Prevalence and Relationships between Alexithymia, Anhedonia, Depression and Anxiety during the Belgian COVID-19 Pandemic Lockdown.

Alexithymia and anhedonia are associated with psychiatric disorders, such as depression and anxiety. The COVID-19 pandemic lead to a significant deterioration in the mental health of the population. It is therefore important to examine the effects of lockdown on alexithymia and anhedonia and their relationships with anxiety and depression. We compared the scores and characteristics of 286 patients divided into two groups: one before lockdown (group 1, N = 127), the other during the progressive lockdown release (group 2, N = 159). The groups were homogeneous in terms of age, sex ratio, socio-professional categories, and somatic and psychiatric comorbidities. The groups were compared on the Toronto Alexithymia Scale (TAS-20) measuring alexithymia, the Beck Depression Inventory (BDI-II) measuring depression, the anhedonia subscale of the BDI-II measuring state-anhedonia and the State Trait Anxiety Inventory (STAI) measuring state and trait anxiety. The ratio of alexithymic subjects in group 1 is 22.83% to 33.33% in group 2 (p-value = 0.034). This suggests a significant increase in the number of alexithymic patients after lockdown. We did not observe any difference in the proportion of depressed and anxious subjects before or after lockdown. Among the different scales, higher scores were only found on the cognitive factor of alexithymia on group 2 comparatively to group 1. This study indicates an increase in the proportion of alexithymic subjects following lockdown. Unexpectedly, this was unrelated to depression, anxiety or anhedonia levels, which remained stable. Further studies are needed to confirm this result and to evaluate precisely which factors related to the lockdown context are responsible for such an increase.

Association of Amlodipine with the Risk of In-Hospital Death in Patients with COVID-19 and Hypertension: A Reanalysis on 184 COVID-19 Patients with Hypertension.

Association between calcium channel blockers (CCBs) or functional inhibitors of acid sphingomyelinase (FIASMAs) use and decreased mortality in people with COVID-19 has been reported in recent studies. Since amlodipine is both a CCB and a FIASMA, the aim of this study was to investigate the association between chronic amlodipine use and the survival of people with hypertension infected with COVID-19. This retrospective cohort study used data extracted from the medical records of adult inpatients with hypertension and laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged from hospital or deceased) from Erasme Hospital (Brussels, Belgium). We re-analyzed the data of the retrospective cohort study using only the 184 patients (103 males, 81 females) with a mean age of 69.54 years (SD = 14.6) with hypertension. The fifty-five participants (29.9%) receiving a chronic prescription of amlodipine were compared with the 129 patients who did not receive a chronic prescription of amlodipine. Univariate and multivariate logistic regressions were used to explore the relationships between mortality and sex, age, comorbidities, smoking, and amlodipine status. Out of the 184 participants, 132 (71.7%) survived and 52 (28.3%) died. The mortality rates were, respectively, 12.73% (n = 7) and 34.88% (n = 45) for the amlodipine and non-amlodipine groups. Multivariate logistic regression was significant (Chi square (5) = 29.11; p < 0.0001). Chronic kidney disease and malignant neoplasm were significant predictors as well as amlodipine status. For chronic kidney disease and malignant neoplasm, the odds ratio with 95% confidence interval (95% CI) were, respectively, 2.16 (95% CI: 1.04-4.5; p = 0.039) and 2.46 (95% CI: 1.01-6.01; p = 0.047). For amlodipine status the odds ratio was 0.29 (95% CI: 0.11-0.74; p = 0.009). The result of the present study suggests that amlodipine may be associated with reduced mortality in people with hypertension infected with COVID-19. Further research and randomized clinical trials are needed to confirm the potential protective effect of amlodipine in people with hypertension infected with COVID-19.

Difficulty in Repurposing Selective Serotonin Reuptake Inhibitors and Other Antidepressants with Functional Inhibition of Acid Sphingomyelinase in COVID-19 Infection.

The rapid spread of COVID-19 has become a health emergency causing an urgent need for drug treatments to control the outbreak, especially in more vulnerable individuals. This is reinforced by the fact that prophylactic vaccines and neutralizing monoclonal antibodies may not be fully effective against emerging variants. Despite all efforts made by the scientific community, efficient therapeutic options currently remain scarce, either in the initial, as well as in the advanced forms of the disease. From retrospective observational studies and prospective clinical trials, selective serotonin reuptake inhibitors (SSRIs), and other antidepressants with functional inhibition of acid sphingomyelinase (FIASMAs), have emerged as potential treatments of COVID-19. This has led to some prematurely optimistic points of view, promoting a large prescription of fluvoxamine in patients with COVID-19, that we think should be reasonably tempered.

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection.

The SARS-CoV-2 outbreak is characterized by the need of the search for curative drugs for treatment. In this paper, we present an update of knowledge about the interest of the functional inhibitors of acid sphingomyelinase (FIASMAs) in SARS-CoV-2 infection. Forty-nine FIASMAs have been suggested in the treatment of SARS-CoV-2 infection using in silico, in vitro or in vivo studies. Further studies using large-sized, randomized and double-blinded controlled clinical trials are needed to evaluate FIASMAs in SARS-CoV-2 infection as off-label therapy.

Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study.

Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multivariate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21-96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most common comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02-1.07; p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03-4.22; p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27-1.04; p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02-1.07; p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33-5.79; p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23-5.97; p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09-0.62; p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.

Repurposing functional inhibitors of acid sphingomyelinase (fiasmas): an opportunity against SARS-CoV-2 infection?

WHAT IS KNOWN AND OBJECTIVE: Infection by SARS-CoV-2, the virus responsible of COVID-19, is associated with limited treatment options. The purpose of this study was to evaluate the rationale for repurposing functional inhibitors of acid sphingomyelinase (FIASMAs), several of which are approved medicines, for the treatment of SAR-CoV-2 infections. COMMENT: We propose and discuss the FIASMAs' lysosomotropism as a possible explanation for their observed in vitro activities against viruses, and more specifically against infections caused by coronaviruses such as SARS-CoV-2. Successful in vitro-to-in vivo translation of FIASMAs requires that their pharmacokinetics (dosing regimen and drug-drug interactions) are matched with viral kinetics. WHAT IS NEW AND CONCLUSION: Drug repurposing to ensure rapid patient access to effective treatment has garnered much attention in this era of the COVID-19 pandemic. The observed lysosomotropic activity of small-molecule FIASMA compounds suggests that their repurposing as potential drugs against SARS-CoV-2 is promising.

Mental Health Outcomes in Healthcare Workers in COVID-19 and Non-COVID-19 Care Units: A Cross-Sectional Survey in Belgium.

BACKGROUND: The literature shows the negative psychological impact of the coronavirus disease 2019 (COVID-19) outbreak on frontline healthcare workers. However, few are known about the mental health of physicians and nurses working in general hospitals during the outbreak, caring for patients with COVID-19 or not. OBJECTIVES: This survey assessed differences in mental health in physicians and nurses working in COVID-19 or non-COVID-19 medical care units. DESIGN: A cross-sectional mixed-mode survey was used to assess burnout, insomnia, depression, anxiety, and stress. SETTING: A total of 1,244 physicians and nurses from five general hospitals in Belgium, working in COVID-19 care units (CCU), non-COVID-19 care units (NCCU), or both (CCU + NCCU) were informed of the study. PARTICIPANTS: Six hundred forty-seven healthcare workers participated in the survey (response rate = 52%). MEASUREMENTS: Validated instruments were used to assess the outcomes: the PFI (burnout/professional fulfillment), the ISI (insomnia), and the DASS-21 (depression, anxiety, and stress). RESULTS: Results showed high prevalence of burnout, insomnia, depression, and anxiety among participants. After adjusting for confounders, multivariate analysis of variance showed no differences between CCU, NCCU, and CCU + NCCU workers. Univariate general linear models showed higher level of burnout, insomnia, and anxiety among nurses in comparison to physicians. Being a nurse, young, isolated, with an increased workload were risk factors for worse mental health outcomes. LIMITATIONS: The mental health of the tested sample, before the outbreak, is unknown. Moreover, this cross-sectional design provides no information on the evolution of the mental health outcomes over time. CONCLUSION: Directly caring for patients with COVID-19 is not associated with worse mental health outcomes among healthcare workers in general hospitals. High prevalence of burnout, insomnia, depression, and anxiety among physicians and nurses requires special attention, and specific interventions need to be implemented. PROTOCOL REGISTRATION: ClinicalTrials.gov, identifier NCT04344145.