONAF y mano izquierda 19,39kg (+/- 8,45) en VMI vs 30,26kg (+/- 12,74) en ONAF;y balance muscular limitado en miembros inferiores (28,6% VMI vs 8,6% ONAF). Las diferencias observadas entre ambos grupos no alcanzaron significación estadística en el estudio multivariable. Conclusiones: Los resultados obtenidos tras el estudio multivariable sugieren no existir diferencias en cuanto a las secuelas físicas percibidas al mes del alta hospitalaria en función de la terapia respiratoria empleada, ya fuera oxigenoterapia nasal de alto flujo o ventilación mecánica prolongada, si bien son precisos más estudios para poder obtener conclusiones al respecto.

Immune, inflammatory and prothrombotic parameters in COVID-19 patients treated with an anti EGFR antibody.

SARS-CoV-2 infection causes a range of clinical presentations and induces changes in both innate and adaptive branches of the immune system. Furthermore, direct viral action to the cells of the lung promotes over-expression of the epidermal growth factor receptor (EGFR) which triggers pro-inflammatory response, contributes to coagulopathy and intravascular thrombi as well as lung fibrosis. Based on the role of this signaling pathway in the pathophysiology of the disease, nimotuzumab, an anti-EGFR monoclonal antibody, was used to treat patients with COVID-19. The aim of this study was to determine IL-6 and PAI-1 concentrations and lymphocyte subpopulations profiles in moderately and severely ill COVID-19 patients diagnosed during the B.1.617.2 variant wave in Cuba and included in a phase I/II trial to evaluate the safety and preliminary effect of nimotuzumab in COVID-19 disease. We observed high serum levels of IL-6, elevated plasma concentration of PAI-1, mean values of neutrophils to lymphocytes ratio (NLR) above three and CD4+ lymphopenia in both groups of patients. PAI-1 and IL-6 circulating levels decreased in patients treated with nimotuzumab. More than 95% of patients in which IL-6 decreased or increased slightly, were alive within 14 days after the monoclonal antibody administration. Patients with moderate and severe disease, were no different regarding the studied parameters, addressing the idea that several immune alterations could be present before the infection becomes clinically relevant. These findings suggest that nimotuzumab could be an attractive therapeutic option to interfere with the negative relationship between cytokines and procoagulant mediators in the inflammatory and prothrombotic phases of the disease.

Blocking EGFR with nimotuzumab: a novel strategy for COVID-19 treatment.

Background: Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. Patients & methods: A phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline. Results: 41 patients (31 severe and 10 moderate) received nimotuzumab. The median age was 62 years and the main comorbidities were hypertension, diabetes and cardiovascular disease. The antibody was very safe and the 14-day recovery rate was 82.9%. Inflammatory markers decreased over time. Patients did not show signs of fibrosis. Conclusion: Nimotuzumab is a safe antibody that might reduce inflammation and prevent fibrosis in severe and moderate COVID-19 patients. Clinical Trial Registration: RPCEC00000369 (rpcec.sld.cu).

Background: After SARS-CoV-2 infection, many cells in the lung express a new receptor called EGFR. Overexpression of EGFR can worsen the pulmonary disease and provoke fibrosis. Patients & methods: The initial impact of using a drug that blocks EGFR, nimotuzumab, was evaluated in COVID-19 patients. Results: 41 patients received nimotuzumab by the intravenous route together with other medications. The median age was 62 years, and patients had many chronic conditions including hypertension, diabetes and cardiac problems. Treatment was well tolerated and 82.9% of the patients were discharged by day 14. Serial laboratory tests, x-rays and CT scan evaluations showed the improvement of the patients. Conclusion: Nimotuzumab is a safe drug that can be useful to treat COVID-19 patients.

Desarrollo y validación prospectiva de la escala TIHCOVID: una herramienta de triaje y priorización del traslado interhospitalario de pacientes COVID-19 graves

Objectives. To develop and validate a triage scale (Spanish acronym, TIHCOVID) to assign priority by predicting critical events in patients with severe COVID-19 who are candidates for interhospital transfer. Methods. Prospective cohort study in 2 periods for internal (February-April 2020) and external (October-December 2020) validation. We included consecutive patients with severe COVID-19 who were transported by the emergency medical service of Catalonia. A risk model was developed to predict mortality based on variables recorded on first contact between the regional emergency coordination center and the transferring hospital. The model's performance was evaluated by means of calibration and discrimination, and the results for the first and second periods were compared. Results. Nine hundred patients were included, 450 in each period. In-hospital mortality was 33.8%. The 7 predictors included in the final model were age, comorbidity, need for prone positioning, renal insufficiency, use of high-flow nasal oxygen prior to mechanical ventilation, and a ratio of PaO2 to inspired oxygen fraction of less than 50. The performance of the model was good (Brier score, 0.172), and calibration and discrimination were consistent. We found no significant differences between the internal and external validation steps with respect to either the calibration slopes (0.92 [95% CI, 0.91-0.93] vs 1.12 [95% CI, 0.6-1.17], respectively;P = .150) or discrimination (area under the curve, 0.81 [95% CI, 0.75-0.84] vs 0.85 [95% CI, 0.81-0.89];P = .121). Conclusion. The TIHCOVID tool may be useful for triage when assigning priority for patients with severe COVID-19 who require transfer between hospitals. Objetivo. Desarrollar y validar una escala predictiva de eventos críticos en pacientes con infección grave por COVID-19 candidatos a traslado interhospitalario (TIH) que facilite el triaje y la priorización del transporte sanitario. Método. Estudio de cohortes prospectivo divido en dos periodos: validación interna (febrero-abril 2020) y validación externa (octubre-diciembre 2020). Se incluyeron consecutivamente los pacientes con infección grave por COVID-19 trasladados por el Sistema de Emergencias Médicas de Cataluña. Se construyó un modelo predictivo de las variables asociadas a la mortalidad recogidas en el momento del primer contacto entre el hospital emisor y el centro de coordinación. Se calculó el rendimiento del modelo y se comparó la validación interna y externa, evaluando la calibración y la discriminación. Resultados. Se incluyeron 900 pacientes, 450 pacientes en cada periodo de estudio. La mortalidad durante el ingreso fue del 33,8%. Las 7 variables predictoras incluidas en el modelo final fueron edad, comorbilidad, pronación, insufi- ciencia renal aguda, uso de oxigenoterapia de alto flujo previa a la ventilación mecánica invasiva, tabaquismo activo y un valor de PaO2/FiO2 < 50. El modelo mostró un buen rendimiento (Brier = 0,172) y consistencia en la calibración y discriminación. No se objetivaron diferencias en la pendiente de calibración [0,92 (IC 95%: 0,91-0,93) vs 1,12 (IC 95%: 0,6-1,17);p = 0,150] ni en la capacidad discriminativa [ABC 0,81 (IC 95%: 0,75-0,84) vs ABC de 0,85 (IC 95%: 0,81-0,89), p = 0,121] entre la validación interna y externa. Conclusiones. La escala TIHCOVID puede ser de ayuda para el triaje de pacientes con infección COVID-19 grave que precisan traslado interhospitalario.

Long-Term Survival of Mechanically Ventilated Patients with Severe COVID-19: An Observational Cohort Study (preprint)

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 90-day and 180-day survival of patients with COVID-19 requiring invasive ventilation and to develop a predictive model for intensive care unit 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 were 90-day and 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model and a nomogram were developed to estimate the probability of ICU 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 90-day and 180-day survival rates were 69% (95% confidence interval [CI] 66%-72%) and 59% (95% CI 56%-62%) respectively. The predictive factors associated with ICU mortality were: age (odds ratio [OR] 1.049 [95% CI 1.032-1.066] per 1-year increase), SAPS3 (OR 1.025 [95% CI 1.008-1.041] per 1-point increase), neutrophil to lymphocyte ratio (OR 1.009 [95% CI 1.002-1.016]), a failed attempt of noninvasive positive pressure ventilation previous to orotracheal intubation(OR 2.131 [95% CI 1.279-3.550]), and use of selective digestive decontamination (OR 0.587 [95% CI 0.358-0.963]).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).