PMC:7558333 / 8508-14677
Annnotations
LitCovid-PD-FMA-UBERON
{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T23","span":{"begin":260,"end":265},"obj":"Body_part"},{"id":"T24","span":{"begin":625,"end":630},"obj":"Body_part"},{"id":"T25","span":{"begin":1210,"end":1215},"obj":"Body_part"},{"id":"T26","span":{"begin":1332,"end":1337},"obj":"Body_part"},{"id":"T27","span":{"begin":1984,"end":1991},"obj":"Body_part"},{"id":"T28","span":{"begin":2378,"end":2381},"obj":"Body_part"},{"id":"T29","span":{"begin":3164,"end":3169},"obj":"Body_part"},{"id":"T30","span":{"begin":4071,"end":4076},"obj":"Body_part"},{"id":"T31","span":{"begin":4319,"end":4324},"obj":"Body_part"},{"id":"T32","span":{"begin":4503,"end":4520},"obj":"Body_part"},{"id":"T33","span":{"begin":4649,"end":4657},"obj":"Body_part"},{"id":"T34","span":{"begin":4864,"end":4869},"obj":"Body_part"},{"id":"T35","span":{"begin":5075,"end":5083},"obj":"Body_part"}],"attributes":[{"id":"A23","pred":"fma_id","subj":"T23","obj":"http://purl.org/sig/ont/fma/fma63083"},{"id":"A24","pred":"fma_id","subj":"T24","obj":"http://purl.org/sig/ont/fma/fma63083"},{"id":"A25","pred":"fma_id","subj":"T25","obj":"http://purl.org/sig/ont/fma/fma9576"},{"id":"A26","pred":"fma_id","subj":"T26","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A27","pred":"fma_id","subj":"T27","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A28","pred":"fma_id","subj":"T28","obj":"http://purl.org/sig/ont/fma/fma74412"},{"id":"A29","pred":"fma_id","subj":"T29","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A30","pred":"fma_id","subj":"T30","obj":"http://purl.org/sig/ont/fma/fma9576"},{"id":"A31","pred":"fma_id","subj":"T31","obj":"http://purl.org/sig/ont/fma/fma63083"},{"id":"A32","pred":"fma_id","subj":"T32","obj":"http://purl.org/sig/ont/fma/fma265130"},{"id":"A33","pred":"fma_id","subj":"T33","obj":"http://purl.org/sig/ont/fma/fma62871"},{"id":"A34","pred":"fma_id","subj":"T34","obj":"http://purl.org/sig/ont/fma/fma63083"},{"id":"A35","pred":"fma_id","subj":"T35","obj":"http://purl.org/sig/ont/fma/fma264783"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-PD-UBERON
{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T15","span":{"begin":260,"end":265},"obj":"Body_part"},{"id":"T16","span":{"begin":625,"end":630},"obj":"Body_part"},{"id":"T17","span":{"begin":1210,"end":1215},"obj":"Body_part"},{"id":"T18","span":{"begin":1332,"end":1337},"obj":"Body_part"},{"id":"T19","span":{"begin":3164,"end":3169},"obj":"Body_part"},{"id":"T20","span":{"begin":4071,"end":4076},"obj":"Body_part"},{"id":"T21","span":{"begin":4319,"end":4324},"obj":"Body_part"},{"id":"T22","span":{"begin":4503,"end":4520},"obj":"Body_part"},{"id":"T23","span":{"begin":4864,"end":4869},"obj":"Body_part"}],"attributes":[{"id":"A15","pred":"uberon_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"A16","pred":"uberon_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"A17","pred":"uberon_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/UBERON_0001443"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A19","pred":"uberon_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A20","pred":"uberon_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/UBERON_0001443"},{"id":"A21","pred":"uberon_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"A22","pred":"uberon_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/UBERON_0000065"},{"id":"A23","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-PD-MONDO
{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T46","span":{"begin":59,"end":67},"obj":"Disease"},{"id":"T47","span":{"begin":119,"end":123},"obj":"Disease"},{"id":"T48","span":{"begin":731,"end":744},"obj":"Disease"},{"id":"T49","span":{"begin":879,"end":892},"obj":"Disease"},{"id":"T50","span":{"begin":1128,"end":1136},"obj":"Disease"},{"id":"T51","span":{"begin":1146,"end":1150},"obj":"Disease"},{"id":"T52","span":{"begin":1433,"end":1435},"obj":"Disease"},{"id":"T53","span":{"begin":1725,"end":1738},"obj":"Disease"},{"id":"T54","span":{"begin":1784,"end":1797},"obj":"Disease"},{"id":"T55","span":{"begin":2020,"end":2033},"obj":"Disease"},{"id":"T56","span":{"begin":2238,"end":2260},"obj":"Disease"},{"id":"T57","span":{"begin":2247,"end":2260},"obj":"Disease"},{"id":"T58","span":{"begin":3838,"end":3840},"obj":"Disease"},{"id":"T59","span":{"begin":3919,"end":3921},"obj":"Disease"},{"id":"T60","span":{"begin":4752,"end":4754},"obj":"Disease"},{"id":"T61","span":{"begin":4811,"end":4813},"obj":"Disease"},{"id":"T62","span":{"begin":5143,"end":5145},"obj":"Disease"},{"id":"T63","span":{"begin":5186,"end":5188},"obj":"Disease"},{"id":"T64","span":{"begin":5281,"end":5289},"obj":"Disease"},{"id":"T65","span":{"begin":5290,"end":5299},"obj":"Disease"},{"id":"T66","span":{"begin":5351,"end":5364},"obj":"Disease"},{"id":"T67","span":{"begin":5423,"end":5436},"obj":"Disease"},{"id":"T68","span":{"begin":5546,"end":5555},"obj":"Disease"},{"id":"T69","span":{"begin":5574,"end":5576},"obj":"Disease"},{"id":"T70","span":{"begin":5684,"end":5697},"obj":"Disease"},{"id":"T71","span":{"begin":5765,"end":5787},"obj":"Disease"},{"id":"T72","span":{"begin":5774,"end":5787},"obj":"Disease"},{"id":"T73","span":{"begin":5838,"end":5840},"obj":"Disease"},{"id":"T74","span":{"begin":6051,"end":6053},"obj":"Disease"}],"attributes":[{"id":"A46","pred":"mondo_id","subj":"T46","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A47","pred":"mondo_id","subj":"T47","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A48","pred":"mondo_id","subj":"T48","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A49","pred":"mondo_id","subj":"T49","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A50","pred":"mondo_id","subj":"T50","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A51","pred":"mondo_id","subj":"T51","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A52","pred":"mondo_id","subj":"T52","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A53","pred":"mondo_id","subj":"T53","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A54","pred":"mondo_id","subj":"T54","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A55","pred":"mondo_id","subj":"T55","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A56","pred":"mondo_id","subj":"T56","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A57","pred":"mondo_id","subj":"T57","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A58","pred":"mondo_id","subj":"T58","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A59","pred":"mondo_id","subj":"T59","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A60","pred":"mondo_id","subj":"T60","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A61","pred":"mondo_id","subj":"T61","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A62","pred":"mondo_id","subj":"T62","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A63","pred":"mondo_id","subj":"T63","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A64","pred":"mondo_id","subj":"T64","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A65","pred":"mondo_id","subj":"T65","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A66","pred":"mondo_id","subj":"T66","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A67","pred":"mondo_id","subj":"T67","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A68","pred":"mondo_id","subj":"T68","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A69","pred":"mondo_id","subj":"T69","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A70","pred":"mondo_id","subj":"T70","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A71","pred":"mondo_id","subj":"T71","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A72","pred":"mondo_id","subj":"T72","obj":"http://purl.obolibrary.org/obo/MONDO_0005657"},{"id":"A73","pred":"mondo_id","subj":"T73","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"},{"id":"A74","pred":"mondo_id","subj":"T74","obj":"http://purl.obolibrary.org/obo/MONDO_0000240"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-PD-CLO
{"project":"LitCovid-PD-CLO","denotations":[{"id":"T55","span":{"begin":44,"end":45},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T56","span":{"begin":56,"end":58},"obj":"http://purl.obolibrary.org/obo/CLO_0053799"},{"id":"T57","span":{"begin":162,"end":163},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T58","span":{"begin":440,"end":442},"obj":"http://purl.obolibrary.org/obo/CLO_0053799"},{"id":"T59","span":{"begin":644,"end":645},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T60","span":{"begin":1210,"end":1215},"obj":"http://www.ebi.ac.uk/efo/EFO_0000965"},{"id":"T61","span":{"begin":1284,"end":1285},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T62","span":{"begin":1332,"end":1337},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"T63","span":{"begin":1332,"end":1337},"obj":"http://www.ebi.ac.uk/efo/EFO_0000296"},{"id":"T64","span":{"begin":1379,"end":1388},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T65","span":{"begin":1413,"end":1414},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T66","span":{"begin":1627,"end":1629},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T67","span":{"begin":1752,"end":1764},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T68","span":{"begin":1821,"end":1822},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T69","span":{"begin":1850,"end":1854},"obj":"http://purl.obolibrary.org/obo/UBERON_0003101"},{"id":"T70","span":{"begin":1850,"end":1854},"obj":"http://www.ebi.ac.uk/efo/EFO_0000970"},{"id":"T71","span":{"begin":2436,"end":2437},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T72","span":{"begin":2620,"end":2621},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T73","span":{"begin":2742,"end":2743},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T74","span":{"begin":2840,"end":2841},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T75","span":{"begin":2898,"end":2899},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T76","span":{"begin":3116,"end":3117},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T77","span":{"begin":3164,"end":3169},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"T78","span":{"begin":3164,"end":3169},"obj":"http://www.ebi.ac.uk/efo/EFO_0000296"},{"id":"T79","span":{"begin":3198,"end":3199},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T80","span":{"begin":3222,"end":3223},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T81","span":{"begin":3252,"end":3253},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T82","span":{"begin":3279,"end":3280},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T83","span":{"begin":3327,"end":3328},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T84","span":{"begin":3529,"end":3530},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T85","span":{"begin":3594,"end":3599},"obj":"http://purl.obolibrary.org/obo/UBERON_0000473"},{"id":"T86","span":{"begin":3686,"end":3688},"obj":"http://purl.obolibrary.org/obo/CLO_0053799"},{"id":"T87","span":{"begin":3827,"end":3828},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T88","span":{"begin":3842,"end":3844},"obj":"http://purl.obolibrary.org/obo/CLO_0050507"},{"id":"T89","span":{"begin":4000,"end":4009},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T90","span":{"begin":4071,"end":4076},"obj":"http://www.ebi.ac.uk/efo/EFO_0000965"},{"id":"T91","span":{"begin":4148,"end":4149},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T92","span":{"begin":4252,"end":4261},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T93","span":{"begin":4289,"end":4290},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T94","span":{"begin":4401,"end":4402},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T95","span":{"begin":4466,"end":4467},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T96","span":{"begin":4586,"end":4587},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T97","span":{"begin":4596,"end":4608},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T98","span":{"begin":4658,"end":4669},"obj":"http://purl.obolibrary.org/obo/UBERON_0000473"},{"id":"T99","span":{"begin":4825,"end":4826},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T100","span":{"begin":5014,"end":5015},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T101","span":{"begin":5194,"end":5206},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T102","span":{"begin":5523,"end":5524},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T103","span":{"begin":5557,"end":5569},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T104","span":{"begin":5709,"end":5721},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T105","span":{"begin":5736,"end":5738},"obj":"http://purl.obolibrary.org/obo/CLO_0050509"},{"id":"T106","span":{"begin":5818,"end":5819},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T107","span":{"begin":5906,"end":5915},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"T108","span":{"begin":5984,"end":5985},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T109","span":{"begin":6113,"end":6116},"obj":"http://purl.obolibrary.org/obo/CLO_0050509"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-PD-GO-BP
{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T5","span":{"begin":4157,"end":4175},"obj":"http://purl.obolibrary.org/obo/GO_0016046"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-PD-GlycoEpitope
{"project":"LitCovid-PD-GlycoEpitope","denotations":[{"id":"T11","span":{"begin":275,"end":277},"obj":"GlycoEpitope"},{"id":"T12","span":{"begin":3290,"end":3292},"obj":"GlycoEpitope"},{"id":"T13","span":{"begin":4303,"end":4305},"obj":"GlycoEpitope"},{"id":"T14","span":{"begin":4881,"end":4883},"obj":"GlycoEpitope"}],"attributes":[{"id":"A11","pred":"glyco_epitope_db_id","subj":"T11","obj":"http://www.glycoepitope.jp/epitopes/EP0510"},{"id":"A12","pred":"glyco_epitope_db_id","subj":"T12","obj":"http://www.glycoepitope.jp/epitopes/EP0510"},{"id":"A13","pred":"glyco_epitope_db_id","subj":"T13","obj":"http://www.glycoepitope.jp/epitopes/EP0510"},{"id":"A14","pred":"glyco_epitope_db_id","subj":"T14","obj":"http://www.glycoepitope.jp/epitopes/EP0510"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-sentences
{"project":"LitCovid-sentences","denotations":[{"id":"T66","span":{"begin":0,"end":2},"obj":"Sentence"},{"id":"T67","span":{"begin":3,"end":10},"obj":"Sentence"},{"id":"T68","span":{"begin":12,"end":16},"obj":"Sentence"},{"id":"T69","span":{"begin":17,"end":43},"obj":"Sentence"},{"id":"T70","span":{"begin":44,"end":137},"obj":"Sentence"},{"id":"T71","span":{"begin":138,"end":201},"obj":"Sentence"},{"id":"T72","span":{"begin":202,"end":324},"obj":"Sentence"},{"id":"T73","span":{"begin":325,"end":418},"obj":"Sentence"},{"id":"T74","span":{"begin":419,"end":671},"obj":"Sentence"},{"id":"T75","span":{"begin":672,"end":772},"obj":"Sentence"},{"id":"T76","span":{"begin":773,"end":1088},"obj":"Sentence"},{"id":"T77","span":{"begin":1089,"end":1458},"obj":"Sentence"},{"id":"T78","span":{"begin":1460,"end":1464},"obj":"Sentence"},{"id":"T79","span":{"begin":1465,"end":1517},"obj":"Sentence"},{"id":"T80","span":{"begin":1518,"end":1630},"obj":"Sentence"},{"id":"T81","span":{"begin":1631,"end":1799},"obj":"Sentence"},{"id":"T82","span":{"begin":1800,"end":1888},"obj":"Sentence"},{"id":"T83","span":{"begin":1889,"end":2041},"obj":"Sentence"},{"id":"T84","span":{"begin":2042,"end":2261},"obj":"Sentence"},{"id":"T85","span":{"begin":2263,"end":2267},"obj":"Sentence"},{"id":"T86","span":{"begin":2268,"end":2299},"obj":"Sentence"},{"id":"T87","span":{"begin":2300,"end":2377},"obj":"Sentence"},{"id":"T88","span":{"begin":2378,"end":2520},"obj":"Sentence"},{"id":"T89","span":{"begin":2521,"end":2755},"obj":"Sentence"},{"id":"T90","span":{"begin":2756,"end":3015},"obj":"Sentence"},{"id":"T91","span":{"begin":3016,"end":3153},"obj":"Sentence"},{"id":"T92","span":{"begin":3154,"end":3243},"obj":"Sentence"},{"id":"T93","span":{"begin":3244,"end":3303},"obj":"Sentence"},{"id":"T94","span":{"begin":3304,"end":3428},"obj":"Sentence"},{"id":"T95","span":{"begin":3429,"end":3566},"obj":"Sentence"},{"id":"T96","span":{"begin":3568,"end":3572},"obj":"Sentence"},{"id":"T97","span":{"begin":3573,"end":3642},"obj":"Sentence"},{"id":"T98","span":{"begin":3643,"end":3743},"obj":"Sentence"},{"id":"T99","span":{"begin":3744,"end":3861},"obj":"Sentence"},{"id":"T100","span":{"begin":3862,"end":4095},"obj":"Sentence"},{"id":"T101","span":{"begin":4096,"end":4262},"obj":"Sentence"},{"id":"T102","span":{"begin":4263,"end":4425},"obj":"Sentence"},{"id":"T103","span":{"begin":4426,"end":4564},"obj":"Sentence"},{"id":"T104","span":{"begin":4565,"end":4708},"obj":"Sentence"},{"id":"T105","span":{"begin":4709,"end":4928},"obj":"Sentence"},{"id":"T106","span":{"begin":4929,"end":5053},"obj":"Sentence"},{"id":"T107","span":{"begin":5054,"end":5319},"obj":"Sentence"},{"id":"T108","span":{"begin":5320,"end":5587},"obj":"Sentence"},{"id":"T109","span":{"begin":5588,"end":5799},"obj":"Sentence"},{"id":"T110","span":{"begin":5800,"end":5896},"obj":"Sentence"},{"id":"T111","span":{"begin":5897,"end":5954},"obj":"Sentence"},{"id":"T112","span":{"begin":5955,"end":6169},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}
LitCovid-PubTator
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ESH:D003643"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"3. Results\n\n3.1. Patient Aspergillus Status\nA cohort of 45 COVID-19 intubated and mechanically ventilated patients for ARDS was followed. Patients benefited from a systematic screening for Aspergillus. Overall, 211 respiratory samples (culture and PCR) and 32 serum samples (GM detection and Aspergillus PCR) were collected. The mean number of respiratory samples until patient discharge from ICU was 3.8 (median = 3).\nWe categorized these 45 patients according to the AspICU algorithm and propose two alternative classification methods presented in Table 1: the AspICU algorithm associated to PCR results in respiratory and serum samples, and a modified AspICU proposal. Thirty patients did not present any biological criteria of aspergillosis with any of the algorithms. According to the AspICU classification incorporating PCR detection, 15 were classified as having putative aspergillosis because they met all criteria reported by Blot et al., i.e., compatible clinical signs, abnormal thoracic medical imaging on CT scan and positive screening for Aspergillus on respiratory samples. However, in this particular context of COVID-19 with all ARDS patients presenting compatible clinical signs and abnormal chest CT imaging in all likelihood lacking specificity, we decided to use a modified AspICU algorithm taking into account blood markers; we classified eight patients as colonized and seven patients with a putative/probable IA (Table 1 and Table 2).\n\n3.2. Demographic, Clinical and Biological Characteristics\nDemographic, clinical and biological baseline characteristics at admission are detailed in Table 3 and Table S1. Basic demographic characteristics were well-balanced between the three groups of patients (no aspergillosis, Aspergillus colonization, putative/probable aspergillosis). Of note, we observed a high proportion (71.1%) of male patients in the study population. Clinical and biological baseline data did not differ among the three groups, except C-reactive protein which was higher in the “no aspergillosis” group. Regarding the severity scores at admission, no differences were observed either, among the groups of patients, but SAPS II and SOFA scores at day one tended to be higher in patients with putative invasive aspergillosis.\n\n3.3. Concordance of Diagnostic Tools\nTable 4 gathers the results of the techniques used for Aspergillus detection. DNA detection by PCR showed the highest sensitivity, with a number of positive respiratory samples near twice higher, compared to the culture. Only one sample grew in culture, whereas PCR was negative, but the species obtained in culture was A. tubingensis (Nigri complex species), which is theoretically not amplified when using the 28S-targeted PCR specific for A. fumigatus. Interestingly, the correlation between cultural and molecular quantification showed a significant difference between the two techniques, with a mean Cq threshold of 32.6 ± 0.7 when cultures were negative, highlighting the higher sensitivity of PCR (Figure 1).\nOverall, the concordance coefficient between PCR and culture on respiratory samples was 90.52% with a Cohen’s Kappa coefficient of 0.588. Regarding blood samples, three patients had a positive detection of a systemic biomarker: 3/3 had a positive PCR and 2/3 had a positive GM (Table 5). All three patients had a simultaneous detection of Aspergillus in respiratory samples by culture (n = 2) and/or PCR (n = 3). Overall, the concordance coefficient between PCR and culture on respiratory samples was 93.75% with a Cohen’s Kappa coefficient of 0.632.\n\n3.4. Relevance of Various Tests and Categorization of Patients and Outcome\nTable 6 presents the classification of the 45 patients using original or modified AspICU algorithms. It appears that using an AspICU algorithm, nine patients were considered as having a putative IA (22% of the cohort). When including PCR, the number of patients with putative IA would increase from 9 to 15 (33%) patients, while most patients might be only colonized because all presented compatible clinical signs and abnormal chest CT scan (Table 5). Regarding Aspergillus detection, eight patients had a single detection of fungi using culture and/or PCR in respiratory samples and thus were classified as colonized. One of these patients had a concomitant GM detection in serum (index = 0.551), was not treated and is still alive, thus was considered as a false positive result. Finally, seven (16%) patients presented a heavy burden of Aspergillus in the respiratory tract with repeated positive cultures and/or PCR. In order to rule out a chronic colonization before the episode, an anti-Aspergillus antibody testing was performed and showed negative results. These patients were classified as putative IA, and three of them could even be considered as probable IA because of a positive biomarker of angioinvasion (serum PCR and/or GM) in agreement with EORTC/MSG classification.\nInterestingly, following these classification criteria, CT scan abnormalities showed a gradation according to patient group. Diffuse reticular or alveolar opacities were observed in patients classified as probable IA (Figure 2), nodules in half of putative IA, and in colonized patients, only non-specific and hard to interpret signs in the context of COVID-19 infection could be described.\nIn addition, putative/probable aspergillosis patients appeared more severely ill than patients without aspergillosis, since SOFA score at day seven was significantly higher in this group (p = 0.01) with a continuum between no infection, colonization and IA (Table 5). Similarly, the mean ICU length of stay increased significantly from 12 days in patients without aspergillosis to 23 days in colonized patients, and 27 days in putative/probable invasive aspergillosis (p = 0.02). All patients with a putative/probable IA were treated either with voriconazole or isavuconazole. Only one colonized patient was treated with voriconazole. Six patients died; there was a trend towards higher mortality in the group of putative/probable IA compared to uninfected patients, although not significant (2/7; 28.6%) versus 4/30 (13.3%), respectively (Table 7)."}