Acquired haemophilia in the elderly is a severe disease: report of five new cases

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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Neutrophils in respiratory viral infections

Mucosal Immunology ◽

10.1038/s41385-021-00397-4 ◽

2021 ◽

Author(s):

Cecilia Johansson ◽

Freja C. M. Kirsebom

Keyword(s):

Viral Infections ◽

Immune Cell ◽

Respiratory Infections ◽

Fungal Infections ◽

Severe Disease ◽

The Elderly ◽

Viral Control ◽

Immunological Mechanisms ◽

Respiratory Viral Infections ◽

Viral Respiratory Infections

AbstractViral respiratory infections are a common cause of severe disease, especially in infants, people who are immunocompromised, and in the elderly. Neutrophils, an important innate immune cell, infiltrate the lungs rapidly after an inflammatory insult. The most well-characterized effector mechanisms by which neutrophils contribute to host defense are largely extracellular and the involvement of neutrophils in protection from numerous bacterial and fungal infections is well established. However, the role of neutrophils in responses to viruses, which replicate intracellularly, has been less studied. It remains unclear whether and, by which underlying immunological mechanisms, neutrophils contribute to viral control or confer protection against an intracellular pathogen. Furthermore, neutrophils need to be tightly regulated to avoid bystander damage to host tissues. This is especially relevant in the lung where damage to delicate alveolar structures can compromise gas exchange with life-threatening consequences. It is inherently less clear how neutrophils can contribute to host immunity to viruses without causing immunopathology and/or exacerbating disease severity. In this review, we summarize and discuss the current understanding of how neutrophils in the lung direct immune responses to viruses, control viral replication and spread, and cause pathology during respiratory viral infections.

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Acquired Haemophilia in the Elderly

Acta Clinica Belgica ◽

10.1080/17843286.1995.11718453 ◽

1995 ◽

Vol 50 (4) ◽

pp. 238-241 ◽

Cited By ~ 4

Author(s):

F. Geurs* ◽

G. Baele ◽

M. Afschrift

Keyword(s):

The Elderly ◽

Acquired Haemophilia

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STOCHASTIC TRANSMISSION DYNAMICS OF COVID-19 WITHIN A DENSITY DEPENDENT POPULATION

FUDMA Journal of Sciences ◽

10.33003/659 ◽

2021 ◽

Vol 5 (2) ◽

pp. 567-573

Author(s):

Lubem M. Kwaghkor ◽

Stephen E. Onah ◽

Ibrahim G. Basi ◽

Theophilus Danjuma

Keyword(s):

Distribution Function ◽

Exponential Distribution ◽

Severe Disease ◽

The Elderly ◽

Control Measures ◽

Special Treatment ◽

Susceptible Population ◽

Density Dependent ◽

Infected People ◽

Population Sizes

Coronavirus diseases (COVID-19) is a respiratory disease. Most infected people are known to develop mild to moderate symptoms and recover without requiring special treatment except for those who have underlying medical conditions and the elderly have a higher risk of developing severe disease. This research is aimed at studying the probable spread of the COVID-19 virus within a completely susceptible density-dependent population using a modified exponential distribution function. The modified exponential distribution function was extended to include the Basic Reproduction Number which was computed using the Nigerian COVID-19 index cases from 27th February to 18th April, 2020 to be. Various interesting results were obtained for the including the time period for the spread for different population sizes. The duration of the spread of the virus is from 4 to 7 hours with an average of 5.5 hours. This indicates that, for one infectious person with to enter a completely susceptible population of size , the virus can spread through the entire population in about hours if no control measures are in place.

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Epidemiology of COVID-19

Journal of Digestive Endoscopy ◽

10.1055/s-0040-1712187 ◽

2020 ◽

Vol 11 (01) ◽

pp. 03-07

Author(s):

Sudipta Dhar Chowdhury ◽

Anu Mary Oommen

Keyword(s):

Healthcare Workers ◽

Severe Disease ◽

Case Series ◽

Case Fatality ◽

Respiratory Illness ◽

The Elderly ◽

The United States ◽

Health System Strengthening ◽

Disease Spread ◽

Limited Access

AbstractCOVID-19, an infectious respiratory illness caused by the severe acute respiratory syndrome–corona virus 2 (SARS-CoV2), has now spread to multiple countries including India. The pace at which the disease spread in the last 4 months, since it was first recognized from China, is unprecedented. This review of the epidemiology of COVID-19 summarizes the burden of infection, transmission dynamics, and other related epidemiological features. While countries such as China, Italy, and the United States have particularly high-rates of infection, the disease is gradually spreading in India as well, threatening the health and economy of the country. Transmission in asymptomatic cases, early symptomatic phase, as well as limited access to testing in different settings are factors that have led to the rapid spread of infection. A large case series from China revealed that 81% of cases had mild symptoms, 14% had severe disease, and 5% were afflicted with critical illness. While the mortality in China was reported as 2.3%, Italy, with a high-proportion of elderly, reported a case fatality report of 7.2% due to higher infection and mortality rates among the elderly. Being a highly infectious disease, with a basic reproduction number between 2 to 3, COVID-19 is affecting a large number of healthcare workers, as evidenced by the fact that a sizeable portion of reported infections in the US included healthcare workers. Delivering health care for both COVID-19 affected individuals, as well those with other acute and chronic conditions, with limited access to healthcare facilities and services, are challenges for the health systems in low- and middle-income countries, which require immediate measures for health system strengthening across sectors.

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Zika Virus Infection in the Elderly: Possible Relationship with Guillain-Barré Syndrome

Gerontology ◽

10.1159/000453579 ◽

2016 ◽

Vol 63 (3) ◽

pp. 210-215 ◽

Cited By ~ 7

Author(s):

Wilson Savino ◽

Carolina V. Messias ◽

Daniella A. Mendes-da-Cruz ◽

Pamela Passos ◽

Ana Carolina A.F. Ferreira ◽

...

Keyword(s):

Zika Virus ◽

Severe Disease ◽

The Elderly ◽

French Polynesia ◽

Therapeutic Interventions ◽

Guillain Barre Syndrome ◽

Zikv Infection ◽

Susceptible Population ◽

Guillain Barré Syndrome ◽

Guillain Barré

The Zika virus (ZIKV) outbreak in French Polynesia, in 2013, and in Brazil, in 2015, was correlated with neurological complications, which comprised, among others, congenital microcephaly and Guillain-Barré syndrome (GBS), which includes a group of acute autoimmune neuropathies generally reported after respiratory or gastrointestinal infectious diseases. Despite being relatively rare, the incidence rate of GBS rises with age, which makes GBS more frequent in the elderly, in whom it is also a more severe disease with slower recovery than in younger patients. Different forms of GBS have been described having diagnostic confirmation of a previous infection with the ZIKV virus. Although we do not have enough evidence that elderly people are a particularly susceptible population to developing GBS following ZIKV infection, this is plausible. We should consider this possibility, particularly taking into account that aging subjects are more susceptible to infections. In this context, a deeper understanding of how the immune system in the elderly functions in relation to ZIKV infection is necessary, as well as an understanding of what kind of alterations of the nervous system such an infection triggers in the elderly, beyond GBS. This will be relevant for better therapeutic interventions and for designing vaccine candidates that can be applied in an aging population, particularly those prone to develop ZIKV-induced autoimmunity.

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New Trends in Pharmacological Treatments for Osteoarthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.645842 ◽

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.

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

Frontiers in Microbiology ◽

10.3389/fmicb.2021.712260 ◽

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.

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Pulmonary insults exacerbate susceptibility to oral Listeria monocytogenes infection through the production of IL-10 by NK cells

PLoS Pathogens ◽

10.1371/journal.ppat.1009531 ◽

2021 ◽

Vol 17 (4) ◽

pp. e1009531

Author(s):

Nikki Bortell ◽

Elizabeth R. Aguilera ◽

Laurel L. Lenz

Keyword(s):

Listeria Monocytogenes ◽

Nk Cells ◽

Severe Disease ◽

Bacterial Pathogen ◽

Myeloid Cell ◽

The Elderly ◽

Interleukin 10 ◽

Human Populations ◽

Phagocytic Capacity ◽

Increase Disease Susceptibility

Most individuals who consume foods contaminated with the bacterial pathogen Listeria monocytogenes (Lm) develop mild symptoms, while others are susceptible to life-threatening systemic infections (listeriosis). Although it is known that the risk of severe disease is increased in certain human populations, including the elderly, it remains unclear why others who consume contaminated food develop listeriosis. Here, we used a murine model to discover that pulmonary coinfections can impair the host’s ability to adequately control and eradicate systemic Lm that cross from the intestines to the bloodstream. We found that the resistance of mice to oral Lm infection was dramatically reduced by coinfection with Streptococcus pneumoniae (Spn), a bacterium that colonizes the respiratory tract and can also cause severe infections in the elderly. Exposure to Spn or microbial products, including a recombinant Lm protein (L1S) and lipopolysaccharide (LPS), rendered otherwise resistant hosts susceptible to severe systemic Lm infection. In addition, we show that this increase in susceptibility was dependent on an increase in the production of interleukin-10 (IL-10) from Ncr1+ cells, including Natural Killer (NK) cells. Lastly, the ability of Ncr1+ derived IL-10 to increase disease susceptibility correlated with a dampening of both myeloid cell accumulation and myeloid cell phagocytic capacity in infected tissues. These data suggest that efforts to minimize inflammation in response to an insult at the respiratory mucosa render the host more susceptible to infections by Lm and possibly other pathogens that access the oral mucosa.

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