ABSTRACT
The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID.
ABSTRACT
This sensing prototype model involves the development of a reusable, twofold graphene oxide (GrO)-glazed double inter-digitated capacitive (DIDC) detecting chip for detecting severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) specifically and rapidly. The fabricated DIDC comprises a Ti/Pt-containing glass substrate glazed with graphene oxide (GrO), which is further chemically modified with EDC-NHS to immobilize antibodies (Abs) hostile to SARS-CoV-2 based on the spike (S1) protein of the virus. The results of insightful investigations showed that GrO gave an ideal engineered surface for Ab immobilization and enhanced the capacitance to allow higher sensitivity and low sensing limits. These tunable elements helped accomplish a wide sensing range (1.0 mg/mL to 1.0 fg/mL), a minimum sensing limit of 1 fg/mL, high responsiveness and good linearity of 18.56 nF/g, and a fast reaction time of 3 s. Besides, in terms of developing financially viable point-of-care (POC) testing frameworks, the reusability of the GrO-DIDC biochip in this study is good. Significantly, the biochip is specific against blood-borne antigens and is stable for up to 10 days at 5 °C. Due to its compactness, this scaled-down biosensor has the potential for POC diagnostics of COVID-19 infection. This system can also detect other severe viral diseases, although an approval step utilizing other virus examples is under development.
Subject(s)
Biosensing Techniques , COVID-19 , Graphite , Viruses , Humans , SARS-CoV-2 , COVID-19/diagnosis , Biosensing Techniques/methods , Antibodies, ViralABSTRACT
BACKGROUND: Decision-makers impose COVID-19 mitigations based on public health indicators such as reported cases, which are sensitive to fluctuations in supply and demand for diagnostic testing, and hospital admissions, which lag infections by up to two weeks. Imposing mitigations too early has unnecessary economic costs while imposing too late leads to uncontrolled epidemics with unnecessary cases and deaths. Sentinel surveillance of recently-symptomatic individuals in outpatient testing sites may overcome biases and lags in conventional indicators, but the minimal outpatient sentinel surveillance system needed for reliable trend estimation remains unknown. METHODS: We used a stochastic, compartmental transmission model to evaluate the performance of various surveillance indicators at reliably triggering an alarm in response to, but not before, a step increase in transmission of SARS-CoV-2. The surveillance indicators included hospital admissions, hospital occupancy, and sentinel cases with varying levels of sampling effort capturing 5, 10, 20, 50, or 100% of incident mild cases. We tested 3 levels of transmission increase, 3 population sizes, and conditions of either simultaneous transmission increase or lagged increase in the older population. We compared the indicators' performance at triggering alarm soon after, but not prior, to the transmission increase. RESULTS: Compared to surveillance based on hospital admissions, outpatient sentinel surveillance that captured at least 20% of incident mild cases could trigger an alarm 2 to 5 days earlier for a mild increase in transmission and 6 days earlier for a moderate or strong increase. Sentinel surveillance triggered fewer false alarms and averted more deaths per day spent in mitigation. When transmission increase in older populations lagged the increase in younger populations by 14 days, sentinel surveillance extended its lead time over hospital admissions by an additional 2 days. CONCLUSIONS: Sentinel surveillance of mild symptomatic cases can provide more timely and reliable information on changes in transmission to inform decision-makers in an epidemic like COVID-19.
Subject(s)
COVID-19 , Humans , Aged , COVID-19/epidemiology , SARS-CoV-2 , Sentinel Surveillance , Outpatients , Public HealthABSTRACT
SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.
Subject(s)
COVID-19 , Humans , Child , SARS-CoV-2 , Inflammation , Severity of Illness IndexABSTRACT
In this study, we evaluated the effects of the pandemic on our trauma population. We performed a retrospective review of the trauma registry in the 2 years prior, and then 2 years during the pandemic. We evaluated age, race, gender, injury severity score (ISS), mechanism of trauma, rate of self-inflicted injury, rate of gunshot wounds (GSW), presence of EtOH, drug screen results, mortality, rate of burn traumas, and zip code of residence. Our query captured 5 054 patients before, and 5 731 during the pandemic. We found no statistical difference in age, gender, mechanism of trauma, rate of self-inflicted injuries, and mortality during the pandemic when compared to before. There were statistically significant differences in race, ISS, rate of GSWs, EtOH use, drug screen results, and burn traumas. Geospatial mapping found a rise in GSWs for zip code 36606. Gun violence and substance use rose in our trauma population during COVID-19.
ABSTRACT
Certain environmental exposures, such as air pollution, are associated with COVID-19 incidence and mortality. To determine whether environmental context is associated with other COVID-19 experiences, we used data from the nationally representative Tufts Equity in Health, Wealth, and Civic Engagement Study data (n=1785; three survey waves 2020-2022). Environmental context was assessed using self-reported climate stress and county-level air pollution, greenness, toxic release inventory site, and heatwave data. Self-reported COVID-19 experiences included willingness to vaccinate against COVID-19, health impacts from COVID-19, receiving assistance for COVID-19, and provisioning assistance for COVID-19. Self-reported climate stress in 2020 or 2021 was associated with increased COVID-19 vaccination willingness by 2022 (odds ratio [OR] = 2.35; 95% confidence interval [CI] = 1.47, 3.76), even after adjusting for political affiliation (OR = 1.79; 95% CI = 1.09, 2.93). Self-reported climate stress in 2020 was also associated with increased likelihood of receiving COVID-19 assistance by 2021 (OR = 1.89; 95% CI = 1.29, 2.78). County-level exposures (i.e., less greenness, more toxic release inventory sites, more heatwaves) were associated with increased vaccination willingness. Air pollution exposure in 2020 was positively associated with likelihood of provisioning COVID-19 assistance in 2020 (OR = 1.16 per ug/m3; 95% CI = 1.02, 1.32). Associations between certain environmental exposures and certain COVID-19 outcomes were stronger among those who identify as a race/ethnicity other than non-Hispanic White and among those who reported experiencing discrimination; however, these trends were not consistent. A latent variable representing a summary construct for environmental context was associated with COVID-19 vaccination willingness. Our results add to the growing body of literature suggesting that intersectional equity issues affecting likelihood of exposure to adverse environmental conditions are also associated with health-related outcomes.
Subject(s)
COVID-19ABSTRACT
INTRODUCTION: Acute care surgeons can experience posttraumatic stress disorder (PTSD) due to the cumulative stress of practice. This study sought to document the potential impact of the COVID-19 pandemic on PTSD in acute care surgeons and to identify potential contributing factors. METHODS: The six-item brief version of the PTSD Checklist-Civilian Version (PCL-6), a validated instrument capturing PTSD symptomology, was used to screen Eastern Association for the Surgery of Trauma members. Added questions gauged pandemic effects on professional and hospital systems-level factors. Regression modeling used responses from attending surgeons that fully completed the PCL-6. RESULTS: Complete responses from 334 of 360 attending surgeons were obtained, with 58 of 334 (17%) screening positive for PTSD symptoms. Factors significantly contributing to both higher PCL-6 scores and meeting criteria for PTSD symptomology included decreasing age, increased administrative duties, reduced research productivity, nonurban practice setting, and loss of annual bonuses. Increasing PCL-6 score was also affected by perceived illness risk and higher odds of PTSD symptomology with elective case cancellation. For most respondents, fear of death and concerns of illness from COVID-19 were not associated with increased odds of PTSD symptomology. CONCLUSIONS: The prevalence of PTSD symptomology in this sample was similar to previous reports using surgeon samples (15%-22%). In the face of the COVID-19 pandemic, stress was not directly related to infectious concerns but rather to the collateral challenges caused by the pandemic and unrelated demographic factors. Understanding factors increasing stress in acute care surgeons is critical as part of pandemic planning and management to reduce burnout and maintain a healthy workforce.
ABSTRACT
Defective viral genomes (DVGs) have been identified in many RNA viruses as a major factor influencing antiviral immune response and viral pathogenesis. However, the generation and function of DVGs in SARS-CoV-2 infection are less known. In this study, we elucidated DVG generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from transcriptome sequencing (RNA-seq) data sets of in vitro infections and autopsy lung tissues of COVID-19 patients. Four genomic hot spots were identified for DVG recombination, and RNA secondary structures were suggested to mediate DVG formation. Functionally, bulk and single-cell RNA-seq analysis indicated the interferon (IFN) stimulation of SARS-CoV-2 DVGs. We further applied our criteria to the next-generation sequencing (NGS) data set from a published cohort study and observed a significantly higher amount and frequency of DVG in symptomatic patients than those in asymptomatic patients. Finally, we observed exceptionally diverse DVG populations in one immunosuppressive patient up to 140 days after the first positive test of COVID-19, suggesting for the first time an association between DVGs and persistent viral infections in SARS-CoV-2. Together, our findings strongly suggest a critical role of DVGs in modulating host IFN responses and symptom development, calling for further inquiry into the mechanisms of DVG generation and into how DVGs modulate host responses and infection outcome during SARS-CoV-2 infection. IMPORTANCE Defective viral genomes (DVGs) are generated ubiquitously in many RNA viruses, including SARS-CoV-2. Their interference activity to full-length viruses and IFN stimulation provide the potential for them to be used in novel antiviral therapies and vaccine development. SARS-CoV-2 DVGs are generated through the recombination of two discontinuous genomic fragments by viral polymerase complex, and this recombination is also one of the major mechanisms for the emergence of new coronaviruses. Focusing on the generation and function of SARS-CoV-2 DVGs, these studies identify new hot spots for nonhomologous recombination and strongly suggest that the secondary structures within viral genomes mediate the recombination. Furthermore, these studies provide the first evidence for IFN stimulation activity of de novo DVGs during natural SARS-CoV-2 infection. These findings set up the foundation for further mechanism studies of SARS-CoV-2 recombination and provide evidence to harness the immunostimulatory potential of DVGs in the development of a vaccine and antivirals for SARS-CoV-2.
ABSTRACT
CARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that "pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival". We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment.
Subject(s)
Antimalarials , Artemisinins , Malaria , Child , Humans , Child, Preschool , Artesunate/therapeutic use , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria/drug therapy , Referral and ConsultationABSTRACT
BACKGROUND AND AIM: Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown. METHODS: Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort. RESULTS: Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed. CONCLUSION: While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.
Subject(s)
COVID-19 , Immunoglobulin G4-Related Disease , Humans , Adolescent , Retrospective Studies , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Prospective Studies , Immunoglobulin G , Vaccination , Hong Kong/epidemiologyABSTRACT
Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Uncertainty , Disease Outbreaks/prevention & control , Public Health , Pandemics/prevention & controlABSTRACT
[This corrects the article DOI: 10.1016/j.eclinm.2022.101762.].