scholarly journals TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Gillina F. G. Bezemer ◽  
Johan Garssen

By mapping the clinical pathophysiology of the novel coronavirus disease 2019 (COVID-19) against insights from virology, immunology, genomics, epidemiology and pharmacology, it is here proposed that the pathogen recognition receptor called toll like receptor 9 (TLR9) might have a pivotal role in the pathogenesis of COVID-19. Severe Acute Respiratory Syndrome Coronavirus 2, is causing the greatest global social and economic disruption since world war II. Lack of a vaccine, lack of successful treatment and limitations of the healthcare workforce and resources needed to safeguard patients with severe COVID-19 on the edge of life, demands radical preventive measures. It is urgently needed to identify biomarkers and drug candidates so that vulnerable individuals can be recognized early and severe multi-organ complications can be prevented or dampened. The TLR9 COVID-19 hypothesis describes a mechanism of action that could explain a wide spectrum of manifestations observed in patients with severe COVID-19. The introduced hypothesis proposes biomarkers for identification of vulnerable individuals and positions TLR9 as a promising multifaceted intervention target for prevention and/or treatment of COVID-19. TLR9 agonists might have value as prophylactic vaccine adjuvants and therapeutic immune stimulators at the early onset of disease. Additionally, in this current manuscript it is proposed for the first time that TLR9 could be considered as a target of “inhibition” aimed to dampen hyperinflammation and thrombotic complications in vulnerable patients that are at risk of developing late stages of COVID-19. The readily availability of TLR9 modulating drug candidates that have reached clinical testing for other disorders could favor a fast track development scenario, an important advantage under the current high unmet medical need circumstances regarding COVID-19.

Author(s):  
И.Б. Симарова ◽  
С.Н. Переходов ◽  
А.Ю. Буланов

Гиперкоагуляционный характер коагулопатии, ассоциированной с новой коронавирусной инфекцией COVID-19, и высокий риск связанных с этим тромботических осложнений — хорошо известный факт на сегодняшний день. Тем не менее в литературе имеются описания и геморрагических событий у больных COVID. В обзоре приведен анализ публикаций, описывающих кровотечения при коронавирусной инфекции; общая частота их в среднем составляет 4–8%. Превалируют желудочно-кишечные кровотечения, существенную часть составляют межмышечные гематомы и кровоизлияния в кожу и слизистые. Показана предиктивная роль применения антикоагулянтов в терапевтических дозах и гипофибриногенемии. Отмечено отсутствие четкого понимания патофизиологических механизмов. Hypercoagulable character of coagulopathy associated with the novel coronavirus infection COVID-19, and the high risk of associated thrombotic complications is a well-known fact. However, there are also case reports of hemorrhagic events in COVID patients in the literature. The review summarizes the publications describing bleedings in coronavirus infection; their overall frequency is on average 4–8%. Gastrointestinal bleeding are prevalent, intermuscular hematomas and hemorrhages in the skin and mucous membranes are frequent. The predictive role of anticoagulants use in therapeutic doses and hypofibrinogenemia is shown. The absence of clear understanding of the pathophysiological mechanisms is noted.


2020 ◽  
Author(s):  
Mitra Feldman ◽  
Lieven Vernaeve ◽  
James Tibenderana ◽  
Leo Braack ◽  
Mark Debackere ◽  
...  

Abstract Background Impressive progress in reducing malaria trends combined with the 2018 report of no malaria related deaths for the first time, puts Cambodia well on track to reaching its malaria elimination goals. However, the novel coronavirus SARS-CoV-2 (COVID-19) pandemic presents a potential challenge to this goal. The path towards malaria elimination is dependent on sustained interventions to prevent rapid resurgence, which can quickly set back any gains achieved. Methods Mobile Malaria Workers (MMWs) need to have a strong understanding of the local geography and, most importantly, build and maintain trust among the communities they serve. To achieve this, Malaria Consortium uses a peer-to-peer approach for the MMWs and ensures the same level of trust operates between the MMWs and Malaria Consortium. Malaria Consortium’s policy during COVID-19 has been to follow national guidelines while continuing to support community-based malaria services via the MMWs / mobile malaria posts (MPs) with as minimal disruption as possible. A risk assessment was carried out by Malaria Consortium, with a mitigation plan quickly developed and implemented, to ensure MMWs were able to continue providing services without putting themselves or their patients at risk. Results Malaria Consortium ensured the MMW/ mobile MP program is built on trust, relevance to, and connection with the communities being served. An overall decline in malaria testing was reported from Health Centres and VMWs among all three provinces in March and April, not seen in previous years and possibly attributable to fear of COVID-19. However, Malaria Consortium supported MMWs have not reported any such decline in the utilization of their services and attribute this to the trust they have among the communities. Conclusion Malaria Consortium has effectively demonstrated care and solidarity with and among the MMWs and communities being served. This has ensured a high level of trust, and therefore willingness among the MMWs and communities to continue providing and utilising malaria services as usual despite the fear of COVID-19. Building trust among rural communities builds resilience and ensures uninterrupted and effective malaria elimination activities can continue even during a potential extraneous disruptive force, such as the Covid-19 pandemic.


2021 ◽  
Vol 13 (4) ◽  
pp. 552-557
Author(s):  
Natalia Kopiczko ◽  
Kamila Kwiatek-Średzińska ◽  
Mirosława Uścinowicz ◽  
Monika Kowalczuk-Krystoń ◽  
Dariusz Marek Lebensztejn

The novel coronavirus disease (COVID-19) was detected for the first time in China in December 2019. Soon after it was declared a pandemic. Main symptoms include fever, dyspnea, cough, muscle pain, headache, anosmia and ageusia, however a growing body of evidence shows that other organs can be affected. Gastrointestinal manifestations have been observed in a considerable number of patients and include abdominal pain, diarrhea and vomiting. The involvement of liver as well as pancreas has been also described, however there are only a few cases of acute pancreatitis reported in patients with COVID-19. Therefore, we present a case of 6-year-old child with mild acute pancreatitis and COVID-19 pneumonia.


2021 ◽  
Vol 2 ◽  
pp. 55-58
Author(s):  
Sutapa Mukherjee

Since its incidence in December 2019, the novel coronavirus, named “Severe acute respiratory syndrome coronavirus-2” (SARS-CoV-2), has undergone excessively rapid human-to-human transmission throughout the globe and remains still unabated. The worldwide uncontrolled expansion of the disease coronavirus 2019 (COVID-19) pursued the World Health Organization to declare it a pandemic on March 11, 2020. The untiring efforts of scientists, clinicians, and researchers have increased our awareness about the pathophysiology of COVID-19 although much of it is shrouded with ambiguity. The wide spectrum of the disease in terms of severity, mortality, age and gender biases, physiological manifestations, and responses adds up to the complications. Of particular concern is the impact of COVID-19 on male reproductive health and fertility outcomes. The present article discusses some of the emerging multiple facets rendering the male reproductive system vulnerable to SARS-CoV-2 infection and/or associated pathological mechanisms.


2020 ◽  
Author(s):  
Namu Park ◽  
Hyeyoung Ryu ◽  
Ying Ding ◽  
Qi Yu ◽  
Yi Bu ◽  
...  

Abstract Drug repurposing may be a pivotal means of fulfilling urgent needs for treatment of the novel coronavirus disease 2019 (COVID-19), but current studies on drug repurposing for COVID-19 seem to show a lack of consensus in their drug candidate focus. Using bibliometric methods in a non-expert perspective, in a review of 34 published articles on the COVID-19 and drug-repurposing, we investigated obvious and less obvious points of consensus on drug candidates. To establish these two types of consensus, we first implemented document clustering. Within a set of five clustered papers, we established an obvious consensus, relying solely on the occurrence of entities by using term frequency and inverse document frequency and a comparison of mentioned drugs, finding that remdesivir and chloroquine were discussed with a certain degree of agreement. For the less obvious consensus, we created a drug entity co-occurrence network to establish low-high centrality combinations to probe the crucial drugs found in article clustering that are not plainly apparent through the mere counting of the occurrence of drug entities occurrences. Lopinavir emerged as having possibly potent effects in spite of underuse, while the mainstream of studies focus more on drugs such as chloroquine that enjoy explicit consent. Using an entitymetrics perspective, we expect that our research will support investigations of drug repurposing, expediting the process of establishing treatment for COVID-19.


Endocrinology ◽  
2021 ◽  
Vol 162 (3) ◽  
Author(s):  
Wenjie Chen ◽  
Yuang Tian ◽  
Zhihui Li ◽  
Jingqiang Zhu ◽  
Tao Wei ◽  
...  

Abstract The novel coronavirus disease 2019 (COVID-19) produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sweeping the world in a very short time. Although much has been learned about the clinical course, prognostic inflammatory markers, and disease complications of COVID-19, the potential interaction between SARS-CoV-2 and the thyroid is poorly understood. In contrast to SARS-CoV-1, limited available evidence indicates there is no pathological evidence of thyroid injury caused by SARS-CoV-2. However, subacute thyroiditis caused by SARS-CoV-2 has been reported for the first time. Thyroid dysfunction is common in patients with COVID-19 infection. By contrast, certain thyroid diseases may have a negative impact on the prevention and control of COVID-19. In addition, some anti–COVID-19 agents may cause thyroid injury or affect its metabolism. COVID-19 and thyroid disease may mutually aggravate the disease burden. Patients with SARS-CoV-2 infection should not ignore the effect on thyroid function, especially when there are obvious related symptoms. In addition, patients with thyroid diseases should follow specific management principles during the epidemic period.


2020 ◽  
Vol 9 (5) ◽  
pp. 1297 ◽  
Author(s):  
Robin N. Thompson ◽  
Francesca A. Lovell-Read ◽  
Uri Obolski

Interventions targeting symptomatic hosts and their contacts were successful in bringing the 2003 SARS pandemic under control. In contrast, the COVID-19 pandemic has been harder to contain, partly because of its wide spectrum of symptoms in infectious hosts. Current evidence suggests that individuals can transmit the novel coronavirus while displaying few symptoms. Here, we show that the proportion of infections arising from hosts with few symptoms at the start of an outbreak can, in combination with the basic reproduction number, indicate whether or not interventions targeting symptomatic hosts are likely to be effective. However, as an outbreak continues, the proportion of infections arising from hosts with few symptoms changes in response to control measures. A high proportion of infections from hosts with few symptoms after the initial stages of an outbreak is only problematic if the rate of new infections remains high. Otherwise, it can simply indicate that symptomatic transmissions are being prevented successfully. This should be considered when interpreting estimates of the extent of transmission from hosts with few COVID-19 symptoms.


2021 ◽  
Vol 8 ◽  
Author(s):  
Setare Kheyrandish ◽  
Amirhossein Rastgar ◽  
Morteza Arab-Zozani ◽  
Gholamreza Anani Sarab

Background and Objective: Infection by the novel coronavirus disease 2019 (COVID-19) has been associated with different types of thrombotic complications same as portal vein thrombosis (PVT). However, by emerging vaccines of COVID, the thrombosis did not seem to be concerning anymore. Until new findings showed that, the vaccine of COVID itself can cause PVT.Method: We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the possibility of occurring PVT due to infection and vaccination of COVID-19. The results were reported in a narrative method and categorized into tables.Result: Overall, 40 cases of PVT from 34 studies were reviewed in this article. The prevalence of PVT following COVID-19 was more remarkable in males. However, it was more common in females after vaccinations of COVID-19 in the reviewed cases. Regardless of etiology, 20 of PVT cases reviewed in this article had at least one comorbidity. The most common clinical presentation was abdominal pain (AP). After anticoagulant therapies, most of the patients improved or discharged.Conclusion: As long as the laboratory findings are not appropriate enough to predict PVT, the diagnosis of this complication with whatever underlying reason is challengeable, while rapid diagnosis and treatment of that are vital. Therefore, by providing available data in an organized way, we aimed to prepare the information of infected patients for better and easier future diagnosis of PVT in new cases.


2021 ◽  
pp. 38-42
Author(s):  
Charles Haddad ◽  
Christopher Scuderi ◽  
Judelle Haddad-Lacle ◽  
Reetu Grewal ◽  
Jeffrey Jacqmein ◽  
...  

The world as we knew it changed at the beginning of 2020 with the explosion of the global pandemic caused by SARS-CoV-2, a.k.a. COVID-19. As of January 10, 2021, the novel coronavirus has infected over 89 million people worldwide and killed over 1.9 million. In the U.S., there have been 22 million people infected and 373,000 deaths. It has never been more important to protect our vulnerable patients and staff from infectious disease, especially during the time they spend in our offices and clinics. It quickly became apparent that there was a need for a dedicated location where patients could be seen that were too ill to be evaluated via telemedicine, but not ill enough to be sent to the Emergency Department (ED). To fill this need, our primary care network developed the Respiratory Evaluation Clinic (REC) concept. These were two geographical locations where the outlying clinics could send potentially infectious patients to evaluate and test COVID-19. Some recommendations, adaptations, lessons learned and the REC clinics' expansions to other locations throughout our network are discussed.


Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 41
Author(s):  
Nourhan Hisham Shady ◽  
Khayrya A. Youssif ◽  
Ahmed M. Sayed ◽  
Lassaad Belbahri ◽  
Tomasz Oszako ◽  
...  

The acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) caused severe panic all over the world. The coronavirus (COVID-19) outbreak has already brought massive human suffering and major economic disruption and unfortunately, there is no specific treatment for COVID-19 so far. Herbal medicines and purified natural products can provide a rich resource for novel antiviral drugs. Therefore, in this review, we focused on the sterols and triterpenes as potential candidates derived from natural sources with well-reported in vitro efficacy against numerous types of viruses. Moreover, we compiled from these reviewed compounds a library of 162 sterols and triterpenes that was subjected to a computer-aided virtual screening against the active sites of the recently reported SARS-CoV-2 protein targets. Interestingly, the results suggested some compounds as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics.


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