Fisiopatología de la enfermedad COVID-19 / Pathophysiology of COVID-19 / Fisiopatologia da doença COVID-19

La enfermedad por coronavirus es una infección respiratoria causada por el virus SARS-CoV 2, el cual genera una cascada de eventos sistémicos, afectando diferentes órganos y tejidos. El entendimiento de la fisiopatología del COVID-19 es indispensable no solo al momento de brindar tratamiento a los pacientes, sino que también para comprender las causas de las complicaciones que presentan un número importante de pacientes recuperados. El objetivo de este trabajo es presentar una revisión actualizada de los efectos de la infección en diferentes órganos y sistemas principales que sea de utilidad como material de referencia para profesionales y estudiantes de la salud. Para ello se realizó una búsqueda bibliográfica en los portales PubMED, Scielo, Google Scholar, Cochrane y Springer Link, así como en las bases de repositorios científicos pre-publicación bioRxiv ("bioarchives") y medRxiv ("med-archives") y sobre un total de cerca de 200 mil artículos, se seleccionaron 100 artículos para esta revisión en base a su relevancia o sugerencias de parte de profesionales especializados.

Coronavirus disease is a respiratory infection caused by the SARS-CoV-2 virus, which causes a cascade of systemic events, affecting various organs and tissues. Understanding the pathophysiology of COVID-19 is essential to treat patients and understand the causes of the complications in a significant number of recovered patients. This article presents a review of the effects of infection on various organs and systems that will be useful as reference material for healthcare professionals and medical students. To this end, a literature search was conducted in PubMED, Scielo, Google Scholar, Cochrane, and Springer Link portals, as well as in the pre-publication scientific repositories bioRxiv ("bioarchives") and medRxiv ("med-archives") databases. From about 200,000 papers, 100 articles were selected for this review based on their relevance or suggestions from experts in the field.

A doença coronavírus é uma infecção respiratória causada pelo vírus SARS-CoV-2, que gera uma cascata de eventos sistêmicos, afetando diferentes órgãos e tecidos. Compreender a fisiopatologia da COVID-19 é essencial não apenas no tratamento de pacientes, mas também para compreender as causas das complicações que um número significativo de pacientes recuperados apresenta. O objetivo deste trabalho é apresentar uma revisão atualizada dos efeitos da infecção em diferentes órgãos e principais sistemas que seja útil como material de referência para profissionais de saúde e estudantes. Para isso, foi realizada uma pesquisa bibliográfica nos portais PubMED, Scielo, Google Scholar, Cochrane e Springer Link, bem como nos repositórios científicos de pré-publicação bioRxiv ("bioarquivos") e medRxiv ("arquivos med"). Num total de cerca de 200 mil artigos, 100 artigos foram selecionados para esta revisão por sua relevância ou sugestões de profissionais especializados.

Relationship between Oral Hypofunction, and Protein Intake: A Cross-Sectional Study in Local Community-Dwelling Adults.

Few studies have investigated the relationship between nutritional status and comprehensive assessment of oral hypofunction, especially protein intake-related sarcopenia. Thus, we explored these relationships in a large-scale cross-sectional cohort study using the seven-item evaluation for oral hypofunction and Diet History Questionnaire for nutritional assessment. We used the data from 1004 individuals who participated in the 2019 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan for analysis. We found that individuals with oral hypofunction were significantly older with a lower skeletal muscle index. Although there were few foods that had a significant difference between the groups with and without oral hypofunction, the consumption of beans and meats was significantly lower in women and men in the oral hypofunction group, respectively. According to the lower limit of the tentative dietary goal defined in Japan, comprehensive evaluation of oral hypofunction was significantly and independently associated with protein intake in both men and women (odds ratio, 1.70; 95% confidence interval, 1.21-2.35). In conclusion, we found that oral hypofunction was associated with targeted protein intake for sarcopenia and frailty prevention in middle-aged and older community-dwelling adults. Comprehensive evaluation of oral function with intervention in cases of hypofunction could inform clinicians to better prevent sarcopenia.

Association between Oral Frailty and Dietary Variety among Community-Dwelling Older Persons: A Cross-Sectional Study.

OBJECTIVE: To examine the association between the severity of oral frailty (OF), which is one of the comprehensive oral functions evaluated, and dietary variety in community-dwelling older persons. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: A total of 769 community-dwelling older persons aged 65 and over. INTERVENTIONS: We examined basic demographic information, functional status, cognitive status, depressive symptoms, medical history, and oral functions of the participants. MEASUREMENTS: OF was defined by 1-2 and 3 or more of 6 items of oral function evaluation in the pre-oral frailty and oral frailty groups, respectively. Dietary variety was assessed using the dietary variety score (DVS). The participants were categorized into 3 groups for evaluation: those with a low score (0-2), medium score (3-5), and high score (≥6). Ordinal logistic regression analysis was performed to examine the association between OF and DVS. RESULTS: The rate of OF in the participants was 21.6%, and its severity was significantly associated with DVS after adjusting for potential confounders (Pre-OF; adjusted odds ratio [OR] = 1.687, 95% confidence interval [CI] = 1.219-2.335, OF; adjusted OR = 2.857, 95% CI = 1.489-5.484). CONCLUSION: The severity of OF was significantly associated with DVS in community-dwelling older persons. This suggests that DVS may be useful in understanding the effects of OF on the nutritional status. Further longitudinal studies are needed to elucidate the association between OF and DVS.

Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease.

Human oral soft tissues provide the first barrier of defence against chronic inflammatory disease and hold a remarkable scarless wounding phenotype. Tissue homeostasis requires coordinated actions of epithelial, mesenchymal, and immune cells. However, the extent of heterogeneity within the human oral mucosa and how tissue cell types are affected during the course of disease progression is unknown. Using single-cell transcriptome profiling we reveal a striking remodelling of the epithelial and mesenchymal niches with a decrease in functional populations that are linked to the aetiology of the disease. Analysis of ligand-receptor interaction pairs identify potential intercellular hubs driving the inflammatory component of the disease. Our work establishes a reference map of the human oral mucosa in health and disease, and a framework for the development of new therapeutic strategies.

Oro-facial fibrosis in systemic sclerosis: a reconstructive journey.

Oro-facial fibrosis presents a significant disease burden in patients with systemic sclerosis, but there remains no established treatment modality. Autologous fat grafting is a minimally invasive surgical procedure that is now increasingly recognised for its regenerative capacity, propagating an expansion of heterogeneous indications beyond volume restoration, including fibrotic diseases such as systemic sclerosis. We present a 42-year-old woman with oro-facial involvement of systemic sclerosis leading to severe limitation in mouth opening and closure, with marked retraction of the lower lip and gingival display. We describe the reconstructive journey over a 12-year period, where the antifibrotic effect of autologous fat grafting served as the basis on which a series of surgical procedures were performed to achieve functional and aesthetic improvement. Autologous fat grafting provides a novel treatment modality for oro-facial skin fibrosis, previously considered a non-treatable disease manifestation of systemic sclerosis.

Associations of Food-Chewing Discomfort with Health Behaviors and Cognitive and Physical Health Using Pooled Data from the Korean Health Panel (2010-2013).

Using 4 years of pooled data from the Korean Health Panel (2010-2013), the prevalence of food-chewing discomfort in adults over the age of 19 was investigated and the cross-sectional relationship between food-chewing discomfort and health behaviors and cognitive and physical health was identified. The prevalence of food-chewing discomfort was 31%: young adults (<40 years), 17.9%; middle-aged adults (40-64 years), 28.9%; and older adults (≥65 years), 57.1% (p < 0.0001). When food-chewing discomfort was sometimes, often, or always rather than never, odds ratios (ORs) were analyzed after controlling for sociodemographic characteristics. Significant OR results of target variables were smoking (OR 1.15, 1.37, 1.50), drinking (1.08, 0.87, 0.73), problem drinking (1.87, 1.67, 1.34), abstinence from drinking (1.23, 1.34, 1.42), nonphysical activity (OR 0.87 only significant, 0.94 nonsignificant, 1.10 nonsignificant), memory decline (2.07, 2.56, 3.31), decision-making difficulty (1.76, 2.78, 4.37), limitation of daily life due to illness (2.29, 3.60, 3.92), and the presence of a chronic disease (1.28, 1.62, 1.73), respectively. In conclusion, there were associations of food-chewing discomfort with increased smoking and decreased alcohol consumption, with increased difficulty in decision-making and memory decline, limitations in daily life due to disease, and the presence of chronic diseases. Therefore, it is necessary to investigate the causal relationship between chewing and health behaviors and cognitive and physical health through longitudinal studies.

Where are oral and dental adverse drug effects in product information?

OBJECTIVES: Oral adverse drug reactions are common and are associated with some of our most frequently used medicines. It is important to identify and manage oral adverse drug effects promptly as they not only negatively impact dental health, but also adversely affect medication adherence, clinical outcomes and patient quality of life. This study assessed the location of oral drug-induced adverse effects in the registered drug company product information (PI) of the top 100 most commonly used drugs in Australia as dispensed on the Pharmaceutical Benefits Scheme in 2018. METHOD: Publicly available data on dispensed medicines were accessed from the Australian Commonwealth Department of Health, to determine the top 100 medicines. The drug company PI for each of these drugs was manually searched to find their oral adverse effects. The number, type and location of the oral adverse drug reactions (ADRs) were recorded. KEY FINDINGS: Oral ADRs were commonly found varying in nature and severity. However, they were difficult to find as there is no dedicated section for oral/dental adverse effects in the PI and the section they are in is inconsistently applied. CONCLUSIONS: We recommend that regulatory authorities such as the Therapeutic Goods Administration in Australia create an additional section for oral/dental adverse effects so they are easier to find, which may assist health professionals detect recognise and report adverse drug effects manifesting in the oral cavity.

[Physiological and pathological effects of nitric oxide and nitric oxide synthase in oral cavity].

Nitric oxide (NO) is a short-lived free radical which is not only involved in regulating many physiological processes of the body, but also closely related to many diseases. Nitric oxide synthase (NOS) is the key enzyme for NO production. NOS exists as three distinct isoforms, the endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS). It has been found that nNOS and eNOS were expressed in normal pulp tissues, periodontal tissues and salivary glands, and the NO produced from nNOS and eNOS was involved in their physiological functions. NO and iNOS are involved in the occurrence and development of pulpitis, periodontitis, salivary gland disease and oral cancer. This review focuses on the physiological and pathological effects of NO and different subtypes of NOS in oral cavity.

Oropharyngeal freezing and its relation to dysphagia - An analogy to freezing of gait.

INTRODUCTION: The pathophysiology of dysphagia in Parkinson's disease (PD) is heterogeneous and poorly understood at present. This study investigated the phenotypes, prevalence and pathophysiology of oropharyngeal freezing (OPF) in PD and its relation to dysphagia. METHODS: In a prospective study, 50 PD patients were systematically screened for OPF using flexible endoscopic evaluation of swallowing (FEES). In addition, FEES-videos of 50 patients with post-stroke dysphagia and 50 healthy subjects were retrospectively evaluated as control groups. In PD patients freezing was assessed with the "freezing of gait (FoG) questionnaire" and the relationship between OPF and FoG was analyzed. RESULTS: In analogy to FoG, signs for OPF presented as either temporarily missing or delayed swallowing reflex in combination with freezing associated movement abnormalities e.g. festination, trembling, or akinesia. Seventeen PD patients (34%) showed considerable signs for OPF (15 cases of festination, 3 cases of trembling, 3 cases of akinesia). In the patients with post-stroke dysphagia, OPF was detected in 2 patients (4%). The healthy subjects showed no signs for OPF. The distribution of OPF differed significantly between the investigated groups (p < 0.01). PD patients with signs for OPF scored significantly higher in the FoG-questionnaire (12.69 ± 6.37) compared to patients without OPF (7.29 ± 5.17; p < 0.01). CONCLUSION: Swallowing in PD patients can be impaired by OPF. We suggest that OPF and FoG share common pathophysiologic mechanisms based on their association and similar semiologies.

Oral Health: The First Step to Well-Being.

Scientific research in the medical field shows this constantly: health starts from the mouth. Having good oral health nowadays is not only aimed at tooth health, but as amply demonstrated in the literature, it is a starting point for the general health and well-being of our body. Retracing the latest scientific findings that demonstrate an interpolation between oral health, oral diseases, and systemic complications, literature support was brought to this manuscript. Oral health, as demonstrated, has potentially multi-organ systemic implications, and as the results of the recent literature demonstrate, these implications range from an insulin resistance, due to a periodontal disease, up to far more complex multi-organ systemic complications involving the cardiovascular system or even neurodegenerative pathology. Therefore, being able to improve oral health could have great systemic implications for the organism, for the prevention of pathologies, and therefore for society and for the quality of life in individuals.

Recognizing Poor Sleep Quality Factors During Oral Health Evaluations.

Oral health practitioners routinely perform oral health assessments for the dental patient to determine if oral disease is present. Systemic health is often a contributor to oral health concerns. One area in particular that has a direct effect on oral structures and oral health is poor sleep quality and open mouth breathing. Sleep is a fundamental process of the human body, which regulates core biological functions. Sleep quality reflects a person's ability to fall asleep, stay asleep, and enter into the various rejuvenating sleep cycles for the full duration. A person who does not obtain quality sleep can exhibit a wide range of oral, systemic, and cognitive health problems. Obstructive sleep apnea, which historically has been considered an adult male disease, is being recognized more often in women children. Research suggests various oral malformations found in newborns and young children can manifest as obstructive sleep apnea in adults. Oral health professionals are in a position to recognize the relationship between sleep and health, identify sleep quality concerns in relation to oral health assessments, administer sleep quality assessments, and determine appropriate referrals for further sleep quality evaluation.

Dental appliance therapy in pantothenate kinase-associated neurodegeneration: Case report.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare condition associated with severe protrusive lingual dystonia, a form of oromandibular dystonia. Dental appliance therapy has been described for oromandibular dystonia however there is a lack of literature regarding its application specifically to PKAN. In this report, the authors describe the use of an appliance in conjunction with botulinum toxin injections for the symptomatic treatment of this condition. A satisfactory outcome is achieved which suggests this technique may be of use to other clinicians.

Vertical contact tightness of occlusion comparison between orofacial myalgia patients and asymptomatic controls: a pilot study.

OBJECTIVE: The association between occlusal contact and orofacial pain remains unclear. The aim of this study was to detect occlusal contact tightness by using a new method and to compare differences between patients and asymptomatic controls. METHODS: Fifteen female patients with orofacial myalgia and fifteen age- and sex-matched asymptomatic controls were enrolled. Occlusal contacts were recorded by making bite imprints. The numbers, sizes, and distributions of the contacts were detected by making photos of bite imprints after biting. The Mann-Whitney U test and ANOVA were used for statistical analysis. RESULTS: In myalgia patients, impact contacts at the molar regions were more frequent, larger in number and area size, and were distributed more on guiding cusps, compared with impact contacts in asymptomatic controls. CONCLUSION: Our new method revealed more prevalent and more severe impact contacts in orofacial myalgia patients, compared with asymptomatic controls.

Association between poor oral health and gastric cancer: A prospective cohort study.

Poor oral health may be involved in the pathogenesis of gastric cancer, however, some aspects have not been explored. Further, for previously studied aspects, for example, tooth-loss, the findings are inconsistent. We conducted a prospective cohort study of 19,831 participants from Uppsala, Sweden, cancer-free at baseline in 1973-1974 and followed until 2012 through linkage to national registers. We found that individuals with fewest teeth at baseline had an increased risk of gastric cancer relative to subjects with all examined teeth present (p = 1.75e-2). Presence of denture-associated lesions was also associated with an increased risk of gastric cancer (p = 1.00e-4). However, these excess risks significantly varied with attained age; estimated hazard ratio (HR) at attained age 50 for tooth loss was 4.24 [95% confidence interval (CI) 1.83-9.80] and 5.91 (95% CI 2.76-12.63) for denture-associated lesions, decreasing at an estimated 4% and 6% per year respectively, resulting in HR of 1.54 (95% CI 0.90-2.64) for tooth loss and HR 1.29 (95% CI 0.90-1.85) for denture-associated lesions at attained age 75. No increased risk of gastric cancer was found for individuals with higher levels of dental plaque, or with Candida-related or tongue lesions. In conclusion, tooth-loss and denture-associated lesions are associated with increased risks of gastric cancer. Previous conflicting findings of tooth-loss and gastric cancer risk may partly be explained by the age-varying relative risk of gastric cancer.

Effect of probiotic lozenges containing Lactobacillus reuteri on oral wound healing: a pilot study.

It has been suggested that beneficial bacteria may stimulate wound healing. The aim was to investigate the effect of topical applications of probiotic lactobacilli on the healing of standardised oral wounds. This pilot study employed a randomised, placebo-controlled, double-blind cross-over design. Standardised biopsies were punched in the oral mucosa of 10 healthy volunteers, with and without exposure to two strains of Lactobacilli reuteri administrated as lozenges and topical oil. The healing was scored clinically after 2, 5 and 8 days. The amount of exudate was quantified through filter papers and the levels of selected cytokines and chemokines were determined with multiplex immunoassays. Saliva samples were collected before the biopsy and after healing for determination of oxytocin with ELISA. Subjectively perceived pain and discomfort was reported through a daily logbook. There was a clear tendency of improved healing in test group at the 2-and 5-day check-ups but the difference compared with the placebo intervention was not statistically significant (P=0.08). Higher but non-significant expressions of the tumour necrosis factor (TNF) superfamily ligand members 13 (APRIL) and 13B (BAFF), as well as the chemokine interleukin 8 (IL-8), were displayed in wound exudates from the probiotic group as compared with placebo, particularly after 5 and 8 days. The salivary levels of oxytocin were significantly lower (P<0.05) in the placebo group at the 8-day follow-up. The mean number of days with pain and/or discomfort after the biopsies was similar in both groups. No side-effects were reported. The findings of this pilot study justify a larger clinical trial to elucidate the possible role of probiotic supplements on oral wound healing.

Oral manifestations of autoinflammatory and autoimmune diseases.

Autoimmune diseases may also be reflected in changes in the oral cavity that represent the first sign of the disease, or they may occur simultaneously with or later in the course of the disease. Oral findings are mostly non-specific, and therefore further investigations are needed to exclude or confirm possible diagnoses. This article presents the most important diseases in this research area, divides them into meaningful groups, and highlights the importance of examining the oral cavity for possible manifestations.

Oral health-related quality of life of Portuguese adults with mild intellectual disabilities.

Individuals with disabilities are regarded as a highly vulnerable population group, particularly as far as oral health is concern. However, few studies have assessed the impact of the oral condition on the quality of life of these individuals. Therefore, the aim of this study is to expand knowledge on the oral health status of the Portuguese adults with mild intellectual disability, and to assess how the patient's oral health is related to their quality of life. A sample of 240 adults with mild intellectual disabilities linked to the Portuguese Federation for Intellectual Disability, were interviewed using a previously validated version of the Oral Health Impact Profile. An oral health examination was also conducted using three oral health indexes: Clinical Oral Health Index (COHI); Clinical Oral Care Needs Index (COCNI) and the Clinical Oral Prevention Index (COPI). Sociodemographic characteristics and dental health factors were also collected, following statistical analysis. More than half of the individuals (54,9%) presented one or more problems of major to severe impact on health (COHI level 2); only 4,6% of the individuals do not need treatment or examination (COCNI level 0) and 85% of the study sample needs measures of educational or preventive action (COPI level 1). In 76,9% of the participants, oral health had impact on the quality of life. The most affected dimensions of life were physical pain with 61,9%, followed by psychological discomfort and psychological disability with 45,1% and 45%, respectively. With relation to oral health factors and sociodemographic variables it was verified that fewer teeth and higher self-perception of need for dental treatment had a negative impact on the quality of life. On the other hand, institutionalization and an increase in at least one category in the self-perception of the oral health status had a positive impact on the quality of life. Given the high burden of oral disease and the considerable impact on quality of life found in this study, the establishment of guidelines to improve the oral health and quality of life of these individuals should be regarded as imperative.

Improved Wound Remodeling Correlates with Modulated TGF-beta Expression in Skin Diabetic Wounds Following Combined Red and Infrared Photobiomodulation Treatments.

Diabetic wounds are a major cause of morbidity among patients with poorly controlled blood glucose levels. Conventional empirical wound care strategies have shown limited efficacy, and there is an urgent need to develop novel therapeutic strategies. Photobiomodulation treatments have shown positive therapeutic effects in several cell culture and animal models. In this study, we examined wound healing in diabetic rats following treatments with two laser wavelengths, namely red (660 nm) and infrared (808 nm) individually and in combination as compared to routine wound dressings. Immunostaining for TGF-ß expression was performed at various times postwounding. We noted that the combination of red and infrared laser treatments correlated with decreased TGF-ß1 levels at late stages in healing. There was no statistical significance with any treatments at an earlier time point. This study emphasizes the role of appropriate laser treatment protocols in modulating wound healing and remodeling responses.

Oral lichen sclerosus: a systematic review of reported cases and two new cases.

Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous disease with uncertain etiology. It occurs as white plaque-like lesions mostly in the anogenital skin. Oral mucosal involvement is extremely rare. This study aims to summarize the features of published oral lichen sclerosus (OLS) and two new cases. A systematic search of the English literature from 1955 to 2016 was performed in MEDLINE, Scopus, and Web of Science, and cross-references were searched manually. Search phrases included "lichen sclerosus," "mouth," "oral," "lip," "palate," "floor of mouth," "tongue," "gingiva," "buccal mucosa," and "mouth diseases." Cases with clinical and histopathological confirmation of diagnosis of OLS were included. A total of 41 (39 published and 2 new) histologically confirmed OLS cases were available. The median age of OLS patients was 31 years, and 66% of the patients were female. Most of the OLS lesions were asymptomatic. They were located in the labial mucosa (n = 20), lip (n = 15), buccal mucosa (n = 14), gingiva (n = 12), tongue (n = 12), and palate (n = 7). OLS is rare and typically presents as asymptomatic, white, plaque-like lesions. Malignant transformation of preexisting OLS has not been reported.

A Force on the Crown and Tug of War in the Periodontal Complex.

The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone and PDL-cementum. Physiologic and pathologic loads on the dentoalveolar fibrous joint prompt natural shifts in strain gradients within mineralized and fibrous tissues and trigger a cascade of biochemical events within the widened and narrowed sites of the periodontal complex. This review highlights data from in situ biomechanical simulations that provide tooth movements relative to the alveolar socket. The methods and subsequent results provide a reasonable approximation of strain-regulated biochemical events resulting in mesial mineral formation and distal resorption events within microanatomical regions at the ligament-tethered/enthesial ends. These biochemical events, including expressions of biglycan, decorin, chondroitin sulfated neuroglial 2, osteopontin, and bone sialoprotein and localization of various hypertrophic progenitors, are observed at the alkaline phosphatase-positive widened site, resulting in mineral formation and osteoid/cementoid layers. On the narrowed side, tartrate-resistant acid phosphatase regions can lead to a sequence of clastic activities resulting in resorption pits in bone and cementum. These strain-regulated biochemical and subsequently biomineralization events in the load-bearing periodontal complex are critical for maintenance of the periodontal space and overall macroscale joint biomechanics.