Literatura académica sobre el tema "SARS-CoV-2 (virus) – 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.

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.

The disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or simply corona virus disease-2019 (COVID-19), has rapidly spread throughout the world. World Health Organization declared a global health emergency on January 30, 2020 announcing it as a Pandemic. The outbreak of the disease has posed serious health threat. A search was conducted for review which included various articles from 2019 to 2021 in PubMed/MEDLINE with keywords ACE2, 2019 NCOV, pandemic, physiopathology, SARS, Transmission. Both humoral and acquired immunity are targeted by the virus during progression of diseases. A cellular biology perceptive of pathogenesis is useful forframing clinical course of the diseases and its related complication. Knowledge of underlying pathophysiology regarding release of innate immune modulators such as CXCL10, beta and alpha interferons will facilitate the development of therapeutic modalities in future. Despite implementing all the preventive efforts SARS-CoV-2, exponential mode of infection rate is still existing with epidemic doubling time less than a week. In this review, an update on pathophysiology, cell biology of virus and immune modulation related to diseases are considered and has been described. Any of the mechanisms and assumptions discussed in the article and in our understanding of SARS-CoV-2 may be revised as further evidence emerges.

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.

We frequently come in contact with animal viruses through the food which we eat, the pets which we have, and our connections with nature. The enormous majority of viruses which enter our bodies pass inoffensively through our physiological systems or eradicate by our immune systems. However, on rare circumstances, a human-encounters by a virus which begins to replicate itself, accomplishing its entire lifecycle within human cells and intensifying themselves into a large number. Replication of an animal virus inside the human body is the key instant in the zoonotic process. SARS CoV-2 is one of these viruses which cause COVID-19 disease. To enter the target cell SARS-CoV-2 uses angiotensinconverting enzyme 2 (ACE2) and the cellular protease transmembrane protease serine 2 (TMPRSS2). Genome stability and maintenance of cellular equilibrium are the main parameters influenced by epigenetically regulated chromatin structure. Implication of regulation by epigenetic machinery has also been found in the physiopathology of the virus infection. By varying the function of gene locus. such regulation links genotype and phenotype without changing the original DNA sequences. However antiviral drugs have been used to treat various viral diseases since long, epi-drugs are now proposed to treat these diseases due to the epigenetic implications found in these infections. Epi-drugs are small agents that are able to reverse some epigenetic changes. This review is aimed to find implication of epigenetics in infection caused due SARS C0V-2 and if there is any epi-drugs approach possible to treat this infection.

The knowledge on the deposition and retention of the viral particle of SARS-CoV-2 in the respiratory tract during the very initial intake from the ambient air is of prime importance to understand the infectious process and COVID-19 initial symptoms. We propose to use a modified version of a widely tested lung deposition model developed by the ICRP, in the context of the ICRP Publication 66, that provides deposition patterns of microparticles in different lung compartments. In the model, we mimicked the "environmental decay" of the virus, determined by controlled experiments related to normal speeches, by the radionuclide 11C that presents comparable decay rates. Our results confirm clinical observations on the high virus retentions observed in the extrathoracic region and the lesser fraction on the alveolar section (in the order of 5), which may shed light on physiopathology of clinical events as well on the minimal inoculum required to establish infection.

COVID-19 global pandemic caused by Sars-CoV-2 virus, has worried to health care providers due to the high mortality rate related to coagulopathy in many patients. COVID-19 coagulopathy is mainly thrombotic, first locally in lungs but later on it becomes micro and macrovascular systemic coagulopathy. It has been associated to endothelial damage, inflammation, neutrophil-extracellular traps, monocyte and macrophage activation, cytokines storm that induce a vicious cycle of thrombosis and inflammation. The increased levels of prothrombotic factors as tissue factor, Von Willebrand factor, fibrinogen, VIII factor and the decreased levels of antithrombotic factos, such as: antithrombin and Protein S have been reported in COVID-19 patients. Insufficiency of fibrinolysis because of the increased levels of PAI-1 (plasminogen activator inhibitor 1) have been reported also. During this disease there are intraalveolar fibrin deposits that needs to be degraded. Fibrinolysis of thrombus and fibrin intraalveolar degradation are responsible for the high increase of D-dimers levels that are an important predictor of severity of the disease. In this report, the physiology of hemostasis, thromboinflamation secondary to Sars-CoV-2 infection are reviewed, as well as the clinical evidence and the physiopathology of COVID-19 coagulopathy from the basic sciences point of view. Keywords:Hemostasis; coagulation; thrombosis; coagulopathy; Sars-CoV-2; COVID-19.

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).

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.