Heterogeneity in the incidence and mortality of COVID-19-associated pulmonary aspergillosis among ICU patients without hematological disorders: A systematic review, subgroup meta-analysis, and meta-regression.

BACKGROUND

The heterogeneity in the incidence and mortality rates of COVID-19 associated pulmonary aspergillosis (CAPA) across studies is striking. However, the implications of this heterogeneity for patients without hematological disorders have been inadequately explored.

OBJECTIVES

This subgroup meta-analysis and meta-regression aimed to examine the clinical characteristics, incidence and mortality rates of CAPA patients without hematological disorders in intensive care units (ICU), and sought to explore the impact of and potential reasons for the observed variability in CAPA incidence and mortality rates.

DATA SOURCES

Data from PubMed, Embase and Web of Science were systematically searched for articles published between November 1, 2019 and March 31, 2024.

STUDY ELIGIBILITY CRITERIA

This study included cross-sectional, case-control and cohort studies published in English with full texts, which examined COVID-19 patients admitted to ICU and assessed both the incidence and mortality of invasive pulmonary aspergillosis, were included.

PARTICIPANTS

COVID-19 patients without hematological disorders admitted in ICU and who were evaluated for invasive pulmonary aspergillosis by any specific published definitions.

INTERVENTIONS

No.

METHODS

The incidence and mortality rates of CAPA patients were calculated using Der Simonian-Laird random effects meta-analyses. The impact and sources of heterogeneity were assessed through meta-regression and subgroup analyses, conducted with Review Manager 5.4 and Stata 17 software. The review protocol has been registered with the International Prospective Register of Systematic Reviews (CRD 42024569801).

RESULTS

A total of 46 studies were included in the analysis. Among 18,487 enrolled ICU patients without hematological disorders, 1608 CAPA cases were reported, resulting in a pooled incidence rate of 0.13 (95 % CI: 0.11-0.14, I = 96.11 %, p-value<0.001). The incidence of CAPA varied significantly based on diagnostic definitions (p-value = 0.009), Newcastle-Ottawa Scale (NOS) (p-value<0.001), and publication time (p-value<0.001). Factors such as diagnostic criteria, NOS, chronic respiratory diseases, solid organ transplantation, smoking history, Extracorporeal Membrane Oxygenation (ECMO), mechanical ventilation, corticosteroid use and anti-interleukin therapies were significantly associated with CAPA incidence. The pooled CAPA mortality rate was found to be 0.58 (95 % CI: 0.52-0.64, I = 83.31 %, p-value<0.001) and varied by NOS (p-value = 0.047). Furthermore, NOS and chronic liver diseases were positively associated with CAPA mortality.

CONCLUSIONS

The incidence and mortality of CAPA in ICU patients without hematological disorders varied significantly across different studies. There is a pressing need for more high-quality research focused on screening for Aspergillus in COVID-19 ICU patients without hematological disorders, particularly those with chronic liver diseases.