Pulmonary aspergillosis in critically ill patients with Coronavirus Disease 2019 (COVID-19)

Dupont, Damien; Menotti, Jean; Turc, Jean; Miossec, Charline; Wallet, Florent; Richard, Jean-Christophe; Argaud, Laurent; Paulus, S.; Wallon, Martine; Ader, Florence; Persat, Florence

doi:10.1093/mmy/myaa078

Cited by 70 publications

(76 citation statements)

References 16 publications

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“…Second, it most likely contributes to the very high rates of nosocomial infections reported not only in the present study (50%) but also in many others [ 26 , 27 , 45 ]. In particular, COVID-19 is characterized by astonishing elevated rates of secondary aspergillosis [ 46 – 48 ], a fungal disease usually seen in the most immunosuppressed patients. Such secondary infectious events may explain the persistently elevated TNF-α levels accompanied by increased neutrophil count in COVID-19 patients with ARDS and in non-survivors [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome

et al. 2021

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Background Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved. Methods We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. Results ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS. Conclusions Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.

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Section: Discussionmentioning

confidence: 99%

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome

et al. 2021

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“…Recently published small case series describe an overall high incidence of CAPA in SARS‐CoV‐2‐positive patients admitted to the ICU with acute respiratory distress syndrome requiring mechanical ventilation. The United Kingdom, 1,2 The Netherlands, 3,4 Belgium, 5 Germany, 6 Italy 7 and France 8,9 report incidences of 12.3%–33.3%. In Denmark, 10 a 25% ( n = 2/8) incidence of invasive aspergillosis in COVID‐19 patients undergoing extracorporeal membrane oxygenation (ECMO) was described, totalling 7.4% when adding the non‐ECMO ICU population ( n = 19).…”

Section: Introductionmentioning

confidence: 99%

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

Meijer

Dofferhoff

Hoiting

et al. 2021

Mycoses

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Background COVID‐19–associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%–33.3% have been reported depending on the geographic area, with high (47%) mortality. Objectives Here, we describe a single‐centre prospective case series with CAPA cases from both the first (March‐May, n = 5/33) and second (mid‐September through mid‐December, n = 8/33) COVID‐19 wave at a 500‐bed teaching hospital in the Netherlands. Patients/Methods In the first COVID‐19 wave, a total of 265 SARS‐CoV‐2 PCR‐positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS‐CoV‐2 PCR‐positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected. Results We found a significant decrease in COVID‐19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%–50%). Moreover, we found environmental TR34/L98H azole‐resistant Aspergillus fumigatus isolates in two separate patients. Conclusions In this series, 19.7% (n = 13/66) of mechanically ventilated SARS‐CoV‐2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID‐19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS‐CoV‐2 therapy.

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“…11,12 Risk factors for CAPA appear to include prolonged ICU admission, lymphopenia, and immunosuppression including corticosteroid use. 11,13,14…”

Section: Introductionmentioning

confidence: 99%

Invasive Mould Disease in Fatal COVID-19: A Systematic Review of Autopsies

Kula

Clancy

Nguyen

et al. 2021

Preprint

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BackgroundInvasive mould disease (IMD) – most commonly pulmonary aspergillosis - is reported to affect up to a third of critically ill COVID-19 patients. Most reported cases are diagnosed with probable/putative COVID-19 associated pulmonary aspergillosis (CAPA) based on a combination of non-specific clinical, radiographic, and mycological findings, but the clinical significance – and whether these cases represent true invasive disease – is unresolved.MethodsWe performed a systematic review of autopsy series of decedents with COVID-19 for evidence of IMD. We searched PubMed, Web of Science, OVID (Embase) and MedRxiv for English- or French-language case series published between January 1, 2019 to September 26, 2020. We included series describing lung histology of ≥3 decedents, and authors were contacted for missing information as necessary.FindingsWe identified 51 case series describing autopsies of 702 decedents. Individual-level data was available for 430 decedents. The median age was 72 (IQR 61 to 80) years. Diabetes mellitus, pre-existing lung disease, and immunocompromising conditions were reported for 129 (32%), 95 (22%), and 25 (6%) decedents, respectively. The median hospitalization length was 10 (IQR 5-22) days. 51.6% of decedents had received mechanical ventilation for a median of nine (IQR 5-20) days. Treatment included immunomodulation in 60 (most often steroids or tocilizumab) and antifungals in 41 decedents. Eleven decedents (1·6%) had autopsy-confirmed IMD (6 with CAPA, 4 with invasive pulmonary mycosis not specified and 1 with disseminated mucormycosis). Among 173 decedents who received mechanical ventilation, 5 had IMD (2·9%).InterpretationAutopsy-proven IMD, including CAPA, is uncommon in fatal COVID-19.FundingThis study is unfundedCategoryReview

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Pulmonary aspergillosis in critically ill patients with Coronavirus Disease 2019 (COVID-19)

Cited by 70 publications

References 16 publications

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

Invasive Mould Disease in Fatal COVID-19: A Systematic Review of Autopsies

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