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Objectives To assess the time to resolution of respiratory and systemic symptoms and their associated factors in outpatients during the coronavirus disease 2019 (COVID-19) pandemic. Methods Cohort study including adult outpatients, managed with Covidom, a telesurveillance solution, with RT-PCR-confirmed diagnosis, from 9 March 2020 until 23 February 2021. Follow up was 30 days after symptom onset. Results Among the 9667 patients included, mean age was 43.2 ± 14.0 years, and 67.5% were female (n = 6522). Median body mass index (BMI) was 25.0 kg/m2 (interquartile range 22.1–28.8 kg/m2). Main co-morbidities were: hypertension (12.9%; n = 1247), asthma (11.0%; n = 1063) and diabetes mellitus (5.5%; n = 527). The most frequent symptom during follow up was dyspnoea (65.1%; n = 6296), followed by tachypnoea (49.9%; n = 4821), shivers (45.6%; n = 4410) and fever (36.7%; n = 3550). Median times to resolution of systemic and respiratory symptoms were 3 days (95% CI 2−4 days) and 7 days (95% CI 6−8 days), respectively. Ultimately, 17.2% (95% CI 15.7%−18.8%) still presented respiratory symptoms at day 30. Longer time to respiratory symptom resolution was associated with older age, increased BMI, chronic obstructive pulmonary disease, coronary artery disease, asthma and heart failure. Regarding systemic symptoms, coronary artery disease, asthma, age above 40 years and elevated BMI were associated with longer time to resolution. Conclusions Time to symptom resolution among outpatients with COVID-19 seemed shorter for systemic than respiratory symptoms. Prolonged respiratory symptoms were common at day 30. Risk factors associated with later resolution included age, and cardiovascular and pulmonary diseases.

Meningeal solitary fibrous tumors (SFT), like somatic SFT, are characterized by the NAB2-STAT6 fusion gene. This fusion induces the nuclear relocation of the STAT6 transcription factor and the activation of EGR transcription, increasing proliferation. Meningeal SFT cells, like meningioma cells, are positive for prostaglandin-D2-Synthase (PGDS), a specific marker of meningeal, especially arachnoid, cells. In Part 1, we showed that benign SFT can transform into malignant TFS - formerly hemangiopericytomas - and we reported the therapeutic efficacy of pazopanib, an inhibitor of vascular endothelial growth factor. Part 2 is devoted to the molecular study of SFT: the comparison of the exome of pairs of SFT, a grade I primary and grade III recurrence, brought out the pathogenic variant of TP53 c.743G> T. The transcriptome of meningeal SFT showed the aggregation of SFT from all localizations, distinct from meningiomas. Part 3 presents the modeling of meningeal SFT in genetically modified mice by the introduction of two NAB2-STAT6 fusion genes (exons 2-16 and 6-17). The RCAS-NAB2-STAT6 retroviruses, injected at birth into the subdural space of PGDS-tva mice, specifically infect arachnoid cells. After more than a year of follow-up, the animals did not develop any SFT. It is likely that, as in many other tumor models, fusion is not sufficient to induce tumor development. In Part 4, we adapted the iDisco method, which usually allows three-dimensional visualization of brain samples, for mouse embryos and whole skulls, and described the expression of PGDS in mice in situ, between the 11th post-conception day and the 7th post-natal day. It is located in the meninges at the skull base in the early stages and at the convexity after birth, and also in the radial glia., Les tumeurs fibreuses solitaires (TFS) méningées, comme les TFS somatiques, sont caractérisées par la présence d’un gène de fusion NAB2-STAT6. Cette fusion induirait la relocalisation nucléaire du facteur de transcription STAT6 et l’activation de la transcription des EGR, augmentant la prolifération. Les cellules des TFS méningées sont, comme celles des méningiomes, positives pour la prostaglandine-D2-Synthase (PGDS), présentes dans les méninges, en particulier l’arachnoïde. Dans la 1ère partie, nous avons montré que les TFS bénignes peuvent se transformer en TFS malignes - anciennement hémangiopéricytomes - et nous avons rapporté l’efficacité thérapeutique du pazopanib, inhibiteur de facteur de croissance de l’endothélium vasculaire. La 2ème partie est consacrée à l’étude moléculaire des TFS : la comparaison de l’exome de paires de TFS, avec un primitif de grade I et la récidive de grade III, a permis d’identifier le variant pathogène de TP53 c.743G>T. L’étude du transcriptome des TFS méningées a mis en évidence l’agrégation des TFS de toutes localisations entre elles, bien distinctes des méningiomes. La 3ème partie présente la modélisation des TFS méningées chez des souris génétiquement modifiées par introduction de deux gènes de fusion NAB2-STAT6 (exons 2-16 et 6-17). Les rétrovirus RCAS-NAB2-STAT6, injectés à la naissance dans l’espace sous-dural de souriceaux PGDS-tva infectent spécifiquement les cellules arachnoïdiennes. Après plus d’un an de suivi, les animaux n’ont développé aucune TFS. Il est probable que, comme dans plusieurs autres modèles tumoraux, la fusion ne suffise pas à induire le développement des tumeurs. Dans la 4ème partie nous avons adapté la méthode iDisco, qui permet l’immunomarquage et la visualisation en trois dimensions d’échantillons cérébraux, aux embryons de souris et aux crânes entiers, et décrit in situ l’expression de PGDS chez la souris, entre le 11ème jour post-conception et le 7ème jour post-natal. Elle concerne la méninge de la base du crâne aux stades précoces et la convexité en post-natal, mais également des cellules de la glie radiaire.

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