Clinical features and prognostic factors in Covid-19: A prospective cohort study

Abstract

Background: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. Methods:We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality.Findings: A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest-specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids.Interpretation: Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19.

Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS

“…Absolute values of inflammatory markers such as PCT and CRP can be readily influenced by disease-modifying agents as we demonstrated earlier [ 23 ]. Previously published patient level data derived from the first wave of the pandemic showed that PCT levels can be sporadic and highly variable, with levels elevated even in the absence of confirmed infection [ 22 , 23 , 24 ]. As such, our study employed a predetermined rise in PCT, utilising trends in serial PCT levels rather than a critical tipping point as an indicator for secondary infection, which could be adopted in clinical practice.…”

Inflammatory biomarkers at hospital discharge are associated with readmission and death in patients hospitalized for COVID-19

“…COVID-19 was defined as a positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR). IL-6 and IL-10 were measured in serial blood samples from March to May 2020 [4]. Patients who died during admission were excluded.…”

“…Readmissions and mortality after hospital discharge were ascertained by contacting the general practitioner (GP). Biomarker measurements were done by using a Luminex platform [4]. Normally distributed data were analyzed by a t-test and nonparametric continuous data by Mann-Whitney U test.…”

Endothelial dysfunction and COVID-19: What's the true impact on surrogate outcomes?

“…Therefore, the authors suggested that endothelial dysfunction might not be characteristic of severe COVID-19 early after ICU admission [ 3 ]. Based on the complex pathophysiology of COVID-19, it seems that endothelial dysfunction may not be pivotal for the development of severe disease, since several other pathways, such as chemotaxis, interleukin production and immunothrombosis also play a significant role [ 4 ].…”