Olfactory dysfunction in COVID-19, new insights from a cohort of 353 patients: The ANOSVID study.

Olfactory disorders (OD) pathogenesis, underlying conditions, and prognostic in coronavirus disease 2019 (COVID-19) remain partially described. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from March 1 2020 to May 31 2020. The aim was to compare COVID-19 patients with OD (OD group) and patients without OD (no-OD group). A second analysis compared patients with anosmia (high OD group) and patients with hyposmia or no OD (low or no-OD group). The OD group presented less cardiovascular and other respiratory diseases compared to the no-OD group (odds ratio [OR] = 0.536 [0.293-0.981], p = 0.041 and OR = 0.222 [0.056-0.874], p = 0.037 respectively). Moreover, history of malignancy was less present in the high OD group compared with the low or no-OD group (OR = 0.170 [0.064-0.455], p < 0.001). The main associated symptoms (OR > 5) with OD were loss of taste (OR = 24.059 [13.474-42.959], p = 0.000) and cacosmia (OR = 5.821 [2.246-15.085], p < 0.001). Most of all ORs decreased in the second analysis, especially for general, digestive, and ENT symptoms. Only two ORs increased: headache (OR = 2.697 [1.746-4.167], p < 0.001) and facial pain (OR = 2.901 [1.441-5.842], p = 0.002). The high OD group had a higher creatinine clearance CKD than the low or no-OD group (89.0 ± 21.1 vs. 81.0 ± 20.5, p = 0.040). No significant difference was found concerning the virological, radiological, and severity criteria. OD patients seem to have less comorbidity, especially better cardiovascular and renal function. Associated symptoms with OD were mostly neurological symptoms. We did not find a significant relationship between OD and less severity in COVID-19 possibly due to methodological bias.

Predicting and treating stress-induced vulnerability to epilepsy and depression.

Accumulation of stressful events can render individuals susceptible to develop epilepsy and comorbidities. Whether such vulnerability can be predicted and reversed is not known. Here we show that social defeat, although not producing depression by itself, produced in 50% of rats reduced threshold for status epilepticus (SE), accelerated epileptogenesis, and once epilepsy was induced, depression-like profile and cognitive deficits. Low serum brain-derived neurotrophic factor (BDNF) levels measured before SE identified this vulnerable population. Treatment with a BDNF analog before SE prevented the occurrence of comorbidities. Thus, vulnerability to comorbidities after epilepsy onset due to unresolved past stressful events may be predicted and reversed.

Vulnerability to depression: from brain neuroplasticity to identification of biomarkers.

A stressful event increases the risk of developing depression later in life, but the possible predisposing factors remain unknown. Our study aims to characterize latent vulnerability traits underlying the development of depressive disorders in adult animals. Four weeks after a priming stressful event, serum corticosterone concentration returned to control values in all animals, whereas the other biological parameters returned to basal level in only 58% of animals (called nonvulnerable). In contrast, 42% of animals displayed persistent decreased serum and hippocampus BDNF concentrations, reduced hippocampal volume and neurogenesis, CA3 dendritic retraction and decrease in spine density, as well as amygdala neuron hypertrophy, constituting latent vulnerability traits to depression. In this group, called vulnerable, a subsequent mild stress evoked a rise of serum corticosterone levels and a "depressive" phenotype, in contrast to nonvulnerable animals. Intracerebroventricular administration of 7,8-dihydroxyflavone, a selective TrkB receptor agonist, dampened the development of the "depressive" phenotype. Our results thus characterize the presence of latent vulnerability traits that underlie the emergence of depression and identify the association of low BDNF with normal corticosterone serum concentrations as a predictive biomarker of vulnerability to depression.

Asthma and Cacosmia Could Be Predictive Factors of Olfactory Dysfunction Persistence 9 Months after SARS-CoV-2 Infection: The ANOSVID Study.

Background. Long-term evolution data of olfactory disorders (OD) in COVID-19 are limited. Method. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from the first wave. The aim was to describe OD evolution, especially in patients with persistent OD (p-OD group) in comparison with patients with resolved OD (r-OD group). Results. Among 354 COVID-19 patients, 229 reported OD were included. Eighty-five percent of patients (n = 195) recovered from their OD within 90 days. However, 9.5 months (in average) after symptoms onset, OD were persisting in 93 patients (40.6%) and resolved in 136 patients (59.4%). In the p-OD group (n = 93), the mean age was 51.4 years (19-98) ± 20.2, and 65 patients (69.9%) were female; the three main comorbidities in the p-OD group were: asthma (20.4%, n = 19), allergic rhinitis (19.4%, n = 18), and arterial hypertension (16.1%, n = 15). Eleven patients (12%) presented anosmia, and 82 patients (88%) presented hyposmia. Asthma was more described in p-OD group than r-OD group (19 (20.4%) versus 10 (7.4%), p = 0.006). Cacosmia was more described in p-OD group than r-OD group (27 (29.0%) versus 18 (13.2%), p = 0.005). There was no significant difference between the two groups concerning other comorbidities and symptoms, clinical, biological, and imaging findings, and outcome or about the impact of OD on the quality of life of the patients between the p-OD group and r-OD group. sQOD-NS brief version score was 10.7 ± 5.89 and 12.0 ± 6.03, respectively (p = 0.137). Conclusion. Forty-one percent of patients with OD reported OD persistence 9.5 months after COVID-19 (hyposmia in 88% of cases). Asthma and cacosmia could be predictive factors of OD persistence.

Chest CT Characteristics are Strongly Predictive of Mortality in Patients with COVID-19 Pneumonia: A Multicentric Cohort Study.

RATIONALE AND OBJECTIVES: The novel coronavirus (COVID-19) has presented a significant and urgent threat to global health and there has been a need to identify prognostic factors in COVID-19 patients. The aim of this study was to determine whether chest computed tomography (CT) characteristics had any prognostic value in patients with COVID-19. MATERIALS AND METHODS: A retrospective analysis of COVID-19 patients who underwent a chest CT-scan was performed in four medical centers. The prognostic value of chest CT results was assessed using a multivariable survival analysis with the Cox model. The characteristics included in the model were the degree of lung involvement, ground glass opacities, nodular consolidations, linear consolidations, a peripheral topography, a predominantly inferior lung involvement, pleural effusion, and crazy paving. The model was also adjusted on age, sex, and the center in which the patient was hospitalized. The primary endpoint was 30-day in-hospital mortality. A second model used a composite endpoint of admission to an intensive care unit or 30-day in-hospital mortality. RESULTS: A total of 515 patients with available follow-up information were included. Advanced age, a degree of pulmonary involvement ≥50% (Hazard Ratio 2.25 [95% CI: 1.378-3.671], p = 0.001), nodular consolidations and pleural effusions were associated with lower 30-day in-hospital survival rates. An exploratory subgroup analysis showed a 60.6% mortality rate in patients over 75 with ≥50% lung involvement on a CT-scan. CONCLUSION: Chest CT findings such as the percentage of pulmonary involvement ≥50%, pleural effusion and nodular consolidation were strongly associated with 30-day mortality in COVID-19 patients. CT examinations are essential for the assessment of severe COVID-19 patients and their results must be considered when making care management decisions.