COVID-19-associated Pulmonary Aspergillosis Research Articles

405. Incidence and Potential Risk Factors of COVID-19 Associated Pulmonary Aspergillosis (CAPA)

Abstract Background Invasive pulmonary aspergillosis (IPA) that develops in coronavirus disease 2019 (COVID-19) patients is called COVID-19 Associated Pulmonary Aspergillosis, CAPA. The incidence of CAPA is reported as high as 1–40 % worldwide. However, the incidence of CAPA is highly variable among reports and it may vary among countries and medical facilities. Therefore, we investigated the incidence of CAPA in severe to critical severity COVID-19 using administrative claims data. Methods A retrospective cohort study was performed using administrative claims data called Diagnosis Procedure Combination (DPC) data from advanced treatment hospital in Japan to explore potential risk factors for CAPA using multivariable regression models. In addition, the contribution of CAPA to mortality in COVID-19 patients was examined. Results Data for 154,731 COVID-19 patients were included from DPC data. Of these, 33,136 were severe or critical COVID-19 and 14,720 were critical COVID-19. The incidence of CAPA were 0.4–1.3 % in severe or critical COVID-19, and 0.5–2.7 % in critical COVID-19. The risk factors for CAPA were steroids (hazard ratio [HR] = 4.753), immunosuppressants (HR = 2.592), intensive care unit admission (HR = 1.677), blood transfusion (HR = 6.206), and dialysis (HR = 2.185). The adjusted mortality HR for CAPA was 2.367 in severe or critical COVID-19, and 1.955 in critical COVID-19. Conclusion The incidence of CAPA in our study was lower than previously reported. It suggests the possibility that appropriate screening test is not being conducted in Japan due to insufficient attention to CAPA. Because CAPA is a significant contributor to mortality in COVID-19 patients, appropriate screening is required in at-risk patients. Disclosures Hiroshi Kakeya, MD, PhD, Asahi Kasei Pharma Corporation: Honoraria|Merck Sharp & Dohme: Honoraria|Sumitomo Pharma Co., Ltd.: Honoraria

Genomic Epidemiology Identifies Azole Resistance Due to TR34/L98H in European Aspergillus fumigatus Causing COVID-19-Associated Pulmonary Aspergillosis.

Aspergillus fumigatus has been found to coinfect patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA, including the prevalence of resistance-associated alleles. We present a population genomic analysis of 21 CAPA isolates from four European countries with these isolates compared against 240 non-CAPA A. fumigatus isolates from a wider population. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically encoded azole-resistant mechanisms. The phylogenetic analysis of the 21 CAPA isolates showed that they were representative of the wider A. fumigatus population with no obvious clustering. The prevalence of phenotypic azole resistance in CAPA was 14.3% (n = 3/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. The relatively high prevalence of azole resistance alleles that we document poses a probable threat to treatment success rates, warranting the enhanced surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes when CAPA is suspected.

Unusual Finding in a Patient of COVID-19 Associated Pulmonary Aspergillosis: A Case Report

Invasive Fungal Infections have posed a difficult challenge in the recovery of people infected with COVID-19. COVID-19-associated pulmonary aspergillosis (CAPA) has been described and found in about 30 % of ICU patients worldwide. Here we present an unusual microscopic finding in a case of CAPA in an ICU patient which was helpful in initiating early definite therapy. A 56-year-old gentleman presented with complaints of fever and shortness of breath and subsequently tested positive for COVID. Post admission, his respiratory distress worsened and his condition deteriorated. A provisional diagnosis of COVID pneumonia with acute respiratory distress syndrome (ARDS) was established based on chest radiographic finding of left lower lobe consolidation, increased pulmonary infiltrates in bilateral lung fields with evidence of pleural effusion. Pleural Aspirate obtained via ultrasound guided thoracocentesis revealed branched hyaline septate hyphae along with structures which were composed of elongated vesicle with one layer of phialides covering two-thirds of the vesicle and bearing globose conidia on KOH direct mount. Aspergillus flavus grew on culture, which was later confirmed by MALDI TOF VITEK MS. Patient was diagnosed with Proven Invasive Pulmonary Aspergillosis with COVID-19 and voriconazole was started. Patient successfully recovered and was discharged. Identifying the Aspergillus species directly on the basis of KOH Mount, helped in decreasing the turnaround time, in early initiation of definite therapy and possibly contributed to the favorable outcome. CAPA is a potentially life-threatening complication in patients with severe COVID-19, thus a timely diagnosis and treatment becomes crucial in the management. Keywords: CAPA, COVID-19, Aspergillus

Diagnostic performance and longitudinal analysis of fungal biomarkers in COVID-19 associated pulmonary aspergillosis

ObjectivesGalactomannan lateral flow assay (GM-LFA) is a reliable test for COVID-19 associated pulmonary aspergillosis (CAPA) diagnosis. We aimed to assess the diagnostic performance of GM-LFA with different case definitions, the association between the longitudinal measurements of serum GM-ELISA, GM-LFA, and the risk of death. MethodsSerum and nondirected bronchial lavage (NBL) samples were periodically collected. The sensitivity and specificity analysis for GM-LFA was done in different time periods. Longitudinal analysis was done with the joint model framework. ResultsA total of 207 patients were evaluated. On the day of CAPA diagnosis, serum GM-LFA had a sensitivity of 42 % (95 % CI: 23–63) and specificity of 82 % (95 % CI: 78–84), while NBL GM-LFA had a sensitivity of 73 % (95 % CI: 45–92), specificity of 85 % (95 % CI: 76–91) for CAPA. Sensitivity decreased through the following days in both samples. Univariate joint model analysis showed that increasing GM-LFA and GM-ELISA levels were associated with increased mortality, and that effect remained same with serum GM-ELISA in multivariate joint model analysis. ConclusionGM-LFA, particularly in NBL samples, seems to be a reliable method for CAPA diagnosis. For detecting patients with higher risk of mortality, longitudinal measurement of serum GM-ELISA can be useful.

Microbiological diagnosis of pulmonary invasive aspergillosis in critically ill patients with severe SARS-CoV-2 pneumonia: a bronchoalveolar study

BackgroundDiagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD).MethodsProspective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose.ResultsOf the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%.ConclusionsUsing a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study

BackgroundInvasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis...

Missed Opportunities for Antifungal Stewardship during the COVID-19 Era.

Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive in comparison with the relatively low rates of bacterial coinfection. Although patients who are critically ill with COVID-19 may be at an increased risk for pulmonary aspergillosis, antifungal use in these populations remained underreported, particularly in later phases of the pandemic. This single-center, population-level cohort analysis compares the monthly use rates of mold-active antifungal drugs in the medical intensive care unit during April 2019-March 2020 (baseline) with those during April 2020-November 2022. The antifungal drugs included in the analysis were liposomal amphotericin B, anidulafungin, isavuconazonium, posaconazole, and voriconazole. We found that during 2020-2022, the usage of antifungal drugs was not significantly different from baseline for all included agents except isavuconazonium, which was used significantly more (p = 0.009). There were no changes in diagnostic modalities between the two time periods. The reported prevalence of and mortality from COVID-19-associated pulmonary aspergillosis (CAPA) may have resulted in higher rates of prescribing antifungal drugs for critically ill patients with COVID-19. Antimicrobial stewardship programs should develop and apply tools to facilitate more effective and appropriate antifungal use.

Effect of glucocorticoids on the development of COVID-19-associated pulmonary aspergillosis: A meta-analysis of 21 studies and 5174 patients.

COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.

Cumulative steroid dose in hospitalized patients and COVID-19-associated pulmonary aspergillosis

Severe COVID-19 elicits a hyperimmune response frequently amenable to steroids, which in turn increase the risk for opportunistic infections. COVID-19 associated pulmonary aspergillosis (CAPA) is a complication known to be associated with immunomodulatory treatment. The role of cumulative steroid dose in the development of CAPA is unclear. This study evaluates the relationship between cumulative steroid dose in hospitalized individuals with COVID-19 pneumonia and the risk for CAPA. This retrospective cohort study includes 135 hospitalized patients with PCR-confirmed COVID-19 pneumonia at a tertiary centre in north Mexico. Patients who developed CAPA were matched by age and gender to two controls with COVID-19 pneumonia who did not develop CAPA defined and classified as possible, probable, or proven according to 2020 ECMM/ISHAM criteria. Cumulative steroid dose in dexamethasone equivalents was obtained from admission until death, discharge, or diagnosis of CAPA (whichever occurred first). The risk of CAPA by the continuous cumulative steroid dose was assessed using a logistic regression model. Forty-five patients were diagnosed with CAPA and matched to 90 controls. Mean age was 61 ± 14 years, and 72% were male. Mean cumulative steroid dose was 66 ± 75mg in patients without CAPA vs 195 ± 226mg in patients with CAPA (P<0.001). The risk for CAPA increased with higher cumulative dose of steroids (OR 1.0075, 95% CI: 1.0033-1.0116). Patients who developed CAPA had a history of higher cumulative steroid dose during hospitalization. The risk for CAPA increases ∼8% for every 10mg of dexamethasone used.

Seroprevalence of Galactomannan Aspergillus in COVID-19 patients in Jakarta: A challenge in the pandemic commotion

COVID-19-associated pulmonary aspergillosis (CAPA) is a severe complication of COVID-19 due to Aspergillus infection. However, the clinical manifestation and radiology findings are not typical and require measurement of Aspergillus galactomannan (GM) level to assist in the diagnosis of CAPA. We evaluated the positivity rate of Aspergillus GM level among COVID-19 patients and investigated the correlation between the GM level and the age of patients. This retrospective observational study compiled the GM results from COVID-19 patients’ sera during the early period of the COVID-19 pandemic from March 2020 to December 2021. All samples underwent an ELISA test to measure Aspergillus GM level. There were 96 patients enrolled in this study. The positivity rate was 33%, with the highest (56%) percentage of positivity observed in the age group 40-59 in the positive Aspergillus GM group. The measurement of Aspergillus GM level among COVID-19 patients with risk factors of CAPA is critical to establish CAPA diagnosis. The availability of Aspergillus GM test in Indonesia is still limited and this issue needs to be addressed by all healthcare experts and stakeholders.

Significance of Aspergillus spp. isolation in defining cases of COVID-19 Associated Pulmonary Aspergillosis - CAPA.

COVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complication in patients with severe forms of the disease caused by the SARS-CoV-2 virus. Diagnosing and confirming CAPA is challenging. In this study, Aspergillus spp. isolation in respiratory specimens from patients with COVID-19 was evaluated for identifying cases of CAPA. In 2020‒2021, 17 Aspergillus spp. were isolated from 15 COVID-19 patients admitted to a university hospital in Brazil. Patient records were retrospectively reviewed to obtain clinical-epidemiological data and other markers of Aspergillus spp. infection and then compared with the ECMM/ISHAM criteria for defining CAPA. Probable CAPA was defined in 5/10 patients, who had Aspergillus spp. isolated from Bronchoalveolar Lavage (BAL) or a positive galactomannan blood test. Additionally, anti-Aspergillus antibodies were detected in two of these patients, during active or follow-up phases of CAPA. In another seven patients with Aspergillus spp. isolated from tracheobronchial aspirate or sputum, CAPA was presumed, mainly due to deterioration of clinical conditions and new lung imaging suggestive of fungal infection. Antifungal agents to control CAPA, particularly voriconazole, were used in 9/15 cases. In cases of probable CAPA and remaining patients, clinical conditions and comorbidities were similar, with lethality being high, at 60% and 71%, respectively. The number of CAPA cases defined by scientific criteria was lower than that assumed in the clinical context. This was largely due to the lack of BAL collection for fungal culture and the non-intensive use of other markers of invasive aspergillosis. The isolation of Aspergillus spp. in different respiratory specimens should alert clinicians to the diagnosis of CAPA.

A retrospective observational study on incidence and clinico-epidemiological features of COVID-19 associated pulmonary aspergillosis among cancer patients hospitalized with COVID-19 in a tertiary care cancer centre of India

Background: COVID-19 associated pulmonary aspergillosis (CAPA) is an emerging complication among patients with COVID-19 but hasn’t been well studied in cancer patients. This study, we try to find out important aspects associated with CAPA among cancer patients with regards to clinico-epidemiological factors. Methods: In this retrospective observational study, we included 198 consecutive patients COVID-19 between April 2020 and February 2021. CAPA cases were classified according to CAPA-European Confederation of Medical Mycology criteria (2020 ECMM/ISHAM consensus criteria). Results: The overall incidence of CAPA was found to be 10.1% in our study population. The incidence among hematological malignancies was 11.25% and solid tumors was 10%. In-hospital mortality was significantly high among patients with CAPA as compared to that among without CAPA (40% versus 16.85%; p&lt;0.012695). Significant number of patients with CAPA had received chemotherapy in last 3 months before diagnosis of COVID-19 (50% versus 28.09%, p=0.043222) and had evidence of culture positive bacterial infection (30% versus 5.62; p=0.000888). Significantly more patients having CAPA were on steroids, required oxygen and/or ventilator support as compared to those without CAPA. Conclusions: CAPA is a significant cause of mortality and length of hospital stay (16 versus 7 days; p=0.00001) among cancer patients with COVID-19. Cancer patients with COVID-19 were at increased risk of CAPA as compared to non-cancer patients.

COVID-19-associated pulmonary aspergillosis in immunocompetent patients: a virtual patient cohort study.

The opportunistic fungus Aspergillus fumigatus infects the lungs of immunocompromised hosts, including patients undergoing chemotherapy or organ transplantation. More recently however, immunocompetent patients with severe SARS-CoV2 have been reported to be affected by COVID-19 Associated Pulmonary Aspergillosis (CAPA), in the absence of the conventional risk factors for invasive aspergillosis. This paper explores the hypothesis that contributing causes are the destruction of the lung epithelium permitting colonization by opportunistic pathogens. At the same time, the exhaustion of the immune system, characterized by cytokine storms, apoptosis, and depletion of leukocytes may hinder the response to A. fumigatus infection. The combination of these factors may explain the onset of invasive aspergillosis in immunocompetent patients. We used a previously published computational model of the innate immune response to infection with Aspergillus fumigatus. Variation of model parameters was used to create a virtual patient population. A simulation study of this virtual patient population to test potential causes for co-infection in immunocompetent patients. The two most important factors determining the likelihood of CAPA were the inherent virulence of the fungus and the effectiveness of the neutrophil population, as measured by granule half-life and ability to kill fungal cells. Varying these parameters across the virtual patient population generated a realistic distribution of CAPA phenotypes observed in the literature. Computational models are an effective tool for hypothesis generation. Varying model parameters can be used to create a virtual patient population for identifying candidate mechanisms for phenomena observed in actual patient populations.

Invasive fungal disease in COVID-19 patients: a single-center prospective observational study.

Invasive fungal diseases (IFDs) are caused by fungal infections that manifest as serious secondary infections in patients with COVID-19. The increased morbidity and mortality rates are most frequently observed in patients with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated candidiasis (CAC). CAPA is the most frequently encountered infection with an incidence rate of 0.7-7.7%, while CAC is a less common and less studied fungal infection in COVID-19 patients. The present article is a prospective observational single-center study that was conducted between 1 September 2021 and 24 December 2021, involving 6,335 patients who were admitted to COVID Hospital "Batajnica," University Clinical Center of Serbia, Belgrade. Of the 6,335 patients hospitalized during the four-month period of the study, 120 patients (1.86%) who had a proven diagnosis of IFD were included in the study. These patients were divided into two groups: CAPA patients (n = 63) and CAC patients (n = 56); however, one of the 120 patients was diagnosed with Cryptoccocus neoformans infection. The mean age of the study population was 65.7 ± 13.9 years, and 78 (65.5%) of them were men. The patients were identified to have the following non-malignant comorbidities: arterial hypertension in 62 (52.1%) patients, diabetes mellitus in 34 (28.65), pre-existing lung damage similar to that observed in COPD and asthma in 20 (16.8%), and chronic renal insufficiency in 13 (10.9%) patients. The hematological malignancies were found to be the most prevalent malignancies and were identified in 20 (16.8%) patients, particularly in CAPA patients [11 (17.5%); p < 0.041]. Fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and microscopic examination confirmed the presence of fungal infections in 17 (14.3%) patients. Serology testing was also performed in the majority of cases. Antibodies against Aspergillus spp. and Candida spp. were predominantly found in CAPA patients (p < 0.001). The patients were also tested for the presence of (1-3)-β-D glucan (p < 0.019), galactomannan, and mannan in the specimens. Blood cultures were found to be positive in 45 (37.8%) patients, mostly in CAC patients. Mechanical ventilation was applied in 41 (34.5%) patients, while a non-invasive technique, such as continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC), was used in 20 (16.8%) patients. The following antifungals were administered: echinocandins in 42 (35.3%), voriconazole in 30 (25.2%), and fluconazole in 27 (22.7%) patients. Most of the patients received systemic corticosteroids (mainly methylprednisolone), while 11 (9.16%) received favipiravir, 32 (26.67%) remdesivir, 8 (6.67%) casirivimab/imdevimab, and 5 (4.16%) sotrovimab. The outcome was lethal in 76 (63.9%) patients, predominantly CAC patients (p < 0.001). Invasive fungal disease is a severe complication associated with COVID-19 and accounts for increased mortality in these patients. Early identification and appropriate treatment may provide a favorable outcome.

COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

A Tale of Two Hospitals: Comparing CAPA Infections in Two ICUs During the Spanish Fourth Pandemic Wave.

COVID-19 associated pulmonary aspergillosis (CAPA) is a new clinical entity linked to SARS-CoV-2 infection that is causing a rise on the risk of complications and mortality, particularly in critical patients. We compared diagnostic and clinical features in two cohorts of patients with severe COVID-19 admitted in the intensive care units (ICU) of two different hospitals in Madrid, Spain, between February and June 2021. Clinical and microbiological relevant aspects for CAPA diagnosis were collected for further classification. CAPA was classified as colonization, possible, probable, proven, and tracheobronchial aspergillosis according to the ECMM/ISHAM consensus, with some modifications to consider tracheobronchial aspirate as sample comparable to non-bronchoscopic lavages (NBL). 56 patients admitted in HULP (Hospital Universitario La Paz) ICU and 61 patients admitted in HEEIZ (Hospital de Emergencias Isabel Zendal) ICU had clinical suspicion of invasive fungal disease in the context of COVID-19 infection. Cultures were positive for Aspergillus spp. in 32 patients. According to 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus, 11 patients were diagnosed with possible CAPA and 10 patients with probable CAPA. Global incidence for CAPA was 6.3%. Global median days between ICU admission and diagnosis was 14day. Aspergillus fumigatus complex was the main isolated species. Antifungal therapy was used in 75% of patients with CAPA suspicion, with inter-hospital differences in the administered antifungals. Global overall mortality rate for CAPA patients was 66.6% (14/21). All-cause mortality in non-CAPA cohorts were of 26.3% in HULP group (34/129) and 56.8% (104/183) in HEEIZ group. There were no significant differences in incidence between the two hospitals, and differences in antifungal therapy did not correlate with differences in mortality, reflecting that both first-line azoles and Amphotericin B could be effective in treating CAPA infections, according to the current guideline indications.

Phenotypic Array for Identification and Screening of Antifungals against Aspergillus Isolates from Respiratory Infections in KwaZulu Natal, South Africa.

The rapid emergence of invasive fungal infections correlates with the increasing population of immunocompromised individuals, with many cases leading to death. The progressive increase in the incidence of Aspergillus isolates is even more severe due to the clinical challenges in treating invasive infections in immunocompromised patients with respiratory conditions. Rapid detection and diagnosis are needed to reduce mortality in individuals with invasive aspergillosis-related infections and thus efficient identification impacts clinical success. The phenotypic array method was compared to conventional morphology and molecular identification on thirty-six Aspergillus species isolated from patients with respiratory infections at the Inkosi Albert Luthuli Hospital in Kwa-Zulu Natal. In addition, an antimicrobial array was also carried out to screen for possible novel antimicrobial compounds for treatment. Although traditional morphological techniques are useful, genetic identification was the most reliable, assigning 26 to Aspergillus fumigatus species, 8 Aspergillus niger, and 2 Aspergillus flavus including cryptic species of A. niger, A. tubingensis and A. welwitschiae. The phenotypic array technique was only able to identify isolates up to the genus level due to a lack of adequate reference clinical species in the database. However, this technique proved crucial in assessing a wide range of possible antimicrobial options after these isolates exhibited some resistance to azoles. Antifungal profiles of the thirty-six isolates on the routine azole voriconazole showed a resistance of 6%, with 61% having moderate susceptibility. All isolates resistant to the salvage therapy drug, posaconazole pose a serious concern. Significantly, A. niger was the only species resistant (25%) to voriconazole and has recently been reported as the species isolated from patients with COVID-19-associated pulmonary aspergillosis (CAPA). Phenotypic microarray showed that 83% of the isolates were susceptible to the 24 new compounds and novel compounds were identified for potentially effective combination treatment of fungal infections. This study also reports the first TR34/98 mutation in Aspergillus clinical isolates which is located in the cyp51A gene.

COVID-19 associated pulmonary aspergillosis-an unusual manifestation of COVID-19

A recently identified condition known as COVID-19-associated pulmonary aspergillosis (CAPA) is connected to the COVID-19 pandemic and is known as post-COVID complications. More data are awaited, and a consensus criterion was recently published in an effort to spur more research and registries to assist clinical decision-making. However, it is evident that CAPA imposes a COVID-19 illness course that worsens with increased morbidity and mortality. Here we present the case of a 53-year-old male patient admitted to our hospital after recovering from COVID-19. Due to his clinical condition, some investigation criteria were performed and Aspergillus fumigatus was identified in his culture test. Treatment was provided with posaconazole as a first-line drug, and the patient showed a good clinical outcome.

Exploring the intersection of Aspergillus fumigatus biofilms, infections, immune response and antifungal resistance.

Aspergillus fumigatus is an opportunistic pathogen that primarily affects the lungs and frequently elicits an allergic immune response in human hosts via inhalation of its airborne asexual spores (conidia). In immunocompromised individuals, the conidia of this fungus can germinate in the lung and result in severe systemic infections characterised by widespread tissue and organ damage. Conversely, in healthy hosts, the innate immune system is instrumental in eliminating the conidia and preventing disease progression. As with numerous other pathogenic fungi, A. fumigatus possesses a set of virulence factors that facilitate its infective mechanism and the circumvention of immune defences in susceptible hosts. The intrinsic capacity of A. fumigatus to form complex 3D-structured biofilms, both on biotic and abiotic surfaces, represents a key determinant of its evasion of the host immune system and resistance to antifungal drugs. This review delineates the pivotal role of A. fumigatus biofilm structure and function as a significant virulence factor in pathogenic infections, such as aspergilloma and invasive pulmonary aspergillosis (IPA). Additionally, we discuss the importance for the development of novel antifungal drugs as drug-resistant strains continue to evolve. Furthermore, co-infections of A. fumigatus with other nosocomial pathogens have a substantial impact on patient's health outcomes. In this context, we provide a brief overview of COVID-19-associated pulmonary aspergillosis (CAPA), a recently documented condition that has gained attention due to its associated high degree of severity.

Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico

Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.