Long COVID: tackling a multifaceted condition requires a multidisciplinary approach.
Ontology highlight
ABSTRACT:
SUBMITTER: Norton A
PROVIDER: S-EPMC7906694 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:The leafhopper genus Arboridia includes several species that feed on Vitis vinifera and cause leaf chlorosis. We report the first alien Arboridia infestation in Italy in 2021 in an Apulian vineyard. To confirm the taxonomic status of the species responsible for crop damage, and reconstruct its demographic history, we barcoded individuals from Apulia together with Arboridia spp. from Crete (Greece), A. adanae from Central Turkey and other specimens of the presumed sister species, A. dalmatina from Dalmatia (Croatia). Molecular phylogenies and barcoding gap analysis identified clades not associated with sampling locations. This result is incongruent with classical specimen assignment and is further supported by morphological analyses, which did not reveal significant differences among the populations. Therefore, we propose A. dalmatina as a junior synonym of A. adanae, which would become the only grapevine-related Arboridia species in the eastern Mediterranean. To further characterise A. adanae evolution, we performed a molecular clock analysis that suggested a radiation during the Pleistocene glaciations. Finally, to assess whether the Apulian individuals carried microorganisms of agricultural relevance, we sequenced their bacterial microbiota using 16S rRNA amplicon sequencing identifying three phytopathogens not generally associated with Arboridia activities as well as Wolbachia in one Apulian haplogroup. We discuss the agricultural implications of this infestation.
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Project description:Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.
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Project description:The rapidly expanding cases of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have exposed vulnerable populations, including pregnant women to an unprecedented public health crisis. Recent data show that pregnancy in COVID-19 patients is associated with increased hospitalization, admission of the intensive care unit, and intubation. However, very few resources exist to guide the multidisciplinary team in managing critically ill pregnant women with COVID-19. We report our experience with managing a morbidly obese pregnant woman at 36 weeks' gestation with history of asthma and malignancy who presented with persistent respiratory symptoms at an outside hospital after being tested positive for SARS-CoV-2 polymerase chain reaction (PCR). Early in the course of the hospitalization, patient received remdesivir, convalescent plasma, bronchodilator, systemic steroids, and IV heparin for COVID-19 and concomitant asthma exacerbation and pulmonary embolism. Due to increasing oxygen requirements, she was eventually intubated and transferred to our institution for higher level of care. Respiratory acidosis, severe hypoxemia, and vent asynchrony were managed with vent setting adjustment and paralytics. After 12 hours from spontaneous rupture of her membranes and with stabilization of maternal status, patient underwent a term cesarean delivery for nonreassuring fetal heart tracing. The neonate was discharged on the 2nd day of life, while the patient was extubated on the 6th postpartum day and was discharged to acute inpatient rehabilitation facility on the 19th hospital day. This report highlights the disease progression of COVID-19 in a pregnant woman, the clinical challenges in the critical care aspect of patient management, and the proposed multidisciplinary strategies utilizing an algorithmic approach to optimize maternal and neonatal outcomes.
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Project description:BackgroundAs modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care.MethodsWe describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy.ResultsThere were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient's recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs.ConclusionsThrough a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.
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Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is causing a global pandemic had a zoonotic origin in China. Considering the inter-connectedness between human, environment, and animal health, the One Health approach is the appropriate strategy to control and mitigate the effects of the ongoing coronavirus disease 2019 (COVID-19). This letter explains the benefits of the One Health approach and recommends specific measures that could be taken to accelerate the fight against COVID-19 and prevent the spread of newly emerging infectious diseases.
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Project description:BackgroundPost-COronaVIrus Disease 2019 (COVID-19) conditions (PCC) include multiple symptoms afflicting different organs and systems. To evaluate the frequency and type of them, we described our multidisciplinary approach with preliminary results of the first enrolled patients.MethodsWe included patients aged ≥ 18 years with hospital admission for confirmed SARS-CoV-2 infection. Symptoms were grouped in five macro groups hereafter referred to as "Symptoms Category" (SC): respiratory SC (dyspnoea or cough), neurological SC (peripheral neuropathies, headache, impaired mobility, behavioural disorders), psychological SC (sleep disorders, mood disorders), muscular SC (arthromyalgia, asthenia), other SC (fever, alopecia, diarrhoea, weight loss, smell and taste alterations, sexual dysfunctions). SC were evaluated at discharge and at follow-up. Association between patients' characteristics and presence of SC at follow up was estimated by a logistic multivariable regression model.ResultsFrom June 2020 to July 2021, we followed up 361 patients: 128 (35.5%) who were previously admitted to Intensive Care Unit (ICU) and 233 patients to ordinary department. The median length of hospital stay was 20 days (Inter-Quartile-Range 13-32). Most patients (317/361, 87.8%) were still symptomatic at discharge, with one third referring three or more SC. At follow up, 67.3% (243/361) of patients still complained at least one SC. Moreover, 159 patients (44%) developed at least one new involved SC during follow up: 116 (72.9%) one SC, 39 (24.5%) two SC, 4 (2.5%) three or more SC. At follow up visit 130 of 361 (36%) were still with SC developed during follow up. At multivariable analysis presence of any SC at follow-up was associated with male gender (Odds Ratio [OR] 3.23, Confidence Interval [CI] 95% 1.46-7.15), ICU admission (OR 2.78, CI 95% 1.29-5.96) and presence of SC at discharge (OR 14.39, CI 95% 6.41-32.32).ConclusionsIn our sample of patients with severe COVID-19, we found that PCC are highly variable and fluctuating over time; in particular, in about 50% of our patients new SC appear during follow up. Moreover, presence of PCC also in patients without SC at discharge and the variability of symptoms underlining the advisability of our multidisciplinary approach.Trial registration numberClinicalTrials.gov Identifier: NCT04424992, registered on 28 February 2020 https://www.Clinicaltrialsgov/ct2/results?recrs=ab&cond=&term=NCT04424992&cntry=&state=&city=&dist The current version of protocol is version 1.0 enrolling since June 2020. The enrollment is still ongoing.
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Project description:After the initial outbreak of the SARS-CoV-2 epidemic (now called COVID-19)-in Wuhan, China-and its subsequent fast dispersion throughout the world, many questions regarding its pathogenesis, genetic evolution, prevention, and transmission routes remain unanswered but fast explored. More than 100,000 confirmed, infected cases within a relatively short period of time globally corroborated the presumption that a pandemic will develop; such a pandemic will require a suite of global intervention measures. Consequently, different countries have reacted differently to the COVID-19 outbreak, but a uniform global response is necessary for tackling the pandemic. Managing the present or future COVID-19 outbreaks is not impossible but surely difficult. Barring the live-animal trade at the markets; revising the regulations and rules of customs, import or export across borders; supporting and expediting projects to develop vaccines and antiviral drugs; immediate quarantine of the involved regions; and also producing and supplying a large number of protective facemasks and preventing its stockpiling or smuggling are the main actions suggested to deal with the present or a forthcoming COVID-19 outbreaks. Increasing numbers of infected cases had heightened concerns about the public health and welfare. Thus, preparing for the next probable pandemic of COVID-19 demands scrutinization of the lessons we have learnt so far.
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