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(searched for: doi:10.1111/myc.13155)
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, , Jeanette Jiang, Emily F. Shortridge, Kalatu Davies, Giridharan Gurumoorthy, Tomomi Kimura
Published: 13 March 2023
by Wiley
Journal: Mycoses
Mycoses, Volume 66, pp 527-539; https://doi.org/10.1111/myc.13579

Mario Ruiz-Bastián, Beatriz Díaz-Pollán, Iker Falces-Romero, Carlos Toro-Rueda, Julio García-Rodríguez
Enfermedades Infecciosas Y Microbiologia Clinica (english Ed.); https://doi.org/10.1016/j.eimce.2022.11.020

Published: 5 January 2023
by MDPI
Journal: Journal of Fungi
Journal of Fungi, Volume 9; https://doi.org/10.3390/jof9010081

Abstract:
Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure due to SARS-CoV-2 infection. Almost 2.5 years since the start of the COVID-19 pandemic, it continues to raise concerns as an extra factor that contributes to increased mortality, which is mostly because its diagnosis and management remain challenging. The present study utilises the cases of forty-three patients hospitalised between August 2020 and February 2022 whose information was gathered from ten ICUs and special care units based in northern Greece. The main aim was to describe the gained experience in diagnosing CAPA, according to the implementation of the main existing diagnostic consensus criteria and definitions, and present the different classification of the clinical cases due to the alternative algorithms.
Somayeh Yazdanpanah, Mohammad Ahmadi, Zahra Zare, Hamed Nikoupour, Sara Arabsheybani, Ahmad Jabrodini, Esmaeel Eghtedarnejad, Parisa Chamanpara, Bita Geramizadeh, Mohammad Hossein Anbardar, et al.
Published: 10 December 2022
Journal: Mycopathologia
Mycopathologia, Volume 188, pp 9-20; https://doi.org/10.1007/s11046-022-00694-x

The publisher has not yet granted permission to display this abstract.
Mario Ruiz-Bastián, Beatriz Díaz-Pollán, Iker Falces-Romero, Carlos Toro-Rueda, Julio García-Rodríguez
Published: 1 December 2022
Enfermedades Infecciosas Y Microbiologia Clinica; https://doi.org/10.1016/j.eimc.2022.11.002

, John K. Obwiin, Florence Pido, Martha Alupo, Charles Ssendikadiwa, Jane Nakibuuka, Edrin Jjuuko, Erasmus E. Okello, Lydia Vn. Ssenyonga, Jacob S. Iramiot
Published: 17 October 2022
Abstract:
Background: The pandemic of COVID-19 has led to an upsurge of critically ill patients requiring advanced life support. Bacteria and fungi have been isolated as etiological agents for co-infections among COVID-19 patients in the intensive care unit (ICU). Co-infection has been associated with worse outcomes among COVID-19 patients in ICUs. The aim of this study was to determine the prevalence of co-infections and their antimicrobial susceptibility patterns among COVID-19 patients admitted to intensive care units in Uganda. Materials and Methods: A multi-center cross-sectional retrospective survey was carried out in Intensive Care Units (ICUs) in Mulago national referral hospital, UMC Victoria and TMR international hospital in Uganda. The records of 216 hospitalized ICU COVID-19 patients were purposively sampled using a standardized data abstraction tool. The collected data were double entered in Epi-data version 3.1 and exported to Stata version 17.0 for statistical analysis. Results: The prevalence of co-infections (bacterial and fungal) was111(51.39%) with respiratory tract infections 57(51.35%) being the most prevalent. Staphylococcus aureus 23(28.75%), Citrobacter freudii 19(23.75%), Pseudomonas aureginosa 15(18.75%) and Klebsiella pneumoniae 10(12.50%) were the most frequently isolated bacterial species. The prevalence of multidrug resistant bacterial species was 75.95%. About 07/8(8.75%) of the bacterial species were extended spectrum beta lactamase or AmpC beta lactamase producers. Some of ESBL producers demonstrated susceptibility to Augmentin, Amikacin and trimethoprim. Augmentin 33/54(61.11%) and ceftriaxone 4/44(9.09%) had the highest and lowest overall antibiotic susceptibility respectively. About 31/111(27.93%) of the organisms were Candida albicans. The fungal species isolated had good overall susceptibility to most commonly used antifungal agents in the study setting. Conclusion: This study found a high prevalence of co-infections (bacterial and fungal). Respiratory tract infection was the most prevalent. There was an overwhelming burden of multidrug resistant infections with some extended spectrum drug resistant organisms isolated among COVID-19 patients admitted in the Ugandan ICUs. There is need for establishment of stronger policy measures in regards to antibiotic stewardship, antimicrobial surveillance and infection control to inform empirical antibiotic therapy and mitigate the spread MDR bacteria and antibiotic drug resistance among COVID-19 patients.
Wonju Hong, P. Lewis White, Matthijs Backx, Jean-Pierre Gangneux, Florian Reizine, Philipp Koehler, Robbert G. Bentvelsen, María Luján Cuestas, Hamed Fakhim, Jung Im Jung, et al.
Published: 23 July 2022
Journal: Clinical Imaging
Clinical Imaging, Volume 90, pp 11-18; https://doi.org/10.1016/j.clinimag.2022.07.003

The publisher has not yet granted permission to display this abstract.
, Alok Nath, Ajmal Khan, Zafar Neyaz, Rungmei S. K. Marak, Prasant Areekkara, Atul Tiwari, Shivani Srivastava, Vikas Agarwal, Swati Saxena, et al.
Published: 7 July 2022
by Wiley
Journal: Mycoses
Mycoses, Volume 65, pp 1010-1023; https://doi.org/10.1111/myc.13485

Sima Sadat Seyedjavadi, Parmida Bagheri, Mohammad Javad Nasiri, Mehdi Razzaghi-Abyaneh, Mehdi Goudarzi
Published: 6 July 2022
Frontiers in Microbiology, Volume 13; https://doi.org/10.3389/fmicb.2022.888452

Abstract:
Fungal co-infections are frequent in patients with coronavirus disease 2019 (COVID-19) and can affect patient outcomes and hamper therapeutic efforts. Nonetheless, few studies have investigated fungal co-infections in this population. This study was performed to assess the rate of fungal co-infection in patients with COVID-19 as a systematic review. EMBASE, MEDLINE, and Web of Science were searched considering broad-based search criteria associated with COVID-19 and fungal co-infection. We included case reports and case series studies, published in the English language from January 1, 2020 to November 30, 2021, that reported clinical features, diagnosis, and outcomes of fungal co-infection in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Totally, 54 case reports and 17 case series were identified, and 181 patients (132 men, 47 women, and 2 not mentioned) co-infected with COVID-19 and fungal infection enrolled. The frequency of fungal co-infection among patients with COVID-19 was 49.7, 23.2, 19.8, 6.6, and 0.5% in Asia, America, Europe, Africa, and Australia, respectively. Diabetes (59.6%) and hypertension (35.9%) were found as the most considered comorbidities in COVID-19 patients with fungal infections. These patients mainly suffered from fever (40.8%), cough (30.3%), and dyspnea (23.7%). The most frequent findings in the laboratory results of patients and increase in C-reactive protein (CRP) (33.1%) and ferritin (18.2%), and lymphopenia (16%) were reported. The most common etiological agents of fungal infections were Aspergillus spp., Mucor spp., Rhizopus spp., and Candida spp. reported in study patients. The mortality rate was 54.6%, and the rate of discharged patients was 45.3%. Remdesivir and voriconazole were the most commonly used antiviral and antifungal agents for the treatment of patients. The global prevalence of COVID-19-related deaths is 6.6%. Our results showed that 54.6% of COVID-19 patients with fungal co-infections died. Thus, this study indicated that fungal co-infection and COVID-19 could increase mortality. Targeted policies should be considered to address this raised risk in the current pandemic. In addition, fungal infections are sometimes diagnosed late in patients with COVID-19, and the severity of the disease worsens, especially in patients with underlying conditions. Therefore, patients with fungal infections should be screened regularly during the COVID-19 pandemic to prevent the spread of the COVID-19 patients with fungal co-infection.
Published: 28 June 2022
by MDPI
Journal: Journal of Fungi
Journal of Fungi, Volume 8; https://doi.org/10.3390/jof8070674

Abstract:
Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated aspergillosis (CAPA), and COVID-19-associated mucormycosis (CAM). Among all studies which reported treatment of CAPA, approximately 10% of patients were reportedly treated with isavuconazole. Considering 14 identified studies that reported the use of isavuconazole for CAPA, isavuconazole was used in 40% of patients (95 of 235 treated patients), being first-line monotherapy in over half of them. We identified six studies that reported isavuconazole use in CAM, either alone or in combination therapy. Overall, isavuconazole was used as therapy in 13% of treated CAM patients, frequently as combination or sequential therapy. The use of isavuconazole in CAPA and CAM is complicated by the challenge of achieving adequate exposure in COVID-19 patients who are frequently obese and hospitalized in the ICU with concomitant renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO). The presence of data on high efficacy in the treatment of aspergillosis, lower potential for drug–drug interactions (DDIs) and for subtherapeutic levels, and no risk of QT prolongation compared to other mold-active azoles, better safety profile than voriconazole, and the possibility of using an intravenous formulation in the case of renal failure are the advantages of using isavuconazole in this setting.
Published: 25 March 2022
Journal of Clinical Medicine, Volume 11; https://doi.org/10.3390/jcm11071815

Abstract:
The SARS-CoV-2 pandemic might have increased the risks of healthcare-associated infections (HAIs); however, several studies of HAI such as urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs) have shown contradictory results. The aim of this study is to assess the clinical features of UTIs and bacterial isolates from urine samples of hospitalized COVID-19 patients. We conducted a retrospective observational study including 87 COVID-19 patients with UTIs admitted to our centre. Bacterial UTIs presented were 87: 9 (10.3%) community-acquired UTIs (coinfection group) and 78 (89.6%) hospital-acquired UTIs (superinfection group). In the coinfection group, the most frequent type was non-CAUTI with 5 (55.5%) patients; however, the most frequent UTI in the superinfection group was CAUTI, with 53 (67.9%) patients. The median number of days of hospitalization in coinfected patients was lower than superinfection patients: 13 (IQR 11, 23) vs. 34 days (IQR 23, 47) p < 0.006. All UTI patients admitted to ICU, 38 (43.7%), belonged to the superinfection group. The mortality rate was 26.4% (23/87), 22/23 in the superinfection group. The most common microorganisms were E. coli 27 (28.4%), E. faecalis 25 (26.3%) and E. faecium 20 (21.1%). There was an increased incidence of E. faecalis and E. faecium in UTIs as well as hospital-acquired UTIs. This can be related to urethral catheterization during hospitalization, UCI admissions and the number of days of hospitalization.
, J. Afeltra, S. Seyedmousavi, S. L. Giudicessi, S. M. Romero
Brazilian Journal of Microbiology, Volume 53, pp 759-775; https://doi.org/10.1007/s42770-022-00704-6

The publisher has not yet granted permission to display this abstract.
Published: 23 February 2022
by MDPI
Journal: Antibiotics
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) caused by A. niger in a Greek patient. Diagnosis was based on ECMM/ISHAM specific criteria and the new algorithm “BM-AspICU” for the invasive pulmonary aspergillosis diagnostic strategy. The fungal isolate was recovered in a non-bronchoalveolar lavage (non-BAL) sample and its identification was performed by standard macroscopic and microscopic morphological studies. MALDI-TOF analysis confirmed the identification of A. niger. In addition, galactomannan antigen and Aspergillus real-time PCR testing were positive in the non-BAL sample, while in serum they proved negative. The A. niger isolate showed an MIC for fluconazole ≥128 μg/mL, for itraconazole and posaconazole 0.25 μg/mL, for voriconazole 0.5 μg/mL, for flucytosine 4 μg/mL, for amphotericin B 1 μg/mL, and for all echinocandins (caspofungin, anidulafungin, micafungin) >8 μg/mL. The patient was initially treated with voriconazole; amphotericin B was subsequently added, when a significant progression of cavitation was demonstrated on chest computed tomography. A. niger was not isolated in subsequent samples and the patient’s unfavorable outcome was attributed to septic shock caused by a pandrug-resistant Acinetobacter baumannii strain.
Published: 13 February 2022
by MDPI
Journal: Journal of Fungi
Journal of Fungi, Volume 8; https://doi.org/10.3390/jof8020184

Abstract:
The association of invasive fungal infections (IFI) and viral infections has been described in patients with hematologic malignancies (HM), in particular in hematopoietic stem cell transplant recipients. Regrettably, the diagnosis is often challenging, making the treatment inappropriate in some circumstances. The present review takes into consideration the viral infections commonly associated with IFI. Clinical presentation of IFI and viral infections, risk factors, and impact on the outcome of HM patients are discussed throughout the paper.
Published: 11 December 2021
by MDPI
Journal: Journal of Fungi
Journal of Fungi, Volume 7; https://doi.org/10.3390/jof7121067

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.
Published: 10 November 2021
by MDPI
Journal: Journal of Fungi
Journal of Fungi, Volume 7; https://doi.org/10.3390/jof7110948

Abstract:
Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center′s intensive care units between January 2020 and March 2021, who also had respiratory cultures positive for Aspergillus species. Among a large cohort of 970 patients admitted to the ICU with severe COVID-19 infections during our study period, 48 patients had Aspergillus species growing in respiratory cultures. Based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, 2 patients in the study had proven CAPA, 9 had probable CAPA, and 37 had possible CAPA. The incidence of CAPA was 5%. The mean duration from a positive COVID-19 test to Aspergillus spp. being recovered from the respiratory cultures was 16 days, and more than half of the patients had preceding fever or worsening respiratory failure despite adequate support and management. Antifungals were given for treatment in 44% of the patients for a mean duration of 13 days. The overall mortality rate in our study population was extremely high with death occurring in 40/48 patients (83%).
Published: 23 September 2021
by MDPI
Journal: Fermentation
Abstract:
Vitamin K deficiency is evident in severe and fatal COVID-19 patients. It is associated with the cytokine storm, thrombotic complications, multiple organ damage, and high mortality, suggesting a key role of vitamin K in the pathology of COVID-19. To support this view, we summarized findings reported from machine learning studies, molecular simulation, and human studies on the association between vitamin K and SARS-CoV-2. We also investigated the literature for the association between vitamin K antagonists (VKA) and the prognosis of COVID-19. In addition, we speculated that fermented milk fortified with bee honey as a natural source of vitamin K and probiotics may protect against COVID-19 and its severity. The results reported by several studies emphasize vitamin K deficiency in COVID-19 and related complications. However, the literature on the role of VKA and other oral anticoagulants in COVID-19 is controversial: some studies report reductions in (intensive care unit admission, mechanical ventilation, and mortality), others report no effect on mortality, while some studies report higher mortality among patients on chronic oral anticoagulants, including VKA. Supplementing fermented milk with honey increases milk peptides, bacterial vitamin K production, and compounds that act as potent antioxidants: phenols, sulforaphane, and metabolites of lactobacilli. Lactobacilli are probiotic bacteria that are suggested to interfere with various aspects of COVID-19 infection ranging from receptor binding to metabolic pathways involved in disease prognosis. Thus, fermented milk that contains natural honey may be a dietary manipulation capable of correcting nutritional and immune deficiencies that predispose to and aggravate COVID-19. Empirical studies are warranted to investigate the benefits of these compounds.
Satish Swain, , Radhika Sarda, Surabhi Vyas, Gagandeep Singh, Pankaj Jorwal, Parul Kodan, Puneet Khanna, Immaculata Xess, Sanjeev Sinha, et al.
Published: 19 September 2021
by Wiley
Journal: Mycoses
Mycoses, Volume 65, pp 57-64; https://doi.org/10.1111/myc.13369

The publisher has not yet granted permission to display this abstract.
, T. Lupia, D. Lombardo, G. Stroffolini, S. Corcione, F. G. De Rosa, L. Brazzi
Published: 15 September 2021
Annals of Intensive Care, Volume 11, pp 1-11; https://doi.org/10.1186/s13613-021-00923-4

Abstract:
Invasive pulmonary aspergillosis (IPA) has always been a challenging diagnosis and risk factors an important guide to investigate specific population, especially in Intensive Care Unit. Traditionally recognized risk factors for IPA have been haematological diseases or condition associated with severe immunosuppression, lately completed by chronic conditions (such as obstructive pulmonary disease, liver cirrhosis, chronic kidney disease and diabetes), influenza infection and Intensive Care Unit (ICU) admission. Recently, a new association with SARS-CoV2 infection, named COVID-19-associated pulmonary aspergillosis (CAPA), has been reported worldwide, even if its basic epidemiological characteristics have not been completely established yet. In this narrative review, we aimed to explore the potential risk factors for the development of CAPA and to evaluate whether previous host factors or therapeutic approaches used in the treatment of COVID-19 critically ill patients (such as mechanical ventilation, intensive care management, corticosteroids, broad-spectrum antibiotics, immunomodulatory agents) may impact this new diagnostic category. Reviewing all English-language articles published from December 2019 to December 2020, we identified 21 papers describing risk factors, concerning host comorbidities, ICU management, and COVID-19 therapies. Although limited by the quality of the available literature, data seem to confirm the role of previous host risk factors, especially respiratory diseases. However, the attention is shifting from patients’ related risk factors to factors characterizing the hospital and intensive care course, deeply influenced by specific features of COVID treatment itself. Prolonged invasive or non-invasive respiratory support, as well as the impact of corticosteroids and/or immunobiological therapies seem to play a pivotal role. ICU setting related factors, such as environmental factors, isolation conditions, ventilation systems, building renovation works, and temporal spread with respect to pandemic waves, need to be considered. Large, prospective studies based on new risk factors specific for CAPA are warranted to guide surveillance and decision of when and how to treat this particular population.
Published: 7 August 2021
Journal of Intensive Medicine, Volume 1, pp 71-80; https://doi.org/10.1016/j.jointm.2021.07.001

Abstract:
Invasive Pulmonary Aspergillosis (IPA) has been recognized as a possible secondary infection complicating Coronavirus disease 2019 (COVID-19) and increasing mortality. The aim of this review was to report and summarize the available data in the literature concerning the incidence, pathophysiology, diagnosis, and treatment of COVID-19-Associated Pulmonary Aspergillosis (CAPA). Currently, the incidence of CAPA is unclear due to different definitions and diagnostic criteria used among the studies. It was estimated that approximately 8.6% (206/2383) of mechanically ventilated patients were diagnosed with either proven, probable, or putative CAPA. Classical host factors of invasive aspergillosis are rarely recognized in patients with CAPA, who are mainly immuno-competent presenting with comorbidities, while the role of steroids warrants further investigation. Direct epithelial injury and diffuse pulmonary micro thrombi in combination with immune dysregulation, hyper inflammatory response, and immunosuppressive treatment may be implicated. Discrimination between two forms of CAPA (e.g., tracheobronchial and parenchymal) is required, whereas radiological signs of aspergillosis are not typically evident in patients with severe COVID-19 pneumonia. In previous studies, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, a clinical algorithm to diagnose Invasive Pulmonary Aspergillosis in intensive care unit patients (AspICU algorithm), and influenza-associated pulmonary aspergillosis (IAPA) criteria were used for the diagnosis of proven/probable and putative CAPA, as well as the differentiation from colonization, which can be challenging. Aspergillus fumigatus is the most commonly isolated pathogen in respiratory cultures. Bronchoalveolar lavage (BAL) and serum galactomannan (GM), β-d-glucan (with limited specificity), polymerase chain reaction (PCR), and Aspergillus-specific lateral-flow device test can be included in the diagnostic work-up; however, these approaches are characterized by low sensitivity. Early treatment of CAPA is necessary, and 71.4% (135/189) of patients received antifungal therapy, mainly with voriconazole, isavuconazole, and liposomal amphotericin B . Given the high mortality rate among patients with Aspergillus infection, the administration of prophylactic treatment is debated. In conclusion, different diagnostic strategies are necessary to differentiate colonization from bronchial or parenchymal infection in intubated COVID-19 patients with Aspergillus spp. in their respiratory specimens vs. those not infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Following confirmation, voriconazole or isavuconazole should be used for the treatment of CAPA.
Elisabeth Paramythiotou, George Dimopoulos, Nikolaos Koliakos, Maria Siopi, Sophia Vourli, Spyros Pournaras,
Infectious Diseases and Therapy, Volume 10, pp 1779-1792; https://doi.org/10.1007/s40121-021-00486-8

The publisher has not yet granted permission to display this abstract.
Андрей Топорков, Анатолий Липницкий, Надежда Половец, Дмитрий Викторов, Раиса Суркова
Abstract:
Частота системных микозов значительно возросла за последние два десятилетия. Такой рост тесно связан с повышением числа иммунокомпрометирующих субъектов, обусловленным иммунотерапией онкологических и гематологических заболеваний, реципиентов трансплантатов, ВИЧ-инфекцией, лечением глюкокортикоидами. Кроме того, такие факторы, как старение населения мира и продолжительное использование антимикробных препаратов приводит к выраженному увеличению инвазивных микозов человека. Госпитализированные с COVID-19 пациенты, особенно тяжело больные или иммунокопромиссные, имеют повышенный риск развития коинфекций с инвазивными системными микозами. Это связано не только с клинической ситуацией и необходимостью инвазивной помощи, но также иммунной перестройкой, вызванной SARS-CoV-2, и используемым лечением (кортикостероиды, некоторые интерфероны, циклоспорин, ингибиторы ИЛ-6 и ИЛ-1). По-видимому у пациентов с COVID-19 наиболее часто развиваются легочный аспергиллез, мукормикоз, кандидоз и пневмоцистные пневмонии.
Published: 13 July 2021
by MDPI
Journal: Journal of Fungi
Journal of Fungi, Volume 7; https://doi.org/10.3390/jof7070556

Abstract:
The physiopathologic characteristics of COVID-19 (high levels of inflammatory cytokines and T-cell reduction) promote fungal colonization and infection, which can go unnoticed because the symptoms in both diseases are very similar. The objective of this work was to study the current epidemiology of systemic mycosis in COVID-19 times. A literature search on the subject (January 2020–February 2021) was performed in PubMed, Embase, Cochrane Library, and LILACS without language restrictions. Demographic data, etiological agent, risk factors, diagnostic methods, antifungal treatment, and fatality rate were considered. Eighty nine publications were found on co-infection by COVID-19 and pneumocystosis, candidiasis, aspergillosis, mucormycosis, coccidioidomycosis, or histoplasmosis. In general, the co-infections occurred in males over the age of 40 with immunosuppression caused by various conditions. Several species were identified in candidiasis and aspergillosis co-infections. For diagnosis, diverse methods were used, from microbiological to molecular. Most patients received antifungals; however, the fatality rates were 11–100%. The latter may result because the clinical picture is usually attributed exclusively to SARS-CoV-2, preventing a clinical suspicion for mycosis. Diagnostic tests also have limitations beginning with sampling. Therefore, in the remainder of the pandemic, these diagnostic limitations must be overcome to achieve a better patient prognosis.
, Iker Falces-Romero, Juan Carlos Ramos-Ramos, Manuela de Pablos, Julio García-Rodríguez
Diagnostic Microbiology and Infectious Disease, Volume 101, pp 115477-115477; https://doi.org/10.1016/j.diagmicrobio.2021.115477

Abstract:
The aim of this study is to review bacterial isolates from respiratory samples of patients with severe COVID-19 disease during the first 2 months of the first wave in our hospital. A single-center retrospective observational study in critically ill adult patients was performed. A total of 1251 respiratory samples from 1195 patients were processed. Samples from 66 patients (5.52%) were determined to be microbiologically significant by a semi-quantitative culture. All patients received broad spectrum antibiotherapy as an empirical treatment. The isolated bacteria were mainly Enterobacterales followed by Staphylococcus aureus and Pseudomonas aeruginosa. Bacterial co-infections in ICU stay could seem not dependent on the virus that has produced the viral pneumonia similarly as with other respiratory viruses such as Influenza virus.
Grégoire Pasquier, Agathe Bounhiol, Florence Robert Gangneux, Jean‐Ralph Zahar, Jean Pierre Gangneux, Ana Novara, Marie‐Elisabeth Bougnoux,
Published: 18 June 2021
by Wiley
Journal: Mycoses
Mycoses, Volume 64, pp 980-988; https://doi.org/10.1111/myc.13341

Abstract:
It is now well known that patients with SARS-CoV-2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS-CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID-19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non-surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.
, G. Ceccarelli, C. Borrazzo, M. Ridolfi, G. D.’Ettorre, F. Alessandri, F. Ruberto, F. Pugliese, G. M. Raponi, A. Russo, et al.
Published: 26 May 2021
Journal: Infection
Infection, Volume 49, pp 965-975; https://doi.org/10.1007/s15010-021-01624-7

Abstract:
Background: Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). Materials/methods: Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. Results: Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58–76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). Conclusions: In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.
Amy Spallone,
Published: 18 May 2021
Infectious Disease Clinics of North America, Volume 35, pp 261-277; https://doi.org/10.1016/j.idc.2021.03.014

Abstract:
Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and clinical knowledge of these emerging fungal pathogens has occurred through improved molecular diagnostics, nucleic sequence databases, and taxonomic reclassification of medically significant fungi. However, emerging fungal diseases carry significant morbidity and mortality and, due to a paucity of published literature, the collective clinical experience with these fungi is often limited. In this review, we focus on unusual emerging fungal pathogens not extensively covered elsewhere in this issue of Infectious Diseases Clinics of North America.
New version
, , Saud A. Almuhaidb, Abdullah M. Aljebreen,
Published: 7 May 2021
Journal: F1000Research
Abstract:
Background: Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). Severe COVID-19 is represented with acute respiratory distress syndrome (ARDS) that requires mechanical ventilation. Moreover, recent studies are reporting invasive fungal infection associated with severe COVID-19. It is unclear whether the prescription of immunotherapies such as corticosteroids, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself is risk factor for COVID-19-associated invasive pulmonary aspergillosis (CAPA). Hence, fungal infections present an additional uncertainty in managing COVID-19 patients and further compromise the outcome. Case study: Here we report a case of SARS-CoV-2 complicated by invasive pulmonary aspergillosis (IPA) in a patient with no traditional risk factors for IPA. Admitted to ICU due to ARDS on mechanical ventilation, the patient deteriorated clinically with unexplained increased of fraction of inspired oxygen (FiO2) requirement from 50% to 80%. Investigations showed borderline serum galactomannan, nonspecific radiological findings reported to be atypical for COVID-19, and the respiratory sample grew Aspergillus spp. Main diagnosis: COVID-19 related fungal infection. The patient was treated with antifungal therapy for four weeks. He improved clinically after one week of starting antimicrobial treatment. After a prolonged ICU stay (87 days) due to infection control precaution, he was discharged from the ICU and moved to a long-term facility for further management and support. Conclusions: This case highlights the diagnostic challenge in such cases. and the importance of early recognition of CAPA which can optimize therapy by administration of appropriate antifungal agents that may impact mortality.
, Lauren Watson, Vishala Parmasad, Nathan Putman-Buehler, Leslie Christensen, Nasia Safdar
Published: 6 May 2021
Journal: PLoS ONE
Abstract:
Introduction: The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. Patients and methods: We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763. Results: Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82–5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively). Conclusions: Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.
Jingwen Peng, Qiong Wang, Huan Mei, Hailin Zheng, Guangzhao Liang, Xiaodong She, Weida Liu
Published: 19 March 2021
Journal: Aging
Aging, Volume 13, pp 7745-7757; https://doi.org/10.18632/aging.202742

Abstract:
Coronavirus disease 2019 (COVID-19) has infected tens of millions of people worldwide within the last year. However, the incidence of fungal co-infection in COVID-19 patients remains unclear. To investigate the association between fungal co-infection and mortality due to COVID-19, we systematically searched Medline, Embase, MedRxiv and Cochrane Library for eligible studies published in the period from 1 January to 1 December 2020. We performed a meta-analysis of nine studies that met the inclusion criteria. In total, data from 2780 patients and 426 patients were included who were admitted to the ICU. In eight of the articles, 211 participants died due to COVID-19 infection, which means an overall mortality rate of 10.9%. The overall pooled proportion of fungal co-infection in COVID-19 patients was 0.12 (95% CI = 0.07-0.16, n = 2780, I2 = 96.8%). In terms of mortality in COVID-19 patients with fungal infection, the overall pooled proportion of mortality was 0.17 (95% CI = 0.10-0.24, n = 1944, I2 = 95.6%). These findings provide evidence suggesting a favorable use for empirical antibiotics in the majority of patients when COVID-19 infection is diagnosed. Our analysis is investigating the use of antifungal therapy to treat COVID-19 can serve as a comprehensive reference for COVID-19 treatment.
, Biplab K. Saha, Ananthakrishnan Ramani, Amit Chopra
Published: 11 March 2021
Journal: Infection
Infection, Volume 49, pp 591-605; https://doi.org/10.1007/s15010-021-01602-z

Abstract:
Background The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. Objective This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. Method We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. Results The incidence of secondary pulmonary infections is low at 16% (4.8–42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9–33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2–21 days) from initial hospitalization and 9 days (4–18 days) after ICU admission. The use of antibiotics is high at 60–100% involving the studies included in our review. Conclusion The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.
, Nasim Khajavirad, , Faezeh Salahshour, Behnaz Jahanbin, Hossein Kazemizadeh, Sayed Jamal Hashemi, , Mohammad Kord, , et al.
Published: 11 February 2021
by Wiley
Journal: Mycoses
Mycoses, Volume 64, pp 809-816; https://doi.org/10.1111/myc.13255

Abstract:
Severe COVID‐19 patients complicated with aspergillosis are increasingly reported. We present a histopathological proven case of fatal COVID‐19 associated pulmonary aspergillosis (CAPA), due to Aspergillus flavus. This report and existing published literature indicate diagnostic challenges and poor outcomes of CAPA in ICU‐patients.
, , Saud A. Almuhaidb, Abdullah M. Aljebreen,
Published: 1 February 2021
Journal: F1000Research
Abstract:
Background: Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). Severe COVID-19 is represented with acute respiratory distress syndrome (ARDS) that requires mechanical ventilation. Moreover, recent studies are reporting invasive fungal infection associated with severe COVID-19. It is unclear whether the prescription of immunotherapies such as corticosteroids, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself is risk factor for COVID-19-associated invasive pulmonary aspergillosis (CAPA). Hence, fungal infections present an additional uncertainty in managing COVID-19 patients and further compromise the outcome. Case study: Here we report a case of SARS-CoV-2 complicated by invasive pulmonary aspergillosis (IPA) in a patient with no traditional risk factors for IPA. Admitted to ICU due to ARDS on mechanical ventilation, the patient deteriorated clinically with unexplained increased of fraction of inspired oxygen (FiO2) requirement from 50% to 80%. Investigations showed borderline serum galactomannan, nonspecific radiological findings reported to be atypical for COVID-19, and the respiratory sample grew Aspergillus spp. Main diagnosis: COVID-19 related fungal infection. The patient was treated with antifungal therapy for four weeks. He improved clinically after one week of starting antimicrobial treatment. After a prolonged ICU stay (87 days) due to infection control precaution, he was discharged from the ICU and moved to a long-term facility for further management and support. Conclusions: This case highlights the diagnostic challenge in such cases. and the importance of early recognition of CAPA which can optimize therapy by administration of appropriate antifungal agents that may impact mortality.
, Andrew Platt, Jeffrey A. Tornheim, Sean X. Zhang, Kausik Datta, Celia Cardozo, Carolina Garcia-Vidal
Emerging Infectious Diseases, Volume 27, pp 18-25; https://doi.org/10.3201/eid2701.202896

Abstract:
Aspergillosis complicating severe influenza infection has been increasingly detected worldwide. Recently, coronavirus disease–associated pulmonary aspergillosis (CAPA) has been detected through rapid reports, primarily from centers in Europe. We provide a case series of CAPA, adding 20 cases to the literature, with review of pathophysiology, diagnosis, and outcomes. The syndromes of pulmonary aspergillosis complicating severe viral infections are distinct from classic invasive aspergillosis, which is recognized most frequently in persons with neutropenia and in other immunocompromised persons. Combined with severe viral infection, aspergillosis comprises a constellation of airway-invasive and angio-invasive disease and results in risks associated with poor airway fungus clearance and killing, including virus- or inflammation-associated epithelial damage, systemic immunosuppression, and underlying lung disease. Radiologic abnormalities can vary, reflecting different pathologies. Prospective studies reporting poor outcomes in CAPA patients underscore the urgent need for strategies to improve diagnosis, prevention, and therapy.
, , , María Olmedo, Cristina Veintimilla, Belén Padilla, , , , María Jesús Ruiz‐Serrano, et al.
Published: 19 November 2020
by Wiley
Journal: Mycoses
Mycoses, Volume 64, pp 132-143; https://doi.org/10.1111/myc.13213

The publisher has not yet granted permission to display this abstract.
Published: 1 January 2020
Memorias do Instituto Oswaldo Cruz, Volume 115; https://doi.org/10.1590/0074-02760200430

Abstract:
In this perspective article, the main risk factors of people to develop IFD are summarised, to aid recognising the impact of fungi on human health, an issue often underestimated and underappreciated. Considering that IFD are often disregarded during routine hospital care, it is very important to emphasise to microbiologists, diagnostic laboratory staff and clinicians, that not only the number but the diversity of patients at-risk for IFD are continuously rising, with mortality rates than remain unacceptably high.3 Additionally, most fungal infections are not reportable diseases, thus reliable information on local and global prevalence is not available. This review recalls the updated definition of IFD, collates recent epidemiological data and describes, in order of frequency, the most susceptible groups of people to acquire an IFD, namely those who undergo medical interventions, people with immunosuppression induced either by the treatment of an associated illnesses or by an underlying disease, people with bacterial or viral co-infections and immunocompetent individuals who acquire an IFD by environmental exposure.
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