Since the outbreak of COVID-19, a large number of infections and deaths were caused worldwide, resulting in a heavy burden on healthcare systems in countries. Research data from both domestic and international indicates a high mortality among severe COVID-19 patients. Combining data from large multicenter studies worldwide, the short-term mortality rate for dialysis patients after contracting COVID-19 is between 20% and 30%[8–10]. Data from the Geneva Dialysis Center in Switzerland in 2020 revealed that the incidence of COVID-19 infection among MHD patients was approximately 4 to 6 times higher than the general population[11], with a mortality rate of 19.5%. Data from the United States Dialysis Registry from February to June 2020 showed that the hospitalization rate for MHD patients infected the novel coronavirus was 67.6%, with an overall mortality rate of 24.9%. The findings from our study show a 37.2% severity rate and a 13.1% mortality rate among MHD patients infected with COVID-19. The relatively low mortality rate in this study is attributed to the transition of prevalent variant to the Omicron strain, improvements in diagnosis and therapies, as well as the policy of prioritizing treatment during the epidemic. The average time from the appearance of prodromal symptoms to diagnosis and hospital admission was 7.0 (3.0, 10.0) days.
COVID-19 infection can cause pulmonary and systemic inflammatory responses[8,9]. Severe patients often present with multi-organ and systemic involvement, such as ARDS, coagulation abnormalities, myocardial injury, renal injury, and gastrointestinal or hepatic injury. After reaching the lungs through the human body's superficial mucous membranes, especially the nasal and throat mucous membranes, the virus enters the peripheral blood and leads to viremia. It binds to the angiotensin converting enzyme-2 (ACE 2) receptor on the endothelium, causing downregulation of ACE 2 and high expression of angiotensin II (Ang II), resulting in endothelial cell activation[12–15] and triggering a series of immune responses. Study has shown that severe patients have higher concentrations of cytokines such as IL-6, IL-10, and TNF-α than mild patients[16], indicating that the severity of the disease is related to the cytokine storm caused by inflammatory responses. In our study, elevated level of IL-6 can be seen in the severe group.
Studies have shown that CRP and lymphocyte count are related to the severity of the disease[17,18], and lymphocyte reduction has been taken as one of the diagnostic criteria for COVID-19 infection. Besides, significant leukopenia (WBC < 4×109/L), and factors such as age, elevated ALT, LDH, high-sensitivity troponin I, creatine kinase, D-dimer, serum ferritin, IL-6, PT, creatinine, and elevated procalcitonin were also found associated with mortality in Wuhan in 2019, when Beta was on pandemic[16,19].Our study observed patients undergoing MHD who were first infected by Omicron variant of COVID-19. The average age of the patients was 63.84 ± 12.11, with a high proportion of patients having underlying chronic diseases. We found that patients in the severe group were more likely to have cerebrovascular diseases compared to non-severe patients. The study also found that in the severe group, the levels of WBC, neutrophils, PCT, CRP, and LDH were higher, while eosinophils and lymphocyte counts were significantly lower than in the non-severe group, and were associated with a longer hospital stay. Neutrophil-lymphocyte ratio (NLR) is taken as an index of systemic inflammation. Additionally, previous reports[20–22] have shown that NLR has a good predictive value for the mortality of severe pneumonia. Our study also found a statistical difference in NLR levels between the two groups, and there was a statistical causality between NLR levels and the occurrence of severe COVID-19 infection. The elevation of inflammatory markers such as NLR, CRP, and PCT in this study may be related to concomitant bacterial infections and the chronic inflammatory state of MHD patients.
The results of the logistic regression analysis in this study suggested that higher levels of Fib and D-dimer are independent risk factors for the severe progression of COVID-19 patients, consistent with previous research results. COVID-19 patients have a higher incidence of thrombotic events, especially pulmonary embolism[23]. Autopsy even reveals a higher incidence of microthrombi[24]. Retrospective analysis showed elevated level of coagulation indicators in 183 COVID-19 patients and found that the levels of D-dimer and FDP were significantly higher in non-survivors, with prolonged PT and APTT, and about 71% of the deceased cases met the diagnostic criteria for disseminated intravascular coagulation (DIC) during the course of the disease[25]. Huang C also found that ICU patients had higher levels of plasma PT and D-dimer upon admission[16]. The elevation of D-dimer and PT usually indicates the activation of the coagulation system, relating to conditions such as thrombosis, infection, or malignancy. This connection is considered to be related to the virus binding to the ACE 2 receptor on the surface of endothelial cells, and the activation of the fibrinolysis system, while ESRD patients are in a hypercoagulable state, exacerbating the impact on their coagulation system, which also emphasized the importance of anticoagulant therapy.
Research has found that in addition to the well-known respiratory symptoms, hospitalized patients infected with COVID-19 also exhibit many neurological manifestations, such as reduced sense of smell, headache, dizziness, seizures, and stroke[26]. In our study, we observed that concomitant cerebrovascular disease significantly increases the chance of severe infection and death in MHD patients, even after adjusting for various confounding factors. The potential pathophysiological mechanisms mainly include hypoxic brain injury, the generation of cytokine storms, and the subsequent immune damage and tendency for thrombus formation[24,27].
In summary, this study suggests that the severity of COVID-19 infection in MHD patients is associated with cerebrovascular disease, increased NLR, elevated Fib, and D-dimer. Early intervention for patients with these clinical features may effectively prevent disease progression to severe cases and thereby improve clinical prognosis. Comorbid diabetes, cerebrovascular disease and elevated NLR and D-dimer levels are associated with mortality and poor clinical outcome. However, due to the limited geographical scope and sample size of this study, and its focus on the Omicron strain, the conclusions have certain limitations. Furthermore, the pathological mechanisms of severe COVID-19 infection and related death require further analysis.