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BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).
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COVID-19 , Imunização Passiva , Adulto , Assistência Ambulatorial , COVID-19/terapia , Progressão da Doença , Método Duplo-Cego , Hospitalização , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Resultado do Tratamento , Estados Unidos , Soroterapia para COVID-19RESUMO
BACKGROUND: The management of mild asthma has lacked an over-the-counter (OTC) option aside from inhaled epinephrine, which is available in the United States. However, inhaled epinephrine use without an inhaled corticosteroid may increase the risk of asthma death. OBJECTIVE: To compare the cost-effectiveness of OTC as-needed budesonide-formoterol as a plausible alternative to inhaled epinephrine. METHODS: We developed a probabilistic Markov model to compare OTC as-needed budesonide-formoterol inhaler use vs inhaled epinephrine use in adults with mild asthma from a US societal perspective over a lifetime horizon, with a 3% annual discount rate (2022 US dollars). Inputs were derived from the SYmbicort Given as-needed in Mild Asthma (SYGMA) trials, published literature, and commercial costs. Outcomes were quality-adjusted life-years (QALY), costs, incremental net monetary benefit (INMB), severe asthma exacerbations, well-controlled asthma days, and asthma-related deaths. Microsimulation was used to evaluate underinsured Americans living with mild asthma (n = 5,250,000). RESULTS: Inhaled epinephrine was dominated (with lower QALYs gains at a higher cost) by both as-needed budesonide-formoterol (INMB, $15,541 at a willingness-to-pay of $100,000 per QALY) and the no-OTC inhaler option (INMB, $1023). Adults using as-needed budesonide-formoterol had 145 more well-controlled asthma days, 2.79 fewer severe exacerbations, and an absolute risk reduction of 0.23% for asthma-related death compared with inhaled epinephrine over a patient lifetime. As-needed budesonide-formoterol remained dominant in all sensitivity and scenario analyses, with a 100% probability of being cost-effective compared with inhaled epinephrine in probabilistic sensitivity analysis. CONCLUSION: If made available, OTC as-needed budesonide-formoterol for treating mild asthma in underinsured adults without HCP management improves asthma outcomes, prevents fatalities, and is cost-saving.
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Asma , Combinação Budesonida e Fumarato de Formoterol , Adulto , Humanos , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Análise Custo-Benefício , Fumarato de Formoterol/uso terapêutico , Etanolaminas/uso terapêutico , Asma/tratamento farmacológico , Epinefrina/uso terapêutico , Combinação de Medicamentos , Administração por InalaçãoRESUMO
The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, and environmental health interconnections. One Health can support the advanced management of allergic diseases and asthma, as complex, multifactorial diseases driven by interactions between the resilience response to the exposome. According to the One Health concept allergic diseases and asthma arising from exposures to a wide range of allergens, infectious agents and irritants (such as pollutants) occurring indoors and outdoors can be heavily influenced by environmental health (air, water, and soil quality) intermingled with animal health. These are currently heavily impacted by climate change, land use, urbanization, migration, overpopulation, and many more. Thus, a coordinated response to address the underlying factors that contribute to the development of allergic diseases and asthma needs to focus on the environment, human, and animal health altogether. Collaborative efforts across multiple sectors, including public health, veterinary medicine, environmental science, and community engagement are thus needed. A wide range of activities, including monitoring and surveillance of environmental and health data, targeted interventions to reduce exposures to allergens and irritants, and research on the underlying mechanisms that drive the development of allergic diseases and asthma are needed to move the field forward. In this consensus document elaborated by the European Academy of Allergy and Clinical Immunology (EAACI) and American Academy of Allergy, Asthma, and Immunology (AAAAI) under the practical allergy (PRACTALL) series, we provide insights into the One Heath approach aiming to provide a framework for addressing the complex and multifactorial nature of allergic diseases and asthma.
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Asma , Hipersensibilidade , Saúde Única , Animais , Humanos , Irritantes , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Hipersensibilidade/terapia , Asma/epidemiologia , Asma/etiologia , Asma/terapia , AlérgenosRESUMO
BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.
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COVID-19 , Reação Transfusional , Urticária , Humanos , COVID-19/terapia , COVID-19/etiologia , Soroterapia para COVID-19 , Imunização Passiva/efeitos adversos , Pacientes Ambulatoriais , SARS-CoV-2 , Reação Transfusional/etiologia , Urticária/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Chronic spontaneous urticaria is defined as migratory evanescent pruritic blanching wheals that occur with variable frequency for 6 weeks or more, with or without accompanying angioedema. This condition affects approximately 0.1% to 1.4% of persons worldwide. Second-generation H1 antihistamines are the mainstay of management, with refractory cases often managed with an array of options, including H2 antihistamines, leukotriene receptor antagonists, glucocorticosteroids, immunosuppressive agents, and omalizumab. However, the degree of practice variation as to what treatments are prescribed is poorly understood, given that clinical care could be driven by patient preferences or lack of clarity as to best practices for refractory cases. We conducted a small, exploratory study of the role of race, ethnicity, and regional geographic distance to specialist care on chronic spontaneous urticaria prescribing practices. A small-area geographic variation in chronic spontaneous urticaria management in a large Chicago-area health care system was identified. Rates of omalizumab use varied by patient zip code, with more omalizumab prescriptions being associated with zip codes closer to the main office of an academic medical center-affiliated allergist-immunologist practice. Higher rates of omalizumab use were associated with White race in regional and patient-level analyses, though the reasons for this race-based finding are not clear.
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Urticária Crônica , Humanos , Geografia , Chicago , Urticária Crônica/tratamento farmacológicoRESUMO
Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.
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COVID-19 , COVID-19/terapia , Humanos , Imunização Passiva , Pacientes Ambulatoriais , Pandemias , SARS-CoV-2 , Estados Unidos , Soroterapia para COVID-19RESUMO
OBJECTIVE: Current standard of care, patient self-report and clinician estimation, overestimates true inhaled corticosteroids (ICS) adherence. We compare self-reported inhaled ICS and short-acting beta 2-agonists (SABA) use with objective data from electronic medication monitors (EMMs). METHODS: Adults with uncontrolled asthma and prescribed ICS and SABA were enrolled. At visit one, participants' ICS and SABA inhalers were fitted with EMMs to track real-time medication usage over 14 days. Participants were asked to complete paper diaries to self-report medication usage over the same period. Participant self-report of ICS adherence and SABA use versus objective ICS adherence and SABA use was compared using Wilcoxon signed-rank tests. RESULTS: One hundred participants (80% female, mean age 48.5 years, 60% completed college, 80% privately insured) had complete data. Participant self-report (median (IQR): 0.8 (0.0, 2.0)) was greater than objectively measured (median (IQR): 0.43 (0.1, 2.1)) SABA use, but the difference was not statistically significant (P = 0.64). Participant self-report (median (IQR): 97 (67, 100)) was significantly greater than objectively measured (median (IQR): 75 (54, 93)) ICS adherence (P = 0.002). CONCLUSIONS: Significant discrepancies between self-report and objective ICS usage were observed. EMM can provide clinicians with accurate data on ICS medication taking behavior, thus reducing medication regimen complexity, side effects, and costs.
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Asma , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração por Inalação , Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Eletrônica , AutorrelatoRESUMO
OBJECTIVE: Psychosocial factors play a role in child asthma morbidity and disparities, but their impact on asthma intervention effectiveness is less understood. This study examined how child, parent, and family psychosocial factors moderated asthma response to, and changed in response to, 2 community asthma interventions among urban minority youth. METHODS: Asthma Action at Erie was a randomized comparative effectiveness trial examining a community health worker (CHW) home intervention versus certified asthma educator (AE-C) services for children aged 5-16 with uncontrolled asthma (N = 223; mean age = 9.37, SD = 3.02; 85.2% Hispanic). Asthma control was assessed via the Asthma Control Test (ACT)/childhood ACT and activity limitation. Baseline child/parent depression and posttraumatic stress disorder (PTSD) symptoms, family chaos, and social support were examined as treatment moderators. We also tested intervention effects on psychosocial outcomes. RESULTS: For parents with higher baseline depression symptoms, youth in the CHW group had greater ACT improvement by 24 months (7.49 points) versus AE-C (4.76 points) and 51% reduction in days of limitation by 6 months versus AE-C (ß = -0.118; p = .0145). For higher parent PTSD symptoms, youth in CHW had 68% fewer days of limitation at 24 months versus AE-C (ß = -0.091; p = .0102). Psychosocial outcomes did not vary by group, but parent depression, parent and child PTSD symptoms, and social support improved for all. CONCLUSIONS: CHW intervention was associated with improved asthma control among families with higher parent strain. Findings have implications for utilizing tailored CHW home interventions to optimize asthma outcomes in at-risk families.
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Asma , Transtornos de Estresse Pós-Traumáticos , Adolescente , Asma/terapia , Criança , Família , Hispânico ou Latino , Humanos , Apoio SocialRESUMO
BACKGROUND: Asthma, a common chronic airway disorder, affects an estimated 25 million persons in the United States and 330 million persons worldwide. Although many asthma patient registries exist, the ability to link and compare data across registries is hindered by a lack of harmonization in the outcome measures collected by each registry. OBJECTIVES: The purpose of this project was to develop a minimum set of patient- and provider-relevant standardized outcome measures that could be collected in asthma patient registries and clinical practice. METHODS: Asthma registries were identified through multiple sources and invited to join the workgroup and submit outcome measures. Additional measures were identified through literature searches and reviews of quality measures and consensus statements. Outcome measures were categorized by using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework. A minimum set of broadly relevant measures was identified. Measure definitions were harmonized through in-person and virtual meetings. RESULTS: Forty-six outcome measures, including those identified from 13 registries, were curated and harmonized into a minimum set of 21 measures in the Outcome Measures Framework categories of survival, clinical response, events of interest, patient-reported outcomes, resource utilization, and experience of care. The harmonized definitions build on existing consensus statements and are appropriate for adult and pediatric patients. CONCLUSIONS: The harmonized measures represent a minimum set of outcomes that are relevant in asthma research and clinical practice. Routine and consistent collection of these measures in registries and other systems would support creation of a national research infrastructure to efficiently address new questions and improve patient management and outcomes.
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Asma , Sistema de Registros , Adulto , Criança , Humanos , Medidas de Resultados Relatados pelo PacienteRESUMO
UNLABELLED: Abstract Objective: Puerto Rican children suffer disproportionately from asthma. Project CURA tested the efficacy of a community health worker (CHW) intervention to improve use of inhaled corticosteroids (ICS) and reduce home asthma triggers in Puerto Rican youth in Chicago. METHODS: This study employed a behavioral randomized controlled trial design with a community-based participatory research approach. Medications and technique were visually assessed; adherence was determined using dose counters. Home triggers were assessed via self-report, visual inspection and salivary cotinine. All participants received education on core asthma topics and self-management skills. Participants in the CHW arm were offered home education by the CHW in four visits over four months. The attention control arm received four newsletters covering the same topics. RESULTS: While most of the participants had uncontrolled persistent asthma, <50% had ICS at baseline. In the CHW arms, 67% of participants received the full four-visit intervention. In the Elementary school cohort (n=51), the CHW arm had lower odds of having an ICS (OR=0.2; p=0.02) at 12-months; no differences were seen in other outcomes between arms at any time point. The only significant treatment arm difference in the high school cohort (n=50) was in inhaler technique where the CHW arm performed 18.0% more steps correct at five months (p<0.01) and 14.2% more steps correct at 12 months (p<0.01). CONCLUSIONS: While this CHW intervention did not increase the number of participants with ICS or reduce home asthma triggers, important lessons were learned including challenges to CHW intervention fidelity and the need for CHWs to partner with clinical providers.
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Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/etnologia , Agentes Comunitários de Saúde , Hispânico ou Latino , Adolescente , Chicago/epidemiologia , Criança , Pesquisa Participativa Baseada na Comunidade , Feminino , Humanos , Masculino , Adesão à Medicação , Educação de Pacientes como Assunto , Porto Rico/etnologia , Instituições AcadêmicasRESUMO
BACKGROUND: Digital health tools have been shown to help address challenges in asthma control, including inhaler technique, treatment adherence, and short-acting ß2-agonist overuse. The maintenance and reliever Digihaler System (DS) comprises 2 Digihaler inhalers (fluticasone propionate/salmeterol and albuterol) with an associated patient App and web-based Dashboard. Clinicians can review patients' inhaler use and Digihaler inhalation parameter data to support clinical decision-making. OBJECTIVE: CONNECT2 evaluated asthma control in participants using the DS versus standard-of-care (SoC) maintenance and reliever inhalers. METHODS: Participants (13 years or older) with uncontrolled asthma (Asthma Control Test [ACT] score <19) were randomized 4:3 (open-label) to the DS (n = 210) or SoC (n = 181) for 24 weeks. The primary endpoint was the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥20 or increase from baseline of ≥3 units at week 24). RESULTS: There was an 88.7% probability that participants using the DS would have greater odds of achieving improvement in asthma control compared with SoC after 24 weeks. The mean odds ratio (95% credible interval) for DS versus SoC was 1.35 (0.846-2.038), indicating a 35% higher odds of improved asthma control with the DS. The DS group had more clinician-participant interactions versus SoC, mainly addressing a poor inhaler technique. DS participants' maintenance treatment adherence was good (month 1: 79.2%; month 6: 68.6%); reliever use decreased by 38.2% versus baseline. App and Dashboard usability was rated "good." CONCLUSION: The positive results in asthma control in this study after 24 weeks demonstrate the effectiveness of the DS in asthma management.
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Antiasmáticos , Asma , Humanos , Budesonida/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Etanolaminas/uso terapêutico , Antiasmáticos/uso terapêutico , Combinação de Medicamentos , Asma/tratamento farmacológico , Albuterol/uso terapêutico , Administração por Inalação , Broncodilatadores/uso terapêuticoRESUMO
Pharmacoequity refers to equity in access to pharmacotherapy for all patients and is an especially large barrier to biologic agents in patients with allergic diseases. Value-based care models can prompt clinicians to address social determinants of health, promoting pharmacoequity. Pharmacoequity is influenced by numerous factors including socioeconomic status, which may be mediated through insurance status, educational attainment, and access to specialist care. In addition to lower socioeconomic status, race and ethnicity, age, locations isolated from care systems, and off-label indications for biologic agents all constitute barriers to pharmacoequity. Whereas pharmaco-inequity is more apparent for expensive biologics, it also affects many other allergy treatments including epinephrine autoinjectors and SMART for asthma. Current programs aimed at alleviating cost barriers are imperfect. Patient assistance programs, manufacturer-sponsored free drug programs, and rebates often increase the complexity of care, with resultant inequity, particularly for patients with lower health literacy. Ultimately, single silver-bullet solutions are elusive. Long-term improvement instead requires a combination of research, advocacy, and creative problem-solving to design more intelligent and efficient systems that provide timely access to necessary care for every patient, every time.
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Produtos Biológicos , Humanos , Produtos Biológicos/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Acessibilidade aos Serviços de SaúdeRESUMO
IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.
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COVID-19 , Humanos , COVID-19/terapia , Soroterapia para COVID-19 , Interleucina-6 , SARS-CoV-2 , Citocinas , Imunização PassivaRESUMO
BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.
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Anticorpos Antivirais , Soroterapia para COVID-19 , COVID-19 , Hospitalização , Imunização Passiva , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/terapia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Imunização Passiva/métodos , Hospitalização/estatística & dados numéricos , SARS-CoV-2/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Método Duplo-Cego , Idoso , Doadores de Sangue/estatística & dados numéricos , Pacientes AmbulatoriaisRESUMO
Background: Evidence-based strategies to improve outcomes in minority children with uncontrolled asthma discharged from the emergency department (ED) are needed. Objectives: This multicenter pragmatic clinical trial was designed to compare an ED-only intervention (decision support tool), an ED-only intervention and home visits by community health workers for 6 months (ED-plus-home), and enhanced usual care (UC). Methods: Children aged 5 to 11 years with uncontrolled asthma were enrolled. The change over 6 months in the Patient-Reported Outcomes Measurement Information System Asthma Impact Scale score in children and Satisfaction with Participation in Social Roles score in caregivers were the primary outcomes. The secondary outcomes included guideline-recommended ED discharge care and self-management. Results: Recruitment was significantly lower than expected (373 vs 640 expected). Of the 373 children (64% Black and 31% Latino children), only 63% completed the 6-month follow-up visit. In multivariable analyses that accounted for missing data, the adjusted odds ratios and 98% CIs for differences in Asthma Impact Scores or caregivers' Satisfaction with Participation in Social Roles scores were not significant. However, guideline-recommended ED discharge care was significantly improved in the intervention groups versus in the UC group, and self-management behaviors were significantly improved in the ED-plus-home group versus in the ED-only and UC groups. Conclusions: The ED-based interventions did not significantly improve the primary clinical outcomes, although the study was likely underpowered. Although guideline-recommended ED discharge care and self-management did improve, their effect on clinical outcomes needs further study.
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Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. Methods: Among 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results: One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC.There was a trend for decreased PCC in those with early CCP treatment (≤5 days after symptom onset) compared to late CCP treatment. Conclusion: Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.
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IMPORTANCE: Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical characteristics. Future treatment studies should be considered to evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , SARS-CoV-2 , Soroterapia para COVID-19 , Anticorpos , InflamaçãoRESUMO
BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.
Assuntos
COVID-19 , Estados Unidos/epidemiologia , Humanos , Feminino , Masculino , Adolescente , Adulto , COVID-19/epidemiologia , Fator A de Crescimento do Endotélio Vascular , SARS-CoV-2 , Vacinas contra COVID-19 , Interleucina-7 , Interleucina-8 , Estudos Prospectivos , Soroterapia para COVID-19 , CitocinasRESUMO
BACKGROUND: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined. METHODS: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis. RESULTS: SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01. CONCLUSION: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460. FUNDING: Defense Health Agency and others.