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Background COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective To determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods Retrospective observational study performed in hospitalized patients diagnosed of COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with pre- and post-administration of TCZ. Multivariable logistic and linear regressions, and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio (PaO 2 /FiO 2 ) or mortality. Results One hundred and forty-six patients were studied, predominantly male (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels>30 pg/ml was the best predictor for IMV (OR:7.1; p<0.001). Early administration of TCZ was associated with improvement of oxygenation (PaO 2 /FiO 2 ) in patients with high IL-6 (p=0.048). Patients with high IL-6 not treated with TCZ showed high mortality (HR: 4.6; p=0.003), as well as those with low IL-6 treated with TCZ (HR: 3.6; p=0.016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusion Baseline IL-6>30 pg/ml predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8 + T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8 + T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients.Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c + conventional dendritic cells also followed this pattern, whereas CD141 + conventional and CD123 hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.

Some recent studies have shown an association between sleep disordered breathing (SDB) and cancer mortality and incidence but no study has focused on a specific type of cancer. The objective of this study was to analyse the relationship between the severity of SDB and factors related to cutaneous malignant melanoma (CMM) aggressiveness.We performed a multicentre observational study in 82 consecutive patients diagnosed with CMM. 56 patients in whom melanoma measurements were available were finally included in the study. Melanoma measurements of aggressiveness included: tumour mitotic rate, Breslow index, presence of ulceration, stage of disease and growth rate of melanoma. A sleep study was performed in all the included patients. Multivariate analyses were used to examine the independent relationship between SDB severity (apnoeahypopnea index (AHI) and nocturnal oxygen desaturation indexes (ODI3% and ODI4%)) and measures of CMM aggressiveness.60.7% of patients had SDB (AHI o5) and 14.3% severe obstructive sleep apnoea (AHI o30). In fully adjusted multivariate analyses, AHI (OR 1.08, 95% CI 1.02-1.14), ODI3% (OR 1.08, 95% CI 1.02-1.11) and ODI4% (OR 1.1, 95% CI 1.02-1.2) were independently associated with an increased melanoma growth rate. Furthermore, AHI, ODI4% and ODI3% were significantly correlated with other aggressiveness factors of CMM, such as Breslow index, presence of ulceration and mitotic index.SDB severity markers are associated with some aggressiveness markers of CMM.@ERSpublications This study adds evidence on the relationship between sleep disordered breathing and cancer aggressiveness

Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis. However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial. We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable. We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation. From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality. The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL. The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%. In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7. We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised.

The severity of SDB was independently associated with greater aggressiveness of cutaneous melanoma, particularly among younger patients.

La infección por SARS-CoV-2 puede favorecer el desarrollo de diversas secuelas respiratorias, sobre todo en los pacientes que han sufrido una neumonía grave por COVID-19. Dado el elevado número de pacientes que sufrieron esta infección en un corto periodo de tiempo, se están llevando a cabo numerosas visitas de control post-COVID-19 sin que se haya establecido un protocolo de seguimiento clínico que aconseje sobre las pruebas complementarias a realizar y la frecuencia de las mismas. Este documento de consenso realizado por profesionales de distintas áreas de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR), pretende ayudar al profesional clínico a la identificación de las posibles complicaciones respiratorias que pueden aparecen durante los meses posteriores al cuadro agudo de la enfermedad y a protocolizar su seguimiento y las pruebas complementarias a realizar. Se sugieren las exploraciones e intervenciones a realizar en diversos momentos de la evolución post-COVID-19, con unos objetivos concretos. Por un lado, garantizar que los pacientes reciban un seguimiento clínico oportuno, con un cronograma preestablecido teniendo en cuenta la gravedad de la enfermedad y la probabilidad de secuelas a largo plazo; por otro lado, evitar sobrecargas del sistema sanitario llevando a cabo exploraciones y/o consultas en muchos casos innecesarias; por último, definir criterios para derivar a aquellos pacientes con determinadas secuelas específicas establecidas (enfermedad pulmonar intersticial, enfermedad vascular pulmonar o bronquiectasias) a las unidades monográficas correspondientes.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.