PMC:7346000 / 14873-19686 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7346000","sourcedb":"PMC","sourceid":"7346000","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7346000","text":"4. CAPA Prevalence\nSeveral studies from China reported high rates of Aspergillus infections among COVID-19 patients. In one study from the Jiangsu province in China, 60/257 COVID-19 (23.3%) patients had throat swab samples that tested positive for Aspergillus spp. and were reported as Aspergillus co-infections [8]. In another Chinese study from the Zhejiang province 8 of the 104 patients with COVID-19 (7.7%) patients were reported to have IPA although questions remain regarding criteria used for diagnosing IPA in this study (authors state EORTC/MSG criteria were used but all 8 patients seemingly lacked host factors) [71]. Another study from China reported that 27% of the COVID-19 patients (13/48) developed fungal infections but lacked further details [7]. In other reports from China, lower rates of fungal infections were reported ranging between 3.2–5% [54,55,72]. None of those studies have used specific definitions and standardized diagnostic algorithms to identify and define CAPA. In fact, diagnosis of pulmonary aspergillosis is challenging with culture exhibiting limited sensitivity [73,74], and galactomannan testing—the current gold standard—is rarely available in China [75]. As a result, some of these reported rates are likely an underestimate of the real burden of IPA in patients with COVID-19 requiring ICU admission, while other rates may be an overestimation due to potentially misinterpreting Aspergillus colonization in the upper respiratory tract as Aspergillus infection.\nMore recently, several studies and case-series from Europe (France, Germany, Belgium, and the Netherlands) have reported high rates of CAPA among COVID-19 cases with ARDS, ranging from 20–35% (Table 1) [47,50,51,52]. The development of CAPA was fairly rapid, with a median of 6 days and range of 3–28 days after ICU admission [47,52]. Moreover, two additional CAPA cases have been reported from Germany [61] and single cases have also been reported from the Netherlands [62], Austria [60], Italy [59], Australia [63], and France [57,58] (Table 1). Among 35 CAPA cases reported to date, there were a total of 5 proven cases [52,59]. The overall mortality rate was 63% (22/35), among whom 4 were female (4/8; 50%) and 14 were male (18/27; 67%). The mortality in case series reported from France, Germany, Belgium and Netherlands ranged between 44.5–66.7% [47,50,51,52]. Of particular importance was the 100% fatality rate of those with underlying diseases reported from the Netherlands, while the two patients without underlying conditions both survived [47]. Noteworthy is the fact that COVID-19 patients presented with ARDS typically fall into the elderly category [6], whereas ARDS in those infected with influenza involves both children \u003c5 years old and elderly \u003e65 years old [76]. The difficulties in diagnosing CAPA, which are outlined in more detail in the next section of this review, may also contribute to increased mortality rates. The most notable example is a study from France [57], where both culture and serology assays were negative for the initial respiratory samples and became only positive after the patient expired [57]. In a case from Italy, initial BALF culture was positive for A. fumigatus but the treatment was delayed for two days and only started after the serum galactomannan test became positive [59]. CAPA was later confirmed by autopsy examination [59]. As a result, authors encouraged prompt initiation of systemic antifungal therapy immediately after obtaining positive results even if Aspergillus is detected in samples from the upper respiratory tract [59]. Since azole resistance can be associated with a higher mortality rate when compared to patients infected with azole susceptible A. fumigatus isolates, it is of paramount importance to use antifungal susceptibility testing to inform targeted antifungal treatment, especially in regions with high azole resistance [77]. Azole-resistant A. fumigatus isolates were also persistently recovered from tracheal aspirates during the course of azole treatment in the most recent study from the Netherlands implicated a CAPA case for whom [62]. The azole-resistant A. fumigatus isolate (itraconazole, voriconazole, and posaconazole MICs were 16, 2, and 0.5 µg/mL, respectively) harbored a well-known mutation, TR34/L98H [62], presumed to have been acquired from the environment [77]. The in vitro MIC value of the isolate obtained at day 19 (2 mg/L) was higher than the voriconazole serum trough concentration measured on day 17 (1.43 mg/L) and despite switching voriconazole to l-AmB, the patient died due to deteriorating health conditions [62]. Overall, A. fumigatus appeared to be the most prevalent Aspergillus spp. isolated among respiratory samples with positive culture (26/29; 90%), followed by A. flavus (2/29; 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