Cytokine Deficiencies in Patients with Long-COVID

Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of Interferon Gamma (IFNγ) and Interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID. We propose immune exhaustion as the driver of long-COVID, with the complete absence of IFNγ and IL-8preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.

Can foodborne illness estimates from different countries be legitimately compared?: case study of rates in the UK compared with Australia, Canada and USA.

OBJECTIVE: Mathematical models have gained traction when estimating cases of foodborne illness. Model structures vary due to differences in data availability. This begs the question as to whether differences in foodborne illness rates internationally are real or due to differences in modelling approaches.Difficulties in comparing illness rates have come into focus with COVID-19 infection rates being contrasted between countries. Furthermore, with post-EU Exit trade talks ongoing, being able to understand and compare foodborne illness rates internationally is a vital part of risk assessments related to trade in food commodities. DESIGN: We compared foodborne illness estimates for the United Kingdom (UK) with those from Australia, Canada and the USA. We then undertook sensitivity analysis, by recreating the mathematical models used in each country, to understand the impact of some of the key differences in approach and to enable more like-for-like comparisons. RESULTS: Published estimates of overall foodborne illness rates in the UK were lower than the other countries. However, when UK estimates were adjusted to a more like-for-like approach to the other countries, differences were smaller and often had overlapping credible intervals. When comparing rates by specific pathogens, there were fewer differences between countries. The few large differences found, such as virus rates in Canada, could at least partly be traced to methodological differences. CONCLUSION: Foodborne illness estimation models are country specific, making international comparisons problematic. Some of the disparities in estimated rates between countries can be shown to be attributed to differences in methodology rather than real differences in risk.

Intervening to eliminate the centre-effect variation in home dialysis use: protocol for Inter-CEPt-a sequential mixed-methods study designing an intervention bundle.

INTRODUCTION: Use of home dialysis by centres in the UK varies considerably and is decreasing despite attempts to encourage greater use. Knowing what drives this unwarranted variation requires in-depth understanding of centre cultural and organisational factors and how these relate to quantifiable centre performance, accounting for competing treatment options. This knowledge will be used to identify components of a practical and feasible intervention bundle ensuring this is realistic and cost-effective. METHODS AND ANALYSIS: Underpinned by the non-adoption, abandonment, scale-up, spread and sustainability framework, our research will use an exploratory sequential mixed-methods approach. Insights from multisited focused team ethnographic and qualitative research at four case study sites will inform development of a national survey of 52 centres. Survey results, linked to patient-level data from the UK Renal Registry, will populate a causal graph describing patient and centre-level factors, leading to uptake of home dialysis and multistate models incorporating patient-level treatment modality history and mortality. This will inform a contemporary economic evaluation of modality cost-effectiveness that will quantify how modification of factors facilitating home dialysis, identified from the ethnography and survey, might yield the greatest improvements in costs, quality of life and numbers on home therapies. Selected from these factors, using the capability, opportunity and motivation for behaviour change framework (COM-B) for intervention design, the optimal intervention bundle will be developed through workshops with patients and healthcare professionals to ensure acceptability and feasibility. Patient and public engagement and involvement is embedded throughout the project. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Health Research Authority reference 20-WA-0249. The intervention bundle will comprise components for all stake holder groups: commissioners, provider units, recipients of dialysis, their caregivers and families. To reache all these groups, a variety of knowledge exchange methods will be used: short guides, infographics, case studies, National Institute for Health and Care Excellence guidelines, patient conferences, 'Getting it Right First Time' initiative, Clinical Reference Group (dialysis).

Clinical significance of measuring serum cytokine levels as inflammatory biomarkers in adult and pediatric COVID-19 cases: A review.

Coronavirus disease 2019 (COVID-19) is a rapidly evolving infectious/inflammatory disorder which has turned into a global pandemic. With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as its etiologic agent, severe COVID-19 cases usually develop uncontrolled inflammatory responses and cytokine storm-like syndromes. Measuring serum levels of pro-inflammatory cytokines (e.g., IL-6 and others) as inflammatory biomarkers may have several potential applications in the management of COVID-19, including risk assessment, monitoring of disease progression, determination of prognosis, selection of therapy and prediction of response to treatment.This is especially true for pediatric patients with COVID-19 associated Kawasaki-like disease and similar syndromes. In this report, we review the current knowledge of COVID-19 associated cytokines, their roles in host immune and inflammatory responses, the clinical significance and utility of cytokine immunoassays in adult and pediatric COVID-19 patients, as well as the challenges and pitfalls in implementation and interpretation of cytokine immunoassays. Given that cytokines are implicated in different immunological disorders and diseases, it is challenging to interpret the multiplex cytokine data for COVID-19 patients. Also, it should be taken into consideration that biological and technical variables may affect the commutability of cytokine immunoassays and enhance complexity of cytokine immunoassay interpretation. It is recommended that the same method, platform and laboratory should be used when monitoring differences in cytokine levels between groups of individuals or for the same individual over time. It may be important to correlate cytokine profiling data with the SARS-CoV-2 nucleic acid amplification testing and imaging observations to make an accurate interpretation of the inflammatory status and disease progression in COVID-19 patients.

How can we decide a fair allocation of healthcare resources during a pandemic?

Whenever the government makes medical resource allocation choices, there will be opportunity costs associated with those choices: some patients will have treatment and live longer, while a different group of patients will die prematurely. Because of this, we have to make sure that the benefits we get from investing in treatment A are large enough to justify the benefits forgone from not investing in the next best alternative, treatment B. There has been an increase in spending and reallocation of resources during the COVID-19 pandemic that may have been warranted given the urgency of the situation. However, these actions do not bypass the opportunity cost principle although they can appear to in the short term, since spending increases cannot continue indefinitely and there are patient groups who lose out when resources are redirected to pandemic services. Therefore, policy-makers must consider who bears the cost of the displaced healthcare resources. Failure to do so runs a risk of reducing overall population health while disproportionally worsening health in socially disadvantaged groups. We give the example of ethnic minorities in England who already had the worst health and, due to structural injustices, were hardest hit by the pandemic and may stand to lose the most when services are reallocated to meet the resource demands of the crisis. How can we prevent this form of health inequity? Our proposal is forward-looking: we suggest that the government should invest our resources wisely while taking issues of equity into account-that is, introduce cost-equity analysis.

Role of Host Immune and Inflammatory Responses in COVID-19 Cases with Underlying Primary Immunodeficiency: A Review.

Coronavirus disease 2019 (COVID-19) has spread rapidly and become a pandemic. Caused by a novel human coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe COVID-19 is characterized by cytokine storm syndromes due to innate immune activation. Primary immunodeficiency (PID) cases represent a special patient population whose impaired immune system might make them susceptible to severe infections, posing a higher risk to COVID-19, but this could also lead to suppressed inflammatory responses and cytokine storm. It remains an open question as to whether the impaired immune system constitutes a predisposing or protective factor for PID patients when facing SARS-CoV-2 infection. After literature review, it was found that, similar to other patient populations with different comorbidities, PID patients may be susceptible to SARS-CoV-2 infection. Their varied immune status, however, may lead to different disease severity and outcomes after SARS-CoV-2 infection. PID patients with deficiency in antiviral innate immune signaling [eg, Toll-like receptor (TLR)3, TLR7, or interferon regulatory factor 7 (IRF7)] or interferon signaling (IFNAR2) may be linked to severe COVID-19. Because of its anti-infection, anti-inflammatory, and immunomodulatory effects, routine intravenous immunoglobulin therapy may provide some protective effects to the PID patients.