Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study.

BACKGROUND: Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. METHODS: In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. RESULTS: We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2-9.7) in the MAFP group and 17.5% (95% CI 9.6-31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01-0.63; p = 0.017). CONCLUSION: In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

Convalescent plasma therapy and mortality in COVID-19 patients admitted to the ICU: a prospective observational study.

BACKGROUND: This study aimed to quantify the potential survival benefit of convalescent plasma therapy (CVP) in critically ill patients with acute respiratory failure related to coronavirus disease-2019 (COVID-19). METHODS: This is a single-center prospective observational cohort study in COVID-19 patients with acute respiratory failure. Immediately after intensive care unit (ICU) admission patients were allocated to CVP treatment following pre-specified criteria to rapidly identify those patients potentially susceptible for this treatment. A propensity score adjustment [inverse probability of treatment weighted (IPTW) analysis] was implemented to account rigorously for imbalances in prognostic variables between the treatment groups. RESULTS: We included 120 patients of whom 48 received CVP. Thirty percent were female with a median age of 66 years [25th-75th percentile 54-75]. Eighty-eight percent of patients presented with severe acute respiratory failure as displayed by a median paO2/FiO2 ratio (Horowitz Index) of 92 [77-150]. All patients required any kind of ventilatory support with more than half of them (52%) receiving invasive ventilation. Thirty-day ICU overall survival (OS) was 69% in the CVP group and 54% in the non-CVP group (log-rank p = 0.049), respectively. After weighing the time-to-event data for the IPTW, the favorable association between CVP and OS became even stronger (log-rank p = 0.035). Moreover, an exploratory analysis showed an overall survival benefit of CVP therapy for patients with non-invasive ventilation (Hazard ratio 0.12 95% CI 0.03-0.57, p = 0.007) CONCLUSION: Administration of CVP in patients with acute respiratory failure related to COVID-19 is associated with improved ICU survival rates.