scholarly journals The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

2022 ◽  
Author(s):  
Jeremy Manry ◽  
Paul Bastard ◽  
Adrian Gervais ◽  
Tom Le Voyer ◽  
Jérémie Rosain ◽  
...  
Keyword(s):  
Relative Risk ◽  
Age Groups ◽  
Type I ◽  
Fatality Rate ◽  
Risk Of Death ◽  
Type I Ifns ◽  
Age Dependent ◽  
Relative Risk Of Death ◽  
Circulating Autoantibodies ◽  
Two Age Groups

Abstract SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Relative Risk of Death in Diabetic and Non Diabetic Dialysis PTS: A Useful Marker of a Cohort Features

1991 ◽  
pp. 455-457
Author(s):  
G. B. Piccoli ◽  
G. Beltrame ◽  
F. Bonello ◽  
M. Salomone ◽  
A. Pacitti ◽  
...  
Keyword(s):  
Relative Risk ◽  
Risk Of Death ◽  
Relative Risk Of Death

scholarly journals White Blood Cell and Platelet Dynamics Define Human Inflammatory Recovery

2021 ◽  
Author(s):  
Brody H Foy ◽  
Thor Sundt ◽  
Jonathan CT Carlson ◽  
Aaron D Aguirre ◽  
John M Higgins
Keyword(s):  
Relative Risk ◽  
Blood Cell ◽  
White Blood Cell ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Good Prognosis ◽  
Adverse Outcomes ◽  
Acute Phase Reactants ◽  
Risk Of Death ◽  
Relative Risk Of Death

Inflammation is the physiologic reaction to cellular and tissue damage caused by pathologic processes including trauma, infection, and ischemia. Effective inflammatory responses integrate molecular and cellular functions to prevent further tissue damage, initiate repair, and restore homeostasis, while futile or dysfunctional responses allow escalating injury, delay recovery, and may hasten death. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not established. Patient responses appear to vary dramatically with no clearly defined signs of good prognosis, leaving physicians reliant on qualitative interpretations of laboratory trends. We studied the human acute inflammatory response to trauma, ischemia, and infection by tracking the longitudinal dynamics of cellular and serum markers in hospitalized patients. Unexpectedly, we identified a conserved pattern of recovery defined by co-regulation of WBC and platelet (PLT) populations. Across all inflammatory conditions studied, recovering patients followed a consistent WBC-PLT trajectory shape that is well-approximated by exponential WBC decay and delayed linear PLT growth. This recovery trajectory shape may represent a fundamental archetype of human physiologic response at the cellular population scale, and provides a generic approach for identifying high-risk patients: 32x relative risk of adverse outcomes for cardiac surgery patients, 9x relative risk of death for COVID-19, and 5x relative risk of death for myocardial infarction.

Reply to: Concerns about estimating relative risk of death associated with convalescent plasma for COVID-19

2022 ◽  
Author(s):  
Philippe Bégin ◽  
Jeannie Callum ◽  
Richard Cook ◽  
Erin Jamula ◽  
Yang Liu ◽  
...  
Keyword(s):  
Relative Risk ◽  
Risk Of Death ◽  
Relative Risk Of Death

scholarly journals Geografias da Diabetes Mellitus em Portugal: Como as Condições do Contexto Influenciam o Risco de Morrer

2014 ◽  
Vol 27 (3) ◽  
pp. 309 ◽  
Author(s):  
Paula Santana ◽  
Cláudia Costa ◽  
Adriana Loureiro ◽  
João Raposo ◽  
José Manuel Boavida
Keyword(s):  
Diabetes Mellitus ◽  
Relative Risk ◽  
Rural Areas ◽  
Public Health Problem ◽  
Standardized Mortality Ratio ◽  
Geographic Pattern ◽  
Bayesian Hierarchical ◽  
Risk Of Death ◽  
Mortality Ratio ◽  
Relative Risk Of Death

<strong>Introduction:</strong> Diabetes Mellitus is a public health problem that is on the increase throughout the world, including in Portugal. This paper aims to identify the changing geographic pattern of this cause of death in Portugal and its association with sociomaterial deprivation.<br /><strong>Material and Methods:</strong> This is a transversal ecological study of the deaths by Diabetes Mellitus in Portuguese municipalities in three periods (1989-1993, 1999-2003 and 2006-2010). It uses a Bayesian hierarchical model in order to obtain a smooth standardized mortality ratio and the relative risk of death by Diabetes Mellitus associated to sociomaterial deprivation.<br /><strong>Results:</strong> In 1989-1993, the highest smooth standardized mortality ratio values were found in coastal urban municipalities (80% of municipalities with smooth standardized mortality ratio ≥ 161, of which 60% are urban); in 2006-2010, the opposite was found, with the highest smooth standardized mortality ratio values occurring in rural areas in southern inland regions (76.9% of municipalities with smooth standardized mortality ratio ≥ 161, of which 69.2% are rural), particularly the Alentejo. The relative risk of death by Diabetes Mellitus increases with vulnerability associated to social and economic conditions in the area of residence, and is significant in the last two periods (relative risk: 1.00; IC95%: 0.98-1.02).<br /><strong>Discussion:</strong> Diabetes Mellitus presents a geographic pattern marked by coastal-inland and urban-rural asymmetry. However, this has been altering over the last twenty years. 48% of the population reside in municipalities where the smooth standardized mortality ratio has increased in the last twenty years, particularly in the rural areas of inland Portugal.<br /><strong>Conclusion: </strong>The highest smooth standardized mortality ratio are currently found in rural municipalities with the highest index of sociomaterial deprivation.<br /><strong>Keywords:</strong> Demography; Diabetes Mellitus/epidemiology; Diabetes Mellitus/mortality; Portugal; Socioeconomic Factors.

scholarly journals Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease

Neurology ◽  
2020 ◽  
Vol 94 (20) ◽  
pp. e2099-e2108 ◽  
Author(s):  
Tatyana Sarycheva ◽  
Piia Lavikainen ◽  
Heidi Taipale ◽  
Jari Tiihonen ◽  
Antti Tanskanen ◽  
...  
Keyword(s):  
Relative Risk ◽  
Alzheimer Disease ◽  
Antiepileptic Drug ◽  
Cognitive Disorder ◽  
Careful Consideration ◽  
Community Dwelling ◽  
Risk Of Death ◽  
Vulnerable Patients ◽  
Relative Risk Of Death ◽  
First 90 Days

ObjectiveTo evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.MethodsThe MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005–2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).ResultsNearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12–1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42–1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67–1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91–3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52–2.16).ConclusionIn older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.

scholarly journals Association between comorbidities and death from COVID-19 in different age groups

2021 ◽  
Author(s):  
Pedro Emanuel Fleitas ◽  
Maria Cristina Almazan ◽  
Sabrina Daniela Cortez ◽  
Jorge Augusto Paz ◽  
Ruben Oscar Cimino ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Decision Trees ◽  
Health Personnel ◽  
Age Groups ◽  
Cardiac Diseases ◽  
Fatality Rate ◽  
Significant Difference ◽  
The World ◽  
Logistic Regressions ◽  
Two Age Groups

Background: This new COVID-19 pandemic challenges health systems around the world; therefore, it is extremely important to determine which patients with COVID-19 can evolve to more severe outcomes. Accordingly, we decided to assess the role that comorbidities play in death from COVID-19. Methods: Two age groups (<60 and ≥ 60 years) were defined for analysis. Decision trees were made to identify which comorbidities had the highest fatality rate (FR). Multiple logistic regressions were performed to measure the association between comorbidities and death. Results: A significant difference was found between the FR of <60 group and ≥ 60 group. The most frequent comorbidity were cardiac diseases and diabetes. The combination of comorbidities with the highest FR was diabetes with kidney disease. Combinations of more than two comorbidities presented higher FR. The comorbidities had higher Odd ratios in the younger group than in the older group. Conclusions: Comorbidities seem to play a greater role in death from COVID-19 in the younger group, while in the ≥ 60 group, age seems to be the most important factor. We assigned a score to the comorbidities and their combinations for both age groups to help the health personnel make decisions.

scholarly journals A common TMPRSS2 variant protects against severe COVID-19

2021 ◽  
Author(s):  
Alessia David ◽  
Nicholas Parkinson ◽  
Thomas P Peacock ◽  
Erola Pairo-Castineira ◽  
Tarun Khanna ◽  
...  
Keyword(s):  
Large Population ◽  
Age Groups ◽  
Target Cells ◽  
Type I ◽  
Type I Ifns ◽  
Postoperative Reflux ◽  
Wide Range ◽  
Life Threatening ◽  
A Minor

SummaryInfection with SARS-CoV-2 has a wide range of clinical presentations, from asymptomatic to life-threatening. Old age is the strongest factor associated with increased COVID19-related mortality, followed by sex and pre-existing conditions. The importance of genetic and immunological factors on COVID19 outcome is also starting to emerge, as demonstrated by population studies and the discovery of damaging variants in genes controlling type I IFN immunity and of autoantibodies that neutralize type I IFNs. The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus’ spike protein, facilitating entry into target cells. We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760), which has a minor allele frequency of ∼25% in the population. In a large population of SARS-CoV-2 positive patients, we show that this variant is associated with a reduced likelihood of developing severe COVID19 (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3×10−3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, impacts the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID19. Further studies are needed to assess the expression of the TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID19. Clinical trials are needed to confirm this.

scholarly journals Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

2021 ◽  
Author(s):  
Young-Il Kim ◽  
Kwang-Min Yu ◽  
June-Young Koh ◽  
Eun-Ha Kim ◽  
Se-Mi Kim ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Age Groups ◽  
Type I ◽  
Activated T Cells ◽  
Virus Shedding ◽  
Viral Loads ◽  
Gene Sets ◽  
M1 Macrophage ◽  
Age Dependent ◽  
Severe Lung

Abstract While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets were infected with SARS-CoV-2. Although SARS-CoV-2 was isolated from all ferrets regardless of age, aged ferrets (≥ 3 years old) showed higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptoms compared to juvenile (≤ 6 months) and young adult (1–2 years) groups. Transcriptome analysis of aged ferret lungs revealed strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

scholarly journals Concerns about estimating relative risk of death associated with convalescent plasma for COVID-19

2022 ◽  
Author(s):  
Michael J. Joyner ◽  
Nigel S. Paneth ◽  
Jonathon W. Senefeld ◽  
DeLisa Fairweather ◽  
Katelyn A. Bruno ◽  
...  
Keyword(s):  
Relative Risk ◽  
Risk Of Death ◽  
Relative Risk Of Death
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