Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 patients undergoing invasive mechanical ventilation: a retrospective cohort study

Yi Yang; Jia Shi; Shuwang Ge; Shuiming Guo; Xue Xing; Yanan Wang; Anying Cheng; Qingquan Liu; Junhua Li; Yong Ning; Fan He; Gang Xu

For example, the average of peaks for IL-6 was 1081.7 pg/mL, which was more than 100 times higher than the upper limit of normal value (reference range: < 7 pg/mL). Inflammatory storm may originate from the following aspects. First, SARS-Cov-2 infects patients by binding human ACE2, 29, 30 which is widely expressed in multiple organs throughout the body. 31 SARS-CoV-2 might lead to multi-system inflammation through ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway. 32, 33 Second, it was reported that antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses might also be involved in COVID-19. ADE can elicit sustained inflammation, lymphopenia, and/or cytokine storm, which makes it a possible explanation for the geographic limitation of severe cases. 34 Third, combined infections may lead to a more severe systemic inflammatory response. Indeed, in our study, some patients combined with infection in other organs (e.g. urinary tract, blood) and other pathogen (e.g. influenza virus, fungus). Fourth, shock, hypoxemia and coagulation pathway abnormalities in critical patients could aggravate systemic inflammatory response, which become a vicious cycle, threatening life. 35, 36 In our study, CRRT was associated with prolonged survival in COVID-19 patients with invasive mechanical ventilation. CRRT is a widely used blood purification therapy, which achieves a high solute clearance rate through diffusion, convection, ultrafiltration, and adsorption. The primary goal of CRRT is to compensate for the loss of renal function and associated sequelae, including uremic toxins, electrolyte disturbances, metabolic acidosis, and volume overload 37 . Besides these, CRRT can also remove cytokines from the bloodstream. Emerging evidence has shown that CRRT was associated with significantly lower mortality in patients with severe sepsis. 18, 19, 38 In addition, in patients with acute respiratory distress syndrome, CRRT could remove All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.