Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

Outbreak of Candida parapsilosis fungemia in an intensive care unit during a COVID surge: an epidemic within a pandemic.

We sought to investigate epidemiology, risk factors, clinical features, and outcome of the C. parapsilosis blood stream infection (BSI) outbreaks observed during the first surges of COVID-19 pandemic in our population. Retrospective, monocentric observational study in the 24 bed intensive care unit (ICU) of a tertiary care medical center in northern Italy, from 2019 to 2021 first 5 months. 2030 patients were enrolled, of whom 239 were COVID-19 positive. The total incidence of Candida-BSI was 41.9 per 1000 admissions, with two outbreaks during 2020 spring and winter's COVID surges. The total numbers of C. parapsilosis BSI cases are 94, of which 21 during the first outbreak and 20 during the second. In our population, COVID-19 was strongly associated with C. parapsilosis BSI (OR 4.71, p < 0.001), as well as continuous renal replacement therapy (CRRT) (OR 3.44, p = 0.001), prolonged antibiotic therapy (OR 3.19, p = 0.004), and delayed infusion sets replacements (OR 2.76, p = 0.015). No statistically significant association was found between Candida-BSI episodes and mortality, when adjusted for other known outcome risk factors. COVID surges undermined the infectious control measures in our ICU, leading to two outbreak of C. parapsilosis BSI. A stricter, thorough management of intravascular devices and infusion set is crucial in prevention of catheter related BSI, and awareness must be kept high, especially in emergencies circumstances, such as the ongoing COVID-19 pandemic.

Endogenous Catecholamine Release in COVID-19 Related Acute Respiratory Distress Syndrome: Link between Enhanced Sympathetic Stimulation, Cardiac Dysfunction and Outcome.

The aim of this study was to measure the serum levels of catecholamines in patients admitted to intensive care unit (ICU) with COVID-19-related acute respiratory distress syndrome (ARDS) and describe their relation with clinical, inflammatory and echocardiographic parameters. Serum levels of endogenous catecholamines (norepinephrine, epinephrine and dopamine) were measured at ICU admission. We enrolled 71 patients consecutively admitted to ICU due to moderate to severe ARDS. 11 patients (15.5%) died during the admission in ICU. Serum levels of endogenous catecholamines were significantly elevated. Norepinephrine levels were higher in those with RV and LV systolic dysfunction, higher CRP, and higher IL-6. Patients with higher mortality rate were those with norepinephrine values ≥ 3124 ng/mL, CRP ≥ 17.2 mg/dL and IL-6 ≥ 102 pg/mL. Univariable analysis by Cox proportional hazards regression modelling showed that norepinephrine, IL-6 and CRP had the highest risk of acute mortality. Multivariable analysis showed that only norepinephrine and IL-6 retained in the model. Marked increase of serum catecholamine levels is present during acute phase of critically ill COVID-19 and it is associated with inflammatory and clinical parameters.