Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study
Authors: Shadrivova Olga V. , Rachina Svetlana A. , Strelkova Daria А. , Panchishina K.A. , Gusev D.A. , Vashukova M.A. , Meshchaninova S.G. , Zavrazhnov A.A. , Mitichkin M.S. , Mamonov A.G. , Khostelidi Sofya N. , Kozlova O.P. , Gusarov Vitaly G. , Zamyatin M.N. , Lovtsevich N.V. , Kuleshov V.G. , Shagdileeva E.V. , Oganesyan E. , Desyatik E.A. , Borzova Yu.V. , Ignatyeva S.M. , Vasilieva N.V. , Klimko Nikolay N. 
Published: March 2023

Objective.

To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU).
Materials and Methods.

A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male – 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male – 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male – 67%.
Results.

64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104–11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177–18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01).
Conclusions.

IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.