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When Viruses and Fungi Act Together

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A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 40445

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Special Issue Editor

Prof. Dr. Katrien Lagrou

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Guest Editor

Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
Interests: invasive aspergillosis; biomarkers; invasive candidiasis; antifungal resistance

Special Issue Information

Dear Colleagues,

Bacterial coinfections complicating viral infections have been well known for decades, but currently, there is an increasing awareness of interactions between viral and fungal pathogens as well. For example, cytomegalovirus infection is known as a risk factor for fungal disease in certain patient populations. Profoundly immunocompromised patients often suffer from bacterial, viral and fungal coinfections, which are better diagnosed nowadays following the use of multiplex panels and broader diagnostic testing. Influenza virus infection was found to be an independent risk factor for invasive aspergillosis in critically ill patients. Most recently, many groups reported about invasive aspergillosis in COVID-19 patients, but crucial questions about the incidence, pathophysiology and optimal diagnostic approach remain unanswered. Also invasive yeast infections are increasingly recognized as a complication of severe COVID-19.

New methods and models are needed to study the interactions between viral and fungal pathogens as well as the interaction with the host. Adequate knowledge about the pathophysiology, epidemiology, risk factors, value of the different diagnostic tests and the optimal therapeutic approach is essential to improve the outcomes of patients suffering from these coinfections.

Prof. Dr. Katrien Lagrou
Guest Editor

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Keywords

viral–fungal interaction
pathogenesis
diagnosis
host interaction
epidemiology
treatment

Published Papers (12 papers)

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Research

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9 pages, 237 KiB

Open AccessArticle

Occurrence of Candidemia in Patients with COVID-19 Admitted to Five ICUs in France

by Marion Blaize, Audrey Raoelina, Dimitri Kornblum, Laure Kamus, Alexandre Lampros, Marie Berger, Sophie Demeret, Jean-Michel Constantin, Antoine Monsel, Julien Mayaux, Charles-Edouard Luyt, Renaud Piarroux and Arnaud Fekkar

J. Fungi 2022, 8(7), 678; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8070678 - 28 Jun 2022

Cited by 11 | Viewed by 1469

Abstract

Whether severe COVID-19 is by itself a significant risk factor for the development of candidemia currently remains an open question as conflicting results have been published. We aim to assess the occurrence of candidemia in patients with severe COVID-19 admitted to the intensive care unit (ICU). We conducted a retrospective study on patients with severe SARS-CoV-2-related pneumonia admitted to 5 ICUs in France who were specifically screened for fungal complications between March 2020 and January 2021. The study population included a total of 264 patients; the median age was 56 years old and most of them were male (n = 186; 70.5%) and immunocompetent (n = 225; 87.5%), and 62.7% (n = 153/244) were on extracorporeal membrane oxygenation support. Microbiological analysis included 4864 blood culture samples and beta-glucan test performed on 975 sera. Candidemia was diagnosed in 13 (4.9%) patients. The species involved were mainly C. albicans (n = 6) and C. parapsilosis (n = 5). Almost all patients (12/13; 92.3%) had a colonization by yeasts. ICU mortality was not significantly impacted by the occurrence of candidemia. Unrelated positive beta-glucan tests were observed in 49 patients (23.4%), including 6 with mold infections and 43 with false positive results. In our series, patients with severe SARS-CoV-2-related pneumonia seemed at low risk of developing invasive candidiasis. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

14 pages, 985 KiB

Open AccessArticle

Revisit of the Association between Cytomegalovirus Infection and Invasive Fungal Infection after Allogeneic Hematopoietic Stem Cell Transplantation: A Real-World Analysis from a High CMV Seroprevalence Area

by Tsung-Jang Yeh, Ching-I Yang, Chien-Tzu Huang, Min-Hung Wang, Tzer-Ming Chuang, Ya-Lun Ke, Yuh-Ching Gau, Jeng-Shiun Du, Hui-Ching Wang, Shih-Feng Cho, Ching-Ping Lee, Chin-Mu Hsu, Hui-Hua Hsiao and Yi-Chang Liu

J. Fungi 2022, 8(4), 408; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8040408 - 16 Apr 2022

Cited by 5 | Viewed by 2170

Abstract

Infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) especially cytomegalovirus (CMV) infection and invasive fungal infection (IFI). Taiwan is a high CMV seroprevalence area. Our study aimed to evaluate the incidence, risk factors, the impact on survival of CMV infection (including reactivation and disease) and the association of CMV infection and IFI in recipients after allo-HSCT during the first 100 days after transplantation. This was a retrospective study including 180 recipients of allo-HSCT. A total of 99 patients had CMV reactivation, and nine patients had CMV diseases. There were more mismatched donors, more ATG usage and more transplantation from CMV IgG-negative donor in patients with CMV reactivation. There was no survival difference in patients with or without CMV reactivation. A total of 34 patients had IFIs, and IFI after allo-HSCT was associated with significantly inferior survival. Patients with CMV reactivation did not increase the incidence of overall IFI, but they did result in more late-onset (>40 days) IFI (p = 0.056). In this study, we demonstrated real-world data of CMV infection and IFI from a high CMV seroprevalence area. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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9 pages, 3670 KiB

Open AccessArticle

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

by Robbert G. Bentvelsen, Andreas L. E. Van Arkel, Tom A. Rijpstra, Merijn K. M. Kant, Simone Van Der Sar-Van Der Brugge, Daan W. Loth, Peter Van Wijngaarden, Arthur W. F. Du Mée, David C. Y. Yick, Bram M. W. Diederen, Peter C. Wever, Alexander C. A. P. Leenders, Laura Van Dommelen, Klaas H. De Groot, Wouter Van den Bijllaardt and Paul E. Verweij

J. Fungi 2022, 8(2), 96; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8020096 - 19 Jan 2022

Cited by 7 | Viewed by 2332

Abstract

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. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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10 pages, 1013 KiB

Open AccessArticle

COVID-19 Associated Pulmonary Aspergillosis: Diagnostic Performance, Fungal Epidemiology and Antifungal Susceptibility

by Nina Lackner, Claudius Thomé, Dietmar Öfner, Michael Joannidis, Timo Mayerhöfer, Rohit Arora, Eldina Samardzic, Wilfried Posch, Robert Breitkopf and Cornelia Lass-Flörl

J. Fungi 2022, 8(2), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8020093 - 18 Jan 2022

Cited by 10 | Viewed by 2785

Abstract

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns as to whether it contributes to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. We implemented a routine screening of respiratory specimens in COVID-19 ICU patients for Aspergillus species using culture and galactomannan (GM) detection from serum and/or bronchoalveolar lavages (BAL). Out of 329 ICU patients treated during March 2020 and April 2021, 23 (7%) suffered from CAPA, 13 of probable, and 10 of possible. In the majority of cases, culture, microscopy, and GM testing were in accordance with CAPA definition. However, we saw that the current definitions underscore to pay attention for fungal microscopy and GM detection in BALs, categorizing definitive CAPA diagnosis based on culture positive samples only. The spectrum of Aspergillus species involved Aspergillus fumigatus, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus nidulans. We noticed changes in fungal epidemiology, but antifungal resistance was not an issue in our cohort. The study highlights that the diagnosis and incidence of CAPA is influenced by the application of laboratory-based diagnostic tests. Culture positivity as a single microbiological marker for probable definitions may overestimate CAPA cases and thus may trigger unnecessary antifungal treatment. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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13 pages, 6560 KiB

Open AccessArticle

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

by Laura Seldeslachts, Cato Jacobs, Birger Tielemans, Eliane Vanhoffelen, Lauren Van der Sloten, Stephanie Humblet-Baron, Lieve Naesens, Katrien Lagrou, Erik Verbeken, Joost Wauters and Greetje Vande Velde

J. Fungi 2022, 8(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8010001 - 21 Dec 2021

Cited by 4 | Viewed by 2690

Abstract

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. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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11 pages, 757 KiB

Open AccessArticle

COVID-19-Associated Pulmonary Aspergillosis in Russia

by Olga Shadrivova, Denis Gusev, Maria Vashukova, Dmitriy Lobzin, Vitaliy Gusarov, Mikhail Zamyatin, Anatoliy Zavrazhnov, Mikhail Mitichkin, Yulia Borzova, Olga Kozlova, Ekaterina Desyatik, Ekaterina Burygina, Svetlana Ignatyeva, Ellina Oganesyan, Natalya Vasilyeva, Nikolay Klimko and Working Group

J. Fungi 2021, 7(12), 1059; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7121059 - 10 Dec 2021

Cited by 13 | Viewed by 2659

Abstract

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%. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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16 pages, 1358 KiB

Open AccessArticle

Global Prevalence of COVID-19-Associated Mucormycosis (CAM): Living Systematic Review and Meta-Analysis

by Salman Hussain, Abanoub Riad, Ambrish Singh, Jitka Klugarová, Benny Antony, Hasanul Banna and Miloslav Klugar

J. Fungi 2021, 7(11), 985; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7110985 - 18 Nov 2021

Cited by 48 | Viewed by 3470

Abstract

Mucormycosis, a secondary fungal infection, gained much attention in the ongoing COVID-19 pandemic. This deadly infection has a high all-cause mortality rate and imposes a significant economic, epidemiological, and humanistic burden on the patients and healthcare system. Evidence from the published epidemiological studies showed the varying prevalence of COVID-19-associated mucormycosis (CAM). This study aims to compute the pooled prevalence of CAM and other associated clinical outcomes. MEDLINE, Embase, Cochrane COVID-19 Study Register, and WHO COVID-19 databases were scanned to retrieve the relevant articles until August 2021. All studies reporting the prevalence of mucormycosis among COVID-19 patients were eligible for inclusion. Two investigators independently screened the articles against the selection criteria, extracted the data, and performed the quality assessment using the JBI tool. The pooled prevalence of CAM was the primary outcome, and the pooled prevalence of diabetes, steroid exposure, and the mortality rate were the secondary outcomes of interest. Comprehensive Meta-Analysis software version 2 was used for performing the meta-analysis. This meta-analysis comprised six studies with a pooled sample size of 52,916 COVID-19 patients with a mean age of 62.12 ± 9.69 years. The mean duration of mucormycosis onset was 14.59 ± 6.88 days after the COVID-19 diagnosis. The pooled prevalence of CAM (seven cases per 1000 patients) was 50 times higher than the highest recorded background of mucormycosis (0.14 cases per 1000 patients). A high mortality rate was found among CAM patients with a pooled prevalence rate of 29.6% (95% CI: 17.2–45.9%). Optimal glycemic control and the judicious use of steroids should be the approach for tackling rising CAM cases. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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23 pages, 4184 KiB

Open AccessArticle

COVID-19-Associated Mucormycosis (CAM): Case-Series and Global Analysis of Mortality Risk Factors

by Abanoub Riad, Alshaimaa Ahmed Shabaan, Julien Issa, Sally Ibrahim, Hatem Amer, Yossef Mansy, Islam Kassem, Amira Bisher Kassem, Hans-Peter Howaldt, Miloslav Klugar and Sameh Attia

J. Fungi 2021, 7(10), 837; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7100837 - 07 Oct 2021

Cited by 34 | Viewed by 6016

Abstract

Background: Since the novel coronavirus disease (COVID-19) outbreak, the cases of COVID-19 co-infections have been increasingly reported worldwide. Mucormycosis, an opportunistic fungal infection caused by members of the Mucorales order, had been frequently isolated in severely and critically ill COVID-19 patients. Methods: Initially, the anamnestic, clinical, and paraclinical features of seven COVID-19-associated mucormycosis (CAM) cases from Egypt were thoroughly reported. Subsequently, an extensive review of the literature was carried out to describe the characteristics of CAM cases globally, aiming to explore the potential risk factors of mortality in CAM patients. Results: Out of the seven reported patients in the case series, five (71.4%) were males, six (85.7%) had diabetes mellitus, and three (42.9%) had cardiovascular disease. All patients exhibited various forms of facial deformities under the computed tomography scanning, and two of them tested positive for Mucorales using the polymerase chain reaction (PCR) testing. Liposomal amphotericin B (LAmB) was prescribed to all cases, and none of them died until the end of the follow-up. On reviewing the literature, 191 cases were reported worldwide, of which 74.4% were males, 83.2% were from low-middle income countries, and 51.4% were aged 55 years old or below. Diabetes mellitus (79.1%), chronic hypertension (30%), and renal disease/failure (13.6%) were the most common medical comorbidities, while steroids (64.5%) were the most frequently prescribed medication for COVID-19, followed by Remdesivir (18.2%), antibiotics (12.7%), and Tocilizumab (5.5%). Conclusions: As the majority of the included studies were observational studies, the obtained evidence needs to be interpreted carefully. Diabetes, steroids, and Remdesivir were not associated with increased mortality risk, thus confirming that steroids used to manage severe and critical COVID-19 patients should not be discontinued. Lung involvement, bilateral manifestation, and Rhizopus isolation were associated with increased mortality risk, thus confirming that proactive screening is imperative, especially for critically ill patients. Finally, surgical management and antimycotic medications, e.g., amphotericin B and posaconazole, were associated with decreased mortality risk, thus confirming their effectiveness. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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13 pages, 704 KiB

Open AccessArticle

Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

by Florian Reizine, Kieran Pinceaux, Mathieu Lederlin, Brice Autier, Hélène Guegan, Arnaud Gacouin, David Luque-Paz, Christelle Boglione-Kerrien, Astrid Bacle, Brendan Le Daré, Yoann Launey, Mathieu Lesouhaitier, Benoit Painvin, Christophe Camus, Alexandre Mansour, Florence Robert-Gangneux, Sorya Belaz, Yves Le Tulzo, Jean-Marc Tadié, Adel Maamar and Jean-Pierre Gangneux Show full author list Hide full author list

J. Fungi 2021, 7(5), 388; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7050388 - 15 May 2021

Cited by 31 | Viewed by 3854

Abstract

Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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Review

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17 pages, 844 KiB

Open AccessReview

Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients

by Kerri Basile, Catriona Halliday, Jen Kok and Sharon C-A. Chen

J. Fungi 2022, 8(1), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8010058 - 06 Jan 2022

Cited by 12 | Viewed by 3075

Abstract

Invasive fungal disease (IFD) associated with Coronavirus Disease 2019 (COVID-19) has focussed predominantly on invasive pulmonary aspergillosis. However, increasingly emergent are non-Aspergillus fungal infections including candidiasis, mucormycosis, pneumocystosis, cryptococcosis, and endemic mycoses. These infections are associated with poor outcomes, and their management is challenged by delayed diagnosis due to similarities of presentation to aspergillosis or to non-specific features in already critically ill patients. There has been a variability in the incidence of different IFDs often related to heterogeneity in patient populations, diagnostic protocols, and definitions used to classify IFD. Here, we summarise and address knowledge gaps related to the epidemiology, risks, diagnosis, and management of COVID-19-associated fungal infections other than aspergillosis. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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20 pages, 2283 KiB

Open AccessReview

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

by Simon Feys, Maria Panagiota Almyroudi, Reinout Braspenning, Katrien Lagrou, Isabel Spriet, George Dimopoulos and Joost Wauters

J. Fungi 2021, 7(12), 1067; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7121067 - 11 Dec 2021

Cited by 54 | Viewed by 5458

Abstract

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. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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Other

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20 pages, 1481 KiB

Open AccessSystematic Review

Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

by Nipat Chuleerarux, Achitpol Thongkam, Kasama Manothummetha, Saman Nematollahi, Veronica Dioverti-Prono, Pattama Torvorapanit, Nattapong Langsiri, Navaporn Worasilchai, Rongpong Plongla, Ariya Chindamporn, Anawin Sanguankeo and Nitipong Permpalung

J. Fungi 2021, 7(5), 327; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7050327 - 23 Apr 2021

Cited by 12 | Viewed by 2734

Abstract

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I² = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon. Full article

(This article belongs to the Special Issue When Viruses and Fungi Act Together)

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