Long COVID: tackling a multifaceted condition requires a multidisciplinary approach.
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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: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.
| S-EPMC8228528 | biostudies-literature
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: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.
| S-EPMC7427749 | biostudies-literature
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.
| S-EPMC10393894 | biostudies-literature
Project description: Not available
| S-EPMC8765823 | biostudies-literature
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.
| S-EPMC7180380 | biostudies-literature
Project description:BackgroundShort-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped.MethodsWe evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status.FindingsEighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients.InterpretationOverall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.
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Project description:Myocarditis lacks systematic characterization in COVID-19 patients. We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up. Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients (n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients (n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses (n = 2) or virus-negative (n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation. Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.
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Project description:After COVID-19 initial diffusion in Europe in March 2020, research has suggested a direct correlation between environmental pollution and contagion dynamics (i.e., environment-to-human pollution), thereby indicating that mechanisms other than human-to-human transmission can explain COVID-19 diffusion. However, these studies did not consider that complex outcomes, such as a pandemic's diffusion patterns, are typically caused by a multiplicity of environmental, economic and social factors. While disciplinary specialties increase scholars' attitudes of concentrating on specific factors, neglecting this multiplicity during a pandemic crisis can lead to misleading conclusions. This communication aims to focus on certain limitations of current research about environmental-to-human COVID-19 transmission and shows the benefit of an interdisciplinary, multi-dimensional approach to understand the geographical diversity of contagion diffusion patterns.
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