SSRIs in the course of COVID-19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study.

INTRODUCTION: Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels. METHODS: The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed. RESULTS: The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison. CONCLUSIONS: Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

Can selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitor antidepressants decrease the "cytokine storm" in the course of COVID-19 pneumonia?

BACKGROUND: Lots of research has been conducted to fight COVID-19 since the outbreak of the pandemic in 2020. The role of "cytokine storm" in the pathogenesis of COVID-19 pneumonia is well known. Relationship between interleukins and depression is still subject matter of the research, but a correlation between interleukin-6 and depressive disorders is proven by now. The aim of this study is to verify differences among interleukin-6 blood levels of inpatients treated with selective serotonin reuptake inhibitors and/or serotonin and norepinephrine reuptake inhibitor before and during hospitalization and of inpatients not treated with these drugs. METHODS: This is an observational study performed during the first wave of SARS Cov-2 pandemic in Italy for three months. The hospitalized patients of Internal Medicine wards and Infectious and Tropical Diseases ward of Azienda Ospedaliero-Universitaria Careggi of Florence for COVID-19 pneumonia have been divided into two subgroups (treated / not treated with antidepressants). Patients admitted to Intensive Care Unit previously have been excluded. Each patient has been evaluated concerning demographic, clinical and therapeutic features. The first dosage of interleukin-6 detected during hospitalization has been noticed. RESULTS: The entire sample included 402 patients and 8.5% (N.=34) had been treated with an antidepressant of the two considered categories before admission until discharge from hospital. Significant lower levels of interleukin-6 of recovered patients of the treated subgroup have been highlighted as compared to recovered patients of not-treated subgroup (12.1 vs. 25.4 P<0.001). These results have been pointed out in spite of higher mean age and more serious comorbidities of the treated subgroup. Nevertheless, the incidence of severe acute respiratory distress syndrome is significantly lower in the subgroup of patients with antidepressant treatment (20.6% vs. 43.2% P<0.02) as well as endotracheal intubation employment (0.0% vs. 11.7% P<0.04). The rate of deceased patients of treated-subgroup is not significantly lower than the rate of not-treated subgroup (23.5% vs. 26.4% P=0.13). CONCLUSIONS: During COVID-19 pneumonia, the production of interleukin-6 seems to be modulated in presence of antidepressant therapy. Further proofs and broader surveys are necessary.

Immune system and COVID-19 by sex differences and age.

In COVID-19 disease, are reported gender differences in relation to severity and death. The aim of this review is to highlight gender differences in the immune response to COVID-19. The included studies were identified using PubMed, until 30 October 2020. The search included the following keywords: SARS-CoV-2, COVID-19, gender, age, sex, and immune system. Literature described that females compared to males have greater inflammatory, antiviral, and humoral immune responses. In female, estrogen is a potential ally to alleviate SARS-COV-2 disease. In male, testosterone reduces vaccination response and depresses the cytokine response. In the older patients, and in particular, in female older patients, it has been reported a progressive functional decline in the immune systems. Differences by gender were reported in infection diseases, including SARS-CoV-2. These data should be confirmed by the other epidemiological studies.

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Performance status and in-hospital mortality of elderly patients with community acquired pneumonia.

To evaluate the role of performance status evaluated by the Eastern Cooperative Oncology Group (ECOG) score in predicting 30-day mortality in subjects hospitalized for community acquired pneumonia (CAP), this was a prospective study of patients consecutively hospitalized for CAP at a large University Hospital in Italy. Performance status was evaluated using the ECOG score that in a 0-5 point scale indicates progressive functional deterioration. The end-point of the study is the 30-day mortality. Two-hundred-sixteen patients were enrolled, 75.9% were aged > 70 years, 31.5% had severe pneumonia at CURB-65 score (3-4), and 27.5% of patients had severe disability (ECOG 3-4). Thirty-day mortality is 15.3%. Progression in ECOG score independently increases the probability of 30-day mortality at multivariable logistic regression analysis (HR 2.19, 95% CI 1.60-3.01, p < 0.0001). ECOG 3 or 4 determines a four-fold increase in 30-day mortality (HR 4.07, 95% CI 1.84-9.02, p < 0.001). ECOG score 3 or 4 is highly predictive of death in patients classified at low risk of mortality by CURB-65 (0-2 points) score. Functional status is directly related to outcome in elderly patients hospitalized for CAP. The use of a very simple and fast tool, such as the ECOG score, might help to better stratify the risk of short-term mortality, especially in patients otherwise classified at low risk of death by CURB-65 score.

Causes of diplopia in the emergency department: diagnostic accuracy of clinical assessment and of head computed tomography.

BACKGROUND: Studies on frequency and underlying diseases causing binocular diplopia in patients presenting to the emergency department (ED) are lacking. OBJECTIVE: To evaluate the prevalence of different diseases causing diplopia and the role of medical history, clinical examination, and unenhanced head computed tomography (UHCT) in the identification of secondary diplopia. METHODS: Diplopic patients presenting to the ED were enrolled prospectively. Cardiovascular risk factors and associated neurological signs and symptoms were reported. UHCT was performed in the ED. RESULTS: Secondary diplopia was diagnosed in 93 of 260 (35.8%) diplopic patients. Among patients with secondary diplopia, the most frequent diagnoses were stroke (45.2%), multiple sclerosis (18.3%), brain tumors (11.8%), and cerebral aneurysms (7.5%). The prevalence of cardiovascular risk factors was similar in primary and secondary diplopia. Among the 118 (45.4%) patients without associated neurological signs or symptoms (isolated diplopia), secondary diplopia was diagnosed in 13 (11%); UHCT was negative in all 13 cases, with a derived null sensitivity. Eighty of 142 (56.3%) patients with associated signs or symptoms had secondary diplopia. The presence of signs or symptoms associated with diplopia showed a sensitivity of 87% [95% confidence interval (CI): 80-92%] and a specificity of 63% (95% CI: 59-66%) for the diagnosis of secondary diplopia. In this group, UHCT identified 30 of 80 (37.5%) cases, increasing the specificity to 98% (95% CI: 96-99%). CONCLUSION: One-third of diplopic patients had secondary diplopia. In patients with isolated diplopia, UHCT does not increase diagnostic sensitivity. In patients with associated neurological signs or symptoms, the prevalence of secondary diplopia was high and UHCT showed incremental diagnostic value.