Key predictors of COVID-19-associated pulmonary aspergillosis (CAPA) in patients with severe COVID-19 are chronic liver disease, hematological malignancies, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, mechanical ventilation, renal replacement therapy, and use of corticosteroids or interleukin (IL)-6 inhibitors for COVID-19. These were among meta-analysis findings reported in The Lancet Respiratory Medicine.
Investigators conducted a systematic review and meta-analysis to identify the risk factors associated with CAPA among patients with severe COVID-19.
The reviewers identified case-control and cohort studies involving adult patients diagnosed with CAPA, searching the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and the WHO COVID-19 database from December 2019 through July 2023 for studies with comparative data from patients with COVID-19, with and without CAPA. Included studies were in English describing at least 6 cases of CAPA and assessing any risk factors for CAPA. All cases of COVID-19 were diagnosed by reverse transcription-polymerase chain reaction (RT-PCR) test.
Overall, 27 articles were included in meta-analysis (N=6848 patients with COVID-19; 36.9% women; 67.5% required mechanical ventilation) of whom 1324 patients (19.3%) were diagnosed with CAPA (78.8% requiring mechanical ventilation). Median onset of CAPA after intensive care unit (ICU) admission ranged from 3 to 18 days. By studies, diagnosis rates ranged from 2.5% to 47.2%. The investigators noted patients with CAPA vs those without tended to be older (mean [SD] age, 66.6 [3.6] years vs 63.5 [5.3] years; mean difference [MD], 2.90; 95% CI, 1.48-4.33; P <.0001; I2=86%); experienced longer duration of mechanical ventilation (19.3 [8.9] days vs 13.5 [6.8] days; MD, 5.53 days; 95% CI, 1.30-9.77; P =.01; I2=88%; n=7 studies).
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In the absence of antifungal prophylaxis, adequate screening for CAPA and recognising its risk factors are essential.
The investigators found risk factors for CAPA included treatment with IL-6 inhibitors (odds ratio [OR], 2.88; 95% CI, 1.52-5.43; P =.001; I2=89%), use of mechanical ventilation (OR, 2.83; 95% CI, 1.88-4.24; P <.0001; I2=69%), use of renal replacement therapy (OR, 2.26; 95% CI, 1.76-2.90; P <.0001; I2=14%), and COVID-19 treatment with corticosteroids (OR, 1.88; 95% CI, 1.28-2.77; P =.001; I2=66%) (mostly moderate and high heterogeneity).
Additional risk factors included pre-existing comorbidities of chronic liver disease (OR, 2.70; 95% CI, 1.21-6.04; P =.02; I2=53%), hematological malignancies (OR, 2.47; 95% CI, 1.27-4.83; P =.008; I2=50%), COPD (OR, 2.00; 95% CI, 1.42-2.83; P <.0001; I2=26%), and cerebrovascular disease (OR, 1.31; 95% CI, 1.01-1.71; P =.05; I2=46%) (mostly low and moderate heterogeneity).
Most included studies did not offer detailed descriptions on type, dose, frequency, and duration of corticosteroid use, or duration of IL-6 inhibitor use. No association was found with body mass index (BMI).
Higher all-cause mortality was noted among patients with CAPA vs those without (OR, 2.65; 95% CI, 2.04-3.45; P <.0001; I2=51%) in post-hoc analysis.
Overall risk of bias was high in 12 studies, moderate in 8, low in 7.
This systematic review and meta-analysis is limited by the use of only descriptive mostly retrospective studies that were mostly done in European countries, which may have resulted in measurement bias. Additionally, most included studies reported pre-COVID-19-vaccine data.
“The identified risk factors for CAPA could eventually be addressed with targeted antifungal prophylaxis in patients with severe COVID-19,” the investigators concluded. “In the absence of antifungal prophylaxis, adequate screening for CAPA and recognising its risk factors are essential.”
