Neurovascular and infectious disease phenotype of acute stroke patients with and without COVID-19.

BACKGROUND: The infectious disease phenotype of acute stroke associated with COVID-19 has been poorly characterized. OBJECTIVE: We investigated the neurovascular and infectious disease phenotype of stroke patients with and without COVID-19 infection, and their effect on in-hospital mortality. METHODS: This is a retrospective cohort study of consecutive patients with acute stroke, admitted to any ward of a hub hospital for stroke in Lombardy, Italy, during the first wave of COVID-19. Demographic, neurovascular, infectious disease, and respiratory characteristics were collected. The effect of clinical variables on survival was evaluated using logistic regression models. RESULTS: One hundred thirty-seven patients with acute stroke were recruited; 30 (21.9%) patients had COVID-19 and represented 2.5% of the 1218 COVID-19 patients hospitalized in the study period. Demographics, comorbidities, stroke type, stroke severity, and etiology did not differ between COVID + stroke patients and non-COVID stroke patients, except for an excess of multi-embolic ischemic stroke in the COVID + group. Most COVID + stroke patients had symptomatic infection (60%) and interstitial pneumonia (70%). COVID + stroke patients required more frequently respiratory support (77% versus 29%; p < 0.0001) and had higher in-hospital mortality (40% versus 12%; p = 0.0005) than non-COVID stroke patients. Mortality was independently associated with symptomatic interstitial pneumonia (aOR 6.7; 95% CI 2.0-22.5; p = 0.002) and, to a lesser extent, with NIHSS on admission (aOR 1.1; 95% CI 1.03-1.2; p = 0.007) and recanalization therapies (aOR 0.2; 95% CI 0.04-0.98; p = 0.046). CONCLUSION: Symptomatic interstitial pneumonia was the major driver of in-hospital mortality in COVID + stroke patients.

Lipopolysaccharide induces platelet activation in HIV patients: the role of different viral load patterns.

OBJECTIVES: This study aimed to assess whether gut-derived lipopolysaccharide (LPS) could affect platelet function in HIV-1 patients with residual viral load. METHODS: In 23 HIV-1 patients on effective antiretroviral treatment, 10 treatment-naïve HIV-1 subjects and 20 healthy subjects (HS), LPS, zonulin, markers of platelet activation and oxidative stress were evaluated. In vitro, platelets from HS were exposed to plasma from HIV-1-infected treated and untreated patients. RESULTS: Compared with HS, LPS was higher in treated and treatment-naïve subjects with HIV-1 (7.7 ± 2.9, 80.9 ± 13.7 and 75.3 ± 22.6 pg/mL, P < 0.001 vs. HS) as well as serum zonulin (1.3 ± 0.5, 6.1 ± 1.5 and 5.3 ± 1.7 ng/mL, P < 0.001 vs. HS). LPS and zonulin were correlated in HIV patients (Spearman correlation coefficient (rS) = 0.73, P < 0.0001). Levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thromboxane B2 (TxB2 ) were higher in HIV-1-treated and treatment-naïve subjects compared with HS as well as NADPH oxidase 2 (NOX2) activation and hydrogen peroxide (H2 O2 ) production. In vitro, sCD40L, sP-selectin and TxB2 production, NOX2 activation and p47phox phosphorylation were higher in platelets exposed to plasma from HIV-1 patients with different viral load compared with the exposure to plasma from HS. This effect was blunted in platelets pre-treated with TLR4 or TLR7 inhibitors. CONCLUSIONS: Low-grade endotoxaemia and persistent viraemia increase platelet function with a mechanism mediated by NOX2 in patients with HIV-1 infection.

Monoclonal antibodies against SARS-CoV-2 to prevent COVID-19 worsening in a large multicenter cohort.

Objective: Monoclonal antibodies (mAbs) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reduced Coronavirus Disease 2019 (COVID-19) hospitalizations in people at risk of clinical worsening. Real-world descriptions are limited. Methods: CONDIVIDIAMO, a two-year multicenter observational study, consecutively enrolled SARS-CoV-2 outpatients with ≥1 risk factor for COVID-19 progression receiving mAbs. Demographic data, underlying medical condition, type of mAbs combination received, duration of symptoms before mAbs administration, COVID-19 vaccination history, were collected upon enrolment and centrally recorded. Data on outcomes (hospitalizations, reasons of hospitalization, deaths) were prospectively collected. The primary endpoint was the rate of hospitalization or death in a 28-day follow-up, whichever occurred first; subjects were censored at the day of last follow-up or up to 28 days. The Kaplan-Meier method was used to estimate the incidence rate curve in time. The Cox regression model was used to assess potential risk factors for unfavorable outcome. Results were shown as hazard ratio (HR) along with the corresponding 95 % Confidence Interval (95%CI). Results: Among 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4-74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab. After 28-day follow-up, 87/1534 (5.6 %, 95%CI: 4.4%-6.8 %) met the primary outcome (85 hospitalizations, 2 deaths). Hospitalizations for COVID-19 (52, 3.4 %) occurred earlier than for other reasons (33, 2.1 %), after a median (IQR) of 3.5 (1-7) versus 8 (3-15) days (p = 0.006) from mAbs administration.In a multivariable Cox regression model, factors independently associated with increased hospitalization risk were age (hazard ratio [HR] 1.02, 95%CI 1.00-1.03, p = 0.021), immunodeficiency (HR 1.78, 95%CI 1.11-2.85, p = 0.017), pre-Omicron calendar period (HR 1.66, 95%CI 1.02-2.69, p = 0.041). Conclusions: MAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening.

Early prone positioning does not improve the outcome of patients with mild pneumonia due to SARS-CoV-2: results from an open-label randomised controlled trial - the EPCoT study.

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio (PaO2/FIO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and PaO2/FIO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a PaO2/FIO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted. Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.