A tale of two hospitals: comparing CAPA infections in two ICUs during the Spanish fourth pandemic wave. (preprint)

Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is a new clinical entity linked to SARS-CoV-2 infection that is causing a rise on the risk of complications and mortality, particularly in critical patients. Methods: We compared diagnostic and clinical features in two cohorts of patients with severe COVID-19 admitted in the intensive care units (ICU) of two different hospitals in Madrid, Spain, between February and June 2021. Results: Cultures were positive for Aspergillus spp. in 32 patients.  According to 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus, 11 patients were diagnosed with possible CAPA and 10 patients with probable CAPA. Global incidence for CAPA was 6.3%. Global median days between ICU admission and diagnosis was 12 days. Aspergillus fumigatuscomplex was the main isolated species. Antifungal therapy was used in 75% of patients with CAPA suspicion, with inter-hospital differences in the administered antifungals. Global overall mortality rate was 66.6% (14/21). Conclusions: There were no significant differences in incidence between the two hospitals, and differences in antifungal therapy did not correlate with differences in mortality, reflecting that both first-line azoles and Amphotericin B could be effective in treating CAPA infections, according to the current guideline indications.

Long-Term Survival of Mechanically Ventilated Patients with Severe COVID-19: An Observational Cohort Study (preprint)

Background: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 90-day and 180-day survival of patients with COVID-19 requiring invasive ventilation and to develop a predictive model for intensive care unit mortality.Methods: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID–19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes were 90-day and 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model and a nomogram were developed to estimate the probability of ICU mortality. Results: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The 90-day and 180-day survival rates were 69% (95% confidence interval [CI] 66%-72%) and 59% (95% CI 56%-62%) respectively. The predictive factors associated with ICU mortality were: age (odds ratio [OR] 1.049 [95% CI 1.032-1.066] per 1-year increase), SAPS3 (OR 1.025 [95% CI 1.008-1.041] per 1-point increase), neutrophil to lymphocyte ratio (OR 1.009 [95% CI 1.002-1.016]), a failed attempt of noninvasive positive pressure ventilation previous to orotracheal intubation(OR 2.131 [95% CI 1.279-3.550]), and use of selective digestive decontamination (OR 0.587 [95% CI 0.358-0.963]).Conclusion: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments.Trial registration: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).

Impact of remdesivir for the treatment of COVID-19 during the first wave in Spain (preprint)

Background: Spain was one of the most affected countries during the first wave of COVID-19, having the highest mortality rate in Europe. The aim of this retrospective study is to estimate the impact that remdesivir -the first drug for COVID-19 approved in EU- would have had in the first wave. Methods: This study estimated the impact on the Spanish National Health System (SNHS) capacity (bed occupancy), and the number of deaths that could have been prevented, based on two scenarios: a real-life scenario (without remdesivir), and an alternative scenario (with remdesivir). It considered the clinical results of the ACTT-1 trial in hospitalized patients with COVID-19 and pneumonia, who required supplemental oxygen. The occupancy rates in general wards and ICUs were estimated in both scenarios. Results: Remdesivir would have avoided the admission of 2,587 patients (43.75%) in the ICUs. It would have also increased the SNHS capacity in 5,656 general wards beds and 1,700 ICU beds, showing an increase in the number of beds available of 17.53% (95% CI: 3.98% - 24.42%), and 23.98% (95% CI: 21.33% - 28.22%), respectively, at the peak of the occupancy rates. Furthermore, remdesivir would have avoided 7,639 deaths due to COVID-19, which implies a 27.51% reduction (95% CI: 14.25% - 34.07%). Conclusions: Remdesivir would have relieved the pressure of the SNHS, and would have reduced the death toll, providing a better strategy for the management of COVID-19 during the first wave.