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Background: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat.Methods: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression).Results: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015).Conclusions: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients. [ABSTRACT FROM AUTHOR]

Objective: The incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients., Methods: This is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed., Results: 255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)]., Conclusion: The immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)