Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: A Noninvasive Screening Model for Additional Diagnostics.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is likely underdiagnosed, and current diagnostic tools are either invasive or insensitive. Methods: A retrospective study of mechanically ventilated patients with COVID-19 admitted to 5 Johns Hopkins hospitals between March 2020 and June 2021 was performed. Multivariable logistic regression was used for the CAPA prediction model building. Performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). Results: In the cohort of 832 patients, 98 (11.8%) met criteria for CAPA. Age, time since intubation, dexamethasone for COVID-19 treatment, underlying pulmonary circulatory diseases, human immunodeficiency virus, multiple myeloma, cancer, or hematologic malignancies were statistically significantly associated with CAPA and were included in the CAPA prediction model, which showed an AUC of 0.75 (95% confidence interval, .70-.80). At a screening cutoff of ≥0.085, it had a sensitivity of 82%, a specificity of 51%, a positive predictive value of 18.6%, and a negative predictive value of 95.3%. (The CAPA screening score calculator is available at www.transplantmodels.com). Conclusions: We developed a CAPA risk score as a noninvasive tool to aid in CAPA screening for patients with severe COVID-19. Our score will also identify a group of patients who are unlikely to have CAPA and who therefore need not undergo additional diagnostics and/or empiric antifungal therapy.

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year.

BACKGROUND: Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated. METHODS: We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression. The impact of IFIs on CLAD stage progression/death was examined by Cox regression. RESULTS: A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2, 30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients was included for analysis. Thirty-one episodes (15%) were associated with secondary IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from 96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85 (2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI) of 2.45 (1.29-4.64). CONCLUSIONS: This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly, secondary IFIs were associated with CLAD stage progression/death, underscoring the importance of screening for fungal infections in this setting.

Characterizing the microbiota of instrumentation in ophthalmology clinics during and beyond the COVID-19 pandemic.

PURPOSE: Increased ophthalmology-specific risk of novel coronavirus 2019 (SARS-CoV-2) transmission is well-established, increasing the fear of infection and causing associated decreased rates of procedures known to save vision. However, the potential transmission from exposure to clinic instrumentation is unknown, including which additional pathogens may be spreading in this context. This study seeks to fill this gap by characterizing the microbiota of instrumentation in ophthalmology clinics during the COVID-19 pandemic and identifying potential sources of pathogenic spread encountered by patients and healthcare workers. METHODS: Thirty-three samples were captured using standard cultures and media. Ten positive and negative controls were used to confirm proper technique. Descriptive statistics were calculated for all samples. Samples were collected from the retina (N = 17), glaucoma (N = 6), cornea (N = 6), and resident (N = 4) clinics with rigorous disinfection standards at a tertiary academic medical center. Standard media cultures and/or polymerase chain reaction (PCR) was performed for each sample. RESULTS: From 33 samples, more than half (17/33, 51.5%) yielded bacterial growth. Using two different molecular methods, three samples (3/33, 9%) tested positive for SARS-CoV-2 (cycle thresholds 36.48, 37.14, and 37.83). There was no significant difference in bacterial growth (95% confidence interval [95% CI]: - 0.644-0.358, p = 0.076) among different clinics (retina, glaucoma, cornea, resident). Staphylococcus (S.) epidermidis grew most frequently (12/35, 34%), followed by S. capitis (7/35, 20%), Micrococcus luteus (2/35, 5.7%), Corynebacterium tuberculostearicum (2/35, 5.7%), and Cutibacterium ([C.], Propionibacterium) acnes (2/35, 5.7%). C. acnes growth was more frequent with imaging device forehead rests (2/7, 28.6%) than other surfaces (0/26, 0%, 95% CI: 0.019-0.619, p = 0.040). No samples isolated fungus or adenovirus. CONCLUSIONS: Most samples across subspecialty clinic instrumentation grew bacteria, and several tested positive for SARS-CoV-2. Many isolated pathogens have been implicated in causing infections such as endophthalmitis, conjunctivitis, uveitis, and keratitis. The clinical implications of the ophthalmology microbiome for transmitting nosocomial infections warrant optimization of disinfection practices, strategies for mitigating spread, and additional study beyond the pandemic.

Coronavirus Disease 2019-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood. METHODS: A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. RESULTS: In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 [calculated as weight in kilograms divided by height in meters squared]; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median [interquartile range], 41.1 [20.5-72.4) vs 18.5 [10.7-31.8] days; P < .001). CONCLUSION: CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.

Aspergillosis Complicating Severe Coronavirus Disease.

Aspergillosis complicating severe influenza infection has been increasingly detected worldwide. Recently, coronavirus disease-associated pulmonary aspergillosis (CAPA) has been detected through rapid reports, primarily from centers in Europe. We provide a case series of CAPA, adding 20 cases to the literature, with review of pathophysiology, diagnosis, and outcomes. The syndromes of pulmonary aspergillosis complicating severe viral infections are distinct from classic invasive aspergillosis, which is recognized most frequently in persons with neutropenia and in other immunocompromised persons. Combined with severe viral infection, aspergillosis comprises a constellation of airway-invasive and angio-invasive disease and results in risks associated with poor airway fungus clearance and killing, including virus- or inflammation-associated epithelial damage, systemic immunosuppression, and underlying lung disease. Radiologic abnormalities can vary, reflecting different pathologies. Prospective studies reporting poor outcomes in CAPA patients underscore the urgent need for strategies to improve diagnosis, prevention, and therapy.