The "Janus-like" RNA-editing machinery in innate antiviral immunity

Our innate immune systems are evolved to provide the first line of immune defense against microbial infections. A key effector component is the adenosine deaminase acting on the RNA-1 (ADAR-1)/ interferon (IFN) pathway of the innate cytoplasmic immunity that mounts rapid responses to many viral pathogens. As an RNA-editing enzyme, ADAR-1 targets viral RNA intermediates in the cytoplasmic compartment to interfere with the infection. However, ADAR-1 may also edit characteristic RNA structures of certain host genes, notably, the 5-hydroxytryptamine (serotonin) receptor 2C (5HT2CR). Dysfunction of 5-HT2CR has been linked to the pathology of several human mental conditions, such as Schizophrenia, anxiety, bipolar disorder, major depression, and the mental illnesses of substance use disorders (SUD). Thus, the ADAR-1mediated RNA editing may be either beneficial or harmful;these effects need to be tightly modulated to sustain innate antiviral immunity while restricting undesired off-target self-reactivity. In this communication, we discuss ideas and tools to identify the orphan drug candidates, including small molecules and biologics that may serve as effective modulators of the ADAR-1/IFN innate immunity and are thereby promising for use in treating or preventing SUD-and/or viral infection-associated mental illnesses.Copyright © 2023, Research Trends (P) LTD.. All rights reserved.

Human Factors and Ergonomics (HFE) applications in responses to the COVID-19 pandemic: Lessons learned and considerations for methods.

Human Factors and Ergonomics (HFE), with the goal to support humans through system design, can contribute to responses to emergencies and crises, like the COVID-19 pandemic. In this paper, we describe three cases presented at the 21st Triennial Congress of the International Ergonomics Association to demonstrate how HFE has been applied during the COVID-19 pandemic, namely to (1) develop a mobile diagnostic testing system, (2) understand the changes within physiotherapy services, and (3) guide the transition of a perioperative pain program to telemedicine. We reflect on methodological choices and lessons learned from each case and discuss opportunities to expand the impact of HFE in responses to future emergencies. The HFE discipline should develop faster, less resource intensive but still rigorous, methods, increase available HFE expertise by growing the field, and proactively enhance individual and public perception of the importance of HFE in crisis response.

A Case Report of Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination and Heparin Use During Hemodialysis.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but life-threatening complication. VITT strongly mimics heparin-induced thrombocytopenia (HIT) and shares clinical features. Heparin is commonly used to prevent coagulation during hemodialysis. Therefore, nephrologists might encounter patients needing dialysis with a history of heparin exposure who developed thrombotic thrombocytopenia after vaccination. A 70-year-old male presented with acute kidney injury and altered mental status due to lithium intoxication. He needed consecutive hemodialysis using heparin. Deep vein thrombosis of left lower extremity and accompanying severe thrombocytopenia of 15,000/µL on 24 days after vaccination and at the same time, nine days after heparin use. Anti-platelet factor 4 antibody test was positive. Anticoagulation with apixaban and intravenous immunoglobulin (IVIG) infusion resolved swelling of his left calf and thrombocytopenia. There were no definitive diagnostic tools capable of differentiating between VITT and HIT in this patient. Although VITT and HIT share treatment with IVIG and non-heparin anticoagulation, distinguishing between VITT and HIT will make it possible to establish a follow-up vaccination plan in a person who has had a thrombocytopenic thrombotic event. Further research is needed to develop the tools to make a clear distinction between the clinical syndromes.

The role of anti-platelet factor 4 antibodies and platelet activation tests in patients with vaccine-induced immune thrombotic thrombocytopenia: Brief report on a comparison of the laboratory diagnosis and literature review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human pathogen causing coronavirus disease 2019 (COVID-19). Rare cases of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) after the ChAdOx1 nCoV-19 (AstraZeneca) vaccination have been reported. We performed a test for anti-heparin/ platelet factor 4 (PF4) antibodies and functional assay using flow cytometry. METHOD: A healthy woman presented to the emergency department with chest pain, headache, and abdominal pain after the first vaccination with AstraZeneca. Polymerase chain reaction (PCR) test for SARS-CoV-2 was negative. Chest computed tomography (CT) showed pulmonary artery embolism and brain magnetic resonance imaging (MRI) revealed cerebral sinus-venous thrombosis. Abdominal CT demonstrated the thrombosis with occlusion in her right hepatic vein. Laboratory studies revealed decreased platelet counts, and high D-dimer level. Finally, laboratory results indicated high PF4 antibodies level high and a positive platelet activation test, confirming the diagnosis of VITT. RESULTS: Treatments including intravenous immunoglobulin, methylprednisolone and direct oral anticoagulant were administered. The results of a follow-up platelet count and D-dimer were normal. In addition, the titer of PF4 antibodies (optical density: 0.425; normal ≤ 0.4, enzyme-linked immunosorbent assay) fell. After a 3-month follow-up, her general condition improved gradually. CONCLUSIONS: The use of COVID-19 vaccines to prevent SARS-CoV-2 infections and complications is considered the most practicable policy for controlling the COVID-19 pandemic and is being forcefully pursued in the global area. Appropriate laboratory diagnosis facilitates the accurate and rapid diagnosis. Early recognizing and appropriate strategies for VITT are required and can provide these patients with more favorable patient outcomes. This report also elected to make comparisons of clinical manifestation, laboratory diagnosis, and management in patients with VITT.

Cutaneous Small-vessel Vasculitis after ChAdOx1 COVID-19 Vaccination: A Report of Five Cases.

Amidst the Coronavirus Disease 2019 (COVID-19) pandemic, vaccination against severe acute respiratory syndrome 2 (SARS-CoV-2) is recommended for everyone over 18 years in South Korea, with the exception of pregnant women. Unexpected adverse cutaneous reactions after the COVID-19 vaccination have been recently reported. Cutaneous small-vessel vasculitis (CSVV) predominantly affects small blood vessels, defined as small intraparenchymal arteries, arterioles, capillaries, and venules, without any detectable involvement of non-cutaneous organs. We report five cases of CSVV after the ChAdOx1 COVID-19 vaccination in 44- to 68-year-old women. The symptoms commonly appeared within 2 days after vaccination. The lesion was localized to the lower limbs in four patients and spread to the upper limbs in one patient. All patients demonstrated a favorable response to oral methylprednisolone, antihistamines, and topical steroids. Considering the importance of the COVID-19 vaccination, clinicians should be aware of CSVV as a potential adverse event. Further studies are required to elucidate the causative link and pathogenesis.

Transverse myelitis and Covid-19 vaccine: A temporal association

Background Transverse myelitis (TM) most often is triggered by an autoimmune reaction, due to infections and perhaps vaccines. In the current pandemic, there are some case reports demonstrating temporal association between TM and COVID-19 vaccine. Then we aim to report a case of TM with temporal association with ChAdOx1 nCoV-19 (AZD1222, Oxford/AstraZeneca) vaccine in a Brazilian public hospital. Case presentation A 27-year-old female started with fever, low back pain and urinary retention three weeks after the first dose of the ChAdOx1 nCoV-19 vaccine. Two days later, decreased strength of lower limbs associated with paresthesias of distal extremities. At the hospital, there was progression of weakness associated with anesthesia in T4-L1. At MRI there were findings suggestive of demyelination and acute inflammation. CSF analysis showed monomorphonuclear pleocytosis, increased protein and decreased glucose. Gram stain, oligoclonal bands, anti-aquaporin-4 antibody and screening for infectious agents and connective tissue disease were all negative. During treatment, she received 5-day pulse therapy with methylprednisolone, acyclovir and seven-day plasmapheresis. Despite all treatments, she persisted with lower limb plegia, areflexia and anesthesia at the level of T4. She was discharged with a monthly cyclophosphamide plan and outpatient follow-up. Conclusions In the absence of other causes, the diagnosis of TM was made with evidence of possible temporal association with ChAdOx1 nCoV-19 vaccine. It is important to emphasize that it is a temporal association only and the benefits of vaccination continue to outweigh the risk of TM.

Thrombosis with Thrombocytopenia Syndrome After Administration of AZD1222 or Ad26.COV2.S Vaccine for COVID-19: A Systematic Review.

BACKGROUND: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS. METHODS: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes. FINDINGS: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered to 140 patients (87·5%). TTS onset occurred in a median of 9 (4) days after vaccination. Venous thrombosis was most common (61.0%). Most patients developed cerebral venous sinus thrombosis (CVST; 66.3%). CVST was significantly more common in female vs male patients (p = 0·001) and in patients aged <45 years vs ≥45 years (p = 0·004). The mortality rate was 36.2%, and patients with suspected TTS, venous thrombosis, CVST, pulmonary embolism, or intraneural complications, patients not managed with non-heparin anticoagulants or IVIG, patients receiving platelet transfusions, and patients requiring intensive care unit admission, mechanical ventilation, or inpatient neurosurgery were more likely to expire than recover. INTERPRETATION: These findings help to understand the pathophysiology of TTS while also recommending diagnostic and management approaches to improve prognosis in patients. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Guillain-Barré syndrome after coronavirus disease 2019 vaccine: A temporal association.

Background: Guillain-Barré syndrome (GBS) is an acute monophasic immune-mediated polyradiculoneuropathy, preceded by gastrointestinal or respiratory infections in up to two-thirds of patients. On rare occasions, people develop GBS after vaccination, but no causal association has been proven. In the current coronavirus disease 2019 (COVID-19) pandemic, some cases have been reported associating COVID-19 vaccine with GBS. Case presentation: We report a case of a 62-year-old woman with GBS after the first dose of the Oxford/AstraZeneca vaccine against SARS-CoV-2. The symptoms started 3 weeks after the vaccine, and were characterized by ascending and progressive paresthesia in the upper and lower limbs, followed by loss of strength of the upper limbs and dysphagia for solids. The hypothesis of GBS was confirmed by clinical presentation compatible with albuminocytologic dissociation in cerebrospinal fluid and based on the Brighton criteria level 2. The treatment was a 5-day course of intravenous immunoglobulin with an improvement of symptoms. Conclusions: In the absence of other causes, the diagnosis of GBS was made, with evidence of a clear temporal association with COVID-19 vaccine. However, a cautious position is important when assigning a particular side-effect directly to a vaccine. It is important to emphasize that it is a temporal association only and the benefits of COVID-19 vaccination continue to outweigh the possible consequences.

Guillain-Barré syndrome following ChAdOx1 nCoV-19 COVID-19 vaccination: A case series.

ChAdOx1 nCoV-19 is an effective and well-tolerated coronavirus disease 2019 (COVID-19) vaccine. Rare cases of serious adverse events have been reported with this vaccine. We report three patients who developed Guillain-Barré syndrome following ChAdOx1 nCoV-19 vaccination, who did not have active or prior COVID-19 infection. The neurological illness in all patients had an onset of 11-13 days after the first dose of vaccine. All were characterized by sensorimotor weakness of the upper and lower limbs, with facial diplegia in one and dysautonomia in the other. Nerve conduction studies were consistent with demyelination in two and axonopathy in one. Cerebrospinal fluid analysis showed albuminocytological dissociation in two patients. All patients had moderate-to-severe disability. They were treated with intravenous immunoglobulin, with stabilization of the disease. Proper monitoring and prompt reporting of such cases is required to ensure safety of the vaccine.

Side Effects of mRNA-Based and Viral Vector-Based COVID-19 Vaccines among German Healthcare Workers.

BACKGROUND: the increasing number of COVID-19 vaccines available to the public may trigger hesitancy or selectivity towards vaccination. This study aimed to evaluate the post-vaccination side effects of the different vaccines approved in Germany; Methods: a cross-sectional survey-based study was carried out using an online questionnaire validated and tested for a priori reliability. The questionnaire inquired about demographic data, medical and COVID-19-related anamneses, and local, systemic, oral, and skin-related side effects following COVID-19 vaccination; Results: out of the 599 participating healthcare workers, 72.3% were females, and 79.1% received mRNA-based vaccines, while 20.9% received a viral vector-based vaccine. 88.1% of the participants reported at least one side effect. Injection site pain (75.6%) was the most common local side effect, and headache/fatigue (53.6%), muscle pain (33.2%), malaise (25%), chills (23%), and joint pain (21.2%) were the most common systemic side effects. The vast majority (84.9%) of side effects resolved within 1-3 days post-vaccination; Conclusions: the mRNA-based vaccines were associated with a higher prevalence of local side effects (78.3% vs. 70.4%; Sig. = 0.064), while the viral vector-based vaccine was associated with a higher prevalence of systemic side effects (87.2% vs. 61%; Sig. < 0.001). Females and the younger age group were associated with an increased risk of side effects either after mRNA-based or viral vector-based vaccines. The gender- and age-based differences warrant further rigorous investigation and standardized methodology.

A review on the advancements in the development of vaccines to combat coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19), the deadly disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a global pandemic that has severely affected lives and economies around the globe. The spread of this virus will be very difficult to contain if no vaccine is ready for implementation. This is because of the high human-to-human transmission rate of this virus and the fact that the virus is in the community spread stage. As of 31st August 2020, 25.3 million individuals have been affected by this deadly virus resulting in about 850,673 deaths. To combat the spread of COVID-19, more than 100 applicant immunizations are being developed around the world. Among them, eight have begun or will be soon beginning preliminary clinical trials. This paper provides a review of the current developments of potential COVID-19 vaccines around the world. It specifically discusses the recombinant vaccine produced by the University of Oxford and AstraZeneca (Cambridge, UK), the use of novel self-amplifying RNA technique to create a vaccine and the progress made by UNAID (US National Institute of Allergy and Infectious Diseases) and World Health Organization (WHO). Furthermore, this review demonstrates the pharmaceutical prophylaxis and treatment protocols for COVID-19 by analysing the documentation set up by the WHO for up to date data with respect to the novel coronavirus of 2019-2020.

Reaching Up, Down, In, and Around: Couple and Family Coping During the Coronavirus Pandemic.

The worldwide coronavirus (COVID-19) has had profound effects on all aspects of life: physical health, the ability to travel locally or to more distant destinations, material and financial resources, and psychosocial wellbeing. Couples, families, and communities and individual persons in those relationships have struggled to cope with emerging depression, anxiety, and trauma, and the rise of relational conflict. In this article, we suggest that the existential nature of the pandemic's challenges requires more than just the usual psychosocial interventions. We propose a taxonomy of responses to foster coping and resilience-"Reaching Up, Down, In, and Around." "Reaching Up" includes accessing spiritual, religious, and ethical values. "Reaching Down" includes ideas and practices that foster a revised relationship with the Earth and its resources, and that engage families to participate in activities that aid the Earth's recovery from decades of human-caused damage. "Reaching In" represents a turn towards experiences available in the mind and in shared minds in relationships that provide pleasure, excitement, joy, and peace, given that external sources of these emotions are of limited availability due to quarantine. "Reaching Around" involves reframing the mandate for "social distancing" as fostering social connection and support while maintaining physical distancing. The challenges for family therapists, whose practices are confined largely to online therapy, and who are struggling with the same fears and constraints as those persons they are attempting to help, are also discussed.

El coronavirus (la COVID-19) mundial ha tenido efectos profundos en todos los aspectos de la vida: en la salud física, en la posibilidad de viajar a nivel local o a destinos más distantes, en los recursos materiales y económicos y en el bienestar psicosocial. Las parejas, las familias, las comunidades y las personas individuales de esas relaciones se han esforzado para hacer frente a la depresión, la ansiedad y el trauma emergentes, y al aumento del conflicto relacional. En este artículo, sugerimos que la índole existencial de las dificultades de la pandemia necesita más que solo las intervenciones psicosociales habituales. Proponemos una taxonomía de respuestas para fomentar el afrontamiento y la resiliencia: "Llegar arriba, abajo, adentro y alrededor". "Llegar arriba" implica acceder a valores espirituales, religiosos y éticos. "Llegar abajo" implica ideas y prácticas que fomenten una relación revisada con la Tierra y sus recursos, y que capten la atención de las familias para participar en actividades que ayuden a la recuperación de la Tierra de décadas de daño causado por los humanos. "Llegar adentro" representa un giro hacia experiencias que hay en la mente y entre mentes por relaciones que brindan placer, entusiasmo, alegría y paz, dado que la disponibilidad de las fuentes externas de estas emociones es limitada debido a la cuarentena. "Llegar alrededor" implica replantear la orden de "distanciamiento social" como fomento de la conexión social y el apoyo mientras se mantiene la distancia física. También se explican las dificultades para los terapeutas familiares, cuyas prácticas están limitadas en gran medida a la terapia en línea, y quienes están luchando contra los mismos miedos y limitaciones que esas personas a quienes intentan ayudar.