Invasive Pulmonary Fungal Infection Research Articles

Case report: Rare pulmonary fungal infection caused by Penicillium digitatum: the first clinical report in China

Penicillium digitatum is a common plant pathogen that causes citrus rot, which is extremely rare in humans. We report a case of a 66-year-old man with a history of consuming large amounts of citrus fruits, smoking for 30 years, and a history of emphysema. He had experienced intermittent coughing with sputum for more than 10 years and was admitted to the hospital due to worsening of symptoms over the past month. Despite antibiotic treatment, his condition did not improve. Subsequently, bronchoalveolar lavage fluid (BALF) was detected by metagenomic next-generation sequencing (mNGS), which showed the presence of P. digitatum. The fungal culture of BALF also indicated the presence of the Penicillium genus. The diagnosis was lung infection caused by P. digitatum, and the patient was treated with itraconazole. The lung infection was controlled. This is the third reported case of invasive pulmonary fungal infection caused by P. digitatum worldwide at the genus level, and the first reported case in China. Although human infections caused by P. digitatum are rare, as an emerging opportunistic pathogen, the detection of this fungus in immunocompromised patients should still be clinically important.

Application and evaluation of topical amphotericin B for the treatment of respiratory fungal infections

BackgroundIn recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections.MethodsWe conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023.ResultsData from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects.ConclusionThe combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

Dual Invasive Pulmonary Mycosis in a Post Covid-19 Patient: An Autopsy Diagnosis

Dual Invasive Pulmonary Mycosis in a Post Covid-19 Patient: An Autopsy Diagnosis

Wedge Resection and Optimal Solutions for Invasive Pulmonary Fungal Infection and Long COVID Syndrome—A Case Report and Brief Literature Review

A rise in fungal infections has been observed worldwide among patients with extended hospital stays because of the severe infection caused by the new coronavirus pandemic. A 62-year-old female patient was admitted with a severe form of Coronavirus disease 2019 (COVID-19) and spent four weeks in the intensive care unit (ICU) requiring mechanical ventilation support before being moved to a tertiary hospital for further testing. Aspergillus fumigatus filamentous fungus, Candida spp., and positive bacteriology for multidrug-resistant Klebsiella pneumoniae and Proteus mirabilis were identified by bronchial aspirate cultures. The patient’s progress was gradually encouraging while receiving oral antifungal and broad-spectrum antibiotic therapy along with respiratory physical therapy; but ultimately, thoracic surgery was necessary. Long-lasting tissue damage and severe, persistent inflammatory syndrome were the two main pathophysiological mechanisms that led to significant outcomes regarding lung lesions that were rapidly colonized by fungi and resistant flora, cardiac damage with sinus tachycardia at the slightest effort, and chronic inflammatory syndrome, which was characterized by marked asthenia, myalgias, and exercise intolerance.

Analytical and clinical validation of multiplex droplet digital PCR assay for detecting pathogenic fungal infection in lungs

ABSTRACT Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis.

Diagnosis of invasive pulmonary fungal infections by a real-time panfungal PCR assay in non-neutropenic patients.

This study explored the utility of quantitative real-time panfungal PCR assay in diagnosing invasive pulmonary fungal diseases (IPFD) in non-neutropenic patients. Panfungal PCR assay was performed on respiratory tract specimens from patients whose clinical signs could not exclude fungal infection. At the same time, the samples were subjected to bacterial and fungal culture, microscopic examination and galactomannan antigen (GM) test in order to find the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 4 diagnostic methods in proven and probable cases. 518 specimens were collected while 63 respiratory tract specimens tested by PCR had positive results. According to diagnostic criteria, 40 patients were diagnosed with IPFD, with 12 proven, 20 probable and 8 possible cases. Among these, 33 patients of PCR results were positive, most of which were from BALF samples (44.12%). 23 cases were caused by Aspergillus species, with Aspergillus fumigatus was the major cause. Other Aspergillus species, including Aspergillus flavus, Aspergillus terreus and Aspergillus nidulans were found in 1 sample respectively. Candida species were found in 5 samples, Pneumocystis jeroveci pneumonia (PJP) in 4 samples and Mucormycosis in 1 sample. An analysis of proven/probable diagnosis showed a sensitivity of 78.13%, specificity of 92.18%, PPV of 39.68% and NPV of 98.46% for PCR and 50%, 85.27%, 35.7%, 95.65% for GM test respectively. The Ct value difference between proven/probable and possible cases had no statistical significance (P = .824). Fungal culture showed a sensitivity of 17.5% while microscopic examination sensitivity of 32.5%. Through stratified analysis, no apparent correlation was found between the Ct value of the PCR assay and GM value (r: 0.223, P = .294). But a conjunction of the 2 tests raised the PPV of Aspergillus to 90%. As shown in this study, the panfungal RT-PCR assay has high sensitivity and consistency with serological test and culture. Its high PPV in the detection of Aspergillus and PJP were also evident.

Post-COVID pulmonary fungal infections: An unanticipated predicament or a ticking time bomb? Clinico-microbiological profile of cases encountered during the second wave of COVID-19 pandemic at a teaching hospital in the Himalayas with a brief literature review.

This study attempts to generate preliminary data regarding post-COVID pulmonary fungal infections, namely, COVID-19-associated pulmonary aspergillosis (CAPA), COVID-19-associated pulmonary mucormycosis (CAPM), and mixed infections from the Himalayas and compares the micro-radio-clinical profile and outcomes of the affected patients. A retrospective data analysis was conducted, where clinical profiles, microbiological and radiological reports, and outcomes of n = 16 patients of post-COVID pulmonary infections were compared. Of n = 16 patients, n = 7 had CAPA (n = 5 Aspergillus fumigatus, n = 1 Aspergillus flavus, and n = 1 Aspergillus niger), n = 5 CAPM (Rhizopus arrhizus), and n = 4 with mixed infections (n = 3 infected with Aspergillus fumigatus and Rhizopus spp. and n = 1 with Aspergillus flavus and Rhizopus arrhizus). Thick-walled cavitary lesions, air-fluid levels, and multiple centrilobular nodules were some of the common radiological findings reported among these patients. The immuno-compromised state following COVID-19 infection and treatment might be responsible for the progression of regular exposure to the dense Himalayan vegetation into an invasive pulmonary fungal infection. Suspecting post-COVID pulmonary fungal infection is necessary for primary care physicians to ensure timely referral to higher centers. Mixed pulmonary fungal infections (coinfection with Aspergillus spp. and Rhizopus spp.) are also emerging as important sequelae of COVID-19.

The Therapeutic Efficacy and Blood Drug Concentration of Posaconazole Enteric-Coated Tablets in Preventing Pulmonary Invasive Fungal Disease after HSCT

Introduction The risk of fungal infection in patients after HSCT is high. Prophylactic use of antifungal drugs can significantly reduce the occurrence of invasive fungal disease (IFD) and potential IFD-related mortality. Posaconazole oral suspension shows good preventive effects for patients with neutropenia and severe GVHD . However, there is still a lack of prospective research confirming the effectiveness of posaconazole enteric-coated tablets in preventing fungal infections in HSCT patients. Methods This study is a prospective, non-randomized, single-arm study. 143 patients who received hematopoietic stem cell transplantation at the Transplantation Center of Blood Diseases Hospital, the Chinese Academy of Medical Sciences from December, 2020 to May, 2022 were included. Posaconazole enteric-coated tablets were administered orally at a dose of 300mg QD (double dose for the first day) for the prevention of pulmonary invasive fungal disease from the first day to the 90th day after transplantation. The study collected baseline data, serum posaconazole concentrations, UGT1A4*3 genotype of the involved patients and observed whether pulmonary invasive fungal disease occurred. Retrospective data on the use of other antifungal drugs for the prevention of pulmonary invasive fungal disease at the center were collected as a control group for comparison. After applying propensity score matching at a ratio of 1:2, a comparative analysis was conducted on 140 cases in the posaconazole enteric-coated tablets group and 280 cases in the non-posaconazole group. Results Among the 143 patients who were included in the clinical trial and treated with posaconazole enteric-coated tablets alone for the prevention of fungal infection from day 1 to day 90 after hematopoietic stem cell transplantation, 4 cases developed invasive pulmonary fungal infection, including 1 case of mold and 3 cases of undefined pathogens, with a breakthrough rate of 2.80%, significantly lower than the historical control group breakthrough rate of 7.86% in the non-posaconazole group (P=0.014). In the 90 days after transplantation, a total of 246 measurements of posaconazole blood concentration were performed in the 143 patients in the clinical trial group. The average blood drug concentrations on the 4th, 8th, 15th, 22nd, and 30th day were 930.97 ng/ml, 1143.97 ng/ml, 1569.8 ng/ml, 1652.57 ng/ml, and 1644.75 ng/ml respectively. The blood drug concentration of posaconazole enteric-coated tablets tended to stabilize since the 15th day after treatment. In the 37 patients who tested the UGT1A4*3 genotype, there was no significant correlation between UGT1A4*3 gene polymorphism and posaconazole blood drug concentration. In terms of adverse reactions, the incidence of liver adverse events in this clinical study was 1.4%. Except for a slight increase in ALT after the 14-day medication (18.29 U/L vs. 26.22 U/L, P<0.001), there were no differences in other liver and kidney function laboratory test before and after treatment. Conclusion Posaconazole enteric-coated tablets is a highly safe prophylactic drug for invasive pulmonary fungal infections after HSCT, and its efficacy is superior to other antifungal prophylaxis regimens. Posaconazole enteric-coated tablet blood drug concentration in transplant patients gradually rose over time and tended to stabilize after 15 days of medication. The UGT1A4*3 gene polymorphism has no effect on the blood drug concentration of posaconazole enteric-coated tablets. Keywords Posaconazole enteric-coated tablets, hematopoietic stem cell transplantation, pulmonary invasive fungal disease

Retracted: Imaging Characteristics of Invasive Pulmonary Fungal Infection Secondary to Hematological Diseases and Comparison before and after Treatment.

[This retracts the article DOI: 10.1155/2021/3736108.].

Primary Mold-Active Antifungal Prophylaxis Decreases the Need for Chest Computed Tomography Scans in Patients with Acute Lymphoblastic Leukemia.

Current guidelines recommend computed tomography (cCT) scans of the chest in children with leukemia following 96h of the onset of idiopathic neutropenia to eliminate pulmonary invasive fungal infections (IFIs). However, cCT exposes some children who are at a very high risk of developing secondary cancers to radiation. We aimed to determine the effect of antifungal prophylaxis (AFP) with voriconazole (VCZ) on the need for cCT scans in children with acute lymphoblastic leukemia (ALL) to eliminate pulmonary IFIs during chemotherapy. We retrospectively screened all patients' data from their electronic charts. Children who were diagnosed as having ALL before February 2013 and did (AFP group) or did not (NoP group) receive AFP were divided into two groups and compared regarding cCT scans and relapse-mortality rates. Ninety-six children were diagnosed before February 2013 and did not receive primary AFP and 146 children were administered VCZ following a diagnosis of ALL. There were no significant demographic differences between the groups. A total of 128 cCTs had been required in 62 children in the NoP group, compared with 64 cCTs in 52 children in the AFP group. The percentage of the patients who had required at least one chest CT scan and the mean number of cCT scans in the NoP group were significantly higher compared with the AFP group. Proven-probable IFIs and relapse-mortality rates were higher in the NoP group compared with the AFP group. Mold-active AFP revealed a significant decrease in the need for cCT scans in children with ALL.

Pulmonary Invasive Fungal Disease: Ultrasound and Computed Tomography Scan Findings.

The importance of ultrasound in diagnosing pulmonary invasive fungal diseases (IFD) has yet to be assessed. Thus, this study aimed to evaluate the frequency of sonographic findings in patients suspected of an invasive pulmonary fungal infection. This prospective longitudinal study examined all patients with lung lesions in imaging modalities and suspected IFDs referred to Dr. Sheikh and Akbar pediatric hospitals from 2019 to 2022. Considered variables were the halo sign in the computed tomography (CT) scan; the target sign in the ultrasound and contrast-enhanced CT scan; the cavity; wedge-shaped consoli- dation; and pleuritis and extrapulmonary invasion to the chest wall or subdiaphragmatic invasion in both modalities. All patients who underwent lung CT scans and ultrasounds until the final diagnosis were followed up. The degree of agreement between ultrasound and CT scan findings and the sensitivity, specificity, and diagnostic accuracy of these signs were assessed. This study involved 40 patients with an average age of 7.16 ± 4.23 years. Acute leukemia was the commonest underlying dis- ease detected in 17 (42.5%) cases. The target sign in ultrasound (61.9%) and the halo sign in CT scan (71.4%) had the highest frequency among the variables in patients with IFD. Cohen's kappa coefficient agreement in both modalities was 0.5 for the cavity, with significant relation (P = .02). The Cohen's kappa was less than .17 for other findings (P > .05). The diagnostic criteria in the simultaneous examina- tion of the fungus target in ultrasound and halo in CT scan showed a sensitivity of 82.4% and specificity of 76.5%, respectively. Combining the characteristic findings of ultrasound and CT-scan provides a higher value in diagnosing pulmonary invasive fungal disease.

Regulation of lung inflammation by adiponectin.

Adiponectin is an insulin sensitizing hormone that also plays a role in the regulation of inflammation. Although adiponectin can exert pro-inflammatory effects, more studies have reported anti-inflammatory effects, even in non-adipose tissues such as the lung. Obesity is considered an inflammatory disease, is a risk factor for lung diseases, and is associated with decreased levels of plasma adiponectin. The results of recent studies have suggested that adiponectin exerts anti-inflammatory activity in chronic obstructive pulmonary disease, asthma and invasive fungal infection. The signaling receptors of adiponectin, AdipoR1 and AdipoR2, are expressed by epithelial cells, endothelial cells, and immune cells in the lung. In this mini-review, we discuss the anti-inflammatory mechanisms of adiponectin in lung cells and tissues.

Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19.

Sequential low-dose CT thorax scans to determine invasive pulmonary fungal infection incidence after allogeneic hematopoietic cell transplantation

Invasive fungal disease (IFD) during neutropenia goes along with a high mortality for patients after allogeneic hematopoietic cell transplantation (alloHCT). Low-dose computed tomography (CT) thorax shows good sensitivity for the diagnosis of IFD with low radiation exposure. The aim of our study was to evaluate sequential CT thorax scans at two time points as a new reliable method to detect IFD during neutropenia after alloHCT. We performed a retrospective single-center observational study in 265/354 screened patients admitted for alloHCT from June 2015 to August 2019. All were examined by a low-dose CT thorax scan at admission (CT t0) and after stable neutrophil recovery (CT t1) to determine the incidences of IFD. Furthermore, antifungal prophylaxis medications were recorded and cohorts were analyzed for statistical differences in IFD incidence using the sequential CT scans. In addition, IFD cases were classified according to EORTC 2008. At CT t0 in 9.6% of the patients, an IFD was detected and antifungal therapy initiated. The cumulative incidence of IFD in CT t1 in our department was 14%. The use of Aspergillus-effective prophylaxis through voriconazole or posaconazole decreased CT thorax t1 suggesting IFD is statistically significant compared to prophylaxis with fluconazole (5.6% asp-azol group vs 16.3% fluconazole group, p = 0.048). In 86%, CT t1 was negative for IFD. Low-dose sequential CT thorax scans are a valuable tool to detect pulmonary IFDs and guide antifungal prophylaxis and therapies. Furthermore, a negative CT t1 scan shows a benefit by allowing discontinuation of antifungal medication sparing patients from drug interactions and side effects.

Wave of Invasive Fungal Disease on the Shores of COVID-19: A Case Series of COVID-19 Associated Rhino-Orbital Fungal Rhinosinusitis and Literature Review.

Coronavirus disease 2019 (COVID-19) may be associated with a wide range of bacterial and fungal co-infections. Acute invasive fungal sinusitis is an aggressive infection affecting immunocompromised patients and high mortality rate. Here, in this case series, we have reviewed three cases of COVID-19 associated rhino-orbital invasive fungal disease. Patients with COVID-19 associated pneumonia with diabetes mellitus are at an increased risk of developing invasive pulmonary fungal infections probably due to their reduced immunological competence. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. Physicians should be aware of and should have high index of suspicion of possible fungal infection in post COVID-19 patients. Aggressive management both medical and surgical, is required to improve outcomes of secondary invasive fungal infections in patients with COVID-19 infection.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12070-022-03213-y.

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease.

BackgroundMetagenomic next-generation sequencing (mNGS) is increasingly being used to detect pathogens directly from clinical specimens. However, the optimal application of mNGS and subsequent result interpretation can be challenging. In addition, studies reporting the use of mNGS for the diagnosis of invasive fungal infections (IFIs) are rare.ObjectiveWe critically evaluated the performance of mNGS in the diagnosis of pulmonary IFIs, by conducting a multicenter retrospective analysis. The methodological strengths of mNGS were recognized, and diagnostic cutoffs were determined.MethodsA total of 310 patients with suspected pulmonary IFIs were included in this study. Conventional microbiological tests (CMTs) and mNGS were performed in parallel on the same set of samples. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the logarithm of reads per kilobase per million mapped reads [lg(RPKM)], and read counts were used to predict true-positive pathogens.ResultThe majority of the selected patients (86.5%) were immunocompromised. Twenty species of fungi were detected by mNGS, which was more than was achieved with standard culture methods. Peripheral blood lymphocyte and monocyte counts, as well as serum albumin levels, were significantly negatively correlated with fungal infection. In contrast, C-reactive protein and procalcitonin levels showed a significant positive correlation with fungal infection. ROC curves showed that mNGS [and especially lg(RPKM)] was superior to CMTs in its diagnostic performance. The area under the ROC curve value obtained for lg(RPKM) in the bronchoalveolar lavage fluid of patients with suspected pulmonary IFIs, used to predict true-positive pathogens, was 0.967, and the cutoff value calculated from the Youden index was −5.44.ConclusionsIn this study, we have evaluated the performance of mNGS-specific indicators that can identify pathogens in patients with IFIs more accurately and rapidly than CMTs, which will have important clinical implications.

P262 Clinico- microbiological profile of post-COVID pulmonary fungal infections encountered during the second wave of COVID-19 pandemic at a tertiary care teaching hospital in the Himalayas

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveThe study aims to generate preliminary data about post-COVID pulmonary fungal infections in the Himalayas and analyze patients’ micro-radio-clinical profiles and outcomes.MethodologyWe conducted a retrospective study at a tertiary care teaching hospital in the Himalayas to generate preliminary post-COVID pulmonary fungal infection data. Sputum, Endotracheal Tube (ET), and Bronchoalveolar lavage (BAL) samples of patients sent to the Mycology laboratory were subjected to KOH mount and aerobic inoculation on Sabouraud dextrose agar plates at 37°C. The patients’ symptoms, diagnosis, clinical-radiological profile, and outcome were collected from the hospital database.ResultsAmong n = 16 cases of post-COVID pulmonary fungal infections aged 53 +/- 13.38 years, n = 7 (43.75%) had Pulmonary Aspergillosis (n = 5 A. fumigatus, n = 1 A. flavus, n = 1 A. niger), n = 5 (31.25%) had Pulmonary Mucormycosis (Rhizopus arrhizus), and n = 4 (25%) had mixed infection. In 2 of 4 mixed infection patients, R. arrhizus was identified on KOH microscopy and A. fumigatus on SDA Agar. Both A. fumigatus and R. arrhizus were identified on KOH Microscopy of the third patient, while only A. fumigatus was cultivated on his SDA Agar. Aspergillus flavus and R. arrhizus were isolated simultaneously from the sample of the last patient, but only R. arrhizus was identified on KOH Microscopy.Clinical symptoms were similar among Pulmonary Aspergillosis and Mucormycosis patients, but hemoptysis was reported only among Pulmonary Aspergillosis patients. Pre-existing co-morbid end-organ damage, AKI, CKD, CLD, COPD, and CAD was more common among Pulmonary Mucormycosis patients and rare among Pulmonary Aspergillosis patients. Treatment requirements and clinical outcomes of patients infected with either mold were similar. The clinical profile of mixed infection patients was notably different from the others. All the patients were males, none complained of chest pain or expectoration, and none had a history of PTB, AKI, CKD, CLD, COPD, or CAD. Only 2 (50%) mixed infection patients needed supplemental high flow oxygen, unlike all (100%) patients diagnosed with single mold infection. None of the mixed infection patients required steroids. Moreover, none of the mixed infection patients died, unlike 60% mortality in cases of single-species infections.On radiological investigation, n = 6 had typical thick-walled cavitary lesions with air-fluid levels and multiple centrilobular nodules giving a tree in bud appearance, of which n = 4 had bilateral lung involvement, and n = 2 had only one lung involved. n = 1 patient had a well-circumscribed lung abscess.ConclusionCOVID patients from the Himalayas had a higher prevalence of invasive pulmonary fungal infections, probably due to the dense surrounding vegetation. The immuno-compromised state following COVID-19 infection/treatment might be responsible for the progression of regular exposure to invasive pulmonary infection.

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020–2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the “2020 ECMM/ISHAM consensus criteria”; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

Invasive pulmonary fungal infections in children with severe human adenovirus type 7 pneumonia: A retrospective study.

There has been a rapid increase in the number of human adenovirus type 7 (HAdV-7) and invasive pulmonary fungal infections (IPFIs) co-infection. In this study, we included patients with confirmed HAdV-7 infection during the period from 2018 to 2019 to explore clinical characteristics of severe HAdV-7 pneumonia combined with IPFIs. Among the 143 patients, 35 cases were co-infected with IPFIs. Others were assigned to the control group (n Z 108). Patients wereprone to be complicated with respiratory failure, heart failure and hemophagocytic syndromein IPFIs group. Thirty-one species of fungi were detected in the IPFIs group, among whichAspergillus was the most common species. Compared to control group, patients had lowerlevels of WBC, CD3þ T lymphocyte counts and CD19þ B lymphocyte counts in IPFIs group. Aspergillus is the most common species in IPFIs combined with severe HAdV-7 pneumonia. For children with severe HAdV-7 pneumonia who are younger, have a long course of disease, and have been admitted to the ICU, we should predict the occurrence of IPFIs when there is multi-system dysfunction and the reduction of CD3+ T lymphocyte counts and CD19+ B lymphocyte counts in course of their disease.

Machine learning-based combined nomogram for predicting the risk of pulmonary invasive fungal infection in severely immunocompromised patients.

BackgroundEarly and accurate diagnosis of invasive fungal infection (IFI) is pivotal for the initiation of effective antifungal therapy for patients with hematologic malignancies.MethodsThis retrospective study involved 235 patients with hematologic malignancies and pulmonary infections diagnosed as IFIs (n=118) or bacterial pneumonia (n=117). Patients were randomly divided into training (n=188) and validation (n=47) datasets. Four feature selection methods with nine classifiers were implemented to select the optimal machine learning (ML) model using five-fold cross-validation. A radiomic signature was constructed using a linear ML algorithm, and a radiomic score (Radscore) was calculated. The combined model was developed with the Radscore, the significant clinical and radiologic factors were selected using multivariable logistic regression, and the results were presented as a clinical radiomic nomogram. A prospective pilot study was also conducted to compare the classification performance of the combined nomogram with practicing radiologists.ResultsSignificant differences were found in the Radscore between IFI and bacterial pneumonia patients in the training (0.683 vs. −0.724, P<0.001) and validation set (0.353 vs. −0.717, P=0.002). The combined model showed good discrimination performance in the validation cohort [area under the curve (AUC) =0.844] and outperformed the clinical (AUC =0.696) and radiomics (AUC =0.767) model alone (both P<0.05).ConclusionsThe clinical radiomic nomogram can serve as a promising predictive tool for IFI in patients with hematologic malignancies.