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.

Diagnosis and Treatment of Fungus and Virus Interaction

“…These findings indicated that CAPA was not uncommon among patients with critical COVID-19 in the ICUs, and the mortality of CAPA remained high. Similar findings were shown in the two other series in Taiwan [ 5 , 6 ]. A single-center, retrospective study by Wu et al reported that 6 (20.7%) of 29 mechanically ventilated COVID-19 patients with severe pneumonia had coinfection with CAPA based on elevated serum galactomannan levels and/or bronchoalveolar lavage fluid [ 5 ].…”

“…This present Special Issue of the Journal of Fungi addresses the clinical interaction between viruses and fungi. Studies cover new epidemiological knowledge, diagnosis, and treatment of virus-associated fungal diseases, including fungal diseases with COVID-19 in four articles [ 3 , 4 , 5 , 6 ] and with Influenza A (H1N1) in two studies [ 7 , 8 ].…”

“…A single-center, retrospective study by Wu et al reported that 6 (20.7%) of 29 mechanically ventilated COVID-19 patients with severe pneumonia had coinfection with CAPA based on elevated serum galactomannan levels and/or bronchoalveolar lavage fluid [ 5 ]. In this study, the relatively high prevalence of CAPA is probably due to aggressively regular check-ups for Aspergillus galactomannan antigen [ 5 ]. However, the authors did not find conclusive evidence about the association between tocilizumab and the risk of CAPA.…”

Overview of COVID-19-Associated Invasive Fungal Infection

“…While Aspergillus is the most well-established fungal infection associated with COVID-19, many less common fungal infections have since been reported. In contrast to aspergillosis, mucormycosis is historically rare following viral infection [59]. However, COVID-19-associated mucormycosis (CAM) is now the most widely reported non-Aspergillus mold infection [64•, 65••, 66, 67].…”