Association of Tocilizumab and Invasive Aspergillosis in Critically Ill Patients with Severe COVID-19 Pneumonia and Acute Respiratory Distress Syndrome

Abstract

Coronavirus disease-2019 (COVID-19) causes severe pneumonia and acute respiratory distress syndrome. According to the current consensus, immunosuppressants, such as dexamethasone and anti-interleukin-6 receptor monoclonal antibodies, are therapeutic medications in the early stages of infection. However, in critically ill patients, viral, fungal, and bacterial coinfection results in higher mortality. We conducted a single-center, retrospective analysis of 29 mechanically ventilated patients with artificial airways. Patients were adults with confirmed COVID-19 infection and severe pneumonia. Acute respiratory distress syndrome was diagnosed according to the Kigali modification of the Berlin definition. Six patients had invasive pulmonary aspergillosis coinfection based on elevated serum galactomannan levels and/or bronchoalveolar lavage fluid. We present two cases with brief histories and available clinical data. We also conducted a literature review to determine whether immunosuppressants, such as tocilizumab, increase infection risk or invasive aspergillosis in patients with COVID-19. There is no conclusive evidence to suggest that tocilizumab increases coinfection risk. However, further studies are needed to determine the optimal dose, between-dose interval, and timing of tocilizumab administration in patients with COVID-19.

Keywords: COVID-19-associated pulmonary aspergillosis; acute respiratory distress syndrome; tocilizumab.

Figure 1

Representative case 1 (Patient 3): (A) Bilateral opacities on chest radiography taken in the emergency department. (B) Chest radiography revealed bilateral lung infiltration, indicating rapidly progressive diffuse pulmonary edema.

Figure 2

Representative case 2 (Patient 5): (A) Bilateral opacities were observed on chest radiography taken in emergency department. (B) On Day 6, chest radiography revealed patchy opacities in the right lower lung and bilateral subcutaneous emphysema. (C) On Day 36, improvement was observed on chest X-ray.