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Abstract
BackgroundTo date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD.MethodsThe clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD.ResultsThe ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time.ConclusionsThe cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.
Highlights
To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described
The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients
The levels of IL-6, IL-8, and IL-10 correlated with disseminated intravascular coagulation (DIC), and the levels of IL-6 and TNF-α were associ‐ ated with acute kidney injury (AKI)
Summary
Specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. In December 2019, the first case of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan City, China. Some COVID-19 patients present with mild illness during the early stage of disease, but develop severe pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) within a few days. The excessive immune responses are characterized by overproduction and prolonged high levels of numerous cytokines, such as proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-8, and tumor necrosis factor α [TNF-α]) and anti-inflammatory cytokines (IL-4, IL-10). Overproduction of proinflammatory and anti-inflammatory cytokines is closely associated with disease severity and poor prognosis [3]
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