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Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Fleta, Vera-Tomé, Jiménez-Fernández, Requena, Roy-Vallejo, Sanz-García, Lozano-Prieto, López-Sanz, Vara, Lancho-Sánchez, Martín-Gayo, Muñoz-Calleja, Alfranca, González-Álvaro, Galván-Román, Aspa, de la Fuente and Sánchez-Madrid.)

Introduction: The increase and persistence of inflammation in community-acquired pneumonia (CAP) patients can lead to higher mortality. Biomarkers capable of measuring this inadequate inflammatory response are likely candidates to be related with a bad outcome. We investigated the association between concentrations of several inflammatory markers and mortality of CAP patients., Material and Methods: This was a prospective study of hospitalised CAP patients in a Spanish university hospital. Blood tests upon admittance and in the early-stage evolution (72-120 hours) were carried out, where C-reactive protein, procalcitonin, proadrenomedullin, copeptin, white blood cell, Lymphocyte Count Percentage (LCP), Neutrophil Count Percentage (NCP) and Neutrophil/Lymphocyte Ratio (NLR) were measured. The outcome variable was mortality at 30 and 90 days. Statistical analysis included logistic regression, ROC analysis and area-under-curve test., Results: 154 hospitalised CAP patients were included. Patients who died during follow-up had higher levels of procalcitonin, copeptin, proadrenomedullin, lower levels of LCP, and higher of NCP and NLR. Remarkably, multivariate analysis showed a relationship between NCP and mortality, regardless of age, severity of CAP and comorbidities. AUC analysis showed that NLR and NCP at admittance and during early-stage evolution achieved a good diagnostic power. ROC test for NCP and NLR were similar to those of the novel serum biomarkers analysed., Conclusions: NLR and NCP, are promising candidate predictors of mortality for hospitalised CAP patients, and both are cheaper, easier to perform, and at least as reliable as the new serum biomarkers. Future implementation of new biomarkers would require comparison not only with classic inflammatory parameters like White Blood Cell count but also with NLR and NCP.