CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

866

ICU-Acquired Infections More Common in Patients With COVID-19 Than in Patients With Influenza Josefine Beck-Friis , Magnus Gisslén, Aylin Yilmaz, Anna Lindblom, Jonatan Oras Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Background: During the covid-19 pandemic, intensive care unit-acquired infections (ICU-AI) were frequently diagnosed in critically ill patients. The primary aim of the study was to determine the impact of ICU-AI on mortality and ICU-stay in patients with covid-19 and influenza. The secondary aim was to compare the microbial pattern in patients with covid-19 vs influenza. Methods: This is an observational study including (1) all patients 18 years and older treated with invasive mechanical ventilation (IMV) due to covid-19 at Sahlgrenska University Hospital (SU) January 2020–March 2022, and (2) all patients 18 years and older treated with IMV due to influenza at SU January 2015–May 2023. Data was collected from medical charts and the microbiology laboratory at SU. The definition of ICU-AI required both clinical criteria and a positive culture of a significant pathogen, according to ECDC's standards. Frequencies were compared by Fisher's exact test and continuous variables by t-test and Mann Whitney U test. Results: A total of 480 participants were included in the final analysis, of whom 436 had covid-19. ICU-AI was confirmed in 190 patients (44%) with covid-19 and 7 patients (16%) with influenza. Ventilator associated lower respiratory tract infection (VA-LRTI) was most common, being present in 149 patients (34%) with covid-19 and in 5 patients (11%) with influenza. The most common pathogens associated with VA-LRTI are presented in the figure below. Blood stream infections were relatively common in patients with covid-19 (n = 77, 18%) but were rare in influenza patients (n = 3, 7%). Gram-positive bacteria and candida were the most frequent findings in blood cultures in both groups. Corticosteroid treatment was associated with an increased risk of ICU-AI in patients with covid-19 (adjusted OR 2.095, 95% CI 1.263–3.475). Median (range) number of days in ICU for patients with an ICU-AI was 27 (4–103) and 12 (2–69) for patients without ICU-AI (p < 0.001). Having an ICU-AI was also associated with an increased risk of 90-day mortality (adjusted OR 1.794, 95% CI 1.134–2.838). Conclusion: Secondary infections were more common in critically ill patients with covid-19 than with influenza and were associated with an increased time in ICU and mortality. Gram-negative bacteria caused a majority of VA-LRTI in patients with covid-19, while S. aureus was the singular most common pathogen in VA-LRTI in patients with influenza and covid-19.

We determined the plasma concentration of sTM in all available frozen samples collected prior to the TE using an automated immunoassay technique. Results: Between March 1st, 2020 and July 31st, 2022, a total of 2524 patients were hospitalized due to SARS-CoV-2 infection (22% Omicron variant). Forty three percent of them were female and the median (Q1, Q3) age at admission was 67 (54, 80) years. There were 75 TE (58 venous-TE: 48 pulmonary embolism (PE) and 10 deep vein thrombosis (DVT); 17 arterial-TE (AT)) accounting for an incidence rate [95% CI] of 1.17 [0.92-1.47] per 1000 patient-days of follow-up. Frozen plasma samples were available in 43 cases (29 PE, 6 DVT, 8 AT) and in 176 PS-matched controls. There was no significant correlation between sTM and D-dimer (DD) (R-Pearson [p-value] +0.01 [0.85]). Elevated plasma concentration of sTM was significantly associated with both mortality (median [Q1, Q3], 3.32 [2.16, 4.65] vs. 1.58 [1.11, 2.73] ng/mL; p=0.001) and TE (2.77 [1.67, 4.01] vs. 1.52 [1.1, 2.65] ng/mL; p=0.001), while DD showed a specific association with TE (2.1 [0.83, 5.6] vs. 0.66 [0.4, 1.12] mcg/mL; p-value=0.001). The association with thrombotic events remained in adjusted models (OR [95%CI] per unit increase, 1.31 [1.03-1.68] for sTM; 1.11 [1.02-1.28] for DD). The adjusted regression model that included both variables (sTM and DD) improved significatively the predictive capacity of the same model without sTM (p-value=0.011; sensitivity 84% and specificity 32% for TE diagnosis). Conclusion: Elevated soluble thrombomodulin levels were significantly associated with both thrombotic events and mortality in hospitalized COVID-19 patients. The measurements of thrombomodulin, along with D-dimer plasma levels, could enhance thrombotic risk assessment in this population. Decline in Time to Recovery From Mild-Moderate COVID-19 in a Large Platform Placebo-Controlled Trial Ahmad Mourad 1 , Yue Gao 2 , Thomas Stewart 3 , Adrian F. Hernandez 1 , Susanna Naggie 1 , Christophor J. Lindsell 1 , for the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators 1 Duke University School of Medicine, Durham, NC, USA, 2 Vanderbilt University, Nashville, TN, USA, 3 University of Virginia, Charlottesville, VA, USA Background: Epidemiological data suggest that the duration of symptoms in patients with COVID-19 has decreased over the course of the pandemic. Robust estimates of the magnitude of change are not yet available. We estimated the change in time to recovery from COVID-19 among participants enrolled in the placebo arms of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 platform, the largest ongoing randomized clinical trial evaluating treatment of outpatients with COVID-19. Methods: Outpatients with mild to moderate COVID-19 were randomized to one of five placebo-controlled intervention groups between June 2021 and January 2023. Participants completed daily symptom reporting for at least 14 days or until symptom resolution. We estimated time to sustained recovery, defined as the third day of 3 consecutive days without symptoms, for participants receiving placebo only. A cox proportional hazards model was used to assess differences in time to sustained recovery over yearly quartiles during the study period. Results: Among 6,708 total participants randomized, 2,435 received a matched placebo to one of the active drugs. Overall, the median age was 48 (IQR 39-58) years, and 61% were female. The median time to sustained recovery decreased from 15 (95% CI 14-17) days in Q3 of 2021 to 10 (95% CI 9-11) days in Q1 of 2023. Among 135 participants recruited in the 3rd quarter (Q3) of 2021, only 20 (14.8%) reported any vaccination for SARS-CoV-2. This increased to 429/486 (88.3%) by Q2 of 2022. Participants recruited later in the trial had quicker time to sustained recovery (p<0.001) (Figure 1). The most important predictors of recovery were baseline symptom severity, the duration of symptoms, sex, and calendar time of enrollment. Conclusion: Time to recovery in outpatients with mild to moderate COVID-19 enrolled in the placebo arms of ACTIV-6 decreased over the duration of the trial. This trend is likely multifactorial including increased vaccination, prior infection, as well as evolving SARS-CoV-2 variants and subvariants. Future trials should take this into consideration when selecting endpoints and developing statistical analysis plans.

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Poster Abstracts

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Plasma Thrombomodulin Predicts Thrombotic Events & Mortality in Patients Hospitalized With COVID-19 Sergio Padilla 1 , Pascual Marco 2 , Ana Marco-Rico 2 , Christian Ledesma 1 , Carolina Ding 1 , Marta Fernández-González 1 , Alba de la Rica 1 , Javier García-Abellán 1 , Paula Mascarell 1 , Angela Botella 1 , Nuria Ena 1 , Lidia García 1 , Jose Carlos Asenjo 1 , Mar Masiá 1 , Félix Gutiérrez 1 1 Hospital General Universitario de Elche, Elche, Spain, 2 Hospital General Universitario de Alicante, Alicante, Spain Background: Plasma concentration of soluble thrombomodulin (sTM) is a marker of endothelial damage, and its elevation has been linked to cardiovascular diseases. The study aims to evaluate the predictive potential of sTM for thrombotic events, one of the most serious complications of COVID-19. Methods: Nested case-control study within a large cohort of hospitalized COVID-19 patients throughout the pandemic. Cases involved serious venous and arterial thrombotic events (TE) up to 28 days following hospital admission and they were compared with controls matched by sex, age, Charlson comorbidity index, and WHO-COVID-19 severity scale by propensity scores (PS) in a 1:3 ratio.

CROI 2024 268