RESUMO
With almost 638 million cases and over 6 million deaths worldwide, the SARS-CoV-2 pandemic represents an unprecedented healthcare challenge. Although the management and natural history of COVID-19 patients have changed after the introduction of active therapies and vaccination, the development of secondary infections complicates hospital stay. This is a single-center, retrospective, observational study that explores the incidence and microbiology of hospital-acquired infections (HAIs) in two subsequent populations of hospitalized patients with COVID-19. Demographic, pre-hospitalization baseline characteristics, therapeutic options and microbiology data about secondary infections were collected for a total of 1153 cases. The second population appeared to have a higher median age (73 vs. 63 years, respectively), comorbidities (median Charlson Comorbidity Index Score was 4 vs. 1, respectively) and incidence of secondary infections (23.5% vs. 8.2%) with respect to the first. A higher incidence of multi-drug resistant organisms (MDROs), including difficult-to-treat resistant (DTR) Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), was also observed. Both patients' characteristics and poor adherence to standard hygiene and infection control protocols may have contributed to the higher incidence of these events and may have impacted on the natural history of the disease. In-hospital mortality rates were similar, despite the introduction of active therapies against COVID-19 (24.7% vs. 23.5%, respectively). The incidence of HAIs may have contributed to the unchanged mortality and prompts for more effective antimicrobial stewardship and infection control procedures in COVID-19.
RESUMO
PTX3 is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation. PTX3 plasma levels are associated with poor outcome in systemic inflammatory conditions and vascular pathology. The present study was designed to assess expression and significance of PTX3 in COVID-19. By bioinformatics analysis of public databases PTX3 expression was detected in lung respiratory cell lines exposed to SARS-CoV-2. By analysis at single cell level of COVID-19 circulating mononuclear cells, we found that PTX3 was selectively expressed by monocytes among circulating leukocytes. Moreover, in lung bronchoalveolar lavage fluid, single cell analysis revealed selective expression of PTX3 in neutrophils and macrophages, which play a major role in the pathogenesis of the disease. By immunohistochemistry, PTX3 was expressed by lung myelomocytic cells, type 2 pneumocytes and vascular endothelial cells. PTX3 plasma levels were determined by ELISA in 96 consecutive patients with a laboratory-confirmed diagnosis of COVID-19. Higher PTX3 plasma levels were observed in 52 (54.2%) patients admitted in ICU (median 21.0ng/mL, IQT 15.5-46.3 vs 12.4ng/mL IQT 6.1-20.2 in ward patients; p=0.0017) and in 22 (23%) patients died by 28 days (39.8ng/mL, IQT 20.2-75.7 vs 15.7ng/mL, IQT 8.2-21.6 in survivors; p=0.0001). After determining an optimal PTX3 cut-off for the primary outcome, the Kaplan-Meier curve showed an increased mortality in patients with PTX3>22.25ng/mL (Log-rank tests p<0.0001). In Cox regression model, PTX3>22.25ng/mL showed an adjusted Hazard Ratio (aHR) of 7.6 (95%CI2.45-23.76) in predicting mortality. Performing a multivariate logistic regression including all inflammatory markers (PTX3, ferritin, D-Dimer, IL-6, and CRP), PTX3 was the only marker significantly associated with death (aHR 1.13;95%CI1.02-1.24; p=0.021). The results reported here suggest that circulating and lung myelomonocytic cells are a major source of PTX3 and that PTX3 plasma levels can serve as a strong prognostic indicator of short-term mortality in COVID-19.
