scholarly journals Tissue Proteases and Immune Responses: Influencing Factors of COVID-19 Severity and Mortality

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 817
Author(s):  
Natália Mulinari Turin de Oliveira ◽  
Isabella Fernandes da Silva Figueiredo ◽  
Liziane Cristine Malaquias da Silva ◽  
Karien Sauruk da Silva ◽  
Laryssa Regis Bueno ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Severity ◽  
Severe Disease ◽  
Age Groups ◽  
The Elderly ◽  
Current Data ◽  
Individual Characteristics ◽  
Expression Levels ◽  
The Individual ◽  
Global Population

The coronavirus disease 19 (COVID-19) is caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected the global population despite socioeconomic status and amazed surveillance agencies for its incidence, mortality, and recovery rates. COVID-19 affects all age groups; however, it is suggested to progress into severe disease and cause mortality in over 10% of the confirmed cases, depending on the individual characteristics of the affected population. One of the biggest unanswered questions it is why only some individuals develop into the severe stages of the disease. Current data indicate that most of the critically ill are the elderly or those with comorbidities such as hypertension, diabetes, and asthma. However, it has been noted that, in some populations, severe disease is mostly observed in much younger individuals (<60-years old) with no reported underlying medical conditions. Certainly, many factors may contribute to disease severity including intrinsic host factors such as genetic variants, the expression levels of tissue proteins, among others. Considering all these aspects, this review aims to discuss how the expression levels of tissue proteases and the different profiles of immune responses influence the susceptibility to COVID-19 as well as disease severity and outcome.

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

scholarly journals AGE AND SEXUAL CHANGES STRUCTURE OF GENES CYTOKINES NETWORKS IN RUSSIAN POPULATION

2013 ◽  
Vol 68 (9) ◽  
pp. 15-21 ◽  
Author(s):  
V. I. Konenkov ◽  
V. F. Prokof'ev ◽  
A. V. Shevchenko ◽  
A. M. Chernyavskii ◽  
A. M. Karas'kov
Keyword(s):  
Methodological Approach ◽  
Age Groups ◽  
High Specificity ◽  
The Elderly ◽  
Vascular Endothelial ◽  
Elderly Age ◽  
Men And Women ◽  
Growth Factor Gene ◽  
The Individual ◽  
Endothelial Growth Factor

Objective: to study frequencies of occurrence of the combined genetic attributes including different variants of cytokines genotypes (TNFA, IL1B, IL4, IL6, IL10, VEGF), in different on sexual  and age groups in population of Siberia Caucasoid. Material and methods. Frequencies of distribution of variants of structure genes cytokines networks  among 500 representatives of Siberia  Caucasian population, men and women  of  two age groups - more younger than 35 years ("young") and 55 and more years ("elderly") are  investigated. In structure of  investigated genes cytokines net  has come 10 variants of polymorphic sites of cytokines genes and  vascular endothelial growth factor gene: TNFА-863 C→A, TNFА-308 G→A, TNFА-238 G→A, IL1B-31 С→T, IL4-590 С→T, IL6-174 G→C, IL10-1082 G → A, IL10-592 А→С, VEGF-2578 C→A and VEGF+936 С→T. Genotyping are carried out by  restriction fragment length polymorphism method. Processing of results carried out on the basis of the original methodological approach including the complex connected computer analysis of genic circuits of various dimension. Results and conclusions. It is shown, that the significant part of variants genes cytokines networks, which   widely distributed among young people is completely absent in the "elderly" age group. Such variants disappearing with age separately for men and women are established. At the program mathematical analysis it is established, that parameters of the odds ratio  achieve two-place sizes (OR =27, p =0,0004), that testifies to high specificity of complex genetic attributes. Presence in genome such variants of genes cytokines networks  , found out in the childhood or young age, as supposed, is unfavorable personalized prognostic factors of life span of the individual. 

scholarly journals Don’t let it disappear: new opportunities to prolong the life of HR+ HER2- advanced breast cancer patients. Event review of the satellite symposium. RUSSCO Big Conference «Breast Cancer» (online). January 28th, 2021

2021 ◽  
Vol 23 (1) ◽  
pp. 53-60
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Median Overall Survival ◽  
Current Data ◽  
Individual Characteristics ◽  
Advanced Breast ◽  
Satellite Symposium ◽  
Breast Cancer Patients ◽  
Risk Of Death ◽  
The Individual

Increasing life expectancy and maintaining its quality are the main goals of the hormone-dependent HER2-negative advanced breast cancer (HR+ HER2- аBC) therapy. A Satellite Symposium of Novartis Pharma was held on January 28th, 2021, within the framework of the RUSSCO Big Conference Breast Cancer. It was dedicated to the benefits of Risarg (ribociclib) therapy in combination with hormone therapy (HT). Experts-oncologists shared current data and their experience with ribociclib. The combination of CDK4/6 inhibitors with HT became a gold standard for the 1st line therapy for HR+ HER2- aBC. And the choice of a specific drug is based on the data of clinical studies and is made taking into account the individual characteristics of the patient. The results of ribociclib studies (MONALEESA-3 and MONALEESA-7) demonstrate a significant increase in the median overall survival and a decrease in the risk of death by 28 and 30%. The tolerance profile of ribociclib is well studied and controlled, therefore the risks of adverse events can be reduced by the competent monitoring, and the necessary dose modification can be made, which allows most patients to maintain highly effective therapy. The use of ribociclib allows to achieve the main goals of therapy to prolong the patients life and maintain or improve its quality.

scholarly journals New Trends in Pharmacological Treatments for Osteoarthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyan Cai ◽  
Shiwen Yuan ◽  
Yanting Zeng ◽  
Cuicui Wang ◽  
Na Yu ◽  
...  
Keyword(s):  
Severe Disease ◽  
The Elderly ◽  
Preclinical Research ◽  
Nociceptive Pathways ◽  
Function Loss ◽  
Significant Burden ◽  
Recent Developments ◽  
Emerging Treatments ◽  
Potential Applications ◽  
The Individual

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

scholarly journals Differential Association of Viral Dynamics With Disease Severity Depending on Patients’ Age Group in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuri Kim ◽  
Shinhyea Cheon ◽  
Hyeongseok Jeong ◽  
Uni Park ◽  
Na-Young Ha ◽  
...  
Keyword(s):  
Viral Load ◽  
Elderly Patients ◽  
Disease Severity ◽  
Acute Phase ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Clinical Severity ◽  
Younger Patients

Despite a clear association of patient’s age with COVID-19 severity, there has been conflicting data on the association of viral load with disease severity. Here, we investigated the association of viral load dynamics with patient’s age and severity of COVID-19 using a set of respiratory specimens longitudinally collected (mean: 4.8 times/patient) from 64 patients with broad distribution of clinical severity and age during acute phase. Higher viral burden was positively associated with inflammatory responses, as assessed by IL-6, C-reactive protein, and lactate dehydrogenase levels in patients’ plasma collected on the same day, primarily in the younger cohort (≤59 years old) and in mild cases of all ages, whereas these were barely detectable in elderly patients (≥60 years old) with critical disease. In addition, viral load dynamics in elderly patients were not significantly different between mild and critical cases, even though more enhanced inflammation was consistently observed in the elderly group when compared to the younger group during the acute phase of infection. The positive correlation of viral load with disease severity in younger patients may explain the increased therapeutic responsiveness to current antiviral drugs and neutralizing antibody therapies in younger patients compared to elderly patients. More careful intervention against aging-associated inflammation might be required to mitigate severe disease progression and reduce fatality in COVID-19 patients more than 60 years old.

scholarly journals ANTIBODY RESPONSE TO COVID-19 INFECTION- CLINICAL VARIABLES AT PLAY

2020 ◽  
Author(s):  
Anuj Parkash ◽  
Parul Singla ◽  
Meenu Bhatia
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Disease Severity ◽  
Statistical Significance ◽  
Severe Disease ◽  
Initial Symptom ◽  
Igg Antibody ◽  
Duration Of Symptoms ◽  
Clinical Variables ◽  
Significant Difference

ABSTRACTBackgroundThe current COVID19 pandemic began in December 2019 and rapidly expanded to become a global pandemic. The COVID 19 presents multitude of clinical disorders, ranges from asymptomatic infection to severe disease, which can accompanied by multisystem failure leading to death. The immune response to SARS CoV 2 is understood to involve all the components of the system that together causes viral elimination and recovery from the infection. However, such immune responses implicated in the disease has varied presentation ranging from mild to a severe form, which appears to hinge on the loss of the immune regulation between protective and altered responses. In this study, we want to unravel this association of immune responses to various clinical variables, which might have a major role to play, while generating the immune response. The objective was to test this hypothesis in our settings and comparing the results of serologic tests from a group of COVID 19 patients and will analyzed the disease severity in comparison.MethodsTesting for SARS COV2 IgG Antibody was done with chemiluminescent assay on the Ortho Clinical Diagnostic’s (OCD) Vitros 5600 platform.ResultsA total of 106 COVID 19 patients were included in this study, of whom 61 were male and 45 were female. Their mean age was 43.7 years (range 17–83) and the median interval between initial symptom onset and sample collection was 12.33 days. Eighty patients (82%) had mild or moderate symptoms and twenty-six patients (18%) had severe symptoms. The antibody titers were positive in 99 patients (93%) and were found negative in 7 patients (7%). When comparing patients with mild/moderate symptoms and patients with severe/critical diseases, no statistically significant difference was observed between their gender ratios (P = 0.373) and age composition (P = 0.224).ConclusionsThe data presented in this research study did not find any statistical significance between SARS CoV 2 IgG antibody levels with COVID 19 disease severity, duration of symptoms, age, gender, and length of convalescence.

scholarly journals Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers

2021 ◽  
Author(s):  
Pinkus Tober-Lau ◽  
Tatjana Schwarz ◽  
Kanika Vanshylla ◽  
David Hillus ◽  
Henning Gruell ◽  
...  
Keyword(s):  
Immune Responses ◽  
The Elderly ◽  
Current Data ◽  
Elderly Persons ◽  
Cell Reactivity ◽  
Vaccination Rates ◽  
High Risk Populations ◽  
T Cell Reactivity ◽  
Elderly Cohort

COVID-19 mRNA vaccine BNT162b2 is highly immunogenic and effective, but recent studies have indicated waning anti-SARS-CoV-2 immune responses over time. Increasing infection rates has led authorities in several countries to initiate booster campaigns for vulnerable populations, including the elderly. However, the durability of vaccine-induced immunity in the elderly is currently unknown. Here, we describe interim results of a prospective cohort study comparing immune responses in a cohort of vaccinated elderly persons to those in healthcare workers (HCW), measured six months after first immunisation with BNT162b2. Anti-SARS-CoV-2 S1-, full Spike- and RBD -IgG seropositivity rates and IgG levels at six months were significantly lower in the elderly compared to HCW. Serum neutralization of Delta VOC measured by pseudovirus neutralisation test was detectable in 43/71 (60.6%, 95%CI: 48.9-71.1) in the elderly cohort compared to 79/83 in the HCW cohort (95.2%, 95%CI: 88.3-98.1) at six months post vaccination. Consistent with the overall lower antibody levels, SARS-CoV-2-S1 T cell reactivity was reduced in the elderly compared to HCW (261.6 mIU/ml, IQR:141.5-828.6 vs 1198.0 mIU/ml, IQR: 593.9-2533.6, p<0.0001). Collectively, these findings suggest that the established two-dose vaccination regimen elicits less durable immune responses in the elderly compared to young adults. Given the recent surge in hospitalisations, even in countries with high vaccination rates such as Israel, the current data may support booster vaccinations of the elderly. Further studies to determine long-term effectiveness of COVID-19 vaccines in high-risk populations and the safety and effectiveness of additional boosters are needed.

scholarly journals Do Older Employees Have a Lower Individual Productivity Potential than Younger Employees?

2021 ◽  
Author(s):  
Pål Børing ◽  
Jens B. Grøgaard
Keyword(s):  
Formal Education ◽  
Age Groups ◽  
Individual Characteristics ◽  
Individual Level ◽  
Positive Effects ◽  
Older Employees ◽  
Younger Workers ◽  
Individual Productivity ◽  
Productivity Potential ◽  
The Individual

AbstractWe examine the relationship between employees’ age and their individual productivity potential (IPP). IPP is measured by individual characteristics which are related to skills utilisation at work. Using PIAAC data for 27 European and non-European countries, we find that the oldest employees have a lower IPP score than the middle-aged employees in 17 of the 27 countries. It seems to be most demanding for the oldest workers to keep up with the IPP of younger workers in countries with high average skill loss for the oldest age group or high average skills level for all age groups (or both). The significant positive effects of formal education and the absence of significant effects of skills on the IPP score in many of the countries (the individual level), are easier to adapt to the human capital perspective on the importance of formal education than to the perspective of the signalling theory.

scholarly journals THE MUCOSAL MICRORNA PROFILE RELATES TO AGE AND SEVERITY OF DISEASE IN PATIENTS WITH ULCERATIVE COLITIS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Mikkel Malham ◽  
Jaslin James ◽  
Christian Jakobsen ◽  
Estrid Høgdall ◽  
Kim Holmstroem ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Severity ◽  
Mirna Expression ◽  
Pediatric Patients ◽  
Severe Disease ◽  
Adult Patients ◽  
Expression Levels ◽  
Microrna Profile ◽  
Severity Of The Disease

Abstract Despite significant evidence that the expression of several microRNA’s (miRNA) impacts on disease activity in patients with ulcerative colitis (UC), it remains unknown if the more severe disease phenotype seen in pediatric-onset UC can be explained by altered miRNA expression. In this study, we aimed to assess the relationship between miRNA expression, age, and disease severity in pediatric and adult patients with UC. Using RT-qPCR, we analyzed the expression of miR-21, miR-31, miR-126, miR-142, and miR-155 in paraffin-embedded rectum biopsies from 30 pediatric and 30 adult-onset UC patients, and found that lesions from adult patients had significantly higher expression levels of miR-21 compared to pediatric patients and that the expression levels of miR-31 (all patients) and miR-155 (pediatric patients only) correlated inversely with histological assessed disease severity. Using in situ hybridization followed by image analysis, the expression estimates of miR-21 and miR-126 were found to correlate with histological assessed disease severity. In conclusion, we found that the expression of miRNAs depends on the age of the patient and/or the severity of the disease, suggesting that miRNAs may contribute to the regulation of inflammation in UC and could be useful biomarkers in the surveillance of disease severity.

scholarly journals Dynamic changes in the immune response correlate with disease severity and outcomes during infection with SARS-CoV-2

2020 ◽  
Author(s):  
Fang Zheng ◽  
Ruochan Chen ◽  
Run Yao ◽  
Yaxiong Huang ◽  
Ning Li ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Disease Severity ◽  
Dynamic Change ◽  
Severe Disease ◽  
Underlying Disease ◽  
Dynamic Changes ◽  
Th Cells ◽  
Lower Baseline ◽  
Kinetics Of

Abstract Background:The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout China and all over the world. Little is known about the dynamic changes in the patient immune responses to SARS-CoV-2, and how different responses are correlated with disease severity and outcomes.Method:74 patients with confirmed COVID-19 were enrolled in this prospective research. The demographic information, medical history, symptoms, signs and laboratory results were analyzed and compared between severe and non-severe patients. The leukocytes, lymphocyte subsets and inflammatory cytokines were longitudinally collected.Results:Of the 74 patients included, 17 suffered from severe disease. The severe patients tended be older (65.29 ± 12.33 years vs. 45.37 ± 18.66 years), and had a greater degree of underlying disease (41.18% vs. 24.56%) , lower baseline lymphocytes counts (0.69 ± 0.36 × 10⁹ vs. 1.46 ± 0.75 × 10⁹) , higher neutrophil-lymphocyte-ratios (NLRs; 3.76 (3.15–5.51) vs. 2.07 (1.48–2.93)) and lower baseline eosinophil counts (0.01 ± 0.01 × 10⁹ vs. 0.05 ± 0.07 × 10⁹), than that in non-severe patients. The baseline helper T (Th) cells (335.47 vs. 666.46/mL), suppressor T(Ts) cells (158 vs. 334/mL), B cells (95 vs. 210/mL), and natural killer (NK) cells (52 vs. 122/mL) were significantly decreased in severe cases compared to that in non-severe cases. In addition, the baseline neutrophils and B cells were positively correlated with the severity of COVID-19 and the baseline lymphocytes and Th cells were negatively correlated with the severity of COVID-19. The dynamic change of T cells, Th cells and IFN-γ in the severe cases were parallel to the amelioration of the disease.Conclusions:Collectively, our study provides novel information on the kinetics of the immune responses in a cohort of COVID-19 patients with different disease severities. Furthermore, our study indicates that both innate and adaptive immune responses correlate with better clinical outcomes.

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