Gotowa bibliografia na temat „SARS-CoV-2 – physiopathologie”

L’émergence récente d’un nouveau coronavirus, le SARS-CoV-2, responsable de la maladie appelée COVID-19, est un nouvel avertissement du risque pour la santé publique représenté par les zoonoses virales et notamment par les coronavirus. Principalement connus pour leur capacité à infecter les voies respiratoires supérieures et inférieures, les coronavirus peuvent également affecter le système nerveux central et périphérique, comme c’est le cas pour de nombreux virus respiratoires, tels que les virus influenza ou le virus respiratoire syncytial. Les infections du système nerveux sont un problème important de santé publique car elles peuvent provoquer des atteintes dévastatrices allant jusqu’au décès du patient, en particulier lorsqu’elles surviennent chez les personnes fragilisées ou âgées plus sensibles à ce type d’infection. Les connaissances de la physiopathologie des infections par les coronavirus émergents (MERS-CoV, SARS-CoV et SARS-CoV-2) et leurs moyens d’accéder au système nerveux central sont, pour l’heure, très sommaires. Les travaux en cours visent notamment à mieux appréhender les mécanismes associés aux atteintes neurologiques observées. Dans cette revue nous aborderons l’état des connaissances actuelles sur le neurotropisme des coronavirus humains et les mécanismes associés en développant tout particulièrement les dernières données concernant le SARS-CoV-2.

L’infection COVID-19 a émergé de façon soudaine en Chine, en décembre 2019 et est devenue rapidement pandémique. Le virus responsable a été identifié comme un nouveau coronavirus probablement issu d’un virus de chauve-souris, dénommé SARS-CoV-2, ce qui a permis de mettre au point des tests diagnostiques permettant l’identification de son ARN par techniques moléculaires. En plus du rappel de quelques données virologiques, l’objet de cette revue est de présenter les tests moléculaires de diagnostic direct et les tests sérologiques actuellement disponibles pour identifier cette infection. Le diagnostic repose principalement sur la détection du génome viral par RT-PCR en temps réel dans les sécrétions respiratoires (prélèvements nasopharyngés à la phase précoce et prélèvements respiratoires profonds au stade de pneumonie) ; les résultats sont disponibles dans un délai d’environ 4 heures. Le pic de l’infectiosité se situe entre le 3e jour avant et le 3e après le début des symptômes. Le virus peut également être détecté dans le sang et dans les selles, même si, à ce jour, l’infectiosité du virus dans ces prélèvements n’est pas avérée. A un stade plus tardif de l’infection, une réponse humorale anti-SARS-CoV-2 peut être mise en évidence, avec des anticorps de classes IgM et IgA à partir du 8 ou 9e jour après le début des symptômes, puis des anticorps de classe IgG qui signent un contact antérieur avec cet agent. L’apparition des anticorps peut se faire très tardivement dans les formes pauci- ou asymptomatiques. De nombreuses questions sont encore non résolues, notamment en ce qui concerne le caractère protecteur de cette réponse humorale et sa durée, ainsi que son rôle dans la physiopathologie des formes sévères.

L’odorat, sens pendant longtemps sous-estimé chez l’homme, a été mis sur le devant de la scène par sa soudaine disparition, survenue pendant la pandémie de Covid-19, dont l’anosmie est un des symptômes majeurs. Pourtant, depuis longtemps, les virus respiratoires ont été associés aux troubles de l’odorat, dont 25 % seraient liés à une infection virale. L’olfaction débute dans le nez, au sein d’un épithélium olfactif qui a la particularité de contenir des neurones en contact direct avec l’environnement. Plusieurs virus respiratoires sont connus pour leur capacité réplicative au sein de cet épithélium. C’est notamment le cas du virus de la grippe (influenza) et du virus de la bronchiolite (VRS, pour virus respiratoire syncytial), mais leur tropisme pour ce tissu est bien moindre que celui du SARS-CoV-2. La physiopathologie de ce virus dans la cavité nasale a permis de commencer à comprendre les liens existant entre une infection virale et les troubles de l’olfaction.

SUMMARY INTRODUCTION A covid-19 pandemic decreed by WHO has raised greater awareness of it. EPIDEMIOLOGY The infection, reached the mark of 2,000,000 patients in 33 countries and caused the risk of the presence of comorbidities and advanced age. TRANSMISSIBILITY The transmissibility calculated so far is similar to the H1N1 epidemic, but with lower mortality rates. PHYSIOPATHOLOGY The SARS-CoV-2 virus, of the Coronaviridae family, has the capacity for cellular invasion through the angiotensin-converting enzyme 2 does not have a lower respiratory epithelium and in the cells of the small intestine mucosa. CLINICAL MANIFESTATIONS a presentation can be divided into mild (fever, fatigue, cough, myalgia, and sputum) and severe (cyanosis, dyspnoea, tachypnea, chest pain, hypoxemia and need for clinical measurement) and has an estimated estimate of 2%. DIAGNOSIS allows the detection of viral load in CRP-TR of patients with high clinical suspicion. TREATMENT based on supportive measures and infection control. In severe cases, the use of medications such as hydroxychloroquine and azithromycin or medication can be promising. Take care to avoid the use of corticosteroids. There are no restrictions on the use of resources and IECAs / BRAs.

The physiopathology of SARS-CoV-2 infection, during pregnancy and in early childhood, is poorly understood. Unfavorable maternal outcomes, the risk of vertical/postpartum transmission, and severe, multisystem involvement in infants and children highlight the importance of developing a cohesive treatment and nuanced prophylaxis strategy. In this study, we evaluate autopsy reports, pathological findings, and SARS-CoV-2 genome expression in three distinct clinical scenarios: maternal death due to severe COVID-19 with in utero fetal demise (27 weeks); mother with moderate COVID-19 and in utero fetal demise (29 weeks); and 2-month-old infant death with confirmed COVID-19 caregivers. We report the presence of the SARS-CoV-2 genome in amniotic fluid and placental tissue in the context of in utero transmission of SARS-CoV-2, but also in postmortem infant pulmonary tissue samples in a case of late postpartum SARS-CoV-2 transmission with asymptomatic, rapidly progressive disease, resulting in infant death. Key pathological findings offer a descriptive portrayal of maternal, in utero, and infantile COVID-19 pathogenesis. Further investigations are necessary to fully comprehend the clinical implications of SARS-CoV-2 infection during pregnancy, a prerequisite for adequate therapeutic management and harm reduction.

Background: Since the first year of the COVID-19 global pandemic, a hypothesis concerning the possible protection/immunity of beta-thalassemia carriers has remained in abeyance. Methods: Three databases (Pubmed Central, Scopus, and Google Scholar) were screened and checked in order to extract all studies about the incidence of confirmed COVID-19 cases, mortality rate, severity assessment, or ICU admission among patients with beta-thalassemia minor, were included in this analysis. The language was limited to English. Studies such as case reports, review studies, and studies that did not have complete data for calculating incidences were excluded. Results and discussion: a total of 3 studies out of 2265 were selected. According to our systematic-review meta-analysis, beta-thalassemia carriers could be less affected by COVID-19 than the general population [IRR = 0.9250 (0.5752; 1.4877)], affected by COVID-19 with a worst severity [OR = 1.5933 (0.4884; 5.1981)], less admissible into the ICU [IRR = 0.3620 (0.0025; 51.6821)], and more susceptible to die from COVID-19 or one of its consequences [IRR = 1.8542 (0.7819; 4.3970)]. However, all of those results remain insignificant with a bad p-value (respectively 0.7479, 0.4400, 0.6881, and 0.1610). Other large case-control or registry studies are needed to confirm these trends.

Despite the development of specific therapies against severe acute respiratory coronavirus 2 (SARS-CoV-2), the continuous investigation of the mechanism of action of clinically approved drugs could provide new information on the druggable steps of virus–host interaction. For example, chloroquine (CQ)/hydroxychloroquine (HCQ) lacks in vitro activity against SARS-CoV-2 in TMPRSS2-expressing cells, such as human pneumocyte cell line Calu-3, and likewise, failed to show clinical benefit in the Solidarity and Recovery clinical trials. Another antimalarial drug, mefloquine, which is not a 4-aminoquinoline like CQ/HCQ, has emerged as a potential anti-SARS-CoV-2 antiviral in vitro and has also been previously repurposed for respiratory diseases. Here, we investigated the anti-SARS-CoV-2 mechanism of action of mefloquine in cells relevant for the physiopathology of COVID-19, such as Calu-3 cells (that recapitulate type II pneumocytes) and monocytes. Molecular pathways modulated by mefloquine were assessed by differential expression analysis, and confirmed by biological assays. A PBPK model was developed to assess mefloquine’s optimal doses for achieving therapeutic concentrations. Mefloquine inhibited SARS-CoV-2 replication in Calu-3, with an EC50 of 1.2 µM and EC90 of 5.3 µM. It reduced SARS-CoV-2 RNA levels in monocytes and prevented virus-induced enhancement of IL-6 and TNF-α. Mefloquine reduced SARS-CoV-2 entry and synergized with Remdesivir. Mefloquine’s pharmacological parameters are consistent with its plasma exposure in humans and its tissue-to-plasma predicted coefficient points suggesting that mefloquine may accumulate in the lungs. Altogether, our data indicate that mefloquine’s chemical structure could represent an orally available host-acting agent to inhibit virus entry.

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: “lung fibrosis”, “fibrosis mediators”, “fibrosis predictors”, “COVID-19”, “SARS-CoV-2 infection”, and “long COVID-19”. In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.

DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, and the immune system, among others. It has recently acquired an especial relevance due to the possibility to act as a receptor or co-receptor for SARS-CoV-2, as it has been already demonstrated for other coronaviruses. In this review, we analyze the evidence for the role of DPP4 on COVID-19 risk and clinical outcome, and its contribution to COVID-19 physiopathology. Due to the pathogenetic links between COVID-19 and diabetes mellitus and the hyperinflammatory response, with the hallmark cytokine storm developed very often during the disease, we dive deep into the functions of DPP4 on carbohydrate metabolism and immune system regulation. We show that the broad spectrum of functions regulated by DPP4 is performed both as a protease enzyme, as well as an interacting partner of other molecules on the cell surface. In addition, we provide an update of the DPP4 inhibitors approved by the EMA and/or the FDA, together with the newfangled approval of generic drugs (in 2021 and 2022). This review will also cover the effects of DPP4 inhibitors (i.e., gliptins) on the progression of SARS-CoV-2 infection, showing the role of DPP4 in this disturbing disease.

Le coronavirus 2 du syndrome respiratoire aigu sévère (severe acute respiratory syndrome-related coronavirus, SARS-CoV-2), de la famille Coronaviridae, est responsable de la maladie à coronavirus de 2019 (coronavirus disease 2019, COVID-19). Malgré la disponibilité de vaccins, en cause dans la fin de l’urgence sanitaire de la COVID-19, la circulation virale du SARS-CoV-2 subsiste ainsi que les recherches sur la compréhension de sa physiopathologie, notamment l’implication et le rôle des microARN (miARN) dans cette infection virale. Les miARN sont des petits ARN non codants régulant l’expression des gènes et connus pour leurs implications dans de nombreuses voies de régulation cellulaire. Récemment, ils se sont révélés l’être également dans l’infection par le SARS-CoV-2. Ces recherches permettraient une meilleure connaissance dans ce domaine et pourraient s’avérer utiles dans le développement de nouveaux diagnostics et de traitements cliniques contre cette infection virale ou d’autres infections de la même famille virale. Ainsi, dans ce projet de recherche, nous avons d’abord caractérisé les miARN cellulaires biomarqueurs de l’infection virale par le SARS-CoV-2 à partir de prélèvements nasopharyngés de patients, qui est le prélèvement recommandé pour le diagnostic de cette infection virale. Nos travaux ont identifié en particulier, des miARN associés à des formes sévères de la COVID-19. Ces derniers ciblent des gènes impliqués dans les infections virales et les réponses antivirales et anti-inflammatoires aux infections virales. Ces potentiels effets antiviraux et anti-inflammatoires des miARN sur l’infection virale par le SARS-CoV-2 n’ont pas pu être démontrés in vitro lors de cette étude. Par la suite, on s’est penché sur l’hypothèse de la dérégulation de la biogénèse des miARN par cette infection virale. On a trouvé aucune sous-expression des ARNm des gènes impliqués de la voie de biogénèse des miARN lors de l’infection par le SARS-CoV-2, que ce soit en ex vivo ou en in vitro. Pour finir, nous avons voulu développer un possible traitement clinique contre l’infection virale par le SARS-CoV-2 ou tout autre pathologie par la délivrance de miARN d’intérêt. Il s’agirait de développer des nanoparticules et des nanomatériaux couplés à des miARN ou autres ARN doubles brins messagers ou non, afin de permettre l’entrée de ces derniers au sein des cellules et rétablir ainsi l’expression basale des gènes impliqués dans l’infection virale
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), a member of the Coronaviridae family, is responsible for coronavirus disease 2019 (COVID-19). Despite the availability of vaccines that helped end the COVID-19 health emergency, the viral circulation of SARS-CoV-2 remains, as well as research on the understanding of its pathophysiology, in particular the involvement and role of microRNAs (miRNAs) in this viral infection. miRNAs are small non-coding RNAs that regulate gene expression and are known to be involved in numerous cellular regulatory pathways. Recently, they have also been shown to be involved in SARS-CoV-2 infection. Such research would provide a better knowledge in this field and could be useful in the development of new diagnoses and clinical treatments against viral infection with SARS-CoV-2 or other infections of the same viral family. Thus, in this research project, we first characterized the cellular miRNA biomarkers of SARS-CoV-2 viral infection from patient nasopharyngeal swabs, which is the first diagnostic tool for this viral infection. In particular, our work has identified miRNAs associated with severe forms of COVID-19. These miRNA target genes involved in viral infections and antiviral and anti-inflammatory responses to viral infections. These potential antiviral and anti-inflammatory effects of miRNAs on SARS-CoV-2 viral infection could not be demonstrated in vitro in this study. Then, the hypothesis of deregulation of miRNA biogenesis by this viral infection was investigated. No under-expression of mRNAs of genes involved in the miRNA biogenesis pathway was found upon infection with SARS-CoV-2, either ex vivo or in vitro. Finally, based on a miRNA of clinical interest, we wanted to develop a possible clinical treatment against viral infection by SARS-CoV-2 or any other pathology through the delivery of miRNAs of interest, in this case antiviral. This would involve developing nanoparticles and nanomaterials coupled to miRNAs or other double-stranded messenger or non-messenger RNAs, to enable the latter to enter cells and thus restore basal expression of the genes involved in viral infection

Les infections virales respiratoires demeurent un enjeu majeur de santé publique dans le monde entier. C’est notamment le cas de la grippe, causée par les virus influenza, et de la COVID-19, une maladie infectieuse émergente due au virus SARS-CoV-2. De manière notable, les populations les plus à risque de développer des formes sévères de grippe ou de COVID-19, sont les individus obèses et les personnes âgées. Bien que l’obésité et le vieillissement soient associées à des altérations fonctionnelles majeures du tissu adipeux blanc, la participation de ce dernier dans la physiopathologie de la grippe ou de la COVID-19 reste très peu étudiée. Le projet de thèse s’inscrit dans cette thématique générale.Les travaux récents de notre équipe ont montré, chez la souris, que l’infection par le virus influenza entraine une reprogrammation métabolique des dépôts sous-cutanés de tissu adipeux blanc, notamment caractérisée par le brunissement du tissu : un phénomène qui correspond à l’émergence d’adipocytes beiges présentant une activité thermogénique accrue. Lors de ma thèse, par des approches expérimentales in vivo, in vitro, ex vivo et in silico complémentaires, nous avons montré que la réponse au stress du réticulum endoplasmique induit par l’infection par le virus de la grippe, et plus spécifiquement la voie signalétique PERK, est impliquée dans le brunissement du tissu adipeux blanc. Outre identifier un nouveau mécanisme moléculaire de régulation de la thermogenèse, nos travaux précisent un peu plus la place du tissu adipeux blanc dans l’infection grippale.En parallèle, nous avons étudié l’impact de l’infection par le virus SARS-CoV-2 sur les tissus adipeux blancs de hamsters jeunes adultes ou âgés - un modèle préclinique de COVID-19 récemment mis en place dans notre équipe. Nos résultats montrent que l’infection est plus sévère, en termes de morbi-mortalité, chez les animaux âgés que chez les jeunes adultes. L’analyse histomorphométrique des tissus adipeux blancs sous-cutanés et viscéraux a permis de montrer que l’infection par SARS-CoV-2 est associée à une diminution de la taille des adipocytes dans ces deux dépôts ; effet qui persiste uniquement chez les animaux âgés. De manière très intéressante, l’analyse histologique des tissus révèle la présence de nombreuses et larges zones de nécrose adipocytaire (ressemblant aux crown-like structures décrites dans les tissus adipeux blancs en contexte d’obésité) uniquement dans les dépôts sous-cutanés de tissu adipeux des animaux âgés, y compris à distance de l’infection. En cela, notre étude confirme et renforce les plus récentes données de la littérature qui décrivent un rôle majeur du tissu adipeux blanc dans la physiopathologie de la COVID-19
Respiratory viral infections remain a major public health issue, worldwide. This is particularly the case with flu, caused by influenza viruses, and COVID-19, an emerging infectious disease caused by the SARS-CoV-2 virus. Importantly, the populations most at risk of developing severe forms of flu or COVID-19 are obese individuals and the elderly. Although obesity and aging are both associated with major functional alterations of the white adipose tissue, the latter's involvement in the pathophysiology of influenza or COVID-19 remains poorly studied. The thesis project falls within this general theme.Recent work by our team has shown, in mice, that infection with the influenza virus causes metabolic reprogramming of the subcutaneous fat depots, mainly characterized by the browning of the tissue: a phenomenon which corresponds to the emergence of beige adipocytes with increased thermogenic activity. During my PhD, using complementary experimental in vivo, in vitro, ex vivo and in silico approaches, we showed that the response to influenza-infection-induced endoplasmic reticulum stress, and more specifically the PERK signaling pathway, is involved in white adipose tissue browning. Besides identifying a novel molecular mechanism that regulates thermogenesis, our work further specifies the role of the white adipose tissue in influenza infection.In parallel, we studied the impact of infection with the SARS-CoV-2 virus on the white adipose tissues of young adult and old hamsters - a preclinical model of COVID-19 recently implemented in our team. Our results showed that the infection is more severe - in terms of morbidity and mortality - in older animals than in young adults. Histomorphometric analysis of subcutaneous and visceral white adipose tissues showed that infection with SARS-CoV-2 is associated with a decrease in the size of adipocytes in these two depots; an effect that persists only in the older animals. Remarkably, the histological analysis of the tissues reveals the presence of numerous and large areas of adipocyte necrosis (resembling the “crown-like structures” that can be observed in white adipose tissues in the context of obesity) only in the subcutaneous fat depots of the older animals, even at distance from infection. As such, our study confirms and strengthens the most recent data in the literature, which describes a major role of the white adipose tissue in the pathophysiology of COVID-19

The current outbreak of the novel coronavirus, SARS-CoV-2 (coronavirus disease 2019; previously 2019- nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries caused an extreme burden for healthcare systems globally. Coronaviruses are traditionally considered nonlethal pathogens to humans, mainly causing approximately 15% of common colds. In this century, we have encountered highly pathogenic human CoVs twice. In this chapter, the authors propose to focus the gastrointestinal physiopathology of the infection of SARS-Cov2. This chapter will develop subject like the gastrointestinal manifestations of the infection to SARS-Cov2. The second part of this chapter will develop the role of the gut microbiome in the SARS-Cov2 diseases susceptibilities. And then the authors will show the etiopathogenesis of SARS-Cov2 associated diarrhea. As reported by previous studies, the SARS-Cov virus entry into host cell is mediated by the interaction between the envelop-anchored viral spike protein and the host receptor named angiotensin-converting enzyme 2 (ACE2).

During SARS-CoV-1 and Middle East Respiratory Distress Syndrome (MERS) outbreaks it was observed a particularly elevated incidence of cardiovascular disease among patients. With COVID-19, this correlation becomes evident again. However, the cardiovascular impacts by COVID-19 pandemic are not yet well established although publications about its potential deleterious effects are constant. Thus, aimed to carry a systematic review of the literature with meta-analysis, the following question was used as a guide: what practical contributions does the scientific literature produced in the period of 2019-2020 has to offer about the impact of the COVID-19 on cardiovascular system? A systematic review of the literature using the Virtual Health Library (VHL) and PubMed with the following descriptors: #1 “cardiovascular disease” [MeSH] AND #2 “COVID-19” [keyword], as well as their equivalents in the Portuguese and Spanish language, during the period from December 2019 to March 2020 was performed. One hundred articles were found in Pubmed and twenty-seven were selected. In VHL there are 59 articles and four were selected totaling thirty-one papers. The findings were then divided into three subcategories: Etiology, Physiopathology and Risk factors of SARS-CoV-2 in Cardiovascular System; Clinical presentation, laboratory markers and imagenological aspects of SARS-CoV-2 in cardiovascular system; and Anti-Hypertensive Drugs, Cardiovascular System and SARS-CoV-2. When it comes to the cardiovascular system, these issues are aggravated and urge as a joint commitment from researchers, medical and governmental organizations to carry out more robust studies with bold methodologies aimed at mapping prognostic factors and assertive therapeutic approaches in the management of cardiovascular complications of COVID- 19.

The past two years were deeply marked by the emergence of a global pandemic caused by the worldwide spread of the virus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. The plethora of repercussions on the health of those affected is extensive, ranging from asymptomatic individuals, mild flu-like disease, and severe respiratory failure, eventually leading to death. Despite this predilection for the respiratory system, the virus is responsible for multisystemic manifestations and soon became clear that neurological involvement was a frequent issue of coronavirus disease 2019 (COVID-19). Much have been pointed out about the neurotropic nature of the virus, the ways by which it invades and targets specific structures of the central nervous system, and the physiopathology behind the neurologic manifestations associated with it (namely encephalomyelitis, Guillain-Barré syndrome, lacunar infarcts, and vascular dysfunction, just to list a few). This chapter aims to raise light about the association between COVID-19 and the mechanisms of acute symptomatic seizures, through neurotropism and neuroinvasion features of SARS-CoV-2, and to review the variety of clinical presentations reported so far.

Introdução: A doença COVID-19, causada pelo novo coronavírus SARSCoV-2 está relacionada a um amplo espectro clínico, isto é, estão presentes desde casos assintomáticos até falência de múltiplos órgãos e morte. Em estágios iniciais de doença, a frequente porta de entrada pela via inalatória nasal e inicio de comprometimento do sistema respiratório resultam em sintomas gripais, incluindo febre, tosse seca, astenia, mialgia, cefaleia, disgeusia e hiposmia/anosmia. No entanto, possivelmente devido ao tropismo do vírus pelos pneumócitos II, 20% dos pacientes evoluem rapidamente para doença grave com pneumonia intersticial, síndrome do desconforto respiratório agudo (SDRA), e outras disfunções envolvendo diferentes órgãos e sistemas. Até 80% destes pacientes evoluem ao óbito. A função imune dos hospedeiros infectados parece ser o principal determinante na apresentação e progressão da doença. Na ausência de comorbidades é frequente a resolução da infecção em estágios iniciais. Por outro lado, idade aumentada ou imunidade prejudicada, combinada com outras comorbidades como hipertensão e diabetes são fatores relacionados a formas graves de doença. Objetivos: revisar as principais características clínicas e mecanismos fisiopatológicos da doença COVID-19 por meio de revisão de literatura. Métodos: Foram Selecionados artigos bem avaliados e canalizados na temática proposta na base de dados MEDLINE/PubMed. Foram buscados artigos entre os anos de 2020 a 2022 combinando os termos MeSH: “clinical”, “COVID”, “mechanism”, “physiopathology” e “SARS-CoV-2”. A área temática do estudo é Clínica Médica. Resultados: O SARS-CoV-2 infecta células humanas ligando-se à enzima conversora de angiotensina 2 (ECA-2) através da proteína “spike” (S) de sua superfície. Esta interação é capaz de desregular o sistema renina-angiotensinaaldosterona diminuindo a conversão de angiotensina II em angiotensina 1- 7. Como resultado, ocorre aumento das vias pró-trombóticas e diminuição das vias antitrombóticas. A partir disso, inicia-se um ciclo de estado inflamatório sistêmico envolvendo inflamação (IL-1, IL-6, quimiocinas), resposta imunológica (Th1) e dano endotelial progressivo. A ativação de células endoteliais pelo Sars-CoV-2 aumenta a externalização do fator de Von Willebrand e moléculas de adesão de leucócitos ICAM-1, VCAM-1, e E selectina, permitindo a adesão de plaquetas e neutrófilos, além da expressão do fator tecidual ativando a via de coagulação extrínseca e, por sua vez, a geração de α-trombina levando à geração de fibrina e ativação de plaquetas. Desse modo, ambas vias de coagulação são ativadas. Como resultado, ocorrem complicações tais quais: tromboembolismo da artéria pulmonar, trombose venosa profunda, infarto agudo do miocárdio, acidente vascular encefálico e Coagulação Intravascular Disseminada associada ao COVID-19. Patologias relacionadas ao dano endotelial crônico como DM e HAS, e as que amplificam a inflamação (como a obesidade) são capazes de atuar sinergicamente com os diversos mecanismos mencionados. Conclusão: O estudo revisa as diversas apresentações clinicas da COVID-19 e revisita asperamente as principais complicações e um possível mecanismo fisiopatológico, demonstrando o aprendizado crescente sobre esta doença emergente e desafiadora. Por fim, reforça-se a necessidade da manutenção de pesquisas sobre a COVID-19 desde sua fisiopatologia até o desenvolvimento de intervenções eficientes para cursos de doença grave e associados a complicações. Resumo- sem apresentação oral. PALAVRAS-CHAVE: COVID-19, Inflamação, Medicina Clínica, Patologia Clínica, SARS-CoV-2