Excipient-Induced Pulmonary Vascular Disease: An Underrecognized and Deadly Complication of Opioid Addiction.

Despite widespread public health concern regarding opioid misuse and overuse, there is a paucity of literature on the acute and chronic pulmonary vascular and cardiac implications of excipient lung disease. This case series describes the clinical presentation of five adult patients who experienced profound pulmonary hypertension and right heart failure in the setting of confirmed or suspected crushed opioid injection at a single academic center between 2012 and 2019. The clinical characteristics and right heart catheterization data presented in these cases demonstrate the acute intravascular effects of the intravenous injection of crushed opioids and potential for hemodynamic collapse. Moreover, these cases suggest that survivors of acute excipient lung disease may develop chronic pulmonary vascular disease. Further studies are needed to explore the epidemiology and outcomes of oral opioid-induced intravascular excipient lung disease to increase awareness of this life-threatening complication among health care professionals and guide treatment and prevention measures.

Development and Psychometric Characteristics of the TBI-QOL Communication Item Bank.

OBJECTIVE: To develop an item response theory (IRT)-based patient-reported outcome measure of functional communication for adults with traumatic brain injury (TBI). SETTING: Five medical centers that were TBI Model Systems sites. PARTICIPANTS: A total of 569 adults with TBI (28% complicated-mild; 13% moderate; and 58% severe). DESIGN: Grounded theory-based qualitative item development, large-scale item calibration testing, confirmatory factor analyses, psychometric analyses with graded response model IRT. MAIN MEASURE: Traumatic Brain Injury-Quality of Life (TBI-QOL) Communication Item Bank, version 1.0. RESULTS: From an initial pool of 48 items, 31 items were retained in the final instrument based on adequate fit to a unidimensional model and absence of bias across several demographic and clinical subgroupings. The TBI-QOL Communication Item Bank demonstrated excellent score precision (reliability ≥ 0.95) across a wide range of communication impairment levels, particularly for individuals with more severe difficulties. The TBI-QOL Communication Item Bank is available as a full item bank, fixed-length short form, and as a computerized adaptive test. CONCLUSIONS: The TBI-QOL Communication Item Bank permits precise measurement of patient-reported functional communication after TBI. Future development will validate the instrument against performance-based, clinician-reported, and surrogate-reported assessments.

Under the bridge: An in-depth examination of online trolling in the gaming context.

Trolling is a subject of apparent academic confusion; the few studies conducted thus far yielded a variety of conflicting definitions regarding what constitutes trolling behaviour and little information regarding trolling motivations. In order to shed further light on this phenomenon, the present study aimed to (1) determine which behaviours actual trolls consider as trolling, (2) explore the motivations behind trolling, and (3) examine the online community's response to trolling as perceived by the troll. After performing semi-structured interviews with 22 self-confessed trolls, we found that there is a variety of behaviours trolls consider trolling which can now be put in clear categories based on target and method. Three key motivations to troll emerged: personal enjoyment, revenge, and thrill-seeking. Trolling also appears to be a cyclical, self-perpetuating phenomenon enabled by the online community at large. Theoretical implications for future trolling research are also discussed.

The Pursuit of Noninvasive Diagnosis of Lung Cancer.

The noninvasive diagnosis of lung cancer remains a formidable challenge. Although tissue diagnosis will remain the gold standard for the foreseeable future, questions pertaining to the risks and costs associated with invasive diagnostic procedures are of prime relevance. This review addresses new modalities for improving the noninvasive evaluation of suspicious lung nodules. Ultimately, the goal is to translate early diagnosis into early treatment. We discuss how biomarkers could assist in distinguishing benign from malignant nodules and aggressive from indolent tumors. The field of biomarkers is rapidly expanding and progressing, and efforts are well underway to apply molecular diagnostics to address the shortcomings of current lung cancer diagnostic tools.

Precision of the Conceptual Research Utilization Scale.

BACKGROUND AND PURPOSE: Conceptual research utilization (CRU) is one indicator of an optimum practice environment that leads to improved patient and organizational outcomes. Yet, its measurement has not been adequately addressed. In this study, we investigated precision of scores obtained with a new CRU scale using item response theory (IRT) methods. METHODS: We analyzed the responses from 1,349 health care aides from 30 Canadian nursing homes using Samejima's (1969, 1996) graded response model (GRM). RESULTS: Findings suggest that the CRU scale is most precise at low to average trait levels with significantly less precision at higher trait levels. CONCLUSIONS: The scale showed acceptable precision at low to average trait levels. New items and/or different response options that capture higher trait levels are needed. Future development of the scale is discussed.

Unexpected: an interpretive description of parental traumas' associated with preterm birth.

BACKGROUND: Preterm birth (PTB) places a considerable emotional, psychological, and financial burden on parents, families, health care resources, and society as a whole. Efforts to estimate these costs have typically considered the direct medical costs of the initial hospital and outpatient follow-up care but have not considered non-financial costs associated with PTB such as adverse psychosocial and emotional effects, family disruption, strain on relationships, alterations in self-esteem, and deterioration in physical and mental health. The aim of this inquiry is to understand parents' experience of PTB to inform the design of subsequent studies of the direct and indirect cost of PTB. The study highlights the traumatic nature of having a child born preterm and discusses implications for clinical care and further research. METHOD: Through interviews and focus groups, this interpretive descriptive study explored parents' experiences of PTB. The interviews were audiotaped, transcribed, and analyzed for themes. Analysis was ongoing throughout the study and in subsequent interviews, parents were asked to reflect and elaborate on the emerging themes as they were identified. RESULTS: PTB is a traumatic event that shattered parents' taken-for-granted expectations of parenthood. For parents in our study, the trauma they experienced was not related to infant characteristics (e.g., gestational age, birth weight, Apgar scores, or length of stay in the NICU), but rather to prolonged uncertainty, lack of agency, disruptions in meaning systems, and alterations in parental role expectations. Our findings help to explain why things like breast feeding, kangaroo care, and family centered practices are so meaningful to parents in the NICU. As well as helping to (re)construct their role as parents, these activities afford parents a sense of agency, thereby moderating their own helplessness. CONCLUSION: These findings underscore the traumatic nature and resultant psychological distress related to PTB. Obstetrical and neonatal healthcare providers need to be educated about the symptoms of Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) to better understand and support parents' efforts to adapt and to make appropriate referrals if problems develop. Longitudinal economic studies must consider the psychosocial implications of PTB to in order to determine the total related costs.

Embracing the population health framework in nursing research.

Individuals' health outcomes are influenced not only by their knowledge and behavior, but also by complex social, political and economic forces. Attention to these multi-level factors is necessary to accurately and comprehensively understand and intervene to improve human health. The population health framework is a valuable conceptual framework to guide nurse researchers in identifying and targeting the broad range of determinants of health. However, attention to the intermediate processes linking multi-level factors and use of appropriate multi-level theory and research methodology is critical to utilizing the framework effectively. Nurse researchers are well equipped to undertake such investigations but need to consider a number of political, societal, professional and organizational barriers to do so. By fully embracing the population health framework, nurse researchers have the opportunity to explore the multi-level influences on health and to develop, implement and evaluate interventions that target immediate needs, more distal factors and the intermediate processes that connect them.

Lessons on Health Literacy and Communication in Post-Stroke Rehabilitation:: A Primer and Proposal.

Health literacy, or the ability to find, understand, and use information to make well-informed health decisions, has been linked to post-stroke rehabilitation outcomes. Importantly, barriers to health literacy stem from stroke survivor characteristics, clinician practices, institutional norms, as well as systemic variables. These barriers impact recovery and rehabilitation outcomes. To address these obstacles, clinicians can learn from the evidence-based practices used by speech-language pathologists in their work with stroke survivors with aphasia, a language impairment that can follow stroke. These methods to overcome communication barriers are appropriate and recommended for patients and family members regardless of stroke impairment, and include a transdisciplinary care model, multimodal approaches to patient education, along with consistent engagement with patients and their care partners. These strategies may be adopted for both personal and organizational health literacy efforts and help optimize the rehabilitation and recovery outcomes of stroke survivors with and without aphasia.

Comparing shades of darkness: trolling victims' experiences on social media vs. online gaming.

Although there is ample literature available on toxicity in games, as there is regarding trolling on social media, there are few to no cross-platform studies on toxicity and trolling. In other words, the extant literature focuses on one platform at a time instead of comparing and contrasting them. The present work aims to rectify this gap by analyzing interviews from a larger study of 22 self-proclaimed victims of in-game trolling to not only determine whether social media or gaming communities are considered more toxic but also to explore how definitions of the word 'trolling' change depending on the platform in question. We found that while definitions of in-game trolling behavior focused on behavioral styles of trolling (e.g., throwing one's avatar into enemy fire to disadvantage one's team, and blocking other players' avatars' movement), social media trolling is defined by more sinister actions such as misinformation spreading and 'canceling' other users. We also found that gaming is perceived as generally more toxic than social media, often due to company policies or lack thereof. Practical and theoretical implications for the study of toxicity in all online communities - gaming or social-media based - are discussed.

HIV and Drug Use: A Tale of Synergy in Pulmonary Vascular Disease Development.

Over the past two decades, with the advent and adoption of highly active anti-retroviral therapy, HIV-1 infection, a once fatal and acute illness, has transformed into a chronic disease with people living with HIV (PWH) experiencing increased rates of cardio-pulmonary vascular diseases including life-threatening pulmonary hypertension. Moreover, the chronic consequences of tobacco, alcohol, and drug use are increasingly seen in older PWH. Drug use, specifically, can have pathologic effects on the cardiovascular health of these individuals. The "double hit" of drug use and HIV may increase the risk of HIV-associated pulmonary arterial hypertension (HIV-PAH) and potentiate right heart failure in this population. This article explores the epidemiology and pathophysiology of PAH associated with HIV and recreational drug use and describes the proposed mechanisms by which HIV and drug use, together, can cause pulmonary vascular remodeling and cardiopulmonary hemodynamic compromise. In addition to detailing the proposed cellular and signaling pathways involved in the development of PAH, this article proposes areas ripe for future research, including the influence of gut dysbiosis and cellular senescence on the pathobiology of HIV-PAH. © 2023 American Physiological Society. Compr Physiol 13:4659-4683, 2023.

ACROBAT Edge: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients With Acromegaly.

CONTEXT: Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly. OBJECTIVE: This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine. METHODS: A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected. RESULTS: Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN]; P = .6285; GH = -0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported. CONCLUSION: These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.

Microbial Drivers of Plant Performance during Drought Depend upon Community Composition and the Greater Soil Environment.

The increasing occurrence of drought is a global challenge that threatens food security through direct impacts to both plants and their interacting soil microorganisms. Plant growth promoting microbes are increasingly being harnessed to improve plant performance under stress. However, the magnitude of microbiome impacts on both structural and physiological plant traits under water limited and water replete conditions are not well-characterized. Using two microbiomes sourced from a ponderosa pine forest and an agricultural field, we performed a greenhouse experiment that used a crossed design to test the individual and combined effects of the water availability and the soil microbiome composition on plant performance. Specifically, we studied the structural and leaf functional traits of maize that are relevant to drought tolerance. We further examined how microbial relationships with plant phenotypes varied under different combinations of microbial composition and water availability. We found that water availability and microbial composition affected plant structural traits. Surprisingly, they did not alter leaf function. Maize grown in the forest-soil microbiome produced larger plants under well-watered and water-limited conditions, compared to an agricultural soil community. Although leaf functional traits were not significantly different between the watering and microbiome treatments, the bacterial composition and abundance explained significant variability in both plant structure and leaf function within individual treatments, especially water-limited plants. Our results suggest that bacteria-plant interactions that promote plant performance under stress depend upon the greater community composition and the abiotic environment. IMPORTANCE Globally, drought is an increasingly common and severe stress that causes significant damage to agricultural and wild plants, thereby threatening food security. Despite growing evidence of the potential benefits of soil microorganisms on plant performance under stress, decoupling the effects of the microbiome composition versus the water availability on plant growth and performance remains a challenge. We used a highly controlled and replicated greenhouse experiment to understand the impacts of microbial community composition and water limitation on corn growth and drought-relevant functions. We found that both factors affected corn growth, and, interestingly, that individual microbial relationships with corn growth and leaf function were unique to specific watering/microbiome treatment combinations. This finding may help explain the inconsistent success of previously identified microbial inocula in improving plant performance in the face of drought, outside controlled environments.

Do factors that influence pregnancy planning differ by maternal age? A population-based survey.

OBJECTIVE: The objectives of this analysis were to describe factors that influenced the decision to conceive among first-time mothers in two Canadian urban centres and to determine if these differed according to the age at which a woman became a mother. METHODS: Women who had given birth to their first live born infant between July 2002 and September 2003 in Calgary and Edmonton were randomly selected from regional notice of birth databases. Women were contacted by telephone, and those who agreed to participate completed a 20-minute survey over the telephone. This analysis was conducted using data from participants with a planned pregnancy. RESULTS: The top three factors that influenced childbearing among women planning a pregnancy were similar regardless of age. They were being in a secure relationship (97%), feeling in control of one's life (82%), and feeling prepared to parent (77%). Less than 30% of women reported career goals as being "very important" in their decision. Women under 25 years of age were less likely than women 25 years or older to indicate the following as being "very important" in the timing of starting a family: being in a stable job (32%), owning a home (36%), financial security (42%), educational training (36%), and career goals (9%) (all P < 0.001). CONCLUSION: This information provides a basis for developing strategies to support couples in their efforts to balance the age-related biomedical risks of delaying childbearing with a desire for relationship security and other factors that strongly influence childbearing decisions.

Symptoms of acute stress disorder in mothers of premature infants.

PURPOSE: : To determine whether significant symptoms of acute stress disorder (ASD) are present in mothers of premature infants in the neonatal intensive care unit (NICU). SUBJECTS: : Forty mothers of premature infants born less than 33 weeks and admitted into NICU. DESIGN: : Prospective, cohort, within-subjects. METHODS: : Mothers completed the Stanford Acute Stress Reaction Questionnaire, Edinburgh Postnatal Depression Scale, and the Acute Stress Disorder Interview to explore the number and severity of stress-related symptoms at 2 separate time periods, 7 to 10 days after birth, and 1 month after birth. RESULTS: : Twenty-eight percent of the mothers met diagnostic criteria of ASD at 7 to 10 days after birth, and at 1 month after birth ASD symptoms persisted. The majority of the mothers described premature birth as a traumatic stressor. The most commonly met criteria were dissociation and anxiety. Significant symptoms of depression were found in 43% of mothers and persisted 1 month after birth. Rates of depression and moderate to severe symptoms of ASD were significantly related in mothers at 1 week and at 1 month after birth. CONCLUSIONS: : The premature birth experience is traumatic for mothers and may lead to various emotional responses including stress-related symptoms such as depression and/or ASD. Mothers with significant symptoms of depression and those with symptoms of stress seem to be more at risk for developing symptoms of ASD.

Exploring extracellular vesicles as mediators of clinical disease and vehicles for viral therapeutics: Insights from the COVID-19 pandemic.

The COVID-19 pandemic has challenged researchers to rapidly understand the capabilities of the SARS-CoV-2 virus and investigate potential therapeutics for SARS-CoV-2 infection. COVID-19 has been associated with devastating lung and cardiac injury, profound inflammation, and a heightened coagulopathic state, which may, in part, be driven by cellular crosstalk facilitated by extracellular vesicles (EVs). In recent years, EVs have emerged as important biomarkers of disease, and while extracellular vesicles may contribute to the spread of COVID-19 infection from one cell to the next, they also may be engineered to play a protective or therapeutic role as decoys or "delivery drivers" for therapeutic agents. This review explores these roles and areas for future study.

Validation of the conceptual research utilization scale: an application of the standards for educational and psychological testing in healthcare.

BACKGROUND: There is a lack of acceptable, reliable, and valid survey instruments to measure conceptual research utilization (CRU). In this study, we investigated the psychometric properties of a newly developed scale (the CRU Scale). METHODS: We used the Standards for Educational and Psychological Testing as a validation framework to assess four sources of validity evidence: content, response processes, internal structure, and relations to other variables. A panel of nine international research utilization experts performed a formal content validity assessment. To determine response process validity, we conducted a series of one-on-one scale administration sessions with 10 healthcare aides. Internal structure and relations to other variables validity was examined using CRU Scale response data from a sample of 707 healthcare aides working in 30 urban Canadian nursing homes. Principal components analysis and confirmatory factor analyses were conducted to determine internal structure. Relations to other variables were examined using: (1) bivariate correlations; (2) change in mean values of CRU with increasing levels of other kinds of research utilization; and (3) multivariate linear regression. RESULTS: Content validity index scores for the five items ranged from 0.55 to 1.00. The principal components analysis predicted a 5-item 1-factor model. This was inconsistent with the findings from the confirmatory factor analysis, which showed best fit for a 4-item 1-factor model. Bivariate associations between CRU and other kinds of research utilization were statistically significant (p < 0.01) for the latent CRU scale score and all five CRU items. The CRU scale score was also shown to be significant predictor of overall research utilization in multivariate linear regression. CONCLUSIONS: The CRU scale showed acceptable initial psychometric properties with respect to responses from healthcare aides in nursing homes. Based on our validity, reliability, and acceptability analyses, we recommend using a reduced (four-item) version of the CRU scale to yield sound assessments of CRU by healthcare aides. Refinement to the wording of one item is also needed. Planned future research will include: latent scale scoring, identification of variables that predict and are outcomes to conceptual research use, and longitudinal work to determine CRU Scale sensitivity to change.

High gestational weight gain and the risk of preterm birth and low birth weight: a systematic review and meta-analysis.

OBJECTIVE: Many women have high gestational weight gain (GWG), but potential neonatal consequences are not yet well quantified. We sought to determine the relationship between high GWG and preterm birth (PTB) and low birth weight (LBW) in singleton births. DATA SOURCES: We searched Medline and Embase and reference lists. STUDY SELECTION: Two assessors independently performed all steps. We selected studies assessing high total or weekly GWG on PTB (< 37 weeks) and LBW (< 2500 grams). DATA EXTRACTION AND SYNTHESIS: Thirty-eight studies, 24 cohort and 14 case-control, were included involving 2 124 907 women. Most contained unadjusted data. Women with high total GWG had a decreased risk overall of PTB < 37 weeks (relative risk [RR] 0.75; 95% CI 0.60 to 0.96), PTB 32 to 36 weeks (RR 0.70; 95% CI 0.70 to 0.71), and < 32 weeks (RR 0.87; 95% CI 0.85 to 0.90). High GWG was associated with lower risk of LBW (RR 0.64; 95% CI 0.53 to 0.78). Women with the highest GWG had lower risks of LBW (RR 0.55; 95% CI 0.32 to 0.94) than women with moderately high GWG (RR 0.73; 95% CI 0.60 to 0.89). Women with the highest weekly GWG had greater risks of PTB (RR 1.51; 95% CI 1.47 to 1.55) than women with moderately high weekly GWG (RR 1.09; 95% CI 1.05 to 1.13). Women with high weekly GWG were at increased risk of PTB 32 to 36 weeks (RR 1.14; 95% CI 1.10 to 1.17 and < 32 weeks (RR 1.81; 95% CI 1.73 to 1.90). CONCLUSION: Although women with high total GWG have lower unadjusted risks of PTB and LBW, high weekly GWG is associated with increased PTB, and more adjusted studies are needed, as are more studies in obese women. Potential benefits of high GWG for the infant must be balanced against maternal risks and other known infant risks such as high birth weight.

Viral Bad News Sent by EVAIL.

This article reviews the current knowledge on how viruses may utilize Extracellular Vesicle Assisted Inflammatory Load (EVAIL) to exert pathologic activities. Viruses are classically considered to exert their pathologic actions through acute or chronic infection followed by the host response. This host response causes the release of cytokines leading to vascular endothelial cell dysfunction and cardiovascular complications. However, viruses may employ an alternative pathway to soluble cytokine-induced pathologies-by initiating the release of extracellular vesicles (EVs), including exosomes. The best-understood example of this alternative pathway is human immunodeficiency virus (HIV)-elicited EVs and their propensity to harm vascular endothelial cells. Specifically, an HIV-encoded accessory protein called the "negative factor" (Nef) was demonstrated in EVs from the body fluids of HIV patients on successful combined antiretroviral therapy (ART); it was also demonstrated to be sufficient in inducing endothelial and cardiovascular dysfunction. This review will highlight HIV-Nef as an example of how HIV can produce EVs loaded with proinflammatory cargo to disseminate cardiovascular pathologies. It will further discuss whether EV production can explain SARS-CoV-2-mediated pulmonary and cardiovascular pathologies.

An Exploration of Mental Health Discussions in Live Streaming Gaming Communities.

Live streaming is a unique form of media that creates a direct line of interaction between streamers and viewers. While previous research has explored the social motivations of those who stream and watch streams in the gaming community, there is a lack of research that investigates intimate self-disclosure in this context, such as discussing sensitive topics like mental health on platforms such as Twitch.tv. This study aims to explore discussions about mental health in gaming live streams to better understand how people perceive discussions of mental health in this new media context. The context of live streaming is particularly interesting as it facilitates social interactions that are masspersonal in nature: the streamer broadcasts to a larger, mostly unknown audience, but can also interact in a personal way with viewers. In this study, we interviewed Twitch viewers about the streamers they view, how and to what extent they discuss mental health on their channels in relation to gaming, how other viewers reacted to these discussions, and what they think about live streams, gaming-focused or otherwise, as a medium for mental health discussions. Through these interviews, our team was able to establish a baseline of user perception of mental health in gaming communities on Twitch that extends our understanding of how social media and live streaming can be used for mental health conversations. Our first research question unraveled that mental health discussions happen in a variety of ways on Twitch, including during gaming streams, Just Chatting talks, and through the stream chat. Our second research question showed that streamers handle mental health conversations on their channels in a variety of ways. These depend on how they have built their channel, which subsequently impacts how viewers perceive mental health. Lastly, we learned that viewers' reactions to mental health discussions depend on their motivations for watching the stream such as learning about the game, being entertained, and more. We found that more discussions about mental health on Twitch led to some viewers being more cautious when talking about mental health to show understanding.

Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity.

Coronavirus disease-2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has lead to a global pandemic with a rising toll in infections and deaths. Better understanding of its pathogenesis will greatly improve the outcomes and treatment of affected patients. Here we compared the inflammatory and cardiovascular disease-related protein cargo of circulating large and small extracellular vesicles (EVs) from 84 hospitalized patients infected with SARS-CoV-2 with different stages of disease severity. Our findings reveal significant enrichment of proinflammatory, procoagulation, immunoregulatory and tissue-remodelling protein signatures in EVs, which remarkably distinguished symptomatic COVID-19 patients from uninfected controls with matched comorbidities and delineated those with moderate disease from those who were critically ill. Specifically, EN-RAGE, followed by TF and IL-18R1, showed the strongest correlation with disease severity and length of hospitalization. Importantly, EVs from COVID-19 patients induced apoptosis of pulmonary microvascular endothelial cells in the order of disease severity. In conclusion, our findings support a role for EVs in the pathogenesis of COVID-19 disease and underpin the development of EV-based approaches to predicting disease severity, determining need for patient hospitalization and identifying new therapeutic targets.