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LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T36","span":{"begin":809,"end":820},"obj":"Body_part"},{"id":"T37","span":{"begin":1691,"end":1696},"obj":"Body_part"},{"id":"T38","span":{"begin":2455,"end":2460},"obj":"Body_part"},{"id":"T39","span":{"begin":2884,"end":2888},"obj":"Body_part"},{"id":"T40","span":{"begin":2985,"end":2990},"obj":"Body_part"},{"id":"T41","span":{"begin":3393,"end":3401},"obj":"Body_part"},{"id":"T42","span":{"begin":3595,"end":3600},"obj":"Body_part"},{"id":"T43","span":{"begin":3608,"end":3613},"obj":"Body_part"},{"id":"T44","span":{"begin":3746,"end":3754},"obj":"Body_part"},{"id":"T45","span":{"begin":4663,"end":4668},"obj":"Body_part"}],"attributes":[{"id":"A36","pred":"fma_id","subj":"T36","obj":"http://purl.org/sig/ont/fma/fma55670"},{"id":"A37","pred":"fma_id","subj":"T37","obj":"http://purl.org/sig/ont/fma/fma9576"},{"id":"A38","pred":"fma_id","subj":"T38","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A39","pred":"fma_id","subj":"T39","obj":"http://purl.org/sig/ont/fma/fma74402"},{"id":"A40","pred":"fma_id","subj":"T40","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A41","pred":"fma_id","subj":"T41","obj":"http://purl.org/sig/ont/fma/fma62871"},{"id":"A42","pred":"fma_id","subj":"T42","obj":"http://purl.org/sig/ont/fma/fma63083"},{"id":"A43","pred":"fma_id","subj":"T43","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A44","pred":"fma_id","subj":"T44","obj":"http://purl.org/sig/ont/fma/fma62871"},{"id":"A45","pred":"fma_id","subj":"T45","obj":"http://purl.org/sig/ont/fma/fma63083"}],"text":"4. Discussion\nIn France, the global burden of severe fungal infection is estimated at approximately 1,000,000 (1.47%) cases each year [13] and IFD account for a higher risk of mortality in patients with co-morbidities from 9 to 40% [14]. During the COVID-19 pandemic, warning messages considering similarities between Sars-CoV-2 and influenza infections stressed the importance of vigilance towards IFD [15,16]. Local experiences are now published and show high numbers of putative IA [17,18,19,20,21,22].\nThe diagnosis of IA still remains challenging because of a wide diversity of underlying conditions and growing number of criteria, particularly biological tools [6]. In deeply immunosuppressed patients, such as neutropenic patients, patients under antineoplastic and prolonged corticosteroid therapy or solid organ transplantation, criteria for classification of IFD and notably IA have recently been revised incorporating Aspergillus molecular detection [2]. In ICU, the AspICU algorithm published by Blot et al., [3] is a robust and helpful tool for aspergillosis classification but needs to be more evaluated and even updated. In order to address limitations of the various classification definitions for ICU patients, the ongoing FUNgal infections Definitions in ICU patients (FUNDICU) project aims to develop a standard set of definitions for IFD in critically ill patients [5].\nThe breaking news of SARS-CoV-2 co-infection urges the need for a critical analysis of the criteria of AspICU algorithm. Indeed, COVID-19 patients, particularly ARDS patients with mechanical ventilation, present with compatible clinical signs as depicted by the algorithm (refractory fever, pleuritic chest pain and rub, dyspnea, hemoptysis and worsening respiratory insufficiency, see [3] for full description) and CT-scan signs are hard to interpret because of COVID-19 CT-scan presentation, leading to absence or very poor discrimination between Aspergillus colonization and infection [19,23]. As a result, IA during COVID-19 has been reported with a possible overestimated high prevalence (until 30%), as favorable outcomes have been described in patients who did not receive any antifungal treatment.\nIn order to have a well-balanced patient management, limiting unnecessary and costly antifungal treatments while not neglecting the life-threatening feature of IA, we included A. fumigatus PCR as a monitoring tool for fungal detection in both respiratory and blood samples in addition to classical culture and GM approaches but with some restrictions. As expected, PCR allowed detecting Aspergillus in much more respiratory samples. We previously showed that PCR improved the detection of Aspergillus in BAL, with a particular added value in ICU patients compared to hematology patients [11]. Furthermore, PCR using in-house but also marketed kits is also capable of identifying specific gene mutations associated with azole resistance [11,24]. Besides, the sensitivity of GM detection in blood is less sensitive in ICU than for patients with hematological malignancies [5]. Here, the higher sensitivity of Aspergillus detection also incites us to adopt modified criteria for case definition to gain in specificity. Two major changes were introduced to modify the granularity of the classification: (i) the first one is to combine Aspergillus detection in respiratory samples and anti-Aspergillus antibody testing, to distinguish chronic colonization (positive serology) from acute massive colonization (negative serology) and (ii) the second is to introduce of obvious biomarkers of angioinvasion (serum GM and blood PCR), similar to those of the EORTC/MSG classification [2]. Of note, the combination of positive culture, positive anti-Aspergillus antibody testing and positive GM in the context of chronic respiratory diseases characterized a transition step from chronic pulmonary aspergillosis to probable IA [25,26].\nUsing this refined classification, we were able to categorize our patients in five classes: no infection, colonization, putative IA, probable IA and proven IA (no case of proven IA in the cohort), with a better relevance than the initial AspICU classification, and better specificity than the AspICU + PCR classification. The decision of antifungal treatment onset was taken according to this modified AspICU classification and the outcome observed gives confidence in this patient management. Of course, the limitation of this work is the relatively small number of patients and should be evaluated on larger cohorts in order to correctly analyze the performance of this alternative. A remaining question is also to determine the place of the serum biomarker (1,3)-β-d-glucan in ICU patients, a question that has recently been raised by Honoré et al. [27]\nIn conclusion, molecular techniques are now key tools for monitoring IFD, particularly IA as recently updated in the EORTC/MSG definitions, but also Pneumocystis jirovecii or mucorales infections. Here, we suggest some adaptations of the AspICU clinical algorithm to gain in sensitivity and specificity. Large multicentric data are needed to confirm this proof of concept study."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T24","span":{"begin":815,"end":820},"obj":"Body_part"},{"id":"T25","span":{"begin":1691,"end":1696},"obj":"Body_part"},{"id":"T26","span":{"begin":2455,"end":2460},"obj":"Body_part"},{"id":"T27","span":{"begin":2985,"end":2990},"obj":"Body_part"},{"id":"T28","span":{"begin":3595,"end":3600},"obj":"Body_part"},{"id":"T29","span":{"begin":3608,"end":3613},"obj":"Body_part"},{"id":"T30","span":{"begin":4663,"end":4668},"obj":"Body_part"}],"attributes":[{"id":"A24","pred":"uberon_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"},{"id":"A25","pred":"uberon_id","subj":"T25","obj":"http://purl.obolibrary.org/obo/UBERON_0001443"},{"id":"A26","pred":"uberon_id","subj":"T26","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A27","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A28","pred":"uberon_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"A29","pred":"uberon_id","subj":"T29","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A30","pred":"uberon_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"}],"text":"4. Discussion\nIn France, the global burden of severe fungal infection is estimated at approximately 1,000,000 (1.47%) cases each year [13] and IFD account for a higher risk of mortality in patients with co-morbidities from 9 to 40% [14]. During the COVID-19 pandemic, warning messages considering similarities between Sars-CoV-2 and influenza infections stressed the importance of vigilance towards IFD [15,16]. Local experiences are now published and show high numbers of putative IA [17,18,19,20,21,22].\nThe diagnosis of IA still remains challenging because of a wide diversity of underlying conditions and growing number of criteria, particularly biological tools [6]. In deeply immunosuppressed patients, such as neutropenic patients, patients under antineoplastic and prolonged corticosteroid therapy or solid organ transplantation, criteria for classification of IFD and notably IA have recently been revised incorporating Aspergillus molecular detection [2]. In ICU, the AspICU algorithm published by Blot et al., [3] is a robust and helpful tool for aspergillosis classification but needs to be more evaluated and even updated. In order to address limitations of the various classification definitions for ICU patients, the ongoing FUNgal infections Definitions in ICU patients (FUNDICU) project aims to develop a standard set of definitions for IFD in critically ill patients [5].\nThe breaking news of SARS-CoV-2 co-infection urges the need for a critical analysis of the criteria of AspICU algorithm. Indeed, COVID-19 patients, particularly ARDS patients with mechanical ventilation, present with compatible clinical signs as depicted by the algorithm (refractory fever, pleuritic chest pain and rub, dyspnea, hemoptysis and worsening respiratory insufficiency, see [3] for full description) and CT-scan signs are hard to interpret because of COVID-19 CT-scan presentation, leading to absence or very poor discrimination between Aspergillus colonization and infection [19,23]. As a result, IA during COVID-19 has been reported with a possible overestimated high prevalence (until 30%), as favorable outcomes have been described in patients who did not receive any antifungal treatment.\nIn order to have a well-balanced patient management, limiting unnecessary and costly antifungal treatments while not neglecting the life-threatening feature of IA, we included A. fumigatus PCR as a monitoring tool for fungal detection in both respiratory and blood samples in addition to classical culture and GM approaches but with some restrictions. As expected, PCR allowed detecting Aspergillus in much more respiratory samples. We previously showed that PCR improved the detection of Aspergillus in BAL, with a particular added value in ICU patients compared to hematology patients [11]. Furthermore, PCR using in-house but also marketed kits is also capable of identifying specific gene mutations associated with azole resistance [11,24]. Besides, the sensitivity of GM detection in blood is less sensitive in ICU than for patients with hematological malignancies [5]. Here, the higher sensitivity of Aspergillus detection also incites us to adopt modified criteria for case definition to gain in specificity. Two major changes were introduced to modify the granularity of the classification: (i) the first one is to combine Aspergillus detection in respiratory samples and anti-Aspergillus antibody testing, to distinguish chronic colonization (positive serology) from acute massive colonization (negative serology) and (ii) the second is to introduce of obvious biomarkers of angioinvasion (serum GM and blood PCR), similar to those of the EORTC/MSG classification [2]. Of note, the combination of positive culture, positive anti-Aspergillus antibody testing and positive GM in the context of chronic respiratory diseases characterized a transition step from chronic pulmonary aspergillosis to probable IA [25,26].\nUsing this refined classification, we were able to categorize our patients in five classes: no infection, colonization, putative IA, probable IA and proven IA (no case of proven IA in the cohort), with a better relevance than the initial AspICU classification, and better specificity than the AspICU + PCR classification. The decision of antifungal treatment onset was taken according to this modified AspICU classification and the outcome observed gives confidence in this patient management. Of course, the limitation of this work is the relatively small number of patients and should be evaluated on larger cohorts in order to correctly analyze the performance of this alternative. A remaining question is also to determine the place of the serum biomarker (1,3)-β-d-glucan in ICU patients, a question that has recently been raised by Honoré et al. [27]\nIn conclusion, molecular techniques are now key tools for monitoring IFD, particularly IA as recently updated in the EORTC/MSG definitions, but also Pneumocystis jirovecii or mucorales infections. Here, we suggest some adaptations of the AspICU clinical algorithm to gain in sensitivity and specificity. Large multicentric data are needed to confirm this proof of concept study."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T6","span":{"begin":1674,"end":1679},"obj":"Phenotype"},{"id":"T7","span":{"begin":1691,"end":1701},"obj":"Phenotype"},{"id":"T8","span":{"begin":1711,"end":1718},"obj":"Phenotype"},{"id":"T9","span":{"begin":1720,"end":1730},"obj":"Phenotype"},{"id":"T10","span":{"begin":1745,"end":1770},"obj":"Phenotype"}],"attributes":[{"id":"A6","pred":"hp_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/HP_0001945"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/HP_0100749"},{"id":"A8","pred":"hp_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/HP_0002094"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/HP_0002105"},{"id":"A10","pred":"hp_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/HP_0002093"}],"text":"4. Discussion\nIn France, the global burden of severe fungal infection is estimated at approximately 1,000,000 (1.47%) cases each year [13] and IFD account for a higher risk of mortality in patients with co-morbidities from 9 to 40% [14]. During the COVID-19 pandemic, warning messages considering similarities between Sars-CoV-2 and influenza infections stressed the importance of vigilance towards IFD [15,16]. Local experiences are now published and show high numbers of putative IA [17,18,19,20,21,22].\nThe diagnosis of IA still remains challenging because of a wide diversity of underlying conditions and growing number of criteria, particularly biological tools [6]. In deeply immunosuppressed patients, such as neutropenic patients, patients under antineoplastic and prolonged corticosteroid therapy or solid organ transplantation, criteria for classification of IFD and notably IA have recently been revised incorporating Aspergillus molecular detection [2]. In ICU, the AspICU algorithm published by Blot et al., [3] is a robust and helpful tool for aspergillosis classification but needs to be more evaluated and even updated. In order to address limitations of the various classification definitions for ICU patients, the ongoing FUNgal infections Definitions in ICU patients (FUNDICU) project aims to develop a standard set of definitions for IFD in critically ill patients [5].\nThe breaking news of SARS-CoV-2 co-infection urges the need for a critical analysis of the criteria of AspICU algorithm. Indeed, COVID-19 patients, particularly ARDS patients with mechanical ventilation, present with compatible clinical signs as depicted by the algorithm (refractory fever, pleuritic chest pain and rub, dyspnea, hemoptysis and worsening respiratory insufficiency, see [3] for full description) and CT-scan signs are hard to interpret because of COVID-19 CT-scan presentation, leading to absence or very poor discrimination between Aspergillus colonization and infection [19,23]. As a result, IA during COVID-19 has been reported with a possible overestimated high prevalence (until 30%), as favorable outcomes have been described in patients who did not receive any antifungal treatment.\nIn order to have a well-balanced patient management, limiting unnecessary and costly antifungal treatments while not neglecting the life-threatening feature of IA, we included A. fumigatus PCR as a monitoring tool for fungal detection in both respiratory and blood samples in addition to classical culture and GM approaches but with some restrictions. As expected, PCR allowed detecting Aspergillus in much more respiratory samples. We previously showed that PCR improved the detection of Aspergillus in BAL, with a particular added value in ICU patients compared to hematology patients [11]. Furthermore, PCR using in-house but also marketed kits is also capable of identifying specific gene mutations associated with azole resistance [11,24]. Besides, the sensitivity of GM detection in blood is less sensitive in ICU than for patients with hematological malignancies [5]. Here, the higher sensitivity of Aspergillus detection also incites us to adopt modified criteria for case definition to gain in specificity. Two major changes were introduced to modify the granularity of the classification: (i) the first one is to combine Aspergillus detection in respiratory samples and anti-Aspergillus antibody testing, to distinguish chronic colonization (positive serology) from acute massive colonization (negative serology) and (ii) the second is to introduce of obvious biomarkers of angioinvasion (serum GM and blood PCR), similar to those of the EORTC/MSG classification [2]. Of note, the combination of positive culture, positive anti-Aspergillus antibody testing and positive GM in the context of chronic respiratory diseases characterized a transition step from chronic pulmonary aspergillosis to probable IA [25,26].\nUsing this refined classification, we were able to categorize our patients in five classes: no infection, colonization, putative IA, probable IA and proven IA (no case of proven IA in the cohort), with a better relevance than the initial AspICU classification, and better specificity than the AspICU + PCR classification. The decision of antifungal treatment onset was taken according to this modified AspICU classification and the outcome observed gives confidence in this patient management. Of course, the limitation of this work is the relatively small number of patients and should be evaluated on larger cohorts in order to correctly analyze the performance of this alternative. A remaining question is also to determine the place of the serum biomarker (1,3)-β-d-glucan in ICU patients, a question that has recently been raised by Honoré et al. [27]\nIn conclusion, molecular techniques are now key tools for monitoring IFD, particularly IA as recently updated in the EORTC/MSG definitions, but also Pneumocystis jirovecii or mucorales infections. Here, we suggest some adaptations of the AspICU clinical algorithm to gain in sensitivity and specificity. Large multicentric data are needed to confirm this proof of concept study."}

LitCovid-PD-GlycoEpitope

{"project":"LitCovid-PD-GlycoEpitope","denotations":[{"id":"T15","span":{"begin":2506,"end":2508},"obj":"GlycoEpitope"},{"id":"T16","span":{"begin":2969,"end":2971},"obj":"GlycoEpitope"},{"id":"T17","span":{"begin":3601,"end":3603},"obj":"GlycoEpitope"},{"id":"T18","span":{"begin":3776,"end":3778},"obj":"GlycoEpitope"}],"attributes":[{"id":"A15","pred":"glyco_epitope_db_id","subj":"T15","obj":"http://www.glycoepitope.jp/epitopes/EP0510"},{"id":"A16","pred":"glyco_epitope_db_id","subj":"T16","obj":"http://www.glycoepitope.jp/epitopes/EP0510"},{"id":"A17","pred":"glyco_epitope_db_id","subj":"T17","obj":"http://www.glycoepitope.jp/epitopes/EP0510"},{"id":"A18","pred":"glyco_epitope_db_id","subj":"T18","obj":"http://www.glycoepitope.jp/epitopes/EP0510"}],"text":"4. Discussion\nIn France, the global burden of severe fungal infection is estimated at approximately 1,000,000 (1.47%) cases each year [13] and IFD account for a higher risk of mortality in patients with co-morbidities from 9 to 40% [14]. During the COVID-19 pandemic, warning messages considering similarities between Sars-CoV-2 and influenza infections stressed the importance of vigilance towards IFD [15,16]. Local experiences are now published and show high numbers of putative IA [17,18,19,20,21,22].\nThe diagnosis of IA still remains challenging because of a wide diversity of underlying conditions and growing number of criteria, particularly biological tools [6]. In deeply immunosuppressed patients, such as neutropenic patients, patients under antineoplastic and prolonged corticosteroid therapy or solid organ transplantation, criteria for classification of IFD and notably IA have recently been revised incorporating Aspergillus molecular detection [2]. In ICU, the AspICU algorithm published by Blot et al., [3] is a robust and helpful tool for aspergillosis classification but needs to be more evaluated and even updated. In order to address limitations of the various classification definitions for ICU patients, the ongoing FUNgal infections Definitions in ICU patients (FUNDICU) project aims to develop a standard set of definitions for IFD in critically ill patients [5].\nThe breaking news of SARS-CoV-2 co-infection urges the need for a critical analysis of the criteria of AspICU algorithm. Indeed, COVID-19 patients, particularly ARDS patients with mechanical ventilation, present with compatible clinical signs as depicted by the algorithm (refractory fever, pleuritic chest pain and rub, dyspnea, hemoptysis and worsening respiratory insufficiency, see [3] for full description) and CT-scan signs are hard to interpret because of COVID-19 CT-scan presentation, leading to absence or very poor discrimination between Aspergillus colonization and infection [19,23]. As a result, IA during COVID-19 has been reported with a possible overestimated high prevalence (until 30%), as favorable outcomes have been described in patients who did not receive any antifungal treatment.\nIn order to have a well-balanced patient management, limiting unnecessary and costly antifungal treatments while not neglecting the life-threatening feature of IA, we included A. fumigatus PCR as a monitoring tool for fungal detection in both respiratory and blood samples in addition to classical culture and GM approaches but with some restrictions. As expected, PCR allowed detecting Aspergillus in much more respiratory samples. We previously showed that PCR improved the detection of Aspergillus in BAL, with a particular added value in ICU patients compared to hematology patients [11]. Furthermore, PCR using in-house but also marketed kits is also capable of identifying specific gene mutations associated with azole resistance [11,24]. Besides, the sensitivity of GM detection in blood is less sensitive in ICU than for patients with hematological malignancies [5]. Here, the higher sensitivity of Aspergillus detection also incites us to adopt modified criteria for case definition to gain in specificity. Two major changes were introduced to modify the granularity of the classification: (i) the first one is to combine Aspergillus detection in respiratory samples and anti-Aspergillus antibody testing, to distinguish chronic colonization (positive serology) from acute massive colonization (negative serology) and (ii) the second is to introduce of obvious biomarkers of angioinvasion (serum GM and blood PCR), similar to those of the EORTC/MSG classification [2]. Of note, the combination of positive culture, positive anti-Aspergillus antibody testing and positive GM in the context of chronic respiratory diseases characterized a transition step from chronic pulmonary aspergillosis to probable IA [25,26].\nUsing this refined classification, we were able to categorize our patients in five classes: no infection, colonization, putative IA, probable IA and proven IA (no case of proven IA in the cohort), with a better relevance than the initial AspICU classification, and better specificity than the AspICU + PCR classification. The decision of antifungal treatment onset was taken according to this modified AspICU classification and the outcome observed gives confidence in this patient management. Of course, the limitation of this work is the relatively small number of patients and should be evaluated on larger cohorts in order to correctly analyze the performance of this alternative. A remaining question is also to determine the place of the serum biomarker (1,3)-β-d-glucan in ICU patients, a question that has recently been raised by Honoré et al. [27]\nIn conclusion, molecular techniques are now key tools for monitoring IFD, particularly IA as recently updated in the EORTC/MSG definitions, but also Pneumocystis jirovecii or mucorales infections. Here, we suggest some adaptations of the AspICU clinical algorithm to gain in sensitivity and specificity. Large multicentric data are needed to confirm this proof of concept study."}

LitCovid-sentences

LitCovid-PubTator

2_test

{"project":"2_test","denotations":[{"id":"32664423-27887809-60101700","span":{"begin":135,"end":137},"obj":"27887809"},{"id":"32664423-24960557-60101701","span":{"begin":233,"end":235},"obj":"24960557"},{"id":"32664423-32835328-60101702","span":{"begin":404,"end":406},"obj":"32835328"},{"id":"32664423-32307254-60101703","span":{"begin":407,"end":409},"obj":"32307254"},{"id":"32664423-32339350-60101704","span":{"begin":492,"end":494},"obj":"32339350"},{"id":"32664423-32396381-60101705","span":{"begin":498,"end":500},"obj":"32396381"},{"id":"32664423-32224310-60101706","span":{"begin":501,"end":503},"obj":"32224310"},{"id":"32664423-22517788-60101707","span":{"begin":1022,"end":1023},"obj":"22517788"},{"id":"32664423-22517788-60101708","span":{"begin":1777,"end":1778},"obj":"22517788"},{"id":"32664423-32339350-60101709","span":{"begin":1979,"end":1981},"obj":"32339350"},{"id":"32664423-32488446-60101710","span":{"begin":1982,"end":1984},"obj":"32488446"},{"id":"32664423-29248586-60101711","span":{"begin":2784,"end":2786},"obj":"29248586"},{"id":"32664423-29248586-60101712","span":{"begin":2933,"end":2935},"obj":"29248586"},{"id":"32664423-25903571-60101713","span":{"begin":2936,"end":2938},"obj":"25903571"},{"id":"32664423-17906086-60101714","span":{"begin":3911,"end":3913},"obj":"17906086"},{"id":"32664423-26699723-60101715","span":{"begin":3914,"end":3916},"obj":"26699723"},{"id":"32664423-32503673-60101716","span":{"begin":4772,"end":4774},"obj":"32503673"}],"text":"4. Discussion\nIn France, the global burden of severe fungal infection is estimated at approximately 1,000,000 (1.47%) cases each year [13] and IFD account for a higher risk of mortality in patients with co-morbidities from 9 to 40% [14]. During the COVID-19 pandemic, warning messages considering similarities between Sars-CoV-2 and influenza infections stressed the importance of vigilance towards IFD [15,16]. Local experiences are now published and show high numbers of putative IA [17,18,19,20,21,22].\nThe diagnosis of IA still remains challenging because of a wide diversity of underlying conditions and growing number of criteria, particularly biological tools [6]. In deeply immunosuppressed patients, such as neutropenic patients, patients under antineoplastic and prolonged corticosteroid therapy or solid organ transplantation, criteria for classification of IFD and notably IA have recently been revised incorporating Aspergillus molecular detection [2]. In ICU, the AspICU algorithm published by Blot et al., [3] is a robust and helpful tool for aspergillosis classification but needs to be more evaluated and even updated. In order to address limitations of the various classification definitions for ICU patients, the ongoing FUNgal infections Definitions in ICU patients (FUNDICU) project aims to develop a standard set of definitions for IFD in critically ill patients [5].\nThe breaking news of SARS-CoV-2 co-infection urges the need for a critical analysis of the criteria of AspICU algorithm. Indeed, COVID-19 patients, particularly ARDS patients with mechanical ventilation, present with compatible clinical signs as depicted by the algorithm (refractory fever, pleuritic chest pain and rub, dyspnea, hemoptysis and worsening respiratory insufficiency, see [3] for full description) and CT-scan signs are hard to interpret because of COVID-19 CT-scan presentation, leading to absence or very poor discrimination between Aspergillus colonization and infection [19,23]. As a result, IA during COVID-19 has been reported with a possible overestimated high prevalence (until 30%), as favorable outcomes have been described in patients who did not receive any antifungal treatment.\nIn order to have a well-balanced patient management, limiting unnecessary and costly antifungal treatments while not neglecting the life-threatening feature of IA, we included A. fumigatus PCR as a monitoring tool for fungal detection in both respiratory and blood samples in addition to classical culture and GM approaches but with some restrictions. As expected, PCR allowed detecting Aspergillus in much more respiratory samples. We previously showed that PCR improved the detection of Aspergillus in BAL, with a particular added value in ICU patients compared to hematology patients [11]. Furthermore, PCR using in-house but also marketed kits is also capable of identifying specific gene mutations associated with azole resistance [11,24]. Besides, the sensitivity of GM detection in blood is less sensitive in ICU than for patients with hematological malignancies [5]. Here, the higher sensitivity of Aspergillus detection also incites us to adopt modified criteria for case definition to gain in specificity. Two major changes were introduced to modify the granularity of the classification: (i) the first one is to combine Aspergillus detection in respiratory samples and anti-Aspergillus antibody testing, to distinguish chronic colonization (positive serology) from acute massive colonization (negative serology) and (ii) the second is to introduce of obvious biomarkers of angioinvasion (serum GM and blood PCR), similar to those of the EORTC/MSG classification [2]. Of note, the combination of positive culture, positive anti-Aspergillus antibody testing and positive GM in the context of chronic respiratory diseases characterized a transition step from chronic pulmonary aspergillosis to probable IA [25,26].\nUsing this refined classification, we were able to categorize our patients in five classes: no infection, colonization, putative IA, probable IA and proven IA (no case of proven IA in the cohort), with a better relevance than the initial AspICU classification, and better specificity than the AspICU + PCR classification. The decision of antifungal treatment onset was taken according to this modified AspICU classification and the outcome observed gives confidence in this patient management. Of course, the limitation of this work is the relatively small number of patients and should be evaluated on larger cohorts in order to correctly analyze the performance of this alternative. A remaining question is also to determine the place of the serum biomarker (1,3)-β-d-glucan in ICU patients, a question that has recently been raised by Honoré et al. [27]\nIn conclusion, molecular techniques are now key tools for monitoring IFD, particularly IA as recently updated in the EORTC/MSG definitions, but also Pneumocystis jirovecii or mucorales infections. Here, we suggest some adaptations of the AspICU clinical algorithm to gain in sensitivity and specificity. Large multicentric data are needed to confirm this proof of concept study."}

PMC:7558333 / 14679-19833 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7558333 / 14679-19833 JSON TXT