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1.
J Investig Med High Impact Case Rep ; 10: 23247096211063332, 2022.
Article in English | MEDLINE | ID: covidwho-1603889

ABSTRACT

We present the case of a 56-year-old woman who was diagnosed with severe coronavirus disease 2019 (COVID-19) pneumonia complicated by severe acute respiratory distress syndrome who was intubated for 19 days. She recovered from COVID-19 after a month. A computed tomography (CT) scan of the chest, after a month, showed improved infiltrates with a small residual cavity within the lingula. A CT angiogram showed a more confluent density in the lingular portion on follow-up 2 months later. She developed intermittent hemoptysis after 3 months in December 2020, which persisted for almost 6 months, and CT of the chest showed the lingular nodular with resolution of the cavitation. She underwent bronchoscopy with bronchoalveolar lavage, confirming Aspergillus fumigatus by galactomannan assay and histology showing branching hyphae. Once she started treatment with itraconazole, her hemoptysis resolved. The follow-up CT of the chest after 2 months of treatment did not show a cavity or a nodule in the lingula. Our patient developed invasive pulmonary aspergillosis (IPA) as a sequela of severe COVID-19 infection. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is an underrecognized complication that needs to be investigated on whether prophylactic treatment is required. Our case also demonstrates that the diagnosis of IPA needs to be considered months after COVID-19 infection when a superimposed fungal infection can occur after a viral infection if the patient continues to have persistent symptoms.


Subject(s)
COVID-19 , Invasive Pulmonary Aspergillosis , Pulmonary Aspergillosis , Aspergillus fumigatus , Female , Humans , Invasive Pulmonary Aspergillosis/complications , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Middle Aged , Pulmonary Aspergillosis/complications , Pulmonary Aspergillosis/drug therapy , SARS-CoV-2
2.
Microbiol Spectr ; 9(2): e0113821, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1476402

ABSTRACT

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (P = 0.001). Antimold treatment did not alter prognosis (P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.


Subject(s)
COVID-19/epidemiology , Coinfection/mortality , Fungemia/epidemiology , Pneumonia, Pneumocystis/epidemiology , Pulmonary Aspergillosis/epidemiology , Aged , Antifungal Agents/therapeutic use , COVID-19/mortality , COVID-19/pathology , Coinfection/epidemiology , Critical Care , Female , France/epidemiology , Fungemia/drug therapy , Fungemia/mortality , Galactose/analogs & derivatives , Galactose/blood , Humans , Intensive Care Units/statistics & numerical data , Male , Mannans/blood , Middle Aged , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/mortality , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/mortality , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
5.
Intensive Care Med ; 47(8): 819-834, 2021 08.
Article in English | MEDLINE | ID: covidwho-1279405

ABSTRACT

PURPOSE: Invasive pulmonary aspergillosis (IPA) is increasingly reported in patients with severe coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Diagnosis and management of COVID-19 associated pulmonary aspergillosis (CAPA) are challenging and our aim was to develop practical guidance. METHODS: A group of 28 international experts reviewed current insights in the epidemiology, diagnosis and management of CAPA and developed recommendations using GRADE methodology. RESULTS: The prevalence of CAPA varied between 0 and 33%, which may be partly due to variable case definitions, but likely represents true variation. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis, allowing for diagnosis of invasive Aspergillus tracheobronchitis and collection of the best validated specimen for Aspergillus diagnostics. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL positive patients, but the decision to treat depends on the patients' clinical condition and the institutional incidence of CAPA. We recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients. CONCLUSION: CAPA is a complex disease involving a continuum of respiratory colonization, tissue invasion and angioinvasive disease. Knowledge gaps including true epidemiology, optimal diagnostic work-up, management strategies and role of host-directed therapy require further study.


Subject(s)
COVID-19 , Invasive Pulmonary Aspergillosis , Pulmonary Aspergillosis , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/epidemiology , SARS-CoV-2
9.
J Infect Chemother ; 27(6): 911-914, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1101366

ABSTRACT

CAPA (COVID-19 associated pulmonary aspergillosis) is an important complication of COVID-19. It has been reported that the incidence of CAPA is as high as 19%-33% worldwide. However, its onset has not been reported in Japan. A 72-year-old Japanese man was diagnosed with COVID-19 and was transferred to our hospital due to deterioration of respiratory condition. Treatment with remdesivir, dexamethasone (DEXA), and antibiotics was performed under mechanical ventilation. Although the condition improved temporarily, a new shadow appeared in the lung, and Aspergillus fumigatus was cultured from sputum. The patient was clinically diagnosed with CAPA and treated with voriconazole. However, his progress deteriorated and he died. High-risk COVID-19 patients should be tested for Aspergillus to ensure early diagnosis of CAPA.


Subject(s)
COVID-19 , Pulmonary Aspergillosis , Aged , Antifungal Agents/therapeutic use , COVID-19/complications , Fatal Outcome , Humans , Japan , Male , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/drug therapy , Respiration, Artificial
10.
Emerg Infect Dis ; 27(4): 1077-1086, 2021.
Article in English | MEDLINE | ID: covidwho-1067634

ABSTRACT

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.


Subject(s)
Aspergillus fumigatus/isolation & purification , COVID-19 , Intensive Care Units/statistics & numerical data , Pulmonary Aspergillosis , Voriconazole/therapeutic use , Aged , Antifungal Agents/therapeutic use , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Incidence , International Cooperation , Male , Outcome and Process Assessment, Health Care , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/mortality , Registries , Respiration, Artificial/methods , Risk Factors , SARS-CoV-2/isolation & purification
11.
Lancet Infect Dis ; 21(6): e149-e162, 2021 06.
Article in English | MEDLINE | ID: covidwho-974782

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.


Subject(s)
Antifungal Agents/therapeutic use , COVID-19/complications , Coinfection/drug therapy , Pulmonary Aspergillosis/complications , Pulmonary Aspergillosis/drug therapy , Amphotericin B , Azoles/pharmacology , Humans , Nitriles , Pyridines , SARS-CoV-2 , Triazoles , Voriconazole/therapeutic use
12.
Mycoses ; 64(4): 364-371, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-939795

ABSTRACT

OBJECTIVE: Our aim was to evaluate the performance of two galactomannan (GM) assays (Platelia Aspergillus EIA, Bio-Rad® , and Aspergillus GM LFA, IMMY® ) in tracheal aspirate (TA) samples of consecutive critically ill patients with COVID-19. METHODS: We included critically ill patients, performed GM-EIA and GM-Lateral Flow Assay (GM-LFA) in TA and followed them until development of COVID-19-associated pulmonary aspergillosis (CAPA) or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS-CoV-2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM-EIA, GM-LFA, the combination of both or either positive results for GM-EIA and GM-LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cut-offs. We described antifungal treatment and 30-day mortality. RESULTS: We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was 8 days; 28.5% received tocilizumab and 30-day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut-off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM-EIA and 60% and 72.6% for GM-LFA, respectively. CONCLUSIONS: The diagnostic performance of GM in tracheal aspirates improved after using a cut-off of 2 OD. Although bronchoalveolar lavage testing is the ideal test, centres with limited access to bronchoscopy may consider this approach to identify or rule out CAPA.


Subject(s)
COVID-19/complications , Mannans/analysis , Pulmonary Aspergillosis/diagnosis , Trachea/chemistry , Adult , Antifungal Agents/therapeutic use , Diabetes Complications/complications , Female , Galactose/analogs & derivatives , Humans , Male , Middle Aged , Obesity/complications , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/etiology , Pulmonary Aspergillosis/mortality , Sensitivity and Specificity , Trachea/microbiology
16.
Clin Rheumatol ; 39(9): 2797-2802, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-608431

ABSTRACT

Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.


Subject(s)
Antiviral Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Coronavirus Infections/therapy , Glucocorticoids/therapeutic use , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Viral/therapy , Pulmonary Aspergillosis/diagnosis , Aged , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Aspergillosis , Aspergillus fumigatus , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Cough/etiology , Cytokine Release Syndrome/etiology , Deprescriptions , Disease Progression , Dyspnea/etiology , Female , Glucocorticoids/adverse effects , Humans , Hydroxychloroquine/therapeutic use , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Interleukin-6/blood , Leflunomide/adverse effects , Leflunomide/therapeutic use , Lung/diagnostic imaging , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/immunology , Methylprednisolone/therapeutic use , Oxygen Inhalation Therapy , Pandemics , Pneumocystis carinii , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/etiology , Pneumonia, Pneumocystis/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/etiology , Pulmonary Aspergillosis/immunology , Recurrence , SARS-CoV-2 , Tomography, X-Ray Computed
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