Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

Expression of exogenous proteins in donor platelets treated with lipid nanoparticles encapsulating mRNA

Background: Platelets are transfused therapeutically for hemostasis, and are an integral part of hemorrhage management. However, transfusions can be ineffective in the most severe cases of hemorrhage. Platelets are also a potential cell therapy in other applications, but development has been hindered by inadequate methods to control which proteins are expressed by platelets. Currently, there are no methods to express exogenous proteins in transfusable platelets, which would expand their use to help treat the diseases they modulate. A method is therefore needed to modify transfusable platelets, and thus enhance their protein composition for specific applications. Aim(s): To produce engineered, transfusable platelets to enhance their natural coagulability and functional repertoire by directly transfecting donor-derived platelets with mRNA via lipid nanoparticle (LNP)-mediated delivery. The recent advances through the COVID-19 mRNA vaccines demonstrates the clinical safety and efficacy of LNP-mediated gene therapy, and thus offers a promising strategy to effectively engineer modified platelets. Method(s): Donor-derived platelets were washed and subsequently incubated with a systematic array of LNPs encapsulating Cy5-labeled mRNA encoding for nanoluciferase in comparison to commercial transfection reagents. LNP uptake and platelet activation via CD62p levels was assessed following 4 hours by flow cytometry, while luciferase expression was assessed by normalizing the luminescence intensity to the total protein content. Result(s): Platelets took up the mRNA through all conditions tested;nanoluciferase was only expressed, however, in platelets treated with LNPs and not commercial reagents. Systematically optimizing LNPs increased nanoluciferase expression nine-fold relative to pre-optimized LNPs. Exogenous protein expression did not appear to correlate with mRNA uptake nor platelet activation. Conclusion(s): Platelets transfected with LNPs can express exogenous protein. Further optimization can eventually lead to the creation of a platform technology that in the long-term will allow platelets to deliver therapeutic proteins and yield more effective platelet products.

The Feasibility of a Pediatric Distance Learning Curriculum for Emergency Nurses During the COVID-19 Pandemic: An Improving Pediatric Acute Care Through Simulation Collaboration

Introduction: To develop and evaluate the feasibility and effectiveness of a longitudinal pediatric distance learning curriculum for general emergency nurses, facilitated by nurse educators, with central support through the Improving Acute Care Through Simulation collaborative. Methods: Kern's 6-step curriculum development framework was used with pediatric status epilepticus aimed at maintaining physical distancing, resulting in a 12-week curriculum bookended by 1-hour telesimulations, with weekly 30-minute online asynchronous distance learning. Recruited nurse educators recruited a minimum of 2 local nurses. Nurse educators facilitated the intervention, completed implementation surveys, and engaged with other educators with the Improving Pediatric Acute Care through Simulation project coordinator. Feasibility data included nurse educator project engagement and curriculum engagement by nurses with each activity. Efficacy data were collected through satisfaction surveys, pre-post knowledge surveys, and pre-post telesimulation performance checklists. Results: Thirteen of 17 pediatric nurse educators recruited staff to complete both telesimulations, and 38 of 110 enrolled nurses completed pre-post knowledge surveys. Knowledge scores improved from a median of 70 of 100 (interquartile range: 66-78) to 88 (interquartile range: 79-94) (P =.018), and telesimulation performance improved from a median of 60 of 100 (interquartile range: 45-60) to 100 (interquartile range: 85-100) (P =.016). Feedback included a shortened intervention and including physician participants. Discussion: A longitudinal pediatric distance learning curriculum for emergency nurses collaboratively developed and implemented by nurse educators and Improving Pediatric Acute Care through Simulation was feasible for nurse educators to implement, led to modest engagement in all activities by nurses, and resulted in improvement in nurses’ knowledge and skills. Future directions include shortening intervention time and broadening interprofessional scope. © 2022 Emergency Nurses Association

Platelets Genetically Modified with mRNA-Lipid Nanoparticles Are Functionally Similar to Clinically Transfused Platelets in Vitro

Background/Case Studies: Platelet transfusions are an essential treatment for attenuating bleeding but are often ineffective in cases of intractable hemorrhage. Although anucleate, mature platelets synthesize protein de novo, making them amenable to mRNA gene therapy;however, there remains to be an effective transfection technique. Advancements in lipid nanoparticle (LNP) technology has enabled leading COVID vaccines and is an efficient method to deliver nucleic acids into target cells. Recently, a LNP approach to successfully express exogenous protein in donor platelets [unpublished data] has been developed, a first step towards demonstrating that donor platelet coagulability can be engineered. However, the effects of LNP treatment on platelet function has yet to be investigated. Study Design/Methods: Donated, pooled platelets were obtained from a regional blood for research centre. The hemostatic profiles of LNP-treated and clinical donor platelets were assessed using an adapted rotational thromboelastometry model of dilutional coagulopathy. Coagulability of whole blood (WB) and hemodiluted WB were assessed. Untreated and LNP-treated platelets were then supplemented into hemodiluted WB and activated using INTEM (ellagic acid) to generate a hemostatic profile. LNP-treated platelets were also stimulated with platelet agonists thrombin (0.1U/mL) and ADP (10 mM) and CD62p levels were evaluated to test if the activation response was similar to clinical platelets using flow cytometry. Statistical analysis was conducted by one-way ANOVA and significance defined by P < 0.05. Results/Findings: LNP-treated platelets have a comparable hemostatic profile to clinically transfused platelets and significantly contributed to clot strength when spiked into hemodiluted WB. After INTEM activation, the maximum clot firmness (MCF) of LNP-treated (45.67 +/-1.15) and untreated platelets (49.77 +/- 0.58) was significantly increased (P < 0.05) compared to diluted WB alone (35.00 +/- 1.00). No significant difference between untreated and LNP-treated donor platelets was observed although MCF trended down. No statistical difference in thrombin or ADP responsiveness, indicated by median fluorescent intensity of CD62p surface presentation, was observed between LNP treated and untreated platelets (P > 0.05). Conclusion(s): LNPs are an effective way to deliver exogenous nucleic acids into platelets;they do not significantly impair the platelet contribution to clot strength or responsiveness to agonists stimulation. The minimal effect of LNP exposure on in vitro platelet characteristics demonstrate that LNP engineering is a promising new approach to load platelets with nucleic acids encoding therapeutic protein to enhance their function.

Expression of Exogenous Proteins in Donor Platelets Treated with Lipid Nanoparticles Encapsulating mRNA

Background/Case Studies: Platelets are transfused therapeutically for hemostasis and are an integral part of hemorrhage management. Transfusions, however, can be ineffective in the most severe cases of hemorrhage. Platelets are also a potential cell therapy in other applications, but development has been hindered by inadequate methods to control which proteins are expressed by platelets. Currently, there are no methods to express exogenous proteins in transfusable platelets, which would expand their use to help treat the diseases they modulate. A method is therefore needed to modify transfusable platelets, and thus enhance their protein composition for specific applications. Lipid nanoparticles (LNPs) represent the most clinically advanced system for non-viral gene delivery, and can potentially be used to transfect donor-derived platelets with mRNA to produce transfusable platelets with an enhanced functional repertoire. The recent advances through the COVID-19 mRNA vaccines demonstrates the clinical safety and efficacy of LNP-mediated gene therapy, and thus offers a promising strategy to effectively engineer modified platelets. Study Design/Methods: Donor-derived platelets were washed and subsequently incubated with a systematic array of LNPs encapsulating Cy5-labeled mRNA encoding for nanoluciferase in comparison to the commercial transfection reagents, lipofectamine and Ribojuice. LNP uptake and platelet activation via CD62p levels was assessed following 4 h by flow cytometry, while nanoluciferase expression was assessed by normalizing the luminescence intensity (RLU) to the total protein content. Data was analyzed via a one-way unpaired Student or Welch's t-test or one-way analysis of variance (ANOVA) as appropriate. A p-value < 0.05 was considered significant. Results/Findings: Platelets internalized the mRNA through all conditions tested, with Ribojuice yielding the highest significant increase in Cy5 median fluorescence intensity relative to the LNP (59815 +/- 6466 A.U. vs. 1253 +/- 44 A.U., respectively, p = 0.002). Nanoluciferase was only expressed, however, in platelets treated with LNPs, yielding a normalized luminescence signal of 62 +/- 17 RLU/mug protein, and not with either of the commercial reagents. Systematically optimizing LNPs increased nanoluciferase expression nine-fold to 589 +/- 241 RLU/mug protein relative to pre-optimized LNPs (p = 0.031). A Pearson correlation analysis revealed that the expression of exogenous protein expression did not appear to correlate with the mRNA uptake (Pearson correlation coefficient, r = -0.35) nor platelet activation (r = -0.07). Conclusion(s): Transfecting platelets with LNPs containing mRNA enable the expression of exogenous protein. Further optimization can eventually lead to the creation of a platform technology that in the long-term will allow platelets to deliver therapeutic proteins and yield more effective platelet products.

The impact of mindfulness training in early adolescence on affective executive control, and on later mental health during the COVID-19 pandemic: a randomised controlled trial.

BACKGROUND: Previous research suggests that mindfulness training (MT) appears effective at improving mental health in young people. MT is proposed to work through improving executive control in affectively laden contexts. However, it is unclear whether MT improves such control in young people. MT appears to mitigate mental health difficulties during periods of stress, but any mitigating effects against COVID-related difficulties remain unexamined. OBJECTIVE: To evaluate whether MT (intervention) versus psychoeducation (Psy-Ed; control), implemented in after-school classes: (1) Improves affective executive control; and/or (2) Mitigates negative mental health impacts from the COVID-19 pandemic. METHODS: A parallel randomised controlled trial (RCT) was conducted (Registration: https://osf.io/d6y9q/; Funding: Wellcome (WT104908/Z/14/Z, WT107496/Z/15/Z)). 460 students aged 11-16 years were recruited and randomised 1:1 to either MT (N=235) or Psy-Ed (N=225) and assessed preintervention and postintervention on experimental tasks and self-report inventories of affective executive control. The RCT was then extended to evaluate protective functions of MT on mental health assessed after the first UK COVID-19 lockdown. FINDINGS: Results provided no evidence that the version of MT used here improved affective executive control after training or mitigated negative consequences on mental health of the COVID-19 pandemic relative to Psy-Ed. No adverse events were reported. CONCLUSIONS: There is no evidence that MT improves affective control or downstream mental health of young people during stressful periods. CLINICAL IMPLICATIONS: We need to identify interventions that can enhance affective control and thereby young people's mental health.

Platelets genetically modified with mRNA-lipid nanoparticles are functionally similar to clinically transfused platelets in vitro

Background: Platelet transfusions are an essential treatment for attenuating bleeding but are often ineffective in cases of intractable haemorrhage. Although anucleate, mature platelets synthesize protein de novo, making them amenable to mRNA gene therapy;however, there remains to be an effective transfection technique. Advancements in lipid nanoparticle technology has enabled leading COVID vaccines and is an efficient method to deliver nucleic acids into target cells. Recently, we developed a LNP approach to successfully express exogenous protein in platelets [unpublished data], a first step towards demonstrating that donor platelet coagulability can be engineered. However, the effects of LNP treatment on platelet function has yet to be investigated. Aims: To determine whether LNP-treated donor platelets are functionally similar, or better, in vitro, than platelets currently transfused clinically as a next step to establish LNP engineered platelets as a new cell therapy. Methods: The hemostatic profiles of LNP-treated and clinical donor platelets were assessed using an adapted rotational thromboelastometry model of dilutional coagulopathy. LNP-treated platelets were also stimulated with conventional platelet agonists to test if responsiveness is similar, or better than clinical platelets using flow cytometry. Results: LNP-treated platelets have a comparable hemostatic profile to clinically transfused platelets and significantly improved clotting dynamics when spiked into hemodiluted whole blood in an in vitro transfusion simulation. LNP-treated platelets also respond comparably, and in some cases more potently to agonist simulation compared to untreated platelets as indicated by similar p-selectin surface presentation. Summary/Conclusions: LNPs are an effective way to deliver exogenous nucleic acids into platelets;they do not significantly change platelet coagulability or responsiveness to agonists. LNP platelet engineering is a promising new approach to load platelets with procoagulant protein to enhance their function.

Cross-National Study of Mental Health and Employment Status Nine Months Post Social Distancing Implementation Practices

This cross-national study (Norway, the UK, the USA and Australia) examined the mental health between those individuals working and not working nine months post initial COVID-19 social distancing implementation. The sample (N=3,474) was recruited through social media (e.g. Facebook, Twitter). Respondents completed an online survey in October/November 2020. Individuals who were working were significantly more likely to experience better mental health, were younger, report high levels of education and significantly less likely to worry about their own situation, health or financial situation than individuals who were not working. If individuals were retired, they reported better mental health than individuals who were not working for other reasons (e.g. laid off/dismissed, receiving benefits, studying). Based on the findings of this study social workers and other health service providers need to address ways to enhance mental health services especially for individuals who are not working when social distancing protocols are in place. This cross-national study examined the mental health between those individuals working and those not working nine months post initial COVID-19 social distancing implementation. Respondents (N = 3,474) were recruited through social media (e.g. Facebook, Twitter) and completed an online survey in October/November 2020. The respondents were from Norway, the UK, the USA and Australia. The mental health of those working and not working were analysed using t tests and socio-demographics were compared using one-way analysis of variance. Respondents who were working were significantly more likely to experience better mental health, were younger, report higher levels of education, and significantly less likely to worry about their own situation, health or financial situation than respondents who were not employed. Respondents who were retired reported better mental health than respondents who were not working for other reasons (laid off/dismissed, receiving benefits, studying, other). These findings raise the importance for social workers and other health service providers to monitor the overall mental health of individuals especially when social distancing protocols are in place and as countries begin to recover from the pandemic.

Migration in the Midst of a Pandemic: A Case Study of Pacific Islanders in Oregon

The Pacific Islander population in the United States continues to grow due to outmigration and a unique immigration arrangement. Under the Compacts of Free Association (COFA), citizens from three Remote Oceania countries can travel to the United States to live and work without restriction. Given the special status of COFA migrants, there is a growing interest among policymakers and researchers to better understand this population, which has often been overlooked. Unfortunately, the COVID-19 pandemic has recently spotlighted this community due to their exceedingly high rates of infection, hospitalization, and morbidity. This study examines how migration is experienced during a pandemic via a case study of first-generation Micronesians living in Oregon’s Willamette Valley, one of the largest Micronesian communities in the United States. Interviews reveal how social determinants of health – such as economic stability, non-discrimination and equal treatment, access to healthcare, employment, and housing – may contribute to unequal health outcomes between Pacific Islander immigrants and other racial and ethnic populations. These determinants also contribute to human dignity. Using the emergent Migration with Dignity framework, this study assesses how the pandemic has challenged the six dimensions of dignity and disrupted the migration experience, including the push-pull factors for deciding to emigrate to and stay in the United States. Finally, the study assesses resources available for COFA citizens and avenues for improved support. © Fuji Technology Press Ltd.

Motivating Ethnic Minority Students in Hong Kong to Learn Chinese Culture with EduVenture VR

This paper presents our initiative for leveraging SV-IVR (spherical video-based immersive virtual reality) to give Hong Kong ethnic minority students exposure to local Chinese culture via EduVenture VR-an interactive learner-immersed virtual interactive learning application. The work was conducted in the COVID-19 pandemic context;outdoor fieldwork-based learning was not recommended in the circumstance. The research participants were 63 ethnic minority students (from Grade 7 to Grade 9) from a Hong Kong secondary school. The ARCS model of instructional motivation was employed to evaluate the motivational effectiveness of the Chinese culture learning activity supported by EduVenture VR. In the study, we obtained positive results in terms of the 4 motivational dimensions: "Attention," "Relevance," "Confidence' and "Satisfaction."

Air dispersal of meticillin-resistant Staphylococcus aureus in residential care homes for the elderly: implications for transmission during the COVID-19 pandemic.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs). AIM: To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs. METHODS: Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong. FINDINGS: During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital. CONCLUSION: MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.

Lessons learned from the first 50 COVID-19 critical care transfer missions conducted by a civilian UK Helicopter Emergency Medical Service team.

BACKGROUND: The COVID-19 pandemic has placed exceptional demand on Intensive Care Units, necessitating the critical care transfer of patients on a regional and national scale. Performing these transfers required specialist expertise and involved moving patients over significant distances. Air Ambulance Kent Surrey Sussex created a designated critical care transfer team and was one of the first civilian air ambulances in the United Kingdom to move ventilated COVID-19 patients by air. We describe the practical set up of such a service and the key lessons learned from the first 50 transfers. METHODS: Retrospective review of air critical care transfer service set up and case review of first 50 transfers. RESULTS: We describe key elements of the critical care transfer service, including coordination and activation; case interrogation; workforce; training; equipment; aircraft modifications; human factors and clinical governance. A total of 50 missions are described between 18 December 2020 and 1 February 2021. 94% of the transfer missions were conducted by road. The mean age of these patients was 58 years (29-83). 30 (60%) were male and 20 (40%) were female. The mean total mission cycle (time of referral until the time team declared free at receiving hospital) was 264 min (range 149-440 min). The mean time spent at the referring hospital prior to leaving for the receiving unit was 72 min (31-158). The mean transfer transit time between referring and receiving units was 72 min (9-182). CONCLUSION: Critically ill COVID-19 patients have highly complex medical needs during transport. Critical care transfer of COVID-19-positive patients by civilian HEMS services, including air transfer, can be achieved safely with specific planning, protocols and precautions. Regional planning of COVID-19 critical care transfers is required to optimise the time available of critical care transfer teams.

COVID-19 INFECTIONS IN THE EOSINOPHILIC GI DISEASE POPULATION ARE NOT SEVERE: INITIAL REPORT FROM A GLOBAL ONLINE REGISTRY

Background: The impact of COVID-19 infection on patients with eosinophilic esophagitis (EoE) and other eosinophilic GI diseases (EGIDs) is not known. Aim: To determine the characteristics of EoE and EGID patients who have COVID-19, assess severity COVID-19 in the EGID population, and evaluate for COVID-19-induced EGID flares. Methods: We established an online global registry (covideoeegid.org) where health care providers could report details of COVID-19 infection in EoE and EGID patients. The registry was publicized and reminders were sent via worldwide patient advocacy groups, professional organizations, and research collaborative groups. De-identified data were entered into the website related to patient demographics, EGID disease features and activity, comorbidities, and treatments. Data collected related to COVID-19 included source of exposure, symptoms, illness severity, hospitalizations, and deaths. Descriptive statistics were used to summarize the findings. Results: A total of 40 cases of COVID-19 in EoE/EGID patients were reported as of November, 2020 (Figure). Patients had a mean age of 25 (±11) years at the time of COVID-19 diagnosis, the majority were male (73%) and had atopy (73%), and nearly all (95%) had EoE, though some non-EoE EGIDs were reported (Table). At the time of COVID-19 infection, EGID disease activity was reported as in remission in 18 (45%) and moderate in 13 (33%). EGID treatments at the time of COVID-19 included PPIs (58%), swallowed/topical steroids (45%), and/or dietary elimination (42%) (Table). Most common exposures for COVID-19 were either unknown (30%) or from household contacts (30%);34 of the reported cases were confirmed with testing, while 6 were suspected based on clinical presentation. Common symptoms included cough (63%), fever (50%), anosmia (20%), and ageusia (18%);15% of cases were asymptomatic. No COVID-19 infections were classified as severe, and 32 (80%) were deemed mild (Table). Only 1 patient was hospitalized (received lopinavir and hydroxychloroquine), and no ICU admissions or deaths were reported. The mean number of days from infection to symptom resolution was 9.8±8.3. No EGID disease activity flares were reported due to COVID-19. Conclusions: In a global EoE/EGID registry, relatively few COVID-19 cases have been reported over an initial 8 month period, despite extensive efforts at outreach. The reported cases of EGID/COVID-19 are mild, with only one hospitalization and no deaths. Despite concerns of possible reporting bias and that EGID patients tend to be younger, based on this registry it does not appear that EGID patients are at increased risk for severe COVID-19 infection or that COVID-19 leads to EGID flares. Future serologic studies are needed to determine the prevalence of COVID in EGIDs. We ask providers to continue to report cases (covideoeegid.org). (Image presented) (Table presented)

Controlled knockdown of fibrinogen with sirna modulates fibrinogen-mediated inflammation

Background: Fibrinogen is an acute phase protein dramatically elevated in several diseases and during severe inflammation, such as COVID-19, cancer and sepsis. While fibrinogen is essential for maintaining hemostasis following vascular injury, overexpression of fibrinogen contributes to thrombosis. Decreasing elevated fibrinogen back to near normal levels may be a way to attenuate both inflammation and thrombosis, but has not been tested, presumably due to lack of a suitable agent that can deplete fibrinogen for long durations. Aims: To develop a potent siRNA approach that safely knocks down fibrinogen for long durations in vivo and to determine if decreasing the concentration of fibrinogen in blood plasma effectively modulates fibrinogen-mediated inflammation. Methods : Three siRNA sequences targeting mouse fibrinogen (siFbg), each encapsulated in lipid nanoparticles, were administered to separate cohorts of mice, from which hepatic mRNA and plasma protein levels were analyzed one-week post-injection. The most potent siFbg was used in subsequent studies in mice, including a monthlong dose titration study, a saphenous vein bleeding model, a lipopolysaccharide (LPS)-induced inflammatory model, and a sterile peritonitis model. Results: siFbg significantly knocked down fibrinogen in blood plasma in mice by one-week post-injection and lasted for at least three weeks, compared to mice treated with siRNA against luciferase as negative control. Dose-response studies with the most effective siFbg are ongoing as to offer unique control of the degree of fibrinogen knockdown. Mice treated with siFbg formed clots with decreased clot strength ex vivo , but hemostasis was not impaired in vivo in a saphenous vein puncture model. Treatment with siFbg protected wild-type C57BL/6J mice from increased fibrinogen 24-hours after challenging them with LPS, and restored macrophage migration in plasminogen deficient mice after thioglycollate-induced peritonitis. Conclusions: siRNA is an effective strategy for decreasing the concentration of fibrinogen in blood plasma long-term without impairing hemostasis, and can effectively modulate fibrinogen-mediated inflammation in mouse models.