COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

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.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

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.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Development and validation of an asthma exacerbation prediction model using electronic health record (EHR) data.

Objective: Asthma exacerbations are associated with significant morbidity, mortality, and cost. Accurately identifying asthma patients at risk for exacerbation is essential. We sought to develop a risk prediction tool based on routinely collected data from electronic health records (EHRs).Methods: From a repository of EHRs data, we extracted structured data for gender, race, ethnicity, smoking status, use of asthma medications, environmental allergy testing BMI status, and Asthma Control Test scores (ACT). A subgroup of this population of patients with asthma that had available prescription fill data was identified, which formed the primary population for analysis. Asthma exacerbation was defined as asthma-related hospitalization, urgent/emergent visit or oral steroid use over a 12-month period. Univariable and multivariable statistical analysis was completed to identify factors associated with exacerbation. We developed and tested a risk prediction model based on the multivariable analysis.Results: We identified 37,675 patients with asthma. Of those, 1,787 patients with asthma and fill data were identified, and 979 (54.8%) of them experienced an exacerbation. In the multivariable analysis, smoking (OR = 1.69, CI: 1.08-2.64), allergy testing (OR = 2.40, CI: 1.54-3.73), obesity (OR = 1.66, CI: 1.29-2.12), and ACT score reflecting uncontrolled asthma (OR = 1.66, CI: 1.10-2.29) were associated with increased risk of exacerbation. The area-under-the-curve (AUC) of our model in a combined derivation and validation cohort was 0.67.Conclusion: Despite use of rigorous methodology, we were unable to produce a predictive model with an acceptable degree of accuracy and AUC to be clinically useful.

Home asthma triggers: barriers to asthma control in Chicago Puerto Rican children.

We sought objectively to measure, summarize, and contextualize the asthma triggers found in the homes of urban high-risk Puerto Rican children and adolescents with asthma in Chicago. Data were from the baseline home assessments of Project CURA. Research assistants interviewed caregivers, conducted a home visual inspection, and collected saliva samples for cotinine analysis. A trigger behavior summary score was created. The housing inspected was old with multiple units and obvious structural deficiencies. Many allergic and irritant triggers were observed. Having a controller medicine or private insurance was associated with lower trigger behavior summary scores; caregiver depression, caregiver perceived stress, and child negative life events were associated with high trigger scores. The final multivariate model retained had a controller medicine, private insurance, and caregiver perceived stress. The data from this high-risk cohort identified modifiable areas where environmental interventions could reduce morbidity in Puerto Rican children and adolescents.

The influence of caregiver's psychosocial status on childhood asthma and obesity.

BACKGROUND: The prevalence of childhood asthma and childhood overweight has increased in the last 2 decades, disproportionately burdening ethnic minority children and those living in poverty with no clear understanding of underlying mechanisms. OBJECTIVE: To explore the influence of demographic variables, childhood obesity (adjusted body mass index > or = 95th percentile), caregivers' smoking status, and caregiver psychosocial status on asthma severity and asthma control in an urban sample of children with persistent asthma. METHODS: Child (with asthma)-caregiver dyads were recruited from public and archdiocese schools in Chicago, Illinois, as part of the Chicago Initiative to Raise Asthma Health Equity. Data were collected as part of the baseline face-to-face surveys conducted within the community. RESULTS: The 531 dyads were divided into 2 groups: 294 taking controller medications were in the asthma control analyses and 237 taking rescue medications only were in the asthma severity analyses. In multivariate models, asthma control was significantly worse in obese children (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.17-3.05), African American children (OR, 2.16; 95% CI, 1.05-4.46), and those with caregivers who had higher stress (OR, 1.09; 95% CI, 1.01-1.18). Older children had better control (OR, 0.79; 95% CI, 0.69-0.90). Children with caregivers who wanted more asthma-specific social support were more likely to have moderate to severe asthma (OR, 2.07; 95% CI, 1.06-4.05). CONCLUSION: In this community-based sample of children with active asthma, asthma control and asthma severity were associated with different factors. Caregiver variables were significant in both outcomes, and childhood obesity was associated only with poor asthma control.