Prevalence and factors associated with symptom persistence: A prospective study of 429 mild COVID-19 outpatients.

INTRODUCTION: Persistent symptoms have recently emerged as a clinical issue in COVID-19. We aimed to assess the prevalence and risk factors in symptomatic non-hospitalized individuals with mild COVID-19. METHODS: We performed a prospective cohort study of symptomatic COVID-19 outpatients, from March to May 2020, with weekly phone calls from clinical onset until day 30 and up to day 60 in case of persistent symptoms. The main outcomes were the proportion of patients with complete recovery at day 30 and day 60 and factors associated with persistent symptoms. RESULTS: We enrolled 429 individuals mostly women (72.5%) and healthcare workers (72.5%), with a median age of 41.6 years [IQR 30-51.5]. Symptoms included: cough (69.7%), asthenia (68.8%), anosmia (64.8%), headaches (64.6%), myalgia (62.7%), gastrointestinal symptoms (61.8%), fever (61.5%), and ageusia (60.8%). Mean duration of disease was 27 days (95%CI: 25-29). The rate of persistent symptoms was 46.8% at day 30 and 6.5% at day 60 consisting in asthenia (32.6%), anosmia (32.6%), and ageusia (30.4%). The probability of complete recovery was 56.3% (95%CI: 51.7-61.1) at day 30 and 85.6% (95%CI: 81.2-89.4) at day 60. Factors associated with persistent symptoms were age>40 (HR 0.61), female sex (HR 0.70), low cycle threshold (HR 0.78), and ageusia (HR 0.59). CONCLUSIONS: COVID-19 - even in its mild presentation - led to persistent symptoms (up to one month) in nearly half of individuals. Identification of risk factors such as age, gender, ageusia and viral load is crucial for clinical management and argues for the development of antiviral agents.

Clinical, biological and radiological features, 4-week outcomes and prognostic factors in COVID-19 elderly inpatients.

OBJECTIVE: To describe clinical, biological, radiological presentation and W4 status in COVID-19 elderly patients. PATIENTS AND METHODS: All patients ≥ 70 years with confirmed SARS-CoV-2 infection and hospitalized in the Infectious Diseases department of the Pitié-Salpêtrière hospital, Paris, France, from March 1st to April 15th 2020 were included. The primary outcome was death four weeks after hospital admission. Data on demographics, clinical features, laboratory tests, CT-scan findings, therapeutic management and complications were collected. RESULTS: All in all, 100 patients were analyzed, including 49 patients ≥ 80 years. Seventy percent had ≥2 comorbidities. Respiratory features were often severe as 48% needed oxygen support upon admission. Twenty-eight out of 43 patients (65%) with a CT-scan had mild to severe parenchymal impairment, and 38/43 (88%) had bilateral impairment. Thirty-two patients presented respiratory distress requiring oxygen support ≥ 6 liters/minute. Twenty-four deaths occurred, including 21 during hospitalization in our unit, 2 among the 8 patients transferred to ICU, and one at home after discharge from hospital, leading to a global mortality rate of 24% at W4. Age, acute renal failure and respiratory distress were associated with mortality at W4. CONCLUSION: A substantial proportion of elderly COVID-19 patients with several comorbidities and severe clinical features survived, a finding that could provide arguments against transferring the most fragile patients to ICU.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

The Drosophila wing differentiation factor vestigial-scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc.

Links between genes involved in development, proliferation and apoptosis have been difficult to establish. In the Drosophila wing disc, the vestigial (vg) and the scalloped (sd) gene products dimerize to form a functional transcription factor. Ectopic expression of vg in other imaginal discs induces outgrowth and wing tissue specification. We investigated the role of the VG-SD dimer in proliferation and showed that vg antagonizes the effect of dacapo, the cyclin-cdk inhibitor. Moreover, ectopic vg drives cell cycle progression and in HeLa cultured cells, the VG-SD dimer induces cell proliferation per se. In Drosophila, ectopic vg induces expression of dE2F1 and its targets dRNR2 and string. In addition vg, but not dE2F1, interacts with and induces expression of dihydrofolate reductase (DHFR). Moreover, a decrease in VG or addition of aminopterin, a specific DHFR inhibitor, shift the dorso-ventral boundary cells of the disc to a cell death sensitive state that is correlated with reaper induction and DIAP1 downregulation. This indicates that vg in interaction with dE2F1 and DHFR is a critical player for both cell proliferation and cell survival in the presumptive wing margin area.

Pathological classification and grading of primary ovarian carcinoma: experience of the ARTAC ovarian study group.

One hundred and fifty-seven cases of high stage ovarian carcinomas (FIGO stage III and IV) have been selected for therapeutic protocol under the aegis of ARTAC. One hundred and forty-six cases have been reviewed, of which 15 were peritoneal tumors: eight ovarian tumors were excluded. One hundred and twenty-three primary ovarian carcinomas have been graded and classified. The slides were reviewed independently by three pathologists with a perfect correlation and no significant difference was observed with the initial diagnosis. The World Health Organisation classification of ovarian epithelial tumors was used as a basis for the study (98 serous types, three mucinous tumors, five endometrioid tumors, two clear cell tumors, five mixed epithelial tumors, seven undifferentiated tumors and three unclassified). The adopted grading associates the degree of architecture differentiation and the cytological features using Broder's classification. The architecture grading or degree of differentiation includes well differentiated, moderately differentiated, poorly differentiated and undifferentiated patterns. The nuclear grading is based on pleomorphism of size and form, hyperchromatism, nucleoli, mitotic figures. The proposed grading based on well-known criterions is simple to use and easily reproducible. Grade 1 (6.5%) are well differentiated tumors with no atypia. Grade 2 (17.89%) are moderately well differentiated tumors without nuclear atypia. Grade 3 (32.52%) correspond to moderately well differentiated tumors with nuclear atypia. Grade 4 (43.09%) are poorly differentiated or undifferentiated tumors with nuclear atypia. The authors consider the different correlations between grade, histological type, stage and prognosis. The implications of these findings are discussed and the results are compared to those of the literature.