scholarly journals Risk surveillance and mitigation: autoantibodies as triggers and inhibitors of severe reactions to SARS-CoV-2 infection

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Catherine Chen ◽  
Aisah Amelia ◽  
George W. Ashdown ◽  
Ivo Mueller ◽  
Anna K. Coussens ◽  
...  
Keyword(s):  
Severe Disease ◽  
Surface Proteins ◽  
Prognostic Indicators ◽  
Individual Risk ◽  
Long Term Effects ◽  
Complement Components ◽  
Screening Strategies ◽  
Life Threatening ◽  
Asymptomatic Infections

AbstractCOVID-19 clinical presentation differs considerably between individuals, ranging from asymptomatic, mild/moderate and severe disease which in some cases are fatal or result in long-term effects. Identifying immune mechanisms behind severe disease development informs screening strategies to predict who are at greater risk of developing life-threatening complications. However, to date clear prognostic indicators of individual risk of severe or long COVID remain elusive. Autoantibodies recognize a range of self-antigens and upon antigen recognition and binding, important processes involved in inflammation, pathogen defence and coagulation are modified. Recent studies report a significantly higher prevalence of autoantibodies that target immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins in COVID-19 patients experiencing severe disease compared to those who experience mild or asymptomatic infections. Here we discuss the diverse impacts of autoantibodies on immune processes and associations with severe COVID-19 disease.

X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3231-3238 ◽  
Author(s):  
Michael H. Albert ◽  
Tanja C. Bittner ◽  
Shigeaki Nonoyama ◽  
Lucia Dora Notarangelo ◽  
Siobhan Burns ◽  
...  
Keyword(s):  
Severe Disease ◽  
Treatment Options ◽  
Gene Mutations ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Increased Risk ◽  
Life Threatening ◽  
Severe Infections

Abstract A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.

Three scenarios illustrating ethical concerns when considering bariatric surgery in obese adolescents with Prader-Willi syndrome

2020 ◽  
Vol 46 (11) ◽  
pp. 738-742
Author(s):  
Maria Luisa Di Pietro ◽  
Drieda Zaçe
Keyword(s):  
Bariatric Surgery ◽  
Intellectual Disability ◽  
Therapeutic Option ◽  
Prader Willi Syndrome ◽  
Long Term Effects ◽  
Ethical Concerns ◽  
Severe Intellectual Disability ◽  
Threatening Condition ◽  
Life Threatening

Prader-Willi syndrome (PWS) is one of the 25 syndromic forms of obesity, in which patients present—in addition to different degrees of obesity—intellectual disability, endocrine disturbs, hyperphagia and/or other signs of hypothalamic dysfunction. In front of a severe/extreme obesity and the failure of non-invasive treatments, bariatric surgery is proposed as a therapeutic option. The complexity of the clinical condition, which could affect the long-term effects of bariatric surgery, and the frequent association with a mild to severe intellectual disability raise some ethical concerns in the treatment of obese PWS adolescents. This article analyses these issues referring to the principles of healthcare ethics: beneficence/non-maleficence (proportionality of treatments; minimisation of risks); respect of autonomy; justice. Based on these principles, three hypothetical scenarios are defined: (1) obese PWS adolescent, capable of making an autonomous decision; (2) obese PWS adolescent with a severe intellectual disability, whose parents agree with bariatric surgery; (3) obese PWS adolescent with a life-threatening condition and a severe intellectual disability, whose parents do not agree with bariatric surgery. The currently available evidence on efficacy and safety of bariatric surgery in PWS adolescents with extreme or severe obesity and the lack of adequate long-term follow-up suggests great caution even in a very life-threatening condition. Clinicians must always obtain a full IQ assessment of patients by psychologists. A multidisciplinary team is needed to analyse the clinical, psychological, social and ethical aspects and organise support for patient and parents, involving also the hospital ethical committee or, if necessary, legal authorities.

scholarly journals SARS-CoV-2 (COVID-19) and the Endocrine System

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Michelle D Lundholm ◽  
Caroline Poku ◽  
Nicholas Emanuele ◽  
Mary Ann Emanuele ◽  
Norma Lopez
Keyword(s):  
Severe Disease ◽  
Clinical Manifestations ◽  
Endocrine System ◽  
The Body ◽  
Active Area ◽  
Gonadal Function ◽  
Long Term Effects ◽  
The World ◽  
The Impact

Abstract As SARS-CoV-2 (COVID-19) overtakes the world, causing moderate to severe disease in about 15% of infected patients, COVID-19 is also found to have widespread effects throughout the body with a myriad of clinical manifestations including the endocrine system. This manuscript reviews what is known about the impact of COVID-19 on the pathophysiology and management of diabetes (both outpatient and inpatient) as well as pituitary, adrenal, thyroid, bone, and gonadal function. Findings in this area are evolving, and long-term effects of infection remain an active area of further research.

scholarly journals Study protocol medical rehabilitation after COVID-19 disease: an observational study with a comparison group with obstructive airway disease / Re_Co

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mercedes Rutsch ◽  
Jördis Frommhold ◽  
Heike Buhr-Schinner ◽  
Levan Djeiranachvili ◽  
Thomas Gross ◽  
...  
Keyword(s):  
Comparison Group ◽  
Qualitative Interviews ◽  
Severe Disease ◽  
Airway Disease ◽  
Subjective Health ◽  
Medical Rehabilitation ◽  
Measurement Instruments ◽  
Long Term Effects ◽  
Positive Effects

Abstract Background Novel coronavirus disease 2019 (COVID-19) has been the subject of a numerous research projects over the past year. In cases with a severe disease course or threatening long-term impairment due to disease, the German health care system offers insured persons the possibility of medical rehabilitation. In contrast to what was observed and expected at the beginning of the pandemic, COVID-19 patients with varying degrees of disease severity are represented in rehabilitation. To date, there is no common consensus on the content and aftercare of rehabilitation nor is there any knowledge about the short- and long-term effects of such a rehabilitation programme. In addition, these aspects were not considered with regard to the varying severity of the course of the disease. The present research project investigates this question. Methods The study sample will consist of N = 350 rehabilitants after COVID-19 and a comparison group (CG) with N = 230 rehabilitants suffering from an obstructive respiratory disease. The participants will be recruited at five German rehabilitation facilities and undergo medical rehabilitation. This prospective, exploratory, multicentre, mixed-methods study will be evaluated as follows: (A) The quantitative portion includes questionnaires at different points in time (at the beginning and end of rehabilitation, after six and twelve months) and contains standardised measurement instruments. For example, participation limitations, quality of life, health status, fatigue, psychomental limitations and disorders, performance in different areas of life and ability to work are measured. (B) Qualitative interviews are held at different times (end of rehabilitation, after six and twelve months), and an expert workshop is conducted. Topics are rehabilitation content, satisfaction and aftercare as well as different outcomes on subjective health and participation impairments. Discussion Studies on other indications have already shown that pneumological rehabilitation has positive effects. Thus, it is expected that an improvement in different dimensions will be observed at the end of rehabilitation in both groups. With regard to the different severities of COVID-19, this study evaluates the long-term developments. Subsequently, the authors will elaborate concrete recommendations for medical rehabilitation after different courses of disease with regard to existing pneumological rehabilitation concepts. Trial Registration German Register of Clinical Trials, www.drks.de.Identifier: DRKS00023642; Registered: 01.12.2020.Date and version identifier: 08.04.2021; version 4.

The unconscious experience

1995 ◽  
Vol 4 (3) ◽  
pp. 227-232 ◽  
Author(s):  
M Lawrence
Keyword(s):  
Significant Others ◽  
Prognostic Indicators ◽  
Long Term Effects ◽  
The Unconscious ◽  
Considerable Research ◽  
Body Experiences ◽  
Chart Audits ◽  
Near Death Experiences ◽  
Primary Family

BACKGROUND: Although considerable research has been done on pathophysiology, metabolic and physical causes, and prognostic indicators, little is known about unconsciousness or coma from the perspective of the patient. OBJECTIVE: To describe the experiences of patients who were once documented as being unconscious. METHODS: Phenomenologic interviews were conducted with 100 patients whose records indicated that they had been unconscious during hospitalization. Interviews were also attempted with primary family members, significant others, or other external observers. Chart audits documenting the unconscious episode, medications, and diagnoses were also carried out. Data were compared, using van Kaam's method, and contrasted. RESULTS: Patients experienced one or more of five states: unconsciousness, inner consciousness, perceived unconsciousness, distorted consciousness, and paranormal experiences. They described hearing, understanding, and responding emotionally to what was being said when it was assumed they were not aware. In addition, 23 subjects reported near-death experiences or visits, out-of-body experiences, or some other paranormal experience. CONCLUSION: Patients' unconscious experiences can cause long-term effects. Patients often need reassurance that other patients subjected to similar conditions also have these experiences.

scholarly journals Cancer Patients Have a Higher Risk Regarding COVID-19–and Vice Versa?

2020 ◽  
Vol 13 (7) ◽  
pp. 143 ◽  
Author(s):  
Franz Geisslinger ◽  
Angelika M. Vollmar ◽  
Karin Bartel
Keyword(s):  
Immune Response ◽  
Disease Progression ◽  
Cancer Patients ◽  
Viral Infections ◽  
Severe Disease ◽  
Special Focus ◽  
Long Term Effects ◽  
Increased Risk ◽  
Inflammatory Immune Response

The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date. The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient. The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer. A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19. However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected. In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. We offer lines of thought to provide ideas for urgently needed studies on the potential long-term effects of SARS-CoV-2 infection.

Long-term effects of pain in children

2013 ◽  
pp. 30-38 ◽  
Author(s):  
Ruth E. Grunau
Keyword(s):  
Medical Care ◽  
Pain Perception ◽  
Primary Concern ◽  
Long Term Effects ◽  
Term Infants ◽  
Surgical Pain ◽  
Biological Substrate ◽  
Life Threatening ◽  
Infant Pain

Major advances in high-technology medical care have led to greatly increased survival of medically fragile infants born extremely preterm, or with major congenital anomalies or other life-threatening conditions. These infants are exposed to procedural, surgical, and post-surgical pain. For millennia human infancy was a prolonged period of adult protection, with pain rarely encountered early in life. While the biological mechanisms for perception of pain develop during the fetal period, endogenous capacities to dampen pain mature later. Until relatively recently, this biological substrate was a good fit, matching the environment of infancy. However, the revolution in medical care has led to unforeseen challenges to understand and manage infant pain. In full-term infants, the primary concern is whether early pain alters later pain sensitivity. In contrast, due to the immaturity of the developing nervous system, the greatest impact of pain is likely to occur in the least maturely born infants. Therefore, in infants born very preterm who undergo lengthy hospitalization, pain may affect multiple aspects of development. This chapter focuses on long-term effects of early pain on subsequent pain perception, neurodevelopment, brain development, and programming of stress systems in the context of clinical studies, and whether caregiving factors may ameliorate potential long-term adverse effects.

scholarly journals Violence: A Prescription of Hope for a Vulnerable Population

2021 ◽  
Author(s):  
Tonita Smith ◽  
Edith Amponsah ◽  
Lia Garman
Keyword(s):  
Risk Factors ◽  
Low Income ◽  
Parental Education ◽  
Exposure To Violence ◽  
Individual Risk ◽  
Long Term Effects ◽  
Family Risk ◽  
Community Risk ◽  
Community Risk Factors

Violence is a preventable disease that has long term effects on health. In the United States, violence has become an epidemic that disproportionately affects the African American community. Risk factors that contribute to the perpetration of youth violence include a combination of individual, relationship, community, and societal factors. Individual risk factors include a personal history of victimization of violence, high emotional stress, and exposure to violence and conflict. Family risk factors include low parental education, low income, poor family functioning and low parental involvement. Community risk factors include diminished economic opportunities, high concentration of poor residents, and socially disorganized neighborhoods – all of which are prevalent in communities with high rates of violence. Preventive strategies aimed at reducing violence need to be collaborative and community based. This multi-city project, A Prescription of Hope, aims to educate community members from Illinois and Missouri on the long- term effects of exposure to violence. The target population for Missouri is Ferguson, a small community with an approximate population of 21,035 (2017); however, it is recognized nationally for the demonstrations and unrest that erupted after the August 9, 2014 shooting death of 18-year-old Michael Brown. Worldwide, an estimated 200,000 homicides occur each year among youth aged 10–29 years, accounting for 43% of all homicide annually.

Acute and long-term effects of infection by the respiratory syncytial virus in children with congenital cardiac malformations

2005 ◽  
Vol 15 (3) ◽  
pp. 266-273 ◽  
Author(s):  
Timothy F. Feltes ◽  
Jessie R. Groothuis
Keyword(s):  
Respiratory Syncytial Virus ◽  
Young Children ◽  
Severe Disease ◽  
Newborn Infants ◽  
Later Life ◽  
Respiratory Morbidity ◽  
Long Term Effects ◽  
Increased Risk ◽  
Syncytial Virus

All newborn infants have limited pulmonary reserve compared with older children. This puts them at increased risk of respiratory complications, such as those associated with infection by the respiratory syncytial virus. Young children with congenital cardiac disease are particularly likely to suffer severe disease related to infection by the virus. In these children, the extreme vulnerability of the lung to pulmonary oedema is compounded by the additional burden caused by the respiratory syncytial virus.In addition to the well-documented acute pulmonary effects of infection with the respiratory syncytial virus, there may also be consequent long-term respiratory morbidity. Clinical studies have shown that infection by the virus in infancy is associated with a higher risk of developing subsequent bronchial obstructive disease. Much debate surrounds the mechanisms underlying this association. It is thought that a combined immunological and neurogenic response mechanism is likely. Prevention of severe respiratory disease in infants and young children with congenital heart disease due to infection by the virus may, therefore, offer both immediate and long-term benefits. Indeed, an increasing body of evidence supports this hypothesis, indicating a clinical rationale for prophylaxis against the virus in infancy, in order to reduce the chance of developing reactive airways disease and asthma in later life.

scholarly journals Diverse Functional Autoantibodies in Patients with COVID-19

2020 ◽  
Author(s):  
Eric Y. Wang ◽  
Tianyang Mao ◽  
Jon Klein ◽  
Yile Dai ◽  
John D. Huck ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthcare Workers ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Surface Proteins ◽  
Complement Components ◽  
Host Immune Responses ◽  
High Prevalence ◽  
The Impact

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–8. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

Sign in / Sign up

Export Citation Format

Share Document