Specific adverse outcomes associated with selective serotonin reuptake inhibitors use in COVID-19 patients might be potentiated by remdesivir use.

BACKGROUND: Due to non-consistent reports in the literature, there are uncertainties about the potential benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in patients with Coronavirus disease 2019 (COVID-19). AIM: To investigate associations of SSRIs with clinical characteristics and unwanted outcomes among real-life severe and critical COVID-19 patients and their relationship with remdesivir (RDV) use. METHODS: This retrospective cohort study evaluated a total of 1558 COVID-19 patients of the white race treated in a tertiary center institution, among them 779 patients treated with RDV and 779 1:1 case-matched patients. RESULTS: A total of 78 (5%) patients were exposed to SSRIs during hospitalization, similarly distributed among patients treated with RDV and matched patients (5.1 and 4.9%). No significant associations of SSRI use with age, sex, comorbidity burden, and COVID-19 severity were present in either of the two cohorts (p > 0.05 for all analyses). In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher mortality among RDV (adjusted odds ratio (aOR) 2.0, p = 0.049) and matched patients (aOR 2.22, p = 0.044) and with higher risk for mechanical-ventilation (aOR 2.57, p = 0.006), venous-thromboembolism (aOR 3.69, p = 0.007), and bacteremia (aOR 2.22, p = 0.049) among RDV treated patients. CONCLUSIONS: Adverse outcomes associated with SSRI use in COVID-19 patients might be potentiated by RDV use, and clinically significant interactions between these two drug classes might exist. Although our findings raise important considerations for clinical practice, they are limited by retrospective nature of the study, lack of ethnic diversity, and the potential for unmeasured confounding factors. Future studies exploring underlying biological mechanisms are needed.

Patterns of corticosteroid use among remdesivir and matched patients and associated clinical outcomes in hospitalized COVID-19 patients.

INTRODUCTION: We aimed to investigate patterns of corticosteroid use and their relationship with remdesivir use and clinical outcomes in a large real-life cohort of COVID-19 patients treated in a tertiary-level institution. METHODS: We retrospectively analyzed a total of 1558 severe and critical COVID-19 patients, including 779 patients treated with remdesivir and 779 matched control patients. RESULTS: A total of 167 (10.7%) patients received none, 710 (45.6%) low, 539 (34.6%) high, and 142 (9.1%) very high corticosteroid doses. Patients treated with remdesivir had significantly longer exposure to corticosteroids, received higher average and maximal daily doses, and cumulative corticosteroid doses. In the multivariate analysis remdesivir use, lower cumulative comorbidity burden, higher severity of COVID-19 symptoms, and mechanical ventilation were recognized as mutually independent predictors of the use of higher corticosteroid doses. Higher corticosteroid doses were associated with significantly increased mortality.Among non-remdesivir treated patients, there was a U-shaped relationship between maximal daily corticosteroid dose and mortality. Among remdesivir treated patients gradual increase in mortality with increasing corticosteroid doses was observed. CONCLUSION: Patterns of corticosteroid use differ regarding the use of remdesivir and may moderate its association with survival among severe and critical COVID-19 patients.

Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients.

COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66-14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29-20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use.

The associations of age, sex, and comorbidities with survival of hospitalized patients with coronavirus disease 2019: data from 4014 patients from a tertiary-center registry.

AIM: To investigate how age, sex, and comorbidities affect the survival of hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 4014 consecutive adults hospitalized for COVID-19 in a tertiary-level institution from March 2020 to March 2021. RESULTS: The median age was 74 years. A total of 2256 (56.2%) patients were men. The median Charlson-comorbidity-index (CCI) was 4 points; 3359 (82.7%) patients had severe or critical COVID-19. A significant interaction between age, sex, and survival (P<0.05) persisted after adjustment for CCI. In patients <57 years, male sex was related to a favorable (odds ration [OR] 0.50, 95% confidence interval [CI] 0.29-0.86), whereas in patients ≥57 years it was related to an unfavorable prognosis (OR 1.19, 95% CI 1.04-1.37). Comorbidities associated with inferior survival independently of age, sex, and severe/critical COVID-19 on admission were chronic heart failure, atrial fibrillation, acute myocardial infarction, acute cerebrovascular insult, history of venous thromboembolism, chronic kidney disease, major bleeding, liver cirrhosis, mental retardation, dementia, active malignant disease, metastatic malignant disease, autoimmune/rheumatic disease, bilateral pneumonia, and other infections on admission. CONCLUSION: Among younger patients, female sex might lead to an adverse prognosis due to undisclosed reasons (differences in fat tissue distribution, hormonal status, and other mechanisms). Patient subgroups with specific comorbidities require additional considerations during hospital stay for COVID-19. Future studies focusing on sex differences and potential interactions are warranted.

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry.

AIM: To evaluate the association of remdesivir use and the survival of hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the medical records of 5959 COVID-19 patients admitted to our tertiary-level hospital from March 2020 to June 2021. A total of 876 remdesivir-treated patients were matched with 876 control patients in terms of age, sex, Charlson comorbidity index (CCI), WHO-defined COVID-19 severity on admission, and oxygen requirement at the time of remdesivir use. RESULTS: Among 1752 COVID-19 patients (median age 66 years, 61.8% men), 1405 (80.2%) had severe and 311 (17.8%) had critically severe COVID-19 on admission. Remdesivir was given at a median of one day after hospital admission and at a median of eight days from the onset of symptoms. Overall, 645 (73.6%) patients received remdesivir before high-flow oxygen therapy (HFOT) or mechanical ventilation (MV), 198 (22.6%) after HFOT institution, and 83 (9.5%) after MV institution. Remdesivir use was associated with improved survival in the entire cohort (hazard ratio 0.79, P=0.006). Survival benefit was evident among patients receiving remdesivir during low-flow oxygen requirement (hazard ratio 0.61, P<0.001) but not among patients who received it after starting HFOT (P=0.499) or MV (P=0.380). CONCLUSION: Remdesivir, if given during low-flow oxygen therapy, might be associated with survival benefit in hospitalized COVID-19 patients.

Impact of an integrated medication reconciliation model led by a hospital clinical pharmacist on the reduction of post-discharge unintentional discrepancies.

WHAT IS KNOWN AND OBJECTIVE: There is no optimal standardized model in the transfer of care between hospitals and primary healthcare facilities. Transfer of care is a critical point during which unintentional discrepancies, that can jeopardize pharmacotherapy outcomes, can occur. The objective was to determine the effect that an integrated medication reconciliation model has on the reduction of the number of post-discharge unintentional discrepancies. METHODS: A randomized controlled study was conducted on an elderly patient population. The intervention group of patients received a medication reconciliation model, led entirely by a hospital clinical pharmacist (medication reconciliation at admission, review and optimization of pharmacotherapy during hospitalization, patient education and counselling, medication reconciliation at discharge, medication reconciliation as part of primary health care in collaboration with a primary care physician and a community pharmacist). Unintentional discrepancies were identified by comparing the medications listed on the discharge summary with the first list of medications prescribed and issued at primary care level, immediately after discharge. The main outcome measures were incidence, type and potential severity of post-discharge unintentional discrepancies. RESULTS AND DISCUSSION: A total of 353 patients were analysed (182 in the intervention and 171 in the control group). The medication reconciliation model, led by a hospital clinical pharmacist, significantly reduced the number of patients with unintentional discrepancies by 57.1% (p < 0.001). The intervention reduced the number of patients with unintentional discrepancies associated with a potential moderate harm by 58.6% (p < 0.001) and those associated with a potential severe harm by 68.6% (p = 0.039). The most common discrepancies were incorrect dosage, drug omission and drug commission. Cardiovascular medications were most commonly involved in unintentional discrepancies. WHAT IS NEW AND CONCLUSION: The integrated medication reconciliation model, led by a hospital clinical pharmacist in collaboration with all health professionals involved in the patient's pharmacotherapy and treatment, significantly reduced unintentional discrepancies in the transfer of care.