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The original version of this Article contained an error in Funding information. “The RELICO study has been sponsored by Menarini Hellas S.A.” now reads: “The SLEPICO study has been sponsored by Menarini Hellas S.A.” The original Article has been corrected. © The Author(s) 2022.

Introduction: Epidemiological data from patients with COVID-19 has been recently published in several countries. Nationwide data of hospitalized patients with COVID-19 in Greece remain scarce. Material and methods: This was an observational, retrospective study from 6 reference centers between February 26 and May 15, 2020. Results: The patients were mostly males (65.7%) and never smokers (57.2%) of median age 60 (95% CI: 57.6–64) years. The majority of the subjects (98%) were treated with the standard-of-care therapeutic regimen at that time, including hydroxychloroquine and azithromycin. Median time of hospitalization was 10 days (95% CI: 10–12). Twenty-five (13.3%) individuals were intubated and 8 died (4.2%). The patients with high neutrophil-to-lymphocyte ratio (NLR) (> 3.58) exhibited more severe disease as indicated by significantly increased World Health Organization (WHO) R&D ordinal scale (4; 95% CI: 4–4 vs 3; 95% CI: 3–4, p = 0.0001) and MaxFiO2% (50; 95% CI: 38.2–50 vs 29.5; 95% CI: 21–31, p < 0.0001). The patients with increased lactate dehydrogenase (LDH) levels (>270 IU/ml) also exhibited more advanced disease compared to the low LDH group (< 270 IU/ml) as indicated by both WHO R&D ordinal scale (4; 95% CI: 4–4 vs 4; 95% CI: 3–4, p = 0.0001) and MaxFiO2% (50; 95% CI: 35–60 vs 28; 95% CI: 21–31, p < 0.0001). Conclusion: We present the first epidemiological report from a low-incidence and mortality COVID-19 country. NLR and LDH may represent reliable disease prognosticators leading to timely treatment decisions. © 2021 PTChP.

A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage1,2. Here, we report that for coronavirus disease 2019 (COVID-19) this paradigm does not apply. By investigating temporal IFN and inflammatory cytokine patterns in 32 moderate-to-severe patients with COVID-19 hospitalized for pneumonia and longitudinally followed for the development of respiratory failure and death, we reveal that IFN-λ and type I IFN production were both diminished and delayed, induced only in a fraction of patients as they became critically ill. On the contrary, pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-8 were produced before IFNs in all patients and persisted for a prolonged time. This condition was reflected in blood transcriptomes wherein prominent IFN signatures were only seen in critically ill patients who also exhibited augmented inflammation. By comparison, in 16 patients with influenza (flu) hospitalized for pneumonia with similar clinicopathological characteristics to those of COVID-19 and 24 nonhospitalized patients with flu with milder symptoms, IFN-λ and type I IFN were robustly induced earlier, at higher levels and independently of disease severity, whereas pro-inflammatory cytokines were only acutely produced. Notably, higher IFN-λ concentrations in patients with COVID-19 correlated with lower viral load in bronchial aspirates and faster viral clearance and a higher IFN-λ to type I IFN ratio correlated with improved outcome for critically ill patients. Moreover, altered cytokine patterns in patients with COVID-19 correlated with longer hospitalization and higher incidence of critical disease and mortality compared to flu. These data point to an untuned antiviral response in COVID-19, contributing to persistent viral presence, hyperinflammation and respiratory failure. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Background We performed metabolomic profiling to identify metabolites that correlate with disease progression and death. Methods We performed a study of adults hospitalized with Influenza A(H1N1)pdm09. Cases (n = 32) were defined by a composite outcome of death or transfer to the intensive care unit during the 60-day follow-up period. Controls (n = 64) were survivors who did not require transfer to the ICU. Four hundred and eight metabolites from eight families were measured on plasma sample at enrollment using a mass spectrometry based Biocrates platform. Conditional logistic regression was used to summarize the association of the individual metabolites and families with the composite outcome and its major two components. Results The ten metabolites with the strongest association with disease progression belonged to five different metabolite families with sphingolipids being the most common. The acylcarnitines, glycerides, sphingolipids and biogenic metabolite families had the largest odds ratios based on the composite endpoint. The tryptophan odds ratio for the composite is largely associated with death (OR 17.33: 95% CI, 1.60–187.76). Conclusions Individuals that develop disease progression when infected with Influenza H1N1 have a metabolite signature that differs from survivors. Low levels of tryptophan had a strong association with death. Registry ClinicalTrials.gov Identifier: NCT01056185 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Proper management of COVID-19 mandates better understanding of disease pathogenesis. Giamarellos-Bourboulis et al. describe two main features preceding severe respiratory failure associated with COVID-19: the first is macrophage activation syndrome; the second is defective antigen-presentation driven by interleukin-6. An IL-6 blocker partially rescues immune dysregulation in vitro and in patients. © 2020 Elsevier Inc. Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation. © 2020 Elsevier Inc.

Objective: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. Methods: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2

A growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on the characteristics of lung microbiome, and specifically the bacteriome, the modes of interaction between lung microbiota and host immune system, the role of the “lung-gut axis”, and the functional effects thereof on asthma pathogenesis. We also attempt to explore the possibilities of therapeutic manipulation of the microbiome, aiming at the establishment of asthma prevention strategies and the optimization of asthma treatment. © 2019, MDPI AG. All rights reserved.

Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Daily sedation interruption (DSI) is a method used since the beginning of the millennium to streamline sedation in critically ill patients under mechanical ventilation and improve clinical outcomes. The purpose was to assess whether there is a correlation between DSI and weaning from mechanical ventilation. We designed a literature review via searching PubMed, UpToDate and Google Scholar for relevant key terms from inception until March 2019. Literature retrieved included nine randomized controlled trials. When compared to usual practice, it is superior in terms of duration of mechanical ventilation, stay in the intensive care unit, hospitalization, adverse effect occurrence and total cost of therapy. Comparison with other sedation protocols produces conflicting results. DSI, and protocolized sedation in general, are safe methods to perform to facilitate earlier weaning and improved clinical outcomes. Future research should focus on minimizing bias by conducting double-blinded studies and studying different patient subgroups. © 2019 Via Medica. All rights reserved.

Background: The concept of buffering generally refers to the ability of a system/organism to withstand attempted changes. For acid-base balance in particular, it is the body’s ability to limit pH aberrations when factors that potentially affect it change. Buffering is vital for maintaining homeostasis of an organism. The present study was undertaken in order to investigate the probable buffering capacity changes in septic patients. Materials and methods: This prospective cohort study included 113 ICU patients (96 septic and 17 critically-ill non-septic/controls). The buffering capacity indices were assessed upon ICU admission and reassessed only in septic patients, either at improvement or upon severe deterioration. Applying Stewart’s approach, the buffering capacity was assessed with indices calculated from the observed central venous-arterial gradients: a) ΔPCO2/Δ[H+] or ΔpH, b) ΔSID/Δ[H+] or ΔpH. Results: In a generalized estimating equation linear regression model, septic patients displayed significant differences in ΔPCO2/ΔpH [beta coefficient = -47.63, 95% CI (-80.09) - (-15.17), p = 0.004], compared to non-septic patients on admission. Lower absolute value of ΔPCO2/ΔpH (%) on admission was associated with a significant reduction in ICU mortality (HR 0.98, 95% CI: 0.97-0.99, p = 0.02). At septic-group reassessment (remission or deterioration), one-unit increase of ΔPCO2/D[H+] reduced the ICU death hazard by 44% (HR 0.56, 95% CI: 0.33-0.96, p = 0.03). Conclusions: In the particular cohort of patients studied, a difference in the buffering capacity was recorded between septic and non-septic patients on admission. Moreover, buffering capacity was an independent predictor of fatal ICU outcome at both assessments, ICU-admission and sepsis remission or deterioration. © 2019, MDPI AG. All rights reserved.

Background: During the past few years, the use of criteria introduced by Global Initiative for Chronic Obstructive Lung Disease (GOLD) is recommended for the diagnosis and classification of Chronic Obstructive Pulmonary Disease(COPD),taking into account the values of a Forced Expiratory Volume In 1 second (FEV1) and a Forced Expiratory Volume In 1 second (FEV1) to Forced Vital Capacity (FVC) ratio. In Europe, the reference values of the European Coal and Steel Community (ECSC), that were originally developed in 1993 are still used. Aim of the Study: The study aimed to carry out measurement of spirometric values in a healthy, non smoking Greek population, development of local equations and comparison with ECSC and Global Lung Initiative(GLI) equations, in order to see if there is a need for separate ones in everyday use. Methods: Normal predicted values for FEV1 and FEV1/FVC% were obtained from a group of 500 healthy subjects, aged 18-89 years. In addition, a group of 124 COPD patients, with no other comorbidities was studied. Patients were classified according to GOLD criteria in four groups with ECSC, GLI predicted values or with our own predicted values. Results: The statistical analysis has revealed that there is no significant difference among the three sets of predicted values and no statistical difference was detected among the classification of COPD patients. Conclusion: It is shown that the 3 sets of predicted values are almost identical, despite the fact that they have been collected from different study populations.Αccording to the study, there is no need in recalculating values for Greek population. © 2018 Tatsis et al.

Objective: The thrombomodulin/protein C and VWF/ADAMTS-13 pathways are disturbed in sepsis and have been implicated in the coagulation disorders that characterize the septic syndrome. We aimed to assess the variation of these endothelial parameters during sepsis and their putative association with outcome, in critically ill, septic patients. Methods: We monitored 34 septic patients, 23 of whom improved (group A) while 11 deteriorated (group B). We assessed ADAMTS-13 levels, VWF activity, soluble thrombomodulin, and protein C activity upon admission to the ICU (time point 0) and at the time of a change in the clinical condition (remission or deterioration, time point 1). Results: In group A, thrombomodulin and VWF increased at time point 1 compared to time point 0 (P = 0.011, P = 0.028, respectively). In group B, protein C and ADAMTS-13 significantly decreased (P = 0.023, P = 0.026, respectively), while VWF, VWF/ADAMTS-13 ratio, and the thrombomodulin/protein C ratio increased (P = 0.02, P = 0.002, P = 0.01, respectively). Protein C (> or ≤17%) and ADAMTS-13 percentage difference (> or ≤22%) were independently associated with sepsis outcome among the endothelial variables tested. Conclusions: An ongoing endothelial/hemostatic disorder was established during sepsis, observed even at clinical improvement. Among the variables tested, protein C and ADAMTS-13 change were associated with outcome. © 2018 John Wiley & Sons Ltd