Invasive pulmonary aspergillosis in the COVID‐19 era: An expected new entity

Abstract

Objectives Information on the recently COVID‐19‐associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID‐19), and review the published literature from Western countries. Methods Prospective study (March to May, 2020) that included all COVID‐19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. Results COVID‐19‐associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non‐immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA‐related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all‐cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. Conclusions COVID‐19‐associated pulmonary aspergillosis must be considered a serious and potentially life‐threatening complication in patients with severe COVID‐19 receiving immunosuppressive treatment.

Pulmonary aspergillosis and mucormycosis in a patient with COVID-19

“…Decline in cell-mediated immunity has been observed in symptomatic patients, including leukopenia, lymphopenia, and T-cell dysregulation [ 6 ]. In addition, the usage of corticosteroids in the treatment of COVID-19 may further predispose to these fungal infections [ [6] , [7] , [8] , [9] ]. Failure to recognize and treat these infectious complications of COVID-19 will likely lead to higher mortality, which has been described [ [7] , [8] , [9] , [10] ].…”

“…Both infections have been recognized as secondary complications of coronavirus disease 2019 (COVID-19), especially among critically ill patients in the intensive care unit (ICU) [ [6] , [7] , [8] ]. Reports have shown that up to 35% of these patients have invasive pulmonary aspergillosis, which has been associated with prior corticosteroid usage and has led to higher mortality [ [6] , [7] , [8] , [9] ]. In contrast, the incidence of invasive pulmonary mucormycosis following COVID-19 is rare, with only two cases currently reported [ 10 , 11 ].…”

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment – A narrative review

“…Furthermore, laboratory features that are typically abnormal in patients suffering from severe COVID-19 include elevated D-Dimer levels, ferritin, and Interleukin (IL)-6 levels, elevated cardiac biomarkers, and hepatic enzymes [ 11 , 77 , 80 , 81 ]. In cases where bacterial superinfection is suspected, procalcitonin might be helpful in addition to microbiological sampling, bronchoalveolar lavage, and galactomannan testing for fungal infection/aspergillosis [ 82 , 83 ].…”

“…Reasons for the increased susceptibility to secondary infections are not yet fully understood, but it is speculated that respiratory stress, a dysregulated immune response, and the use of immunosuppressive drugs (e.g., steroids) may play a role [ 156 ]. The latter might also be responsible for an increased incidence of invasive pulmonary aspergillosis in patients with CARDS [ 83 ]. In patients with superinfections, a careful antibiotic/anti-mycotic stewardship should be applied [ 156 ].…”

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

“…Since antagonistic TLR and NLR interactions tend to be initiated over time measured by many hours or several days (see Section 2.3), Figure 8 may well explain how the cytokine storm in severe COVID-19 is initiated and Figure 3A the status of the innate system as it attempts to moderate its cytokine production. One final complication is that many severe COVID-19 patients are treated with multiple antibiotics [201][202][203][204][205][206][207][208][209][210][211][212], which may further modify the expression of bacterially activated TLR and NOD1/NOD2.…”