La mélatonine contre le virus?

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Melatonin as a potential adjuvant treatment
Rui Zhang Life Sciences Volume 250, 1 June 2020, 117583

This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death.

Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation.

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Traduction de l'étude

La mélatonine comme traitement adjuvant potentiel
Rui Zhang Life Sciences Volume 250, 1er juin 2020, 117583

Cet article résume les avantages probables de la mélatonine dans l'atténuation du COVID-19 en fonction de sa pathogenèse putative. La récente flambée de COVID-19 est devenue une pandémie avec des dizaines de milliers de patients infectés. Sur la base des caractéristiques cliniques, de la pathologie, de la pathogenèse des troubles respiratoires aigus induits par des coronavirus hautement homogènes ou d'autres agents pathogènes, les preuves suggèrent qu'une inflammation excessive, une oxydation et une réponse immunitaire exagérée contribuent très probablement à la pathologie COVID-19. Cela conduit à une tempête de cytokines et à une progression ultérieure vers une lésion pulmonaire aiguë (ALI) / syndrome de détresse respiratoire aiguë (SDRA) et souvent la mort.

La mélatonine, une molécule anti-inflammatoire et anti-oxydante bien connue, protège contre les ALI / SDRA causés par des agents viraux et autres. La mélatonine est efficace chez les patients en soins intensifs en réduisant la perméabilité des vaisseaux, l'anxiété, l'utilisation de la sédation et en améliorant la qualité du sommeil, ce qui pourrait également être bénéfique pour de meilleurs résultats cliniques pour les patients COVID-19. En particulier, la mélatonine a un profil de sécurité élevé. Il existe des données importantes montrant que la mélatonine limite les maladies liées au virus et serait également probablement bénéfique chez les patients COVID-19. Des expériences et des études cliniques supplémentaires sont nécessaires pour confirmer cette spéculation.

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Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial
Seyed Abbas Mousavi J Med Virol. 2021 Aug 30.

This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation.

Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003).

This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.

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Melatonin is significantly associated with survival of intubated COVID-19 patients
Vijendra Ramlall, medRxiv. 2020 Oct 18;2020.

Background Respiratory distress requiring intubation is the most serious complication associated with coronavirus disease 2019 (COVID-19).

Methods In this retrospective study, we used survival analysis to determine whether or not mortality following intubation was associated with hormone exposure in patients treated at New York Presbyterian/ Columbia University Irving Medical Center. Here, we report the overall hazards ratio for each hormone for exposure before and after intubation for intubated and mechanically ventilated patients. <br> Results Among the 189,987 patients, we identified 948 intubation periods across 791 patients who were diagnosed with COVID-19 or infected with SARS-CoV2 and 3,497 intubation periods across 2,981 patients who were not. Melatonin exposure after intubation was statistically associated with a positive outcome in COVID-19 (demographics and comorbidities adjusted HR: 0.131, 95% CI: 7.76E-02 - 0.223, p -value = 8.19E-14) and non-COVID-19 (demographics and comorbidities adjusted HR: 0.278, 95% CI: 0.142 - 0.542, p -value = 1.72E-04) intubated patients. Additionally, melatonin exposure after intubation was statically associated with a positive outcome in COVID-19 patients (demographics and comorbidities adjusted HR: 0.127, 95% CI: 6.01E-02 - 0.269, p -value = 7.15E-08).

Conclusions Melatonin exposure after intubation is significantly associated with a positive outcome in COVID-19 and non-COVID-19 patients. Additionally, melatonin exposure after intubation is significantly associated with a positive outcome in COVID-19 patients requiring mechanical ventilation. While our models account for many covariates, including clinical history and demographics, it is impossible to rule out confounding or collider biases within our population. Further study into the possible mechanism of this observation is warranted.

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Traduction de l'étude

La mélatonine est significativement associée à la survie des patients COVID-19 intubés
Vijendra Ramlall, medRxiv. 18 octobre 2020 ; 2020.

Contexte La détresse respiratoire nécessitant une intubation est la complication la plus grave associée à la maladie à coronavirus 2019 (COVID-19).

Méthodes Dans cette étude rétrospective, nous avons utilisé une analyse de survie pour déterminer si oui ou non la mortalité après intubation était associée à l'exposition aux hormones chez les patients traités au New York Presbyterian/Columbia University Irving Medical Center. Ici, nous rapportons le rapport de risque global pour chaque hormone pour l'exposition avant et après l'intubation pour les patients intubés et ventilés mécaniquement. <br> Résultats Parmi les 189 987 patients, nous avons identifié 948 périodes d'intubation sur 791 patients diagnostiqués avec COVID-19 ou infectés par le SRAS-CoV2 et 3 497 périodes d'intubation sur 2 981 patients qui ne l'étaient pas. L'exposition à la mélatonine après intubation était statistiquement associée à un résultat positif dans COVID-19 (RH ajusté en fonction de la démographie et des comorbidités : 0,131, IC à 95 % : 7,76E-02 - 0,223, valeur p = 8,19E-14) et non-COVID-19 (HR ajusté en fonction des données démographiques et des comorbidités : 0,278, IC à 95 % : 0,142 - 0,542, valeur p = 1,72E-04) patients intubés. De plus, l'exposition à la mélatonine après l'intubation était associée de manière statique à un résultat positif chez les patients COVID-19 (HR ajusté en fonction des données démographiques et des comorbidités : 0,127, IC à 95 % : 6,01E-02 - 0,269, valeur p = 7,15E-08).

Conclusions L'exposition à la mélatonine après l'intubation est significativement associée à un résultat positif chez les patients COVID-19 et non-COVID-19. De plus, l'exposition à la mélatonine après l'intubation est significativement associée à un résultat positif chez les patients COVID-19 nécessitant une ventilation mécanique. Bien que nos modèles tiennent compte de nombreuses covariables, y compris les antécédents cliniques et la démographie, il est impossible d'exclure les biais de confusion ou de collision au sein de notre population. Une étude plus approfondie du mécanisme possible de cette observation est justifiée.

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Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2
Erika Cecon, Journal of Pineal Research 29 September 2021

As the COVID-19 pandemic grows, several therapeutic candidates are being tested or undergoing clinical trials. Although prophylactic vaccination against SARS-CoV-2 infection has been shown to be effective, no definitive treatment exists to date in the event of infection. The rapid spread of infection by SARS-CoV-2 and its variants fully warrants the continued evaluation of drug treatments for COVID-19, especially in the context of repurposing of already available and safe drugs.

Here, we explored the therapeutic potential of melatonin and melatonergic compounds in attenuating COVID-19 pathogenesis in mice expressing human ACE2 receptor (K18-hACE2), strongly susceptible to SARS-CoV-2 infection. Daily administration of melatonin, agomelatine, or ramelteon delays the occurrence of severe clinical outcome with improvement of survival, especially with high melatonin dose. Although no changes in most lung inflammatory cytokines are observed, treatment with melatonergic compounds limits the exacerbated local lung production of type I and type III interferons, which is likely associated with the observed improved symptoms in treated mice.

The promising results from this preclinical study should encourage studies examining the benefits of repurposing melatonergic drugs to treat COVID-19 and related diseases in humans.

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Melatonin and other indoles show antiviral activities against swine coronaviruses in vitro at pharmacological concentrations
Xiaofeng Zhai Journal of Pineal Research 17 June 2021

The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights major gaps in our knowledge on the prevention control and cross-species transmission mechanisms of animal coronaviruses. Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta coronavirus (PDCoV) are three common swine coronaviruses and have similar clinical features. In the absence of effective treatments, they have led to significant economic losses in the swine industry worldwide.

We reported that indoles exerted potent activity against swine coronaviruses, the molecules used included melatonin, indole, tryptamine, and L-tryptophan. Herein, we did further systematic studies with melatonin, a ubiquitous and versatile molecule, and found it inhibited TGEV, PEDV, and PDCoV infection in PK-15, Vero, or LLC-PK1 cells by reducing viral entry and replication, respectively. Collectively, we provide the molecular basis for the development of new treatments based on the ability of indoles to control TGEV, PEDV, and PDCoV infection and spread.

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Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
Yadi Zhou Cell Discov. 2020 Mar 16;6:14.

Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV.

Using network proximity analyses of drug targets and HCoV-host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the "Complementary Exposure" pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.

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A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19
Yadi Zhou PLoS Biol. 2020 Nov 6;18(11):e3000970.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2).

To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio [OR] = 0.72, 95% CI 0.56-0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription-polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54-0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52-0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31-0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.

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Traduction de l'étude

Une approche de la médecine en réseau pour l'investigation et la validation basée sur la population des manifestations de la maladie et la réorientation des médicaments pour COVID-19
Yadi Zhou PLoS Biol. 6 novembre 2020 ; 18 (11) : e3000970.

La pandémie mondiale de la maladie à coronavirus 2019 (COVID-19), causée par le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2), a entraîné des conséquences sociales et économiques sans précédent. Le risque de morbidité et de mortalité dues au COVID-19 augmente considérablement en présence de conditions médicales coexistantes, tandis que les mécanismes sous-jacents restent flous. De plus, il n'existe pas de thérapies approuvées pour le COVID-19. Cette étude vise à identifier la pathogenèse du SRAS-CoV-2, les manifestations de la maladie et les thérapies COVID-19 en utilisant des méthodologies de médecine en réseau ainsi que des observations cliniques et multi-omiques. Nous intégrons les interactions, la transcriptomique et la protéomique du virus-hôte du SRAS-CoV-2 dans l'interactome humain. La mesure de la proximité du réseau a révélé la pathogenèse sous-jacente des manifestations générales de la maladie associées au COVID-19. Les analyses des données de séquençage de l'ARN unicellulaire montrent que la co-expression d'ACE2 et de TMPRSS2 est élevée dans les entérocytes absorbants des tissus iléaux enflammés des patients atteints de la maladie de Crohn par rapport aux tissus non enflammés, révélant une pathobiologie partagée entre COVID-19 et la maladie intestinale inflammatoire. Des analyses intégratives des données de métabolomique et de transcriptomique (en vrac et unicellulaires) de patients asthmatiques indiquent que COVID-19 partage un profil moléculaire inflammatoire intermédiaire avec l'asthme (y compris IRAK3 et ADRB2).

Pour hiérarchiser les traitements potentiels, nous avons combiné la prédiction basée sur le réseau et une étude observationnelle correspondant au score de propension (PS) de 26 779 individus d'un registre COVID-19. Nous avons identifié que l'utilisation de mélatonine (rapport de cotes [OR] = 0,72, IC à 95 % 0,56-0,91) est significativement associée à une probabilité réduite de 28 % d'un résultat de test de laboratoire positif pour le SRAS-CoV-2 confirmé par transcription inverse-amplification en chaîne par polymérase essai. À l'aide d'une conception de comparateur actif de l'utilisateur correspondant à la PS, nous avons déterminé que l'utilisation de la mélatonine était associée à une probabilité réduite de résultat de test positif pour le SRAS-CoV-2 par rapport à l'utilisation de bloqueurs des récepteurs de l'angiotensine II (OR = 0,70, IC à 95 % 0,54-0,92) ou inhibiteurs de l'enzyme de conversion de l'angiotensine (OR = 0,69, IC à 95 % 0,52-0,90). Fait important, l'utilisation de mélatonine (OR = 0,48, IC à 95 % 0,31-0,75) est associée à une probabilité réduite de 52 % d'un résultat de test de laboratoire positif pour le SRAS-CoV-2 chez les Afro-Américains après ajustement pour l'âge, le sexe, la race, les antécédents de tabagisme , et diverses comorbidités de la maladie en utilisant l'appariement PS. En résumé, cette étude présente une plate-forme de médecine de réseau intégrative pour prédire les manifestations de la maladie associées à COVID-19 et identifier la mélatonine pour la prévention et le traitement potentiels de COVID-19

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What if melatonin could help patients with severe COVID-19?
Miguel Ángel Sánchez-González Journal of Clinical Sleep MedicineVolume 18, Issue 1 January 1, 2022

In March 2020, a protocol recommending the prescription of melatonin, among other sleep- and biorhythms-promoting measures, to hospitalized patients with coronavirus disease 2019 (COVID-19) with sleep problems or delirium was sent from the consultation-liaison psychiatrist to the medical staff of the Fundación Jiménez Díaz University Hospital (FJDUH) in Madrid, Spain. Several authors have suggested a potential benefit of melatonin use in COVID-19.1–4 In addition to its circadian function, melatonin is thought to have several health-promoting properties, including immune response modulation and anti-inflammatory and antioxidant properties.5 We here report a retrospective analysis showing an association of melatonin with survival in a sample of 2,463 patients with COVID-19 hospitalized during the first wave of the pandemic, 265 of whom (10.75%) were given 2–6 mg of oral melatonin at 21 hours during admission (median of first day of administration was day 4, and 25% of patients received melatonin from the first day). Our work and that of Ramlall et al6 are the first to show real-world clinical data supporting a possible benefit of melatonin in COVID-19.

To reduce the possibility of a biased, biologically nonrelevant association of melatonin with survival, we excluded from the sample patients who died during the first 72 hours of admission without taking melatonin and patients who started on melatonin in the last 7 days of their admittance, having completed 75% of their stay. The remaining sample comprised 224 patients who received melatonin and 1,952 patients who did not receive melatonin. Both groups included patients admitted in the intensive care unit (or intermediate respiratory care unit), with the patients of the melatonin group having more probability of intensive care unit/intermediate respiratory care unit admission (Table 1). To control for baseline differences between the 2 groups we performed a propensity score matching. The melatonin group showed a much lower mortality rate (10.7% vs 23.7%) compared with the non-melatonin matched group, with an odds ratio of 0.39 (Table 1). We had data available on CURB-65 (confusion, blood urea nitrogen >19 mg/dL, respiratory rate ≥30 breaths/minute, low blood pressure, and age ≥ 65 years; a validated scale of clinical severity7) for 343 (76.5%) out of 448 patients in the matched groups, 179/224 in the melatonin group, and 164/224 in the non-melatonin matched group. No differences were found between the 2 groups in the distribution of their CURB-65 scores, suggesting that they were similar in terms of illness severity at admission.

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Traduction de l'étude

Et si la mélatonine pouvait aider les patients atteints de COVID-19 sévère ?
Miguel Ángel Sánchez-González Journal of Clinical Sleep MedicineVolume 18, numéro 1 1er janvier 2022

En mars 2020, un protocole recommandant la prescription de mélatonine, entre autres mesures favorisant le sommeil et les biorythmes, aux patients hospitalisés atteints de la maladie à coronavirus 2019 (COVID-19) souffrant de troubles du sommeil ou de délire a été transmis par le psychiatre de consultation-liaison au service médical. personnel de l'hôpital universitaire Fundación Jiménez Díaz (FJDUH) à Madrid, Espagne. Plusieurs auteurs ont suggéré un avantage potentiel de l'utilisation de la mélatonine dans COVID-19.1-4. En plus de sa fonction circadienne, la mélatonine aurait plusieurs propriétés bénéfiques pour la santé, notamment la modulation de la réponse immunitaire et des propriétés anti-inflammatoires et antioxydantes.5 Nous rapportons ici une analyse rétrospective montrant une association de la mélatonine avec la survie dans un échantillon de 2 463 patients atteints de COVID-19 hospitalisés pendant la première vague de la pandémie, dont 265 (10,75 %) ont reçu 2 à 6 mg de mélatonine orale à 21 heures lors de l'admission (la médiane du premier jour d'administration était le jour 4, et 25 % des patients ont reçu de la mélatonine dès le premier jour). Nos travaux et ceux de Ramlall et al6 sont les premiers à montrer des données cliniques réelles soutenant un bénéfice possible de la mélatonine dans COVID-19.

Pour réduire la possibilité d'une association biaisée et biologiquement non pertinente de la mélatonine avec la survie, nous avons exclu de l'échantillon les patients décédés au cours des 72 premières heures d'admission sans prendre de mélatonine et les patients qui ont commencé à prendre de la mélatonine au cours des 7 derniers jours de leur admission, ayant effectué 75 % de leur séjour. L'échantillon restant comprenait 224 patients qui ont reçu de la mélatonine et 1 952 patients qui n'ont pas reçu de mélatonine. Les deux groupes comprenaient des patients admis en unité de soins intensifs (ou unité de soins respiratoires intermédiaires), les patients du groupe mélatonine ayant plus de probabilité d'admission en unité de soins intensifs/unité de soins respiratoires intermédiaires (tableau 1). Pour contrôler les différences de base entre les 2 groupes, nous avons effectué un appariement des scores de propension. Le groupe mélatonine a montré un taux de mortalité beaucoup plus faible (10,7 % contre 23,7 %) par rapport au groupe sans mélatonine, avec un rapport de cotes de 0,39 (tableau 1). Nous disposions de données sur CURB-65 (confusion, azote uréique du sang >19 mg/dL, fréquence respiratoire ≥30 respirations/minute, hypotension artérielle et âge ≥ 65 ans ; une échelle validée de sévérité clinique7) pour 343 (76,5% ) sur 448 patients dans les groupes appariés, 179/224 dans le groupe mélatonine et 164/224 dans le groupe sans mélatonine. Aucune différence n'a été trouvée entre les 2 groupes dans la distribution de leurs scores CURB-65, suggérant qu'ils étaient similaires en termes de gravité de la maladie à l'admission.

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Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels
Erika Cecon BioRxiv January 03, 2022. This article is a preprint and has not been certified by peer review

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post COVID condition. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevent SARS-CoV-2 entry in the brain thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Brain entry of SARS-CoV-2 through endothelial cells is prevented by melatonin through allosteric binding to human angiotensin-converting enzyme 2 (ACE2), which interferes with the cell entry receptor function of ACE2 for SARS-CoV-2.

Our findings open new perspectives for the repurposing of melatonergic drugs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.

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cette étude donne toute son importance à la précédente

Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia
Jennifer A. Frontera Alzheimer’s & Dementia® 13 January 2022

Introduction
Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers.

Methods
Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161).

Results
Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD.

Discussion
Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.