Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

A randomized controlled trial comparing non-invasive ventilation delivered using neurally adjusted ventilator assist (NAVA) or adaptive support ventilation (ASV) in patients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: No study has compared neurally adjusted ventilator assist (NAVA) with adaptive support ventilation (ASV) during non-invasive ventilation (NIV) in subjects with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MATERIALS AND METHODS: In this randomized controlled trial, we compared NAVA-NIV with ASV-NIV for delivering NIV in consecutive subjects with AECOPD. The primary outcome was NIV failure rate (invasive mechanical ventilation). The key secondary outcomes were number of NIV manipulations, asynchrony index, and 90-day mortality. RESULTS: We enrolled 76 subjects (NAVA-NIV, n = 36, ASV-NIV, n = 40; 74% males) with a mean ± SD age of 61.4 ± 8.2 years. We found no difference in NIV failure rates between the two arms (NAVA-NIV vs. ASV-NIV; 8/36 [22.2%] vs. 8/40 [20%]; p = 0.83). The median physician manipulations for NIV were significantly less in the ASV-NIV arm than in the NAVA-NIV arm (2 [0.8-4] vs. 3 [2-5]; p= 0.014) during the initial 24-h. We found no difference in median asynchrony index (NAVA-NIV vs. ASV-NIV, 16.6% vs. 16.4%, p = 0.5) and 90-day mortality (22.2% vs. 17.5%, p = 0.67). CONCLUSION: The use of NAVA-NIV was not superior to ASV-NIV in reducing NIV failure rates in AECOPD. Both NAVA-NIV and ASV-NIV had similar asynchrony index and 90-day mortality. TRIAL REGISTRY: www. CLINICALTRIALS: gov (NCT04414891).

Role of flexible bronchoscopy in the diagnosis of invasive fungal infections.

BACKGROUND: There are sparse data on the role of flexible bronchoscopy (FB) in diagnosing invasive mould infections (IMIs). OBJECTIVE: To investigate the safety and usefulness of FB in IMI. We evaluate the factors associated with a successful diagnosis of IMI using FB. Further, we compare subjects of invasive pulmonary aspergillosis (IPA) with pulmonary mucormycosis (PM). METHODS: We retrospectively reviewed the clinical features, imaging data, bronchoscopy, microbiology and pathology details of subjects who underwent FB for suspected IMI. We categorised FB as diagnostic if it contributed to the diagnosis of IMI. We performed a multivariate analysis to identify the factors associated with a diagnostic bronchoscopy. RESULTS: Of the 3521 FB performed over 18 months, 132 (3.7%) were done for suspected IMIs. We included 107 subjects for the final analysis. The risk factors for IMI included renal transplantation (29.0%), diabetes (27.1%), haematological malignancy (10.3%) and others. We found bronchoscopic abnormalities in 33 (30.8%) subjects, and these were more frequent in those with confirmed PM (67%) than IPA (27%). IMI was confirmed in 79 (14 proven, 48 probable and 17 possible) subjects. FB was diagnostic in 71%. We experienced major complications in three cases (2.7%), including one death. On multivariate analysis, the visualisation of endobronchial abnormalities during FB (OR [95%, CI], 8.5 [1.4-50.4]) was the only factor associated with a diagnostic FB after adjusting for age and various risk factors. CONCLUSIONS: Flexible bronchoscopy is a useful and safe procedure in diagnosing IMIs. The presence of endobronchial abnormalities predicts a successful diagnostic yield on FB.

Comparing Noninvasive Ventilation Delivered Using Neurally-Adjusted Ventilatory Assist or Pressure Support in Acute Respiratory Failure.

BACKGROUND: The use of neurally-adjusted ventilatory assist (NAVA) during noninvasive ventilation (NIV) results in better patient-ventilator interaction. Whether this improves clinical outcomes lacks dedicated study. METHODS: In this randomized controlled trial, we compared NAVA with PSV for delivering NIV in consecutive subjects with de novo acute respiratory failure. The primary outcomes were NIV failure rates and 28-d mortality. The secondary outcomes were asynchrony index, NIV-related complications, and others. RESULTS: We enrolled 100 subjects (50 subjects each for NAVA and PSV, 60% male) with a mean ± SD age of 56.7 ± 12 y. There was no difference in NIV failure rates (30% vs 32%, P = .83) and 28-d mortality rates (18% vs 34%, P = .07) between the NAVA and PSV arms, respectively. The median asynchrony index was significantly lower with NAVA (6.7 vs 44.8, P < .001). The use of NAVA significantly reduced NIV-related complications (32% vs 58%, P = .01). In a post hoc analysis, the use of NAVA significantly reduced the 28-d mortality in subjects with COPD exacerbation. CONCLUSIONS: The use of NAVA during NIV did not improve NIV failure rate or 28-d mortality in subjects with acute respiratory failure. However, patient-ventilator asynchrony and NIV-related complications were reduced with NAVA. TRIAL REGISTRY: www.clinicaltrials.gov (NCT03271671).