COVID-19-associated Pulmonary Aspergillosis Research Articles

Mortality in critically ill COVID‑19 patients with fungal infections: a comprehensive systematic review and meta‑analysis.

Patients with COVID‑19 may develop concomitant viral, bacterial, or fungal infections. Such patients are at a higher risk of death, especially from a critical illness. Although much attention has been recently given to fungal infections that may have devastating consequences, data on this issue are scarce. The aim of the study was to assess the impact and prevalence of fungal infections in critically ill patients with COVID 19. We systematically searched for studies that focused on critically ill adults diagnosed with COVID‑19 and a fungal coinfection. Mortality was our outcome of interest. The search was conducted within MEDLINE, Web of Science, clinicaltrials.gov, Embase, and Cochrane Library on January 8, 2022. We reviewed 38 papers covering 17 695 patients, 1182 (6.7%) of whom had an acquired fungal infection. The overall mortality in the papers retrieved for a systematic review (n = 38) varied from 29% to 100% (median [IQR], 56% [40%-77%]). In a meta‑analysis (19 studies), the patients with a fungal infection were more likely to die than the controls (odds ratio [OR], 2.987; 95% CI, 2.369-3.767; P <0.001; I2 = 26.63%). Subgroup analyses showed that COVID‑19-associated pulmonary aspergillosis (CAPA) increased mortality by 3 times (OR, 3.279; 95% CI, 2.692-3.994; P <0.001; I2 = 0%), and that COVID‑19-associated candidiasis (CAC) increased mortality by 2 times (OR, 2.254; 95% CI, 1.322-3.843; I2 = 26.14%). In critically ill patients with COVID‑ 19, CAPA is rather common and significantly increases mortality. The evidence regarding other fungal infections is weaker, with CAC occurring less frequently but also impacting mortality. Therefore, clinical awareness and screening are needed, followed by personalized antifungal therapy stewardship, which is strongly recommended in order to improve the patients' prognosis.

P20 COVID-19-associated pulmonary aspergillosis (CAPA): review of utility of local CAPA guideline and MDT in directing diagnosis and antifungal stewardship

BackgroundCOVID-19-associated pulmonary aspergillosis (CAPA) is a recognized but incompletely characterized secondary fungal infection reported to be associated with increased mortality in patients in the ICU. Case definitions have been published but lack clarity: clinical and radiological features are non-specific and rely heavily on mycological tests for which both a timely availability and accuracy pose an issue contributing to the wide range of incidence reported of 4%–34%. In April 2021, we introduced a CAPA guideline for ICU patients at St George's University Hospital including when to suspect and how to investigate for CAPA (see Figure 1). The aim of this study was to evaluate its utility in identifying patients meeting ECMM_ISHAM criteria for possible/probable CAPA.Figure 1.St George's Hospital CAPA Guideline 2021.MethodsBetween March 2020 and May 2021 a retrospective audit was completed that identified all PCR-confirmed COVID-19 ICU patients prescribed either voriconazole, caspofungin, anidulafungin and AmBisome and reviewed their medical records, imaging and microbiology results categorizing patients into proven, probable, possible or unlikely CAPA based on ECMM/ISHAM criteria.ResultsTwenty-one patients were prescribed the specified antifungals. All had CT imaging and varying microbiological investigations. Real-time clinical decisions on empirical antifungal prescribing for CAPA (start or stop) were made by a multidisciplinary team (MDT) comprising Microbiology and ICU physicians in light of clinical, microbiology and radiology findings. Nine of 21 patients prescribed empirical antifungals had radiological evidence of CAPA. Aspergillus fumigatus was cultured in six patients from bronchoalveolar lavage and two patients from sputum/trachea. Of these, seven were deemed significant and one attributed to colonization. Two patients were diagnosed with ‘probable’ and five as ‘possible’ CAPA, of whom one died. All seven patients received antifungal treatment for CAPA of varying duration (range 18–49 days). Only one patient had an underlying host risk factor (B cell lymphoma). Of those defined with probable/possible CAPA, average time from intubation to treatment was 18.4 days (range 8–31) and from onset of COVID symptoms to treatment was 28.5 days (range 18–49). Three of 21 patients were treated empirically for CAPA and all 3 died prior to further investigation and 15 patients following an MDT were felt to have unlikely CAPA. Serum BDG and GM were negative in all patients with probable/possible CAPA.ConclusionsThe St George's CAPA guideline would have picked up two out of seven cases; two cases had antifungals started in another hospital so the utility of this guideline could not be assessed. Based on analysis of these cases the following changes were made to the guideline: (i) to assess patients ≥8 days post ICU admission (rather than ≥10 days) and (ii) assess patients following ≥3 days post appropriate antibiotic therapy (rather than following ≥5 days). Serum BDG and GM were negative in all patients with probable/possible CAPA prior to starting treatment therefore negative serum markers do not exclude diagnosis; this is consistent with experience reported elsewhere. Radiological presentations of CAPA were variable and wide ranging, and BAL sampling was not always possible, therefore we found the MDT approach including radiology, infection, respiratory and ICU invaluable in making decisions regarding treatment. This helped to reduce the use of fungal diagnostics, antifungal agents and appropriately manage patients with potential CAPA. The rationalization of antifungal use by the introduction of this guidelines was particularly important and also expedited the introduction of in-house fungal diagnostics.

Invasive fungal infections in critically ill COVID-19 patients in a large tertiary university hospital in Israel.

An increasing number of studies have tried to determine the incidence of invasive fungal infections (IFIs) in COVID-19 patients. Challenges in the diagnosis of pulmonary aspergillosis in these patients have led to new definitions of COVID-19-associated pulmonary aspergillosis (CAPA). The aim of this study was to determine the incidence and outcomes of and risk factors for IFIs in critically-ill COVID-19 patients, using the new definitions, in a tertiary center in Israel.MethodsA case-controlled study (from 1 September 2020 to 31 March 2021) in which data from COVID-19 critically-ill patients with a diagnosis of IFI were collected and compared to a control group without IFI.ResultsThe incidence of IFI amongst 311 COVID-19 critically-ill patients was 6.1%. 3.5% had CAPA and 3.5% had candidemia. In-hospital mortality was higher amongst patients with IFI compared to those without IFI (89.4% vs 60%, p < 0.03). The most significant predictors of IFI were cardiovascular co-morbidity and carbapenem use.ConclusionsThe low incidence of CAPA in our group of COVID-19 critically-ill patients was consistent with recent reports, underscoring the importance of differentiating between true infection and colonization. Awareness and timely diagnosis of IFIs in COVID-19 critically-ill patients are imperative considering the associated high mortality.

Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis

Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without Aspergillus infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested LGALS2, MMP1, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during Aspergillus infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.

Association of COVID-19-Associated Pulmonary Aspergillosis with Cytomegalovirus Replication: A Case-Control Study.

Introduction: Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. However, its association with COVID-19-associated pulmonary aspergillosis (CAPA) has not been described. We aimed to examine the possible link between CMV replication and CAPA occurrence. Methods: A single-center, retrospective case–control study was conducted. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. Two controls were selected for each case among critically ill COVID-19 patients. Results: In total, 24 CAPA cases were included, comprising 14 possible CAPA and 10 probable CAPA. Additionally, 48 matched controls were selected. CMV replication was detected more frequently in CAPA than in controls (75.0% vs. 35.4%, p = 0.002). Probable CMV end-organ disease was more prevalent in CAPA (20.8% vs. 4.2%, p = 0.037). After adjusting for possible confounding factors, CMV replication persisted strongly associated with CAPA (OR 8.28 95% CI 1.90–36.13, p = 0.005). Among 11 CAPA cases with CMV PCR available prior to CAPA, in 9 (81.8%) cases, CMV replication was observed prior to CAPA diagnosis. Conclusions: Among critically ill COVID-19 patients, CMV replication was associated with CAPA and could potentially be considered a harbinger of CAPA. Further studies are needed to confirm this association.

COVID-19-associated pulmonary aspergillosis in hemodialysis patients.

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a fatal complication in the general population. However, there are few reports on CAPA in patients undergoing hemodialysis (HD).MethodsThis retrospective observational cohort study was conducted at a single center between December 2020 and June 2021. We enrolled 21 HD patients with COVID-19 undergoing treatment and divided them into two groups, CAPA and non-CAPA (COVID-19 with and without pulmonary aspergillosis), and evaluated their characteristics, clinical outcomes and comorbidities.ResultsThe log-rank test revealed that the 90-day survival rate after the initiation of treatment for COVID-19 was significantly lower in the CAPA (n = 6) than in the non-CAPA group (n = 15) (P = 0.0002), and the 90-day mortality rates were 66.6% and 0% in the CAPA and non-CAPA groups, respectively. In the CAPA group, four patients died due to respiratory failure (on Days 6 and 20), gastrointestinal bleeding (Day 8) and sepsis (Day 33); the reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained positive when they died. The remaining two patients survived and the negative conversion of RT-PCR for SARS-CoV-2 was confirmed on Days 10 and 15. The negative conversion of serum (1, 3)-β-d-glucan (BDG) was confirmed on Day 15 in one patient; the BDG remained positive on Day 64 in the other.ConclusionsCAPA is a fatal complication in HD patients and the general population. Therefore, clinicians should consider the possibility of testing for CAPA in patients undergoing HD. Mycological workups may be helpful for the early detection of CAPA.

Corticosteroids as risk factor for COVID-19-associated pulmonary aspergillosis in intensive care patients

PurposeCorticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA.MethodsWe performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA.ResultsAltogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112–8.697) and SAPS (OR 1.063, CI95 1.028–1.098) to be independent risk factors for CAPA.ConclusionIn our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA.Trial registrationRegistration number DRKS00024578, Date of registration March 3rd, 2021.

Regional Impact of COVID-19-Associated Pulmonary Aspergillosis (CAPA) during the First Wave.

Background: Critically ill COVID-19 patients have proven to be at risk for developing invasive fungal infections. However, the incidence and impact of possible/probable COVID-19-associated pulmonary aspergillosis (CAPA) in severe COVID-19 patients varies between cohorts. We aimed to assess the incidence, risk factors, and clinical outcome of invasive pulmonary aspergillosis in a regional cohort of COVID-19 intensive care patients. Methods: We performed a regional, multicentre, retrospective cohort study in the intensive care units (ICUs) in North Brabant, The Netherlands. We included adult patients with rt-PCR-confirmed SARS-CoV-2 infection (COVID-19), requiring mechanical ventilation for acute respiratory distress syndrome. Demographics, clinical course, biomarker value, and treatment outcomes were compared between the groups with possible/probable CAPA from the main study centre and the regional centres, and without signs of CAPA from the main study centre as controls. The primary aim was to assess the regional impact of possible/probable CAPA in COVID-19 ICU patients, measured as all-cause mortality at 30 days after ICU admission. Secondary outcomes were risk factors for developing CAPA, based on underlying host factors and to identify the value of the mycological arguments for the diagnosing of CAPA. Results: Between 1 March and 30 April 2020, we included 123 patients with severe COVID-19: 29 patients (30.9%) in the main ICU with possible/probable CAPA, and 65 (69.1%) with no signs of CAPA; 29 patients in the regional ICUs with signs of CAPA. Patients’ characteristics and risk factors did not differ for CAPA and non-CAPA patients. Patients with COPD and/or chronic steroid medication developed CAPA more frequently, although this was not statistically significant. CAPA patients were admitted to the ICU earlier, had lower PF-ratios, and more often required renal replacement therapy. All-cause 30-day mortality was significantly higher in mechanically ventilated COVID-19 patients with possible/probable CAPA 39.7% (23/58) compared to patients without evidence for CAPA 16.9% (11/65) (OR 3.2 [95% CI 1.4–7.4] p = 0.005). Conclusion: The high incidence of possible and probable CAPA in critically ill COVID-19 patients is alarming. The increase in 30-day mortality in CAPA highlights the need for active surveillance and management strategies in critically ill COVID-19 patients.

COVID-19-Associated Pulmonary Aspergillosis in a Tertiary Hospital.

Our study aims to assess the prevalence of CAPA (COVID-19-associated pulmonary aspergillosis) and describe the associated risk factors and their impact on mortality. A prospective study was conducted. We included patients with COVID-19 disease who were admitted to the ICU with a diagnosis of respiratory failur. Mycological culture and other biomarkers (calcofluor staining, LFD, LFA, PCR, GM, and B-D-glucan) were performed. A total of 300 patients were included in the study. Thirty-five patients were diagnosed with CAPA (prevalence 11.7%). During admission, 57 patients died (19%), and, in the group of CAPA patients, mortality was 31.4%. In multivariate analysis, independent risk factors associated with CAPA diagnosis were age (OR: 1.05; 95% CI 1.01–1.09; p = 0.037), chronic lung disease (OR: 3.85; 95% CI 1.02–14.9; p = 0.049) and treatment with tocilizumab during admission (OR: 14.5; 95% 6.1–34.9; p = 0.001). Factors independently associated with mortality were age (OR: 1.06; 95% CI 1.01–1.11; p = 0.014) and CAPA diagnosis during admission (OR: 3.34; 95% CI 1.38–8.08; p = 0.007). CAPA is an infection that appears in many patients with COVID-19 disease. CAPA is associated with high mortality rates, which may be reduced by early diagnosis and initiation of appropriate antifungal therapy, so screening of COVID-19 ARDS (acute respiratory distress syndrome) patients for CAPA is essential.

Invasive aspergillosis in coronavirus disease 2019: a practical approach for clinicians.

Purpose of reviewInvasive pulmonary aspergillosis (IPA) can affect patients with severe coronavirus disease 2019 (COVID-19), but many questions remain open about its very variable incidence across the world, the actual link between the viral infection and the fungal superinfection, the significance of Aspergillus recovery in a respiratory sample, and the management of such cases. This review addresses these questions and aims at providing some clues for the practical diagnostic and therapeutic approaches of COVID-19-associated pulmonary aspergillosis (CAPA) in a clinical perspective.Recent findingsDefinitions have been proposed for possible/probable/proven CAPA, but distinction between colonization and invasive fungal infection is difficult and not possible in most cases in the absence of histopathological proof or positive galactomannan in serum. Most importantly, the recovery of an Aspergillus by a direct (culture, PCR) or indirect (galactomannan) test in a respiratory sample is an indicator of worse outcome, which justifies a screening for early detection and initiation of preemptive antifungal therapy in such cases.SummaryThe COVID-19 pandemic has increased our awareness of IPA among ICU patients. Although current recommendations are mainly based on experts’ opinions, prospective studies are needed to get more evidence-based support for the diagnostic approach and management of CAPA.

COVID-19 associated pulmonary aspergillosis (CAPA) case series in NHS Greater Glasgow and Clyde (GGC)

The aim of this study was to describe the patient's characteristics and clinical course of CAPA and to investigate possible association of Dexamethasone with CAPA incidence.This is a retrospective descriptive study. All adult patients in GGC NHS with laboratory proven SARS-CoV-2 infection who subsequently had Aspergillus species isolated from their respiratory samples between 01/02/20 and 31/01/21were included.A total of 24 patients fulfilled the inclusion criteria.79% of the cases were between October/2020-January/2021 coinciding with the second wave of COVID-19 and the increased use of steroids after the RECOVERY trial results. Based on the proposed screening and diagnostic algorithm for CAPA and Modified AspITU classification, 6 patients had likely/putative, and 2 patients had highly likely/probable CAPA, respectively.Based on the CAPA algorithm, for 11 patients CAPA was not excluded and 5 considered colonization. Based on Modified AspITU, 10 considered query Putative CAPA and 6 colonization. 13 patients were males. The median age was 62. 46% of patients had underlying lung disease, 20% had previous exposure to inhaled steroids, 8% to Methotrexate, 4% to each of systemic steroids and Rituximab. 79% of patients received Dexamethasone and 12.5% received Tocilizumab for COVID-19. 75% of patients were in ITU at time of first Aspergillus isolation. 67% of patients received antifungal for CAPA.CAPA remains an area of research. From our limited data, we observed an association between Dexamethasone use and incidence of CAPA. We also noticed a correlation between the number of samples with positive Aspergillus species culture from the same patient and the likelihood of CAPA diagnosis.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BackgroundCoronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.MethodsThis multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.ResultsAmong 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089).ConclusionOur study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

COVID-19-associated pulmonary aspergillosis: from invasive to chronic form

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with SARS-CoV-2 infection. Since the emerging number of cases and the high mortality rate, there is an acute need for more information about the interaction between SARS‐CoV‐2 and Aspergillus spp., and the treatment for CAPA. We present a case diagnosed with a severe form of CAPA, lung lesions being followed-up for 6 months.

Study to assess aetiology, clinical and imaging characteristics of post Covid-19 pulmonary cavitation.

Objective:The aim of this study is to determine the aetiology and characteristics of pulmonary cavities that developed in patients recovering from COVID-19 infection.Materials and Methods:Between 1st May 2021 and 30st June 2021, we found 9 post COVID-19 patients who developed lung cavities on chest radiograph or CT during the follow-up period. These patients underwent routine blood examination, sputum examination and bronchoscopy to identify the aetiologies for the lung cavities.Results:The duration from the onset of COVID-19 symptoms to the detection of lung cavities ranged from 18 to 82 days. Out of 7 patients, 4 had recovered from severe COVID-19 disease, 2 from moderate and 1 from mild disease. After the diagnostic workup, 5 patients were found to have COVID-19 associated pulmonary aspergillosis (CAPA), 1 patient with mucormycosis and 1 patient with mycobacterium infection. Two patients with CAPA also had bacterial infection; sputum culture from both these patients grew Klebsiella pneumonia.Conclusion:Lung cavities can develop in patients recovering from COVID-19 pneumonia and fungal infection is the most common cause for such cavities.

Potential links between COVID-19-associated pulmonary aspergillosis and bronchiectasis as detected by high resolution computed tomography.

The aim of this observational study was to highlight high resolution CT scan characteristics of COVID-19-associated pulmonary aspergillosis (CAPA) with a focus on the detection of de-novo appeared or evolved bronchiectasis. From March 2020 to May 2021, we enrolled 350 consecutive mechanically ventilated ICU patients with COVID-19. Patients with CAPA and at least one chest CT scan performed within 15 days from the diagnosis were included. Two radiologists were asked to identify typical and atypical signs of COVID-19 pneumonia. Bronchiectasis locations were described and a modified Reiff score was calculated, as severity score. A total of 19 CAPA patients (median age 71.0, Interquartile range (IQR) 62.5-75.0; male 16, 84.2%) were included. According to the 2020 ECMM/ISHAM criteria, 18 patients had probable CAPA and one had proven CAPA. The median time between hospital admission and CT scan was 21 days (IQR 14.5-25.0). The incidence of bronchiectasis in the study population was 57.9% (n = 11). Tubular bronchiectasis was detected in 10 patients and were scored as follows: three patients had a score of 1, three patients had a score of score 2, one patient had a score of 5 and four patients had a score of 6. Eight patients had a previous CT scan (performed at hospital admission), among them: 5 patients developed de-novo bronchiectasis, while 2 patients demonstrated a volumetric increase of bronchiectasis. At the 6-months follow-up, the mortality rate for patients with CAPA was >60%. the radiologic detection of de-novo appearance or volumetric increase of bronchiectasis in COVID-19 should lead clinicians to search for fungal superinfections.

COVID-19-Associated Pulmonary Aspergillosis in the Critical Care Setting.

The first confirmed case of COVID-19 in the United States was reported on January 20, 2020. Most infected individuals experience a mild illness with loss of taste and smell, body aches, fatigue, cough, and fever. However, about 5% of patients become critically ill and experience more serious symptoms such as respiratory distress, pulmonary emboli, or even multisystem organ failure. Those who become critically ill with COVID-19 are at high risk for superinfections, including pulmonary, bloodstream, and urinary tract infections. Invasive aspergillosis is emerging as a serious secondary pulmonary infection in patients with COVID-19 who experience respiratory distress syndrome. If these patients are not accurately diagnosed and subsequently treated, the infection can be fatal. This case study describes COVID-19-associated pulmonary aspergillosis in the critically ill patient.

A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA).

Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a severe fungal infection complicating critically ill COVID-19 patients. Numerous retrospective and prospective studies have been performed to get a better grasp on this lethal co-infection. We performed a qualitative review and summarized data from 48 studies in which 7047 patients had been included, of whom 820 had CAPA. The pooled incidence of proven, probable or putative CAPA was 15.1% among 2953 ICU-admitted COVID-19 patients included in 18 prospective studies. Incidences showed great variability due to multiple factors such as discrepancies in the rate and depth of the fungal work-up. The pathophysiology and risk factors for CAPA are ill-defined, but therapy with corticosteroids and anti-interleukin-6 therapy potentially confer the biggest risk. Sampling for mycological work-up using bronchoscopy is the cornerstone for diagnosis, as imaging is often aspecific. CAPA is associated with an increased mortality, but we do not have conclusive data whether therapy contributes to an increased survival in these patients. We conclude our review with a comparison between influenza-associated pulmonary aspergillosis (IAPA) and CAPA.

COVID-19-Associated Pulmonary Aspergillosis in Russia.

We studied the risk factors, etiology, clinical features and the effectiveness of therapy of COVID-19-associated pulmonary aspergillosis (CAPA) in adult patients. In this retrospective study, we included 45 patients with proven (7%) and probable (93%) CAPA. The ECMM/ISHAM, 2020 criteria were used to diagnose CAPA. A case-control study was conducted to study the risk factors of CAPA; the control group included 90 adult COVID-19 patients without IA. In CAPA patients, the main underlying diseases were diabetes mellitus (33%), and hematological and oncological diseases (31%). The probability of CAPA developing significantly increased with lymphocytopenia >10 days (OR = 8.156 (3.056–21.771), p = 0.001), decompensated diabetes mellitus (29% vs. 7%, (OR = 5.688 (1.991–16.246), p = 0.001)), use of glucocorticosteroids (GCS) in prednisolone-equivalent dose > 60 mg/day (OR = 4.493 (1.896–10.647), p = 0.001) and monoclonal antibodies to IL-1ß and IL-6 (OR = 2.880 (1.272–6.518), p = 0.01). The main area of localization of CAPA was the lungs (100%). The clinical features of CAPA were fever (98% vs. 85%, p = 0.007), cough (89% vs. 72%, p = 0.002) and hemoptysis (36% vs. 3%, p = 0.0001). Overall, 71% of patients were in intensive care units (ICU) (median—15.5 (5–60) days), mechanical ventilation was used in 52% of cases, and acute respiratory distress syndrome (ARDS) occurred at a rate of 31%. The lung CT scan features of CAPA were bilateral (93%) lung tissue consolidation (89% vs. 59%, p = 0.004) and destruction (47% vs. 1%, p = 0.00001), and hydrothorax (26% vs. 11%, p = 0.03). The main pathogens were A. fumigatus (44%) and A. niger (31%). The overall survival rate after 12 weeks was 47.2%.

279. Clinical Characteristics of Critically Ill Patients with COVID-19 and Invasive Pulmonary Aspergillosis: A Case Series From Mexico City

BackgroundCOVID-19 has emerged as a global public health emergency and has been the main cause of intensive care admission during the pandemic. COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in case series of critically ill patients. However, the criteria for CAPA diagnosis has been inconsistent among most of the reports. Mexico has been widely affected by SARS-CoV-2. We present a series of CAPA cases at a teaching hospital in Mexico City.MethodsWe performed a retrospective analysis of COVID-19 patients admitted to the ABC Medical Center from May 1st, 2020, to May 1st, 2021. Including only those with critical COVID-19 who required invasive mechanical ventilation (IMV). Patients with a diagnosis of CAPA were analyzed. We followed the 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. Aspergillus antigen testing in tracheal aspirate and serum was done with Aspergillus-specific galactomannoprotein (GP) ELISA (Euroimmun Medizinische Labordiagnostika).ResultsAmong the 230 admitted patients who required IMV, we identified 49 (21.3%) cases of CAPA, 46 probable CAPA and 3 proven CAPA. Nineteen (38%) of those died in the hospital. The mean age was 64.5 ± 12.6 years and 11 were female. Proven CAPA was diagnosed with culture in three cases (one A. niger, one A. terreus and one A. fumigatus). Probable CAPA was diagnosed by a positive serum GP in 27 (55.1%) patients and by a positive bronchoalveolar lavage (BAL) GP in 29 (59.2%) cases. Seven patients had both serum and BAL positive GP. Forty-six (93.9%) patients received corticosteroids, and 22 (49.9%) were treated with tocilizumab before CAPA diagnosis. All but one received isavuconazole as CAPA treatment. We detected 35 (71.4%) patients who had a bacterial co-infection. Eighteen of those died (51.4%) compared to only one dead in the subgroup without coinfections (7.1%). The mean time from hospital admission to CAPA diagnosis was 6.2 days (SD 7.1) among those who survived compared to 13.2 (SD 6.3) days in those who died p< 0.01. ConclusionCAPA had a lower prevalence than previously reported in other series. However, it appears to be linked to high mortality when it occurs with other bacterial coinfections and when it is diagnosed late from admission. Disclosures All Authors: No reported disclosures

324. COVID-19-Associated Pulmonary Aspergillosis (CAPA) at Veterans Affairs (VA) Hospitals in Southern California and Arizona

BackgroundThe data on CAPA in the U.S. are limited to date and clinical characteristics unique to this phenomenon have not been widely reported.MethodsThis retrospective observational study was conducted at multiple VA hospitals across southern California and Arizona. CAPA cases were identified in inpatients with laboratory-confirmed COVID-19 based on microbiologic or serologic evidence of aspergillosis and pulmonary abnormalities on imaging, and were classified according to ECMM/ISHAM consensus definitions. Characteristics of interest included immunosuppressive/modulatory agents used prior to onset of CAPA, COVID-19 disease course, length of hospitalization, and mortality.ResultsSeventeen patients with probable (18%) or possible (82%) CAPA were identified from April 2020 to March 2021. Values below reported as medians. All patients were male and 13 (76%) were white, with age 74 years and BMI 26 kg/m2. Baseline comorbidities included diabetes mellitus (47%), cardiovascular disease (65%), and pulmonary disease (71%). Evidence of aspergillosis was mostly based on respiratory culture, with mainly A. fumigatus (75%). Systemic corticosteroids were used in 14 patients, with a total dose of 400 mg prednisone equivalents starting 10 days prior to Aspergillus detection. Patients also received tocilizumab (18%), leflunomide (6%), tacrolimus (6%), mycophenolate (6%), and investigational agent LSALT or placebo (6%); 2 patients (12%) did not receive any immunosuppression/modulation. Length of hospitalization for COVID-19 was 22 days. Death occurred in 12 patients (71%), including all patients with probable CAPA, at 34 days after COVID-19 diagnosis and 16 days after CAPA diagnosis. Eight patients (47%) were treated for aspergillosis; mortality did not appear to differ with treatment (75% vs. 67%).Table 1. COVID-19 Inpatient Characteristics Table 2. Incidence of Aspergillus Growth on Respiratory Culture ConclusionThis case series reports high mortality among patients with CAPA; the primary contributor to this outcome is unclear. Frequency of lower respiratory tract sampling in patients with COVID-19 may have limited diagnosis of CAPA. Interestingly, inpatient respiratory cultures with Aspergillus spp. increased compared to previous years. Future work will attempt to identify risk factors for CAPA and attributable mortality via comparison to inpatients with COVID-19 without CAPA.Disclosures Matthew B. Goetz, MD, Nothing to disclose Martin Hoenigl, MD, Astellas (Grant/Research Support)Gilead (Grant/Research Support)Pfizer (Grant/Research Support) Martin Hoenigl, MD, Astellas (Individual(s) Involved: Self): Grant/Research Support; F2G (Individual(s) Involved: Self): Grant/Research Support; Gilead (Individual(s) Involved: Self): Grant/Research Support; Pfiyer (Individual(s) Involved: Self): Grant/Research Support; Scýnexis (Individual(s) Involved: Self): Grant/Research Support Sanjay Mehta, MD, D(ABMM), DTM&H, MedialEarlySign (Consultant)ZibdyHealth (Employee, Medical Officer - Unpaid)