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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319960

ABSTRACT

Background: Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern, in particular for those with acute respiratory distress syndrome (ARDS). As observed previously for influenza-associated ARDS, the SARS-CoV-2 pandemic has shown a high proportion of COVID-19 patients with ARDS to be at risk of developing invasive fungal diseases.MethodsWe used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological and radiological aspects of IAPA and CAPA in a monocentric retrospective study.ResultsAmong the 120 ARDS patients included, we observed equivalent prevalence of IPA in Influenza and COVID-19 populations: 17 IAPA (23.9%) and 10 CAPA (20.4%). There were no significant differences in demographic or admission characteristics between patients with and without IPA. Kaplan-Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA. The duration of mechanical ventilation was higher for IPA patients (23 days [IQR 17–40] than those without (17 days [IQR 9–25], p  = 0.038). Patients with COVID-19 and influenza associated ARDS treated with corticosteroids were more likely to develop IPA. Radiological findings of IPA in both populations using the new criteria increased sensitivity but with still poor specificity. Nonetheless, they also showed interesting differences between IAPA and CAPA with a higher proportion of features suggestive of IPA in IAPA patients. Lastly, therapeutic drug monitoring also appeared challenging since a wide proportion of IPA patients had low plasma voriconazole concentrations, with a significant higher delay to reach voriconazole concentrations > 2mg/L in CAPA versus IAPA patients ( p  = 0.045).ConclusionsICU patients presenting with ARDS during COVID-19 are very similar to those with severe influenza pneumonia in terms of prevalence of IPA and outcome, while CAPA is mainly favored by advanced age irrespective of the background. The dramatic consequences on the patients' prognosis emphasize the need for a better awareness in these particular populations. Larger prospective studies may help in designing the most well-adapted personalized management to prevent IPA, which represents a high burden of death in severe COVID-19 and Influenza pneumonia.

2.
Lancet Respir Med ; 10(2): 180-190, 2022 02.
Article in English | MEDLINE | ID: covidwho-1537209

ABSTRACT

BACKGROUND: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. METHODS: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. FINDINGS: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001). INTERPRETATION: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. FUNDING: Pfizer.


Subject(s)
COVID-19 , Pulmonary Aspergillosis , Adolescent , Adult , Child, Preschool , Humans , Intensive Care Units , Male , Middle Aged , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
3.
Mycoses ; 64(9): 980-988, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1273123

ABSTRACT

It is now well known that patients with SARS-CoV-2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS-CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID-19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non-surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.


Subject(s)
Antifungal Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/microbiology , Cause of Death , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Intensive Care Units , Male , Middle Aged , SARS-CoV-2
4.
J Fungi (Basel) ; 7(5)2021 May 15.
Article in English | MEDLINE | ID: covidwho-1234760

ABSTRACT

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

5.
J Fungi (Basel) ; 6(3)2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-646390

ABSTRACT

(1) Background: The diagnosis of invasive aspergillosis (IA) in an intensive care unit (ICU)remains a challenge and the COVID-19 epidemic makes it even harder. Here, we evaluatedAspergillus PCR input to help classifying IA in SARS-CoV-2-infected patients. (2) Methods: 45COVID-19 patients were prospectively monitored twice weekly for Aspergillus markers and anti-Aspergillus serology. We evaluated the concordance between (Ι) Aspergillus PCR and culture inrespiratory samples, and (ΙΙ) blood PCR and serum galactomannan. Patients were classified asputative/proven/colonized using AspICU algorithm and two other methods. (3) Results: Theconcordance of techniques applied on respiratory and blood samples was moderate (kappa = 0.58and kappa = 0.63, respectively), with a higher sensitivity of PCR. According to AspICU, 9/45 patientswere classified as putative IA. When incorporating PCR results, 15 were putative IA because theymet all criteria, probably with a lack of specificity in the context of COVID-19. Using a modifiedAspICU algorithm, eight patients were classified as colonized and seven as putative IA. (4)Conclusion: An appreciation of the fungal burden using PCR and Aspergillus serology was addedto propose a modified AspICU algorithm. This proof of concept seemed relevant, as it was inagreement with the outcome of patients, but will need validation in larger cohorts.

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