Incidence, Risk Factors, and Outcomes of Patients with COVID‑19‑Associated Pulmonary Aspergillosis (CAPA) in Intensive Care Units: A Systematic Review and Meta-Analysis Of 29 Cohort Studies

Abstract

Background Patients with Coronavirus disease 2019 (COVID-19) admitted to an intensive care unit (ICU) might develop COVID-19-related pulmonary Aspergillosis (CAPA). We aimed to identify studies systematically that describe the incidence and risks factors of CAPA, and to assess its outcome. Methods Two authors independently searched ScienceDirect, PubMed, CNKI, MEDLINE (OVID), and MedRXIV from December 31, 2019 to Feb 27, 2021. We included observational cohort studies that investigated patients with CAPA admitted to an ICU. We assessed the quality of all included studies using the Newcastle–Ottawa Scale). The meta-analysis was registered with PROSPERO (CRD42021242179).ResultsTwenty-nine cohort studies with 2095 patients with COVID-19 admitted to an ICU and 264 patients who developed to CAPA were included (Pooled incidence: 0.14, 95% confidence interval [CI] = 0.11–0.17). The overall mortality and case fatality rate of CAPA were 0.07 (0.05–0.09) and 0.51 (0.44–0.58), respectively. Patients with COVID‑19 would develop CAPA at 7.28 days after mechanical ventilation (range, 5.48–9.08). Compared with patients without CAPA, those with CAPA had a significantly lower median body mass index (27.32 vs. 28.97 kg/m2, P = 0.034), higher median creatinine level (127.94 vs. 88.23 µmol/L, P = 014), and were more likely to receive corticosteroids therapy (41.0% vs. 38.0%, risk ratio [RR] = 1.98, 95% CI=1.08–3.63) and renal replacement therapy (42.0% vs. 28.2%, RR = 1.61, 95% CI=1.04–2.50) during admission. Remarkably, patients with CAPA were associated significantly with a 1.66‑fold higher mortality (RR = 1.66, 95% CI=1.31–2.12) without significant heterogeneity and publication bias. ConclusionsPatients with COVID-19 admitted to an ICU might develop CAPA and have higher all‑cause mortality. We recommend conducting prospective screening for CAPA among patients with severe COVID-19, especially for those who receive mechanical ventilation over 7 days.

SARS-CoV-2 Associated Immune Dysregulation and COVID-Associated Pulmonary Aspergilliosis (CAPA): A Cautionary Tale

“…In a meta-analysis of cohort studies of ITU COVID-19 patients, glucocorticoid use was linked with a 10-fold increase in candiademia and a relative risk ratio for CAPA of 1.98 (95% CI 1.08–3.63) [ 65 ]. Other immunosuppressive treatments deployed in the SARS-CoV-2 arena include the soluble IL-6 receptor inhibitor Tocilizumab, which is used for a diverse range of rheumatological conditions.…”

“…Through effective inhibition of IL-6, decreased inflammation, cytokine storm progression and tissue fibrosis are possible with evidence of reconstituted cytotoxic potential of immune cells including NK cells. Overall efficacy suggests that when administered at 8 mg/kg, Tocilizumab significantly reduces mortality (OR 0.62; CI 0.55–0.70, p < 0.00001), and length of hospital stay, particularly in mechanically ventilated ITU patients [ 65 , 66 ]. However, similar to Dexamethasone, coinfection and superinfection are key risks and may go undetected due to delayed/absent CRP rise due to IL-6’s role in CRP production.…”