Summary A wide range of microorganisms can replicate in macrophages, and cell entry of these pathogens via non-neutralising IgG antibody complexes can result in increased intracellular infection ...through idiosyncratic Fcγ-receptor signalling. The activation of Fcγ receptors usually leads to phagocytosis. Paradoxically, the ligation of monocyte or macrophage Fcγ receptors by IgG immune complexes, rather than aiding host defences, can suppress innate immunity, increase production of interleukin 10, and bias T-helper-1 (Th1) responses to Th2 responses, leading to increased infectious output by infected cells. This intrinsic antibody-dependent enhancement (ADE) of infection modulates the severity of diseases as disparate as dengue haemorrhagic fever and leishmaniasis. Intrinsic ADE is distinct from extrinsic ADE, whereby complexes of infectious agents with non-neutralising antibodies lead to an increased number of infected cells. Intrinsic ADE might be involved in many protozoan, bacterial, and viral infections. We review insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe at unprecedented speed and is showing no signs of slowing down. The outbreak of coronavirus disease ...2019 (COVID-19) has led to significant health burden in infected patients especially in those with underlying comorbidities. The aim of this study was to evaluate the correlation between comorbidities and their role in the exacerbation of disease in COVID-19 patients leading to fatal outcomes. A systematic review was conducted using data from MEDLINE, Scopus, Web of Science, and EMBASE databases published from 1 December 2019 to 15 September 2020. Fifty-three articles were included in the systematic review. Of those 53 articles, 8 articles were eligible for meta-analysis. Hypertension, obesity, and diabetes mellitus were identified to be the most prevalent comorbidities in COVID-19 patients. Our meta-analysis showed that cancer, chronic kidney diseases, diabetes mellitus, and hypertension were independently associated with mortality in COVID-19 patients. Chronic kidney disease was statistically the most prominent comorbidity leading to death. However, despite having high prevalence, obesity was not associated with mortality in COVID-19 patients.
COVID-19 has plagued the world since it was first identified in December 2019. Previous systematic reviews and meta-analysis were limited by various factors such as the usage of non-peer reviewed data and were also limited by the lack of clinical data on a global scale. Comorbidities are frequently cited as risk factors for severe COVID-19 outcomes. However, the degree to which specific comorbidities impact the disease is debatable. Our study selection involves a global reach and covers all comorbidities that were reported to be involved in the exacerbation of COVID-19 leading to fatal outcomes, which allows us to identify the specific comorbidities that have higher risk in patients. The study highlights COVID-19 high-risk groups. However, further research should focus on the status of comorbidities and prognosis in COVID-19 patients.
COVID-19 emerged in late 2019 and has rapidly spread through many countries globally. The causative SARS-CoV-2 virus was not known until recently, and there is little or no natural immunity in human ...populations. There is an urgent need for vaccines and drugs to combat this new pandemic. In just a few months, huge efforts and resources by government, academia, and industry have been thrown into the race to develop a vaccine. This brief review summarizes and discusses the array of technologies being applied to vaccine development, highlighting the strengths and weaknesses of the various approaches.
Chikungunya: a re-emerging virus Burt, Felicity J, Dr; Rolph, Micheal S, PhD; Rulli, Nestor E, PhD ...
The Lancet (British edition),
02/2012, Letnik:
379, Številka:
9816
Journal Article
Recenzirano
In the past decade, chikungunya—a virus transmitted by Aedes spp mosquitoes—has re-emerged in Africa, southern and southeastern Asia, and the Indian Ocean Islands as the cause of large outbreaks of ...human disease. The disease is characterised by fever, headache, myalgia, rash, and both acute and persistent arthralgia. The disease can cause severe morbidity and, since 2005, fatality. The virus is endemic to tropical regions, but the spread of Aedes albopictus into Europe and the Americas coupled with high viraemia in infected travellers returning from endemic areas increases the risk that this virus could establish itself in new endemic regions. This Seminar focuses on the re-emergence of this disease, the clinical manifestations, pathogenesis of virus-induced arthralgia, diagnostic techniques, and various treatment modalities.
Summary
Sensitization of the humoral immune response to invading viruses and production of antiviral antibodies forms part of the host antiviral repertoire. Paradoxically, for a number of viral ...pathogens, under certain conditions, antibodies provide an attractive means of enhanced virus entry and replication in a number of cell types. Known as antibody‐dependent enhancement (ADE) of infection, the phenomenon occurs when virus‐antibody immunocomplexes interact with cells bearing complement or Fc receptors, promoting internalization of the virus and increasing infection. Frequently associated with exacerbation of viral disease, ADE of infection presents a major obstacle to the prevention of viral disease by vaccination and is thought to be partly responsible for the adverse effects of novel antiviral therapeutics such as intravenous immunoglobulins. There is a growing body of work examining the intracellular signaling pathways and epitopes responsible for mediating ADE, with a view to aiding rational design of antiviral strategies. With in vitro studies also confirming ADE as a feature of infection for a growing number of viruses, challenges remain in understanding the multilayered molecular mechanisms of ADE and its effect on viral pathogenesis.
There is a small number of other reported LAV that have shown utility in animal models of COVID-19 3,4, such as a temperature-sensitive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) ...mutant that is able to replicate in the upper, but not the lower, respiratory tract 3. Even accounting for waning immunity after natural infection, the risk in vaccinees was still 5.96-fold more than in naturally infected individuals 16. ...natural immunity was stronger and longer-lasting than in BNT162b2 vaccinees and provided superior protection against infection, symptomatic disease, and hospitalisation caused by the SARS-CoV-2 delta variant. ...transmission, if not prevented, is also considerably temporally reduced 18. In addition to antibodies, SARS-CoV-2 infection induces a strong T cell response. Since viral proteins are present in the cytosol of infected cells, the T cell response includes CD8+ T cells, which have the potential to directly kill infected cells.
Summary Re-emergence of chikungunya virus, a mosquito-transmitted pathogen, is of serious public health concern. In the past 15 years, after decades of infrequent, sporadic outbreaks, the virus has ...caused major epidemic outbreaks in Africa, Asia, the Indian Ocean, and more recently the Caribbean and the Americas. Chikungunya virus is mainly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions, but the potential exists for further spread because of genetic adaptation of the virus to Aedes albopictus , a species that thrives in temperate regions. Chikungunya virus represents a substantial health burden to affected populations, with symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. The inflammatory response coincides with raised levels of immune mediators and infiltration of immune cells into infected joints and surrounding tissues. Animal models have provided insights into disease pathology and immune responses. Although host innate and adaptive responses have a role in viral clearance and protection, they can also contribute to virus-induced immune pathology. Understanding the mechanisms of host immune responses is essential for the development of treatments and vaccines. Inhibitory compounds targeting key inflammatory pathways, as well as attenuated virus vaccines, have shown some success in animal models, including an attenuated vaccine strain based on an isolate from La Reunion incorporating an internal ribosome entry sequence that prevents the virus from infecting mosquitoes and a vaccine based on virus-like particles expressing envelope proteins. However, immune correlates of protection, as well as the safety of prophylactic and therapeutic candidates, are important to consider for their application in chikungunya infections. In this Review, we provide an update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines.
Mosquito-borne viruses, or arboviruses, have been part of the infectious disease landscape for centuries, and are often, but not exclusively, endemic to equatorial and subtropical regions of the ...world. The past two decades saw the re-emergence of arthritogenic alphaviruses, a genus of arboviruses that includes several members that cause severe arthritic disease. Recent outbreaks further highlight the substantial public health burden caused by these viruses. Arthritogenic alphaviruses are often reported in the context of focused outbreaks in specific regions (eg, Caribbean, southeast Asia, and Indian Ocean) and cause debilitating acute disease that can extend to chronic manifestations for years after infection. These viruses are classified among several antigenic complexes, span a range of hosts and mosquito vectors, and can be distributed along specific geographical locations. In this Review, we highlight key features of alphaviruses that are known to cause arthritic disease in humans and outline the present findings pertaining to classification, immunogenicity, pathogenesis, and experimental approaches aimed at limiting disease manifestations. Although the most prominent alphavirus outbreaks in the past 15 years featured chikungunya virus, and a large body of work has been dedicated to understanding chikungunya disease mechanisms, this Review will instead focus on other arthritogenic alphaviruses that have been identified globally and provide a comprehensive appraisal of present and future research directions.
Chikungunya virus (CHIKV) has come to prominence as a global, re-emerging pathogen over the last two decades, progressing from sporadic, remote outbreaks to worldwide explosive epidemics. From ...contained, though considerable, outbreaks in the southern Indian Ocean, parts of South America and the Caribbean, CHIKV continues to be a significant pathogen in Southeast Asia and India. CHIKV circulates during epidemics through an urban mosquito-to-human transmission cycle, and with no available treatments or licensed vaccines to specifically target CHIKV disease, limiting transmission relies on vector control, which poses significant challenges, especially in developing countries. This review summarizes the current findings and progress in the development of safe, effective and affordable therapeutics and vaccines for CHIKV disease.
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