Proven COVID-19-associated pulmonary aspergillosis in patients with severe respiratory failure.

BACKGROUND: An increasing number of reports have described the COVID-19-associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA. METHODS: We report the incidence of histologically diagnosed CAPA in a series of 45 consecutive COVID-19 laboratory-confirmed autopsies, performed at Padova University Hospital during the first and second wave of the pandemic. Clinical data, laboratory data and radiological features were also collected for each case. RESULTS: Proven CAPA was detected in 9 (20%) cases, mainly in the second wave of the pandemic (7/17 vs. 2/28 of the first wave). The population of CAPA patients consisted of seven males and two females, with a median age of 74 years. Seven patients were admitted to the intensive care unit. All patients had at least two comorbidities, and concomitant lung diseases were detected in three cases. CONCLUSION: We found a high frequency of proven CAPA among patients with severe COVID-19 thus confirming at least in part the alarming epidemiological data of this important complication recently reported as probable CAPA.

A review of significance of Aspergillus detection in airways of ICU COVID-19 patients.

It is now well known that patients with SARS-CoV-2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS-CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID-19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non-surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.

Mortality in critically ill patients with coronavirus disease 2019-associated pulmonary aspergillosis: A systematic review and meta-analysis.

Reports of COVID-19 associated pulmonary aspergillosis (CAPA) are rising, but the associated mortality and factors affecting it are not well-characterised. We performed a systematic review including 20 peer-reviewed English language studies reporting mortality in CAPA published till 18 February 2021from PubMed, Ovid SP, Web of Science, Embase and CINHAL. The pooled mortality in CAPA was 51.2% (95% CI: 43.1-61.1, I2  = 38%). The leave one out sensitivity analysis and influential case diagnostics revealed one outlier and its exclusion resulted in a mortality estimate of 54% (95% CI: 45-62). Higher odds of mortality: 2.83 (95% CI: 1.8-4.5) were seen in CAPA compared to controls. No significant difference in various subgroups according to the country of study, the continent of study, income category of country and quality of the included study was seen. None of the host risk factors, mycological test results, therapy for COVID-19 and antifungal therapy affected mortality. Thus, patients with CAPA have a high probability of mortality and early diagnosis with prompt therapy must be ensured to optimally manage these patients. However, more prospective studies with global and multi-centre coordination may help to address CAPA in a better way.

Incidence and mortality of COVID-19-associated pulmonary aspergillosis: A systematic review and meta-analysis.

COVID-19-associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, basic epidemiological characteristics have not been well established. In this systematic review and meta-analysis, we aimed to determine the incidence and mortality of CAPA in critically ill patients with COVID-19 to improve guidance on surveillance and prognostication. Observational studies reporting COVID-19-associated pulmonary aspergillosis were searched with PubMed and Embase databases, followed by an additional manual search in April 2021. We performed a one-group meta-analysis on the incidence and mortality of CAPA using a random-effect model. We identified 28 observational studies with a total of 3148 patients to be included in the meta-analysis. Among the 28 studies, 23 were conducted in Europe, two in Mexico and one each in China, Pakistan and the United States. Routine screening for secondary fungal infection was employed in 13 studies. The modified AspICU algorithm was utilised in 15 studies and was the most commonly used case definition and diagnostic algorithm for pulmonary aspergillosis. The incidence and mortality of CAPA in the ICU were estimated to be 10.2% (95% CI, 8.0-12.5; I2  = 82.0%) and 54.9% (95% CI, 45.6-64.2; I2  = 62.7%), respectively. In conclusion, our estimates may be utilised as a basis for surveillance of CAPA and prognostication in the ICU. Large, prospective cohort studies based on the new case definitions of CAPA are warranted to validate our estimates.

Fatal Invasive Pulmonary Aspergillosis in COVID-19 Patient with Acute Myeloid Leukemia in Iran.

Although patients with severe immunodeficiency and hematological malignancies has been considered at highest risk for invasive fungal infection, patients with severe pneumonia due to influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV) are also at a higher risk of developing invasive pulmonary aspergillosis (IPA). Recently, reports of IPA have also emerged among SARS-CoV-2 infected patients admitted to intensive care units (ICUs). Here, we report a fatal case of probable IPA in an acute myeloid leukemia patient co-infected with SARS-CoV-2 and complicated by acute respiratory distress syndrome (ARDS). Probable IPA is supported by multiple pulmonary nodules with ground glass opacities which indicate halo sign and positive serum galactomannan results. Screening studies are needed to evaluate the prevalence of IPA in immunocompromised patients infected with SARS-CoV-2. Consequently, testing for the presence of Aspergillus in lower respiratory secretions and galactomannan in consecutive serum samples of COVID-19 patients with timely and targeted antifungal therapy based on early clinical suspicion of IPA are highly recommended.

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

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.