ABSTRACT
Background: Understanding the role of crucial biomolecules and mechanistic pathways supporting coronavirus disease 2019 (COVID-19) pathophysiology is essential to handle the immune dysregulation and complications driven by uncontrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, we evaluated the proteomics, metabolomics and lipidomics plasma profile in a well-characterized cohort of COVID-19 patients ranging from asymptomatic to critical illness. Methods: This multicenter case-control study enrolled 273 adults with SARS-CoV-2 infection, confirmed by Polymerase chain reaction (PCR), who were recruited within the first 21 days of the infection during the first wave (March-May 2020) of COVID-19 pandemic. Participants were categorized into three groups of severity according to the inclusion criteria described in "Diagnosis and Treatment Protocol for COVID-19 Patients" and distributed as mild (n=77), severe (n=134) and critical (n=62). Serum profile of COVID-19 patients was characterized in the acute phase of the infection using a nontargeted multiomics approach. Univariate and multivariate analyses were performed to identify key molecules involved in critical COVID-19 and to evaluate their predictive power as biomarkers of COVID-19 severity. Results: COVID-19 critically ill patients presented a well-differentiated blood pattern for severe disease. The multiomic analysis identified specific alterations in pathways linked to complement and coagulation cascades, platelet activation, cell adhesion, acute inflammation, energy production (Krebs cycle and Warburg effect), amino acid catabolism and lipid transport as hallmarks of critical COVID-19. A new biomarker panel including the combination of selected proteins, metabolites and lipids predicted with high accuracy the most adverse COVID-19 outcomes (AUC: 0.994, 85.9% specificity and 100% sensitivity). Conclusion: The identification of predictive molecules related to critical COVID-19 outcomes provides a valuable tool for the rapid and efficient identification of clinical worsening in the early stage of SARS-CoV-2 infection. The association of a distinctive proteomic, metabolomic and lipidomic fingerprint with COVID-19 severity provides a better understanding of the immunopathogenesis and the host response to SARS-CoV-2 infection which could help in the identification of potential therapeutic targets.
ABSTRACT
Objective To describe the clinical and respiratory characteristics of a cohort of 43 patients with COVID-19 after an evolutive period of 28 days. Design A prospective, single-center observational study was carried out. Setting Intensive care. Patients Patients admitted due to COVID-19 and respiratory failure. Interventions None. Variables Automatic recording was made of demographic variables, severity parameters, laboratory data, assisted ventilation (HFO: high-flow oxygen therapy and IMV: invasive mechanical ventilation), oxygenation (PaO2, PaO2/FiO2) and complications. The patients were divided into three groups: survivors (G1), deceased (G2) and patients remaining under admission (G3). The chi-squared test or Fisher exact test (categorical variables) was used, along with the Mann-Whitney U-test or Wilcoxon test for analyzing the differences between medians. Statistical significance was considered for p < 0.05. Results A total of 43 patients were included (G1 = 28 [65.1%], G2 = 10 [23.3%] and G3 = 5[11.6%]), with a mean age of 65 years (range 52-72), 62% males, APACHE II 18 (15-24), SOFA 6 (4-7). Arterial hypertension (30.2%) and obesity (25.6%) were the most frequent comorbidities. High-flow oxygen therapy was used in 62.7% of the patients, with failure in 85%. In turn, 95% of the patients required IMV and 85% received ventilation in prone decubitus. In the general population, initial PaO2/FiO2 improved after 7 days (165 [125-210] vs.194 [153-285];p = 0.02), in the same way as in G1 (164 [125-197] vs. 207 [160-294];p = 0.07), but not in G2 (163 [95-197] vs. 135 [85-177]). No bacterial coinfection was observed. The incidence of IMV-associated pneumonia was high (13 episodes/1000 days of IMV). Conclusions Patients with COVID-19 require early IMV, a high frequency of ventilation in prone decubitus, and have a high incidence of failed HFO. The lack of improvement of PaO2/FiO2 at 7 days could be a prognostic marker. Resumen Objetivo Describir las características clínicas y respiratorias de una cohorte de 43 pacientes con COVID-19 tras 28 días de evolución. Diseño Prospectivo observacional en un solo centro Ámbito Medicina intensiva Pacientes Pacientes ingresados por COVID-19 e insuficiencia respiratoria Intervenciones Ninguna. Variables Se obtuvieron de forma automática variables demográficas, de gravedad, de laboratorio, de asistencia ventilatoria recibida (OAF: oxigenoterapia alto flujo y VMI: ventilación mecánica invasiva), de oxigenación (PaO2, PaO2/FiO2) y de complicaciones. Los pacientes se dividieron en 3 grupos: supervivientes(G1), fallecidos(G2) y aquellos que continuaban ingresados(G3). Se utilizó “chi” cuadrado o Fisher (variables categóricas) y “U” Mann-Whitney o Wilcoxon para analizar la diferencia entre medianas. Se consideró significativo un valor de p < 0.05. Resultados Se incluyeron 43 pacientes (G1 = 28[65,1%],G2 = 10[23,3%] y G3 = 5[11,6%]), edad 65(52-72) años, 62% hombres, APACHE II 18(15-24), SOFA 6(4-7), Hipertensión arterial(30,2%) y obesidad(25,6%) fueron las comorbilidades más frecuentes. La OAF fue usada en el 62,7% de pacientes, 85% fracasó. El 95% de los pacientes necesitó VMI y el 85% ventilación en prono. En la población general, la PaO2/FiO2 inicial mejoró a los 7 días (165[125-210] vs. 194[153-285], p = 0.02), al igual que en G1(164[125-197] vs. 207[160-294], p = 0.07) pero no en G2 (163[95-197] vs. 135[85-177]). No se observó co-infección bacteriana. El desarrollo de neumonía asociada a la VMI fue elevado (13 episodios/1000 días de VMI). Conclusiones Los pacientes con Covid-19 requieren VMI precoz, elevada frecuencia de ventilación en prono y presentan alta prevalencia de fracaso a OAF. La falta de mejoría de la PaO2/FiO2 a los 7 días podría ser un marcador de pronóstico.
ABSTRACT
OBJECTIVE: To describe the clinical and respiratory characteristics of a cohort of 43 patients with COVID-19 after an evolutive period of 28 days. DESIGN: A prospective, single-center observational study was carried out. SETTING: Intensive care. PATIENTS: Patients admitted due to COVID-19 and respiratory failure. INTERVENTIONS: None. VARIABLES: Automatic recording was made of demographic variables, severity parameters, laboratory data, assisted ventilation (HFO: high-flow oxygen therapy and IMV: invasive mechanical ventilation), oxygenation (PaO2, PaO2/FiO2) and complications. The patients were divided into three groups: survivors (G1), deceased (G2) and patients remaining under admission (G3). The chi-squared test or Fisher exact test (categorical variables) was used, along with the Mann-Whitney U-test or Wilcoxon test for analyzing the differences between medians. Statistical significance was considered for p<0.05. RESULTS: A total of 43 patients were included (G1=28 [65.1%]; G2=10 [23.3%] and G3=5 [11.6%]), with a mean age of 65 years (range: 52-72), 62% males, APACHE II 18 (15-24), SOFA 6 (4-7). Arterial hypertension (30.2%) and obesity (25.6%) were the most frequent comorbidities. High-flow oxygen therapy was used in 62.7% of the patients, with failure in 85%. In turn, 95% of the patients required IMV and 85% received ventilation in prone decubitus. In the general population, initial PaO2/FiO2 improved after 7 days (165 [125-210] vs.194 [153-285]; p=0.02), in the same way as in G1 (164 [125-197] vs. 207 [160-294]; p=0.07), but not in G2 (163 [95-197] vs. 135 [85-177]). No bacterial coinfection was observed. The incidence of IMV-associated pneumonia was high (13 episodes/1000 days of IMV). CONCLUSIONS: Patients with COVID-19 require early IMV, a high frequency of ventilation in prone decubitus, and have a high incidence of failed HFO. The lack of improvement of PaO2/FiO2 at 7 days could be a prognostic marker. .