Aspergillus Co-infection Research Articles

Pulmonary aspergillosis after COVID-19, a case report

COVID-19 is an infectious disease that spreads worldwide, can progress rapidly, affect individuals of all ages, and cause death, especially in the elderly and people with chronic diseases. It has predisposed a relatively high number of patients to acute respiratory distress syndrome, and co-infections are a frequent complication, especially during prolonged hospital stays. Bacterial or viral co-infections with SARS-CoV-2 have been reported in many studies, but knowledge of Aspergillus co-infection in patients with COVID-19 is limited. This study presents a 57-year-old male patient with COVID-19 who had had no lung disease before COVID-19 pneumonia. However, after COVID-19 pneumonia with sequels and treatments that include corticosteroids and IL-6 receptor antagonists, an invasive pulmonary aspergillus (IPA) cavity occurred immediately. In addition to the fact that COVID-19 infection progresses with destructive parenchymal damage and sequelae, the effectiveness of treatment is limited, and treatment-related side effects and complications can be examined. Therefore, clinical and radiological follow-up of patients whose symptoms persist after infection is essential.

Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2.

The aim of this study is to describe the novel epidemiological and clinical characteristics of influenza A-induced severe pneumonia occurring after the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to further assess its potential risk factors for mortality. We retrospectively studied the consecutive case series of 30 patients with confirmed influenza A-induced severe pneumonia treated in the intensive care unit at Dazhou Central Hospital in Sichuan, China, from March 1 to April 30, 2023. Logistic regression was used to analyze the independent risk factors, and receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of associated risk factors for mortality. The mortality rate was 33.3% in this study. Independent risk factors for mortality of patients were acute respiratory distress syndrome (ARDS) (p = 0.044) and septic shock (p = 0.012). ROC statistics for ARDS and septic shock to predict mortality in patients with influenza A-induced severe pneumonia demonstrated an area under the curve of 0.800 (sensitivity 80.0%, specificity 80.0%) and 0.825 (sensitivity 70.0%, specificity 95.0%), respectively. ARDS and septic shock were the independent risk factors for mortality in patients with influenza A-induced severe pneumonia following the end of the SARS-CoV-2 pandemic. But high level of next generation sequencing reads Aspergillus coinfection, and comorbidities did not increase death risk of the study population.

Mortality and Clinical Outcomes of Aspergillus and COVID-19 Co-infection: A Retrospective Analysis.

Patients with coronavirus disease (COVID-19)are more susceptible to secondary infections.Aspergillus co-infection has emerged as one of the most alarming complications in critically ill COVID-19 patients due to the disease itself or the use of immunomodulators and immunosuppressants for treatment. This study aimed to examine the mortality rates and clinical outcomes associated with Aspergillus and COVID-19 co-infection using data obtained from the largest nationwide inpatient sample database in the United States. The National (Nationwide) Inpatient Sample (NIS) database is a vast and openly accessible collection of data that records millions of hospital admissions in the United States. For our research, we utilized the NIS 2020 database to identify adult patients diagnosed with COVID-19 and categorized them based on co-infection with Aspergillus. To examine the NIS database, we utilized various statistical methods such as univariate and multivariate analyses, descriptive statistics, and regression analysis. Of the 16.7 million patients hospitalized due to COVID-19 infection, 1485 developed Aspergillus co-infection. The demographics showed a predominance of males with 920 males and 565 women. A total of 46% were Caucasians, 17.2% were African-Americans, and 29.5% were Hispanics. The most common comorbidities were chronic pulmonary disease (40.7%), hypertension (41.4%), diabetes with chronic complications (37.7%), leukemia (4.0%), lymphoma (3.7%), and solid tumors (3.7%). Hospital mortality with co-infection was 53.2%, length of stay (LOS) 26.9 days, and economic utilization $138,093 in comparison to patients without co-infectionwith in-hospital mortality of 13.2%, LOS of 7.9 days, and cost of 21,490. Age-adjusted mortality was 6.6 (confidence interval: 5.9-7.3). Our study indicated that the mortality ratein COVID-19 patients with Aspergillus infection was four-fold higher. Furthermore, comorbidities,such as diabetes mellitus, chronic pulmonary disease, and obesity, havebeen associated with worse outcomes. Further research is necessary to understand the etiological relationship between Aspergillus infection and COVID-19 in order to develop effective treatment strategies that mitigate the impact of this lethal combination on patient health outcomes.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India

ObjectivesTo compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. MethodsWe performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. ResultsWe included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209–4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34–10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23–23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DiscussionCAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Aspergillus coinfection in critically Ill patients with severe dengue

In 2014–2015, a significant outbreak of dengue fever occurred in southern Taiwan, with a subsequent decline in dengue incidence. Despite this, there is emerging concern about virus-associated aspergillosis, yet limited research has explored coinfections involving dengue and aspergillosis. We conducted a retrospective study at a single center in Southern Taiwan, specifically focusing on dengue patients admitted to the intensive care unit during the period between July and November 2015. Among the 142 dengue patients studied, only 8.06 % (10/142) underwent serum galactomannan testing, with a single patient undergoing bronchoalveolar lavage (BAL) galactomannan assay. Out of those tested, 20 % (2/10) returned positive serum galactomannan results. Herein, we present two consecutive cases of coinfection involving dengue and pulmonary aspergillosis in immunocompetent patients.

Respiratory co-infections in COVID-19-positive patients

BackgroundOpportunistic respiratory infections may complicate critically ill patients with COVID-19. Early detection of co-infections helps to administrate the appropriate antimicrobial agent, to guard against patient deterioration. This study aimed at estimating co-infections in COVID-19-positive patients.MethodsEighty-nine COVID-19-positive patients confirmed by SARS-COV-2 PCR were tested for post-COVID-19 lower respiratory tract co-infections through bacterial culture, fungal culture and galactomannan (GM) testing.ResultsFourteen patients showed positive coinfection with Klebsiella, nine with Acinetobacter, six with Pseudomonas and three with E. coli. As for fungal infections, nine showed coinfection with Aspergillus, two with Zygomycetes and four with Candida. Galactomannan was positive among one patient with Aspergillus coinfection, one with Zygomycetes coinfection and three with Candida, 13 samples with negative fungal culture were positive for GM. Ten samples showed positive fungal growth, however, GM test was negative.ConclusionIn our study, SARS-COV-2 respiratory coinfections were mainly implicated by bacterial pathogens; most commonly Klebsiella species (spp.), Aspergillus spp. were the most common cause of fungal coinfections, GM test showed low positive predictive value for fungal infection. Respiratory coinfections may complicate SARS-COV-2 probably due to the prolonged intensive care units (ICU) hospitalization, extensive empiric antimicrobial therapy, steroid therapy, mechanical ventilation during the COVID-19 outbreak. Antimicrobial stewardship programs are required so that antibiotics are prescribed judiciously according to the culture results.

The factors associated with mortality and progressive disease of nontuberculous mycobacterial lung disease: a systematic review and meta-analysis

This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted a literature search to identify the eligible studies, dated between January 1, 2007, and April 12, 2021. Forty-one studies with total 10,452 patients were included. The overall all-cause mortality rate was 20% (95% CI 17–24%). The overall rates of clinical and radiographic progressive disease were 46% (95% CI 39–53%) and 43% (95% CI 31–55%), respectively. Older age, male sex, history of TB, diabetes, chronic heart disease, malignancy, systemic immunosuppression, chronic liver disease, presence of cavity, consolidative radiologic features, acid-fast bacillus (AFB) smear positivity, hypoalbuminemia, anemia, increasing platelet count, high CRP, and high ESR were significantly associated with increased all-cause mortality, whereas increasing body mass index (BMI), hemoptysis, and treatment with rifamycin regimen (in M. xenopi) were significantly associated with decreased all-cause mortality in multivariable analysis. History of TB, Aspergillus co-infection, cough, increased sputum, weight loss, presence of cavity, and AFB smear positivity were significantly associated with increased clinical progression with treatment, while older age and low BMI were significantly associated with decreased clinical progression in multivariable analysis. Older age, interstitial lung disease, presence of cavity, consolidative radiologic feature, anemia, high CRP, and leukocytosis were significantly associated with increased radiographic progression after adjusting for covariates. Older age, history of tuberculosis, presence of cavity, consolidative radiologic features, AFB smear positivity, anemia, and high C-reactive protein were common significant factors associated with the all-cause mortality and clinical or radiographic progressive disease of NTM-LD. These factors are thought to directly affect NTM-LD related mortality. The future prediction models for the prognosis of NTM-LD should be established considering these factors.

Atypical Presentation of Alcoholic Liver Disease as Isolated Direct Hyperbilirubinaemia with Non Resolving Pneumonia Secondary to Multidrug Resistant Escherichia coli and Aspergillus Co-infection: A Case Report

It is uncommon for a patient with Alcoholic Liver Disease (ALD) to arrive with solitary hyperbilirubinaemia that is not accompanied by substantial hepatic abnormalities. Patients with ALD are more likely to develop bacterial and Invasive Fungal Infections (IFI) early in the course of their disease and both are linked with more severe systemic inflammation, a poorer clinical prognosis, and a higher mortality. Because of escalating antibiotic usage, lengthy hospital stays, and intensive medical procedures, hospitalised cirrhotic patients are increasingly at risk of acquiring IFI. In patients with alcoholic liver failure, persistent IFI are a primary cause of death and treatment resistance. This was a case of a 34-year-old male with an unusual combination of worsening sepsis and worsening jaundice without any other significant abnormalities in liver function. He was given adequate antibiotics to treat the isolated organism Escherichia coli (E. coli), but his pneumonia persisted. After positive tests for an IFI, he was given antifungal medications as well. He failed to improve and finally gave into his illness.

Clinical characteristics of patients with coronavirus disease 2019–associated pulmonary aspergillosis on mechanical ventilation: A single-center retrospective study in Japan

BackgroundAspergillus is one of the important pathogens that contribute to high mortality in patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). Although incidence rates of Aspergillus coinfection are high globally, a Japanese national survey reported a low incidence. This study aimed to describe the clinical characteristics of patients with COVID-19-associated pulmonary aspergillosis at our institute. MethodsWe identified patients with microbiologically confirmed COVID-19 on mechanical ventilation in the ICU. Of these patients, we identified patients in whom Aspergillus was cultured from the respiratory specimen. ResultsOf a total of 169 patients, seven had aspergillosis (4.1%), which included three patients, three patients, and one patient with possible, probable, and proven aspergillosis, respectively, according to the criteria of the European Confederation of Medical Mycology International Society. All patients received systemic steroid therapy. Two patients (one each with proven and probable aspergillosis) had tracheobronchitis diagnosed by bronchoscopy. All patients in whom Aspergillus was repeatedly isolated from samples died. The mortality rates for all cases and probable and proven cases were 57% (4/7) and 75% (3/4), respectively. ConclusionsThe incidence rate of aspergillosis in patients with COVID-19 in the ICU was higher in our institute than that reported by a Japanese national survey (4.1% vs. 0.5%). Repeated detection of Aspergillus might suggest a true Aspergillus infection, such as chronic aspergillosis, rather than colonization. In patients with severe COVID-19 patients, it is important to always keep CAPA in mind.

Clinical Characteristics and Mortality-Associated Factors in COVID-19 Critical Patients in a Portuguese ICU.

Severe COVID-19 is associated with serious complications and poor outcomes. Older age and underlying comorbidities are known risk factors for severe COVID-19, but a better understanding of baseline characteristics and outcomes of patients with severe COVID-19 is urgently needed. This study was a retrospective case series of 227 consecutive patients with laboratory-confirmed COVID-19 admitted to the intensive care unit (ICU) at our institution between March 2020 and December 2021. Demographic and clinical data were collected. The median age of patients was 65 years, and 180 (79.3%)were male. Cardiovascular comorbidities were frequent and included hypertension (n=148; 65.2%), dyslipidemia (n=116; 51.1%), obesity (n=114; 50.2%), and diabetes mellitus (n=80; 35.2%). About 20% of the patients had the chronic respiratory disease, with sleep apnea being the most common. Immunosuppression was identified in 13% of the patients, with autoimmunity, post-transplantation, and neoplasms being the most represented causes. Most patients were admitted to the ICU at six to 15 days after symptom onset, corresponding to stages IIb (pulmonary involvement/hypoxia) and III (hyperinflammatory). All patients received systemic steroids, with an average treatment duration of 22 days. Several ventilatory support strategies were used; 80 patients were supported entirely noninvasively with high flow nasal oxygenation and noninvasive ventilation, while 164 patients were invasively ventilated. Most intubations (65%) occurred in the first 24 hours after admission, and the mean duration of mechanical ventilation was 14 days. The reintubation rate was 10%, occurring on average two to three days after planned extubation. Thirty-two tracheostomies were performed. Bacterial co-infection was treated in 75% of patients, and Aspergillus co-infection complicating COVID-19 pneumonia was diagnosed in eight patients. Median ICU and hospital stays were 15 and 25 days, respectively, and the 28-day mortality rate was 38%. Patients over 75 years experienced a higher mortality rate (56%). Increased age and multimorbidity, particularly comprising cardiovascular disease and associated risk factors, were significantly more common in patients who died within 28 days after ICU admission. A large proportion of critically ill COVID-19 patients required prolonged mechanical ventilation. ICU/hospital stay and mortality were particularly elevated in older patients and patients with cardiovascular risk factors. Considerable discrepancy existed between the proportion of patients with microbiological documentation of bacterial infections and those receiving antimicrobials. Improved methods for adequate microbiological diagnosis are needed and stewardship programs should be reinforced.

COVID-19-associated pulmonary aspergillosis (CAPA) in Iranian patients admitted with severe COVID-19 pneumonia.

PurposeBacterial or virus co-infections with SARS-CoV-2 have been reported in many studies; however, the knowledge on Aspergillus co-infection among patients with COVID-19 was limited. This study was conducted to identify and isolate fungal agents and to evaluate the prevalence of pulmonary aspergillosis (CAPA) as well as antifungal susceptibility patterns of Aspergillus species in patients with COVID-19 admitted to Shahid Beheshti Hospital, Kashan, Iran.MethodsThe study involved 119 patients with severe COVID-19 pneumonia referred to the Shahid Beheshti Hospital, Kashan, Iran. A total of 17 Aspergillus spp. that were isolated from COVID-19 patients suspected of CAPA were enrolled in the study. CAPA was defined using ECMM/ISHAM consensus criteria. The PCR amplification of the β-tubulin gene was used to identify the species. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B against Aspergillus spp. were evaluated according to the Clinical and Laboratory Standards Institute manual (M38-A3).ResultsFrom the 119 patients with severe COVID-19 pneumonia, CAPA was confirmed in 17 cases (14.3%). Of these, 12 (70.6%) were males and 5 (29.4%) were females; the mean age at presentation was 73.8 years (range: 45–88 years; median = 77; IQR = 18). Aspergillus fumigatus (9/17; 52.9%), Aspergillus flavus (5/17; 29.4%), Aspergillus oryzae (3/17, 17.6%), were identified as etiologic agents of CAPA, using the molecular techniques. Voriconazole and amphotericin B showed more activity against all isolates. Moreover, the MIC of fluconazole, itraconazole varied with the tested isolates. For 3 clinical isolates of A. fumigatus, 2 isolate of A. flavus and 3 A. oryzae, the MIC of fluconazole and itraconazole were ≥ 16 µg/mL.ConclusionsWe observed a high incidence (14.3%) of probable aspergillosis in 119 patients with COVID-19, which might indicate the risk for developing IPA in COVID-19 patients. When comparing patients with and without CAPA regarding baseline characteristics, CAPA patients were older (p =0 .024), had received more frequent systemic corticosteroids (p = 0.024), and had a higher mortality rate (p = 0.018). The outcome of CAPA is usually poor, thus emphasis shall be given to screening and/or prophylaxis in COVID-19 patients with any risk of developing CAPA.

Investigation of the value of precipitins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with a positive marker for Aspergillus species.

Although a high prevalence of COVID-19-associated pulmonary aspergillosis has been reported, it is still difficult to distinguish between colonization with Aspergillus fumigatus and infection. Concomitantly, similarities between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hypersensitivity pneumonitis were suggested. The objective of this study was to investigate retrospectively if precipitin assays targeting A. fumigatus could have been useful in the management of SARS-CoV-2 patients hospitalized in an Intensive Care Unit (ICU) in 2020. SARS-CoV-2 ICU patients were screened for Aspergillus co-infection using biomarkers (galactomannan antigen, qPCR) and culture of respiratory samples (tracheal aspirates and bronchoalveolar lavage). For all these patients, clinical data, ICU characteristics and microbial results were collected. Electrosyneresis assays were performed using commercial A. fumigatus somatic and metabolic antigens. ELISA were performed using in-house A. fumigatus purified antigen and recombinant antigens.Our study population consisted of 65 predominantly male patients, with a median ICU stay of 22 days, and a global survival rate of 62%. Thirty-five patients had at least one positive marker for Aspergillus species detection. The number of arcs obtained by electrosyneresis using the somatic A. fumigatus antigen was significantly higher for these 35 SARS-CoV-2 ICU patients (P 0.01, Welch's t-test). Our study showed that SARS-CoV-2 ICU patients with a positive marker for Aspergillus species detection more often presented precipitins towards A. fumigatus. Serology assays could be an additional tool to assess the clinical relevance of the Aspergillus species in respiratory samples of SARS-CoV-2 ICU patients.Lay SummaryThis study showed retrospectively that precipitin assays, such as electrosyneresis, could be helpful to distinguish between colonization and infection with Aspergillus fumigatus during the management of severe acute respiratory syndrome Coronavirus-2 (SARS CoV-2) patients in an intensive care unit.

COVID19 in Lung Transplanted Patients: Chronicles from an Italian Epicenter

PurposeLombardy was one of the hardest hit regions in Italy during the COVID19 pandemic. We hereby report our experience with SARS-CoV2 infection in lung transplant recipients.MethodsWe retrospectively collected clinical data on all the consecutive cases of COVID19 in our centre, based in Milan, from March 2020 to August 2021. Diagnosis was always confirmed by a positive nucleic acid amplification test (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab and/or tracheal aspirate.Results21 patients were diagnosed with COVID19. Figure 1 summarizes the clinical course of these individuals. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids; when hospitalized, everybody received initial empiric antibiotic treatment with piperacillin/tazobactam and high-dose LMWH. Hydroxychloroquine was used only in the "first wave" (4 patients). One patient was compassionately administered anakinra and remdesivir as a “rescue therapy”. Lymphocitopenia was a common presenting sign (14 patients, 66%). Aspergillus co-infection occurred in 5 patients (24%). Mortality rate was 29%; 4 out of these 6 patients were affected by CLAD and 3 had chronic kidney disease. Of note, in March 2021, we tested all our patients for anti-SARS-CoV-2 nucleocapsid antibodies before starting vaccinations: we found three additional seropositive patients, who were not included in the present analysis, but had been presumably affected by an asymptomatic/mild form of the disease.ConclusionApart from immunosuppression, the majority of our patients presented at least one risk factor for mortality in COVID-19 (diabetes, chronic kidney disease, arterial hypertension) and, for this reason, we felt that they should be hospitalized to enable close monitoring and prompt management of possible complications and deterioration. Clinical course seemed favorable in only two thirds of our patients but, for the time being, none of these individuals showed sign of new-onset CLAD after COVID19.

An unusual combination of aspergillus- scopulariopsis brumptii coinfection in an immunosuppressed adult male

Aspergillus coinfection with Scopulariopsis brumptii in an immunosuppressed adult male is rare. Patients with Aspergillosis have been described to be coinfected with other organisms, including fungi but the combination with fungi from the Scopulariopsis group has not been so far reported to the best of our knowledge. We report the case of an adult male with monoclonal gammopathy of unknown significance and concurrent COPD, Rheumatoid arthritis on monoclonal antibody therapy and Methotrexate, presenting with recurrent chest infections. Initially, the patient was diagnosed with allergic bronchopulmonary Aspergillosis and treated with antifungal and corticosteroid therapy. During follow up, repeated chest infection was noted despite a range of broad-spectrum antibiotics. Scopulariopsis brumptii was detected on the sputum sample, and specific antifungal treatment was commenced until the full recovery. The patient was on follow up for several years. He is now asymptomatic with no further growth of Aspergillus or Scopulariopsis in his sputum.

Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis.

Influenza-associated pulmonary aspergillosis (IAPA) is a global recognized superinfection in critically ill influenza patients. Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is a newly approved anti-influenza therapeutic. Although the benefits as a treatment for influenza are clear, its efficacy against an influenza-A. fumigatus co-infection has yet to be determined. We investigated the therapeutic effect of baloxavir marboxil in a murine model for IAPA. Immunocompetent mice received intranasal instillation of influenza A followed by orotracheal inoculation with Aspergillus fumigatus 4 days later. Administration of baloxavir marboxil or sham was started at day 0, day 2 or day 4. Mice were monitored daily for overall health status, lung pathology with micro-computed tomography (µCT) and fungal burden with bioluminescence imaging (BLI). In vivo imaging was supplemented with virological, mycological and biochemical endpoint investigations. We observed an improved body weight, survival and viral clearance in baloxavir marboxil treated mice. µCT showed less pulmonary lesions and bronchial dilation after influenza and after Aspergillus co-infection in a treatment-dependent pattern. Furthermore, baloxavir marboxil was associated with effective inhibition of fungal invasion. Hence, our results provide evidence that baloxavir marboxil mitigates severe influenza thereby decreasing the susceptibility to a lethal invasive Aspergillus superinfection.

Management of Severe Influenza.

Influenza infection causes severe illness in 3 to 5 million people annually, with up to an estimated 650,000 deaths per annum. As such, it represents an ongoing burden to health care systems and human health. Severe acute respiratory infection can occur, resulting in respiratory failure requiring intensive care support. Herein we discuss diagnostic approaches, including development of CLIA-waived point of care tests that allow rapid diagnosis and treatment of influenza. Bacterial and fungal coinfections in severe influenza pneumonia are associated with worse outcomes, and we summarize the approach and treatment options for diagnosis and treatment of bacterial and Aspergillus coinfection. We discuss the available drug options for the treatment of severe influenza, and treatments which are no longer supported by the evidence base. Finally, we describe the supportive management and ventilatory approach to patients with respiratory failure as a result of severe influenza in the intensive care unit.

Invasive pulmonary aspergillosis in critically ill patients with COVID-19 in Australia: implications for screening and treatment.

We report four cases of invasive pulmonary aspergillus co-infection in patients with coronavirus disease 2019 (COVID-19) infection and acute respiratory distress syndrome requiring intensive care unit (ICU) admission. Aspergillus fumigatus and Aspergillus terreus were isolated, with early infection onset following ICU admission. Clinicians should be aware of invasive pulmonary aspergillosis in ICU patients with COVID-19 infection, particularly those receiving dexamethasone. We propose screening of these high-risk patients with twice-weekly fungal culture from tracheal aspirate and, if feasible, Aspergillus polymerase chain reaction. Diagnosis is challenging and antifungal treatment should be considered in critically ill patients who have new or worsening pulmonary changes on chest imaging and mycological evidence of infection.

A case series of mucormycosis and aspergillus coinfection in post-covid-19 patient with uncontrolled diabetic

Mucormycosis is an angioinvasive infection caused by fungi Mucorales which mainly occurs in immunocompromised patients. Aspergillosis is also an opportunistic fungal infection caused by Aspergillus species. Coinfection with mucormycosis and aspergillosis is very rare and very few cases were published in the literature till now. There is an increase in the incidence of mucormycosis infection in post-COVID-19 patients. Here, we are going to report a case series of three cases of combined infection of mucormycosis with Aspergillus. All three patients were treated with extensive surgical debridement and intravenous liposomal amphotericin B. Even after aggressive treatment, the mortality rate is high in these types of patients.

Early oseltamivir reduces risk for influenza-associated aspergillosis in a double-hit murine model

ABSTRACT Invasive pulmonary aspergillosis (IPA) is a life-threatening fungal infection occurring mainly in immunocompromised patients. We recently identified IPA as an emerging co-infection with high mortality in critically ill, but otherwise immunocompetent influenza patients. The neuraminidase inhibitor oseltamivir is the current standard-of-care treatment in hospitalized influenza patients; however, its efficacy in influenza-associated pulmonary aspergillosis (IAPA) is not known. Therefore, we have established an imaging-supported double-hit mouse model to investigate the therapeutic effect of oseltamivir on the development of IAPA. Immunocompetent mice received intranasal instillation influenza A or PBS followed by orotracheal inoculation with Aspergillus fumigatus 4 days later. Oseltamivir treatment or placebo was started at day 0, day 2, or day 4. Daily monitoring included micro-computed tomography and bioluminescence imaging of pneumonia and fungal burden. Non-invasive biomarkers were complemented with imaging, molecular, immunological, and pathological analysis. Influenza virus-infected immunocompetent mice developed proven airway IPA upon co-infection with Aspergillus fumigatus, whereas non-influenza-infected mice fully cleared Aspergillus, confirming influenza as a risk factor for developing IPA. Longitudinal micro-CT showed pulmonary lesions after influenza infection worsening after Aspergillus co-infection, congruent with bioluminescence imaging and histology confirming Aspergillus pneumonia. Early oseltamivir treatment prevented severe influenza pneumonia and mitigated the development of IPA and associated mortality. A time-dependent treatment effect was consistently observed with imaging, molecular, and pathological analyses. Hence, our findings underscore the importance of initiating oseltamivir as soon as possible, to suppress influenza infection and mitigate the risk of potentially lethal IAPA disease.

COVID-19 associated pulmonary aspergillosis (CAPA) in a pregnant woman.

ABSTRACTViral or bacterial co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in the literature. However, the knowledge on Aspergillus co-infection among patients with coronavirus disease 2019 (COVID-19) is limited. COVID‐19‐associated pulmonary aspergillosis (CAPA) has been seen in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS), which has raised concerns about the worsening disease course of COVID-19 and increasing mortality. We describe a clinical case of CAPA infection and acute respiratory distress syndrome (ARDS) with a deathly outcome in a previously well, non-immunocompromised pregnant woman with intrauterine death of the fetus. Hence, we suggest that clinicians and pathologists keep alerting the possible occurrence of pulmonary aspergillosis in severe/critical COVID-19 patients, and aggressive investigations should be done to rule out the possibility of CAPA so that early treatment can be administrated.