Abstract 4144823: Persistent Prothrombotic State in Post-Acute Sequelae of Mild SARS-CoV-2 Infection: Role of Extracellular Histones and Immune Complexes

Circulation, Volume 150, Issue Suppl_1, Page A4144823-A4144823, November 12, 2024. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have become a significant healthcare burden. Sustained increases in prothrombotic markers have been reported in hospitalized acute COVID-19 patients. However, whether patients with less severe acute infection also endure a persistent prothrombotic state remains uncertain. We tested for a prothrombotic state in this cohort and examined potential mediators. We enrolled 70 adult patients with prior mild acute SARS-CoV-2 infection and sustained PASC symptoms (per WHO criteria). A control healthy group matched for age and sex was also enrolled who were not previously diagnosed with COVID-19. Markers of platelet activation and platelet-neutrophil aggregates (PNA) were quantified using whole-blood flow cytometry. Markers of extracellular traps (citrullinated histones [H3Cit] and cell-free DNA [cfDNA]), anti-dsDNA IgG, and thrombin generation potential were measured in plasma. At recruitment (6 weeks to 3 years post infection), there was increased potential for thrombin generation in the plasma from PASC compared to control reflected by increased peak and velocity index (P

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Novembre 2024

Abstract 4138507: Uncovering Risk Factors for Myocarditis and Cardiac Arrhythmia in Youth Post-SARS-CoV-2 Infection: Insights from the N3C Database and Advanced Machine Learning

Circulation, Volume 150, Issue Suppl_1, Page A4138507-A4138507, November 12, 2024. Background:SARS-CoV2 infection has been associated with cardiovascular consequences, including myocarditis and cardiac arrhythmias. Myocarditis secondary to SARS-CoV2 infection and cardiac arrhythmias may often go unrecognized and can present with late and nonspecific symptoms. Predicting those at risk allows for prompt treatment and prevention of their potentially life-threatening consequences.Methods:The National COVID Cohort Collaborative (N3C) database was used to identify patients aged 0-30 years with COVID-19 index date between 1/1/2020 and 3/31/2022, whose sites provided data for at least six months beyond the index date. Outcomes included myocarditis and new arrythmias within 6 months of the index visit. Patients with known cardiac comorbidities were excluded. Predictors included gender, race, COVID severity as an ordinal scale, vaccination status, clinical comorbidities, and Area Deprivation Index (ADI). The data were stratified by age groups (0-4, 5-17, 18-30). Random forest models were used for data analysis and SHapley Additive exPlanations (SHAP) method was applied to optimize results. These analyses were conducted using the NCATS N3C Data Enclave.Results:Of the 1,487,741 patients in our study population, 4,105 (0.28%) had the measured outcomes; 404 had myocarditis only, 3,634 had arrhythmia only and 67 had both. Severity of COVID (SHAP 0.2344 for 0-4 years, 0.2114 for 5-17, 0.1370 for 18-30) was identified as the most important risk factor for de-novo myocarditis and arrhythmias overall. Increase in ADI (indicating lower socioeconomic status) was the second most important risk factor for the 0-4 and 5-17 age groups (SHAP: 0.0370, 0.0223). Among the 18-30 age group, race (SHAP 0.0321) and gender (SHAP 0.0289) were the second and third most important risk factors, with White and Black patients more likely to develop an event and Hispanic patients less likely. Women were less likely to develop a cardiac outcome than men.Conclusion:The severity of COVID was identified as the most important risk factor for the occurrence of myocarditis or cardiac arrhythmia within 6 months of infection. ADI, race, and gender were also identified as important, though less influential, risk factors.

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Novembre 2024

Using digital tools and antigen rapid testing to support household-level SARS-CoV-2 detection by community health workers in Rwanda: an operational pilot study

Objective
To evaluate the use of antigen-based rapid diagnostic tests (Ag-RDTs) alongside a digital tool to deliver household-level COVID-19 testing by community health workers (CHWs), in line with Rwanda’s ambition to decentralise COVID-19 testing.

Design
This was an operational pilot study to evaluate the impact and operational characteristics of using the digital e-ASCov tool combined with Ag-RDTs to support COVID-19 symptom screening and rapid testing by CHWs across eight districts in Rwanda. A total of 800 CHWs selected from both rural and urban areas were trained in delivering Ag-RDTs for COVID-19 testing and using the e-ASCOV application for data capture on a smartphone. Laboratory technicians repeated a subset of Ag-RDTs to assess the concordance of results obtained by CHWs. The study also assessed CHWs’ experience of the intervention using a mixed-methods approach.

Setting
Eight rural, urban and semiurban districts in Rwanda.

Participants
A total of 19 544 individuals were enrolled and screened for signs and symptoms of COVID-19.

Interventions
Community-based screening for COVID-19 by CHWs using the digital tool e-ASCov combined with rapid testing using Ag-RDTs.

Main outcome measures
Number of participants screened and tested; concordance of Ag-RDT results between CHWs and laboratory technicians; feasibility of study procedures by CHWs and CHWs perceptions of the digital tool and Ag-RDT testing.

Results
From February to May 2022, CHWs screened 19 544 participants, of whom 4575 (23.4%) had COVID-19-related symptoms or a history of exposure to the infection. Among them, 86 (1.9%) were positive on Ag-RDTs. Concordance of Ag-RDT results between CHWs and laboratory technicians was 100%. Of the 800 trained CHWs, 746 (93.3%) were independently able to conduct household-based COVID-19 screening, perform the Ag-RDTs and send data to the central server. Most CHWs ( >80%) found Ag-RDTs and e-ASCOV easy to use.

Conclusions
This study demonstrated the feasibility of deploying a digital tool and Ag-RDTs for household-level SARS-CoV-2 detection in Rwanda. The findings support a broader roll-out of digitally supported rapid testing by CHWs to broaden access to testing for priority diseases.

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Ottobre 2024

Productive infection of primary human hepatocytes with SARS-CoV-2 induces antiviral and proinflammatory responses

We read with interest the article by Luxenburger and Thimme, summarising current knowledge about hepatic sequelae in the context of SARS-CoV-2 infection.1 As acute liver injury is observed in one-third of the patients with hospitalised COVID-192 3 and chronic liver disease is associated with higher mortality rates,4 a detailed understanding of hepatic susceptibility and dysfunction in the context of SARS-CoV-2 infection is of utmost importance. Previous studies have provided evidence of hepatic infection,5–7 however, the molecular mechanisms underlying acute liver injury associated with SARS-CoV-2 infection are not well understood. Here we show that primary human hepatocytes (PHH) can be productively infected with SARS-CoV-2. Donor-specific production kinetics were observed, with de novo viral secretion from PHH increasing in a time-dependent manner for four out of six donors (figure 1A). To explore virus replication and…

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Settembre 2024