Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19

Abstract

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2–5 and 7–10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79–0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.

Clinical Performance of Paraoxonase-1-Related Variables and Novel Markers of Inflammation in Coronavirus Disease-19. A Machine Learning Approach

“…Several studies have shown that reduced PON1 activity is associated with an enhanced inflammatory response, CCL2 synthesis, and secretion [ 35 , 36 , 37 ]. High levels of this chemokine have been found in the circulation [ 38 , 39 , 40 , 41 , 42 , 43 ], the bronchoalveolar lavage fluid [ 44 ], and the lung tissue of COVID-19 patients [ 45 ]. One study reported that CCL2 expression increases rapidly in the early acute phase of infection and then progressively decreases as the disease advances [ 46 ].…”

C-C motive chemokine ligand 2 and thromboinflammation in COVID-19-associated pneumonia: A retrospective study

“…2 ). While other works have focused on P/F at admission (which may be highly variable among a large population with a such rapidly evolving disease), respiratory failure occurrence or ICU admittance as markers of respiratory impairment [ 14 , 15 , 24 ], to our knowledge, the present study is the first to use the P/F nadir in order to provide a reliable standard for severity impairment of gas exchange evaluation across the whole sample, independently of the patient's respiratory status at hospital admission. Interestingly, diffuse thrombosis of small vessels and pulmonary capillaries has been implied, along with a failure in the hypoxic pulmonary vasoconstriction mechanism, in the pathogenesis of the ventilation/perfusion mismatching, causing the severe hypoxemia in COVID-19 patients [ 25 ].…”

The story of an extraordinary year: Challenges and opportunities in responding to Covid-19

“…Samples from covid-19 patients and convalescent blood donors have been used to evaluate a test for the inflammatory marker protein, Neopterin, which is increased in covid-19 infection [8]. Further studies of inflammatory marker proteins calprotectin, Syndecan-1 and NETS are ongoing [9], as well as one in which possible antiviral effect of an extract (Andosan™) of the medicinal mushroom Agaricus blazei with antimicrobial property, is examined in corona-infected host cells [9] From the Norwegian SARS-CoV-2 cohort study, several interesting results have been published [10][11][12][13].…”