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. 2023 Nov 21:13:1287496.
doi: 10.3389/fcimb.2023.1287496. eCollection 2023.

Risk factors and the value of microbiological examinations of COVID-19 associated pulmonary aspergillosis in critically ill patients in intensive care unit: the appropriate microbiological examinations are crucial for the timely diagnosis of CAPA

Xiaoyi Zhou #  1   2 , Xiaojing Wu #  2 , Ziying Chen  1   2 , Xiaoyang Cui  2 , Ying Cai  2 , Youfang Liu  2   3 , Bingbing Weng  2   3 , Qingyuan Zhan  1   2   3 , Linna Huang  2
Affiliations

Risk factors and the value of microbiological examinations of COVID-19 associated pulmonary aspergillosis in critically ill patients in intensive care unit: the appropriate microbiological examinations are crucial for the timely diagnosis of CAPA

Xiaoyi Zhou et al. Front Cell Infect Microbiol. .

Abstract

Introduction: During the Omicron pandemic in China, a significant proportion of patients with Coronavirus Disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) necessitated admission to intensive care unit (ICU) and experienced a high mortality. To explore the clinical risk factors and the application/indication of microbiological examinations of CAPA in ICU for timely diagnosis are very important.

Methods: This prospective study included patients with COVID-19 admitted to ICU between December 1, 2022, and February 28, 2023. The clinical data of influenza-associated pulmonary aspergillosis (IAPA) patients from the past five consecutive influenza seasons (November 1, 2017, to March 31, 2022) were collected for comparison. The types of specimens and methods used for microbiological examinations were also recorded to explore the efficacy in early diagnosis.

Results: Among 123 COVID-19 patients, 36 (29.3%) were diagnosed with probable CAPA. CAPA patients were more immunosuppressed, in more serious condition, required more advanced respiratory support and had more other organ comorbidities. Solid organ transplantation, APACHEII score ≥20 points, 5 points ≤SOFA score <10 points were independent risk factors for CAPA. Qualified lower respiratory tract specimens were obtained from all patients, and 84/123 (68.3%) patients underwent bronchoscopy to obtain bronchoalveolar lavage fluid (BALF) specimens. All patients' lower respiratory tract specimens underwent fungal smear and culture; 79/123 (64.2%) and 69/123 (56.1%) patients underwent BALF galactomannan (GM) and serum GM detection, respectively; metagenomic next-generation sequencing (mNGS) of the BALF was performed in 62/123 (50.4%) patients. BALF GM had the highest diagnostic sensitivity (84.9%), the area under the curve of the mNGS were the highest (0.812).

Conclusion: The incidence of CAPA was extremely high in patients admitted to the ICU. CAPA diagnosis mainly depends on microbiological evidence owing to non-specific clinical manifestations, routine laboratory examinations, and CT findings. The bronchoscopy should be performed and the BALF should be obtained as soon as possible. BALF GM are the most suitable microbiological examinations for the diagnosis of CAPA. Due to the timely and accuracy result of mNGS, it could assist in early diagnosis and might be an option in critically ill CAPA patients.

Keywords: Coronavirus Disease 2019; influenza; intensive care unit; invasive pulmonary aspergillosis; microbiological examination; risk factors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study flowchart. A total of 123 patients with confirmed COVID-19 were admitted to the RICU between December 1, 2022, and February 28, 2023. Among them, 36 patients were diagnosed with CAPA (34 with probable CAPA, 2 with possible CAPA), while the remaining 87 patients were classified into the non-CAPA group. CAPA, COVID-19-associated pulmonary aspergillosis; IAPA, Influenza-Associated Pulmonary Aspergillosis.
Figure 2
Figure 2
Time between onset, COVID-19 diagnosis, ICU admission, Death/transfer out of ICU and CAPA diagnosis. The time from onset, COVID-19 diagnosis and ICU admission to CAPA diagnosis was 18 (14-31) days, 14(7-25) days, and 3 (2-7) days, respectively.
Figure 3
Figure 3
Microbiological specimens (A) and microbiological detection methods (B) in COVID-19 patients. N—number of COVID-19 patients; %—the proportion of patients from the total number of CAPA patients.
Figure 4
Figure 4
ROC curves for serum GM, BALF GM, smear/culture and mNGS detection. The areas under the ROC curve were 0.668 for the serum GM test (A), 0.783 for the BALF GM test (B), 0.750 for the smear/culture test (C), and 0.812 for the mNGS test (D).
Figure 5
Figure 5
Comparison of the diagnostic time for CAPA after ICU admission based on different pathogen diagnostic criteria. “*” a patient was diagnosed with CAPA before admission to the ICU, resulting in a negative value. “Including mNGS”: Patients with positive mNGS when diagnostic criteria for pathogens included mNGS, serum GM, BALF GM, smear/culture. “Without mNGS”: Patients with positive mNGS when diagnostic criteria for pathogens included serum GM, BALF GM, smear/culture but without mNGS. “Including mNGS 1”: Patients with positive serum GM and mNGS when diagnostic criteria for pathogens included mNGS, serum GM, BALF GM, smear/culture. “Including mNGS 2”: Patients with positive BALF GM and mNGS when diagnostic criteria for pathogens included mNGS, serum GM, BALF GM, smear/culture. “Including mNGS 3”: Patients with positive smear/culture and mNGS when diagnostic criteria for pathogens included mNGS, serum GM, BALF GM, smear/culture. After adding positive mNGS to pathogen diagnostic criteria, the diagnostic time can be shortened compared to without mNGS (p=0.0039), BALF GM (p=0.0156) and smear/culture (p=0.0010).
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The funding source of the study [National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-01)] is an academic non-profit organization that played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.