ABSTRACT
INTRODUCTION: Severe acute respiratory failure is a common complication of COVID-19, with refractory hypoxemia being a hallmark finding in severe illness and a common cause of mortality. With limited therapeutic strategies, management centers on good supportive care. Prone positioning has been shown to improve oxygenation and survival in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) but the impact of prone positioning in COVID-19 with severe hypoxemia is unknown. This study aims to examine the response to proning as a predictor of COVID-19 related mortality. METHODS: This is a single-center, retrospective analysis of critically ill patients with COVID-19 confirmed by PCR. Patients were included if they were invasively ventilated, and if supportive care included prone positioning for management of refractory hypoxemia. Data points collected include demographics, ventilator settings, rates of mortality and progression to ECMO, ventilator-days, and time between symptom onset and intubation, hospital and ICU admission. Endpoints included response in oxygenation (PaO2:FiO2) and mortality. RESULTS: Forty-nine patients were included in the analysis. The average age was 56.9, and 61% of the patients were male. Patients had an average of 19 ventilator-days (2-52), 21 ICU-days (4-54), 26 hospital-days (8-65), an ECMO rate of 27%, and a mortality rate of 55%. Of the 22 survivors, there was an average increase in PaO2:FiO2 by 108, 93.1, and 93 for each of the first three pronations respectively. For the 27 nonsurvivors, there was an average increase in PaO2:FiO2 by 76.1, 84.3, and 50.9 for the first three pronations. The difference in improvement in PaO2:FiO2 was not statistically significant between survivors and non-survivors. There was no inflection point that could be determined that provided a high sensitivity and specificity to predict mortality or need for ECMO based on response to pronation at any of the time points. CONCLUSIONS: Proning improves PaO2:FiO2 in patients with severe hypoxemia related to COVID-19. Survivors in our study had a numerically greater response to proning, but this finding was not statistically significant. The clinical significance remains unclear. Larger studies assessing the efficacy of proning in critically ill patients with COVID-19 are needed.
ABSTRACT
INTRODUCTION: Early commentary on SARS-CoV-2 infection proposed a mechanism of cytokine release syndrome (CRS) to explain severe acute respiratory failure associated with COVID-19. Management strategies have included targeted immunomodulation with biologic agents. The role of IL-6 and other cytokines in the pathogenesis of COVID-19 is not well defined. Evidence for use of immunomodulators has been mixed and these agents may expose patients to harm. This study aims to characterize the expression of cytokines and their association with inflammatory biomarkers and outcomes in critically ill patients with COVID-19. METHODS: This was a single-center, retrospective analysis of critically ill patients with COVID-19 confirmed by PCR. Patients were included if they had a partial or full cytokine panel drawn while admitted. Descriptive statistics were used to assess demographics, outcomes, and relationships between cytokine levels and inflammatory markers. The Mann- Whitney U Test was used to compare IL-6 levels between survivors and nonsurvivors. RESULTS: Eighty-nine patients were included with 68 full cytokine panels and 108 IL-6 levels. Patients had a mean (range) of 10 ventilator-days (0-47), 15 ICU-days (1-60), 20 hospital-days (3-69) and a mortality rate of 31%. Cytokine levels were assessed a median of 10 days from symptom onset and 1 day from ICU admission. Levels of IL-1B, IL-2, IL-4, IL-5, IL-8, IL-12, IL-13, IL-17, IFN-G, and TNF-A were undetectable in at least 80% of patients, and expression did not correlate with other inflammatory biomarkers (CRP, ferritin), severity of illness (SOFA), or outcome. IL-2R levels were numerically elevated in most patients (n=68;median 1227, range: 76-30670). IL-6 levels were mildly elevated (n=108;median: 31, range: 2-882, SD: 150), and levels were statistically significantly higher in nonsurvivors (p = 0.002). CONCLUSIONS: Assessment of cytokine levels in critically ill patients with COVID-19 does not support a hypothesis of CRS. While IL-6 levels were numerically higher in nonsurvivors, the clinical significance of this finding is unknown. The role of IL-2R in the pathogenesis of COVID-19 remains unclear. Larger studies exploring the role of inflammatory mediators in pathogenesis and targeted immunomudulators in management of COVID-19 are warranted.