Remdesivir use in severe and critical COVID-19 patients might be associated with lower incidence of arterial thrombotic events.

INTRODUCTION: Venous thromboembolism (VTE) and arterial thrombotic (AT) events are a striking feature of severe COVID-19, however, relationship of remdesivir use and the risk of thrombotic events is unknown and has not been investigated before. METHODS: We retrospectively analyzed a cohort of 876 consecutive hospitalized severe and critical COVID-19 patients who were treated with remdesivir and compared them to 876 case-matched control patients. All patients were treated in our tertiary-level institution in period from 10/2020 to 6/2021. VTE and AT were diagnosed by objective imaging and laboratory methods. RESULTS: After exclusion of 71 VTE and 37 AT events present at the time of hospital admission, there were a total of 70 VTE (35 in the remdesivir and 35 in the control group) and 38 AT events occurring during hospitalization (13 in the remdesivir and 25 in the control group). There was a similar cumulative post-admission VTE incidence among both remdesivir and matched control patients (P = 0.287). Significantly lower cumulative post-admission AT incidence was observed among patients treated with remdesivir than among matched control patients (1.7% vs 3.3%, HR = 0.51, P = 0.035). Tendency for lower AT rates was evident in subgroups of patients stratified according to the type of AT, as well as according to the intensity of required oxygen supplementation at the time of remdesivir use. CONCLUSION: Remdesivir use in severe and critical COVID-19 patients might be associated with lower occurrence of AT during hospitalization, whereas similar rates of VTE events were observed among both patients treated with remdesivir and control patients.

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.

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.

Risks associated with prior oral anticoagulation use in hospitalized COVID-19 patients - A retrospective cohort study on 5392 patients from a tertiary centre.

INTRODUCTION: There are conflicting data on prior oral-anticoagulant (OAC) use and outcomes of hospitalized COVID-19 patients. Due to uncertainties regarding associated risks with the prior OAC use, we have investigated this issue in a large cohort of hospitalized COVID-19 patients from our institution. METHODS: We have retrospectively evaluated a total of 5392 consecutive COVID-19 patients hospitalized in our tertiary center institution in period 3/2020 to 6/2021. Majority of patients received low-molecular-weight-heparin thromboprophylaxis and corticosteroids during hospitalization. Patients' characteristics and clinical outcomes were documented as a part of a hospital registry project and were evaluated according to the prior non-OAC, warfarin and direct oral anticoagulants (DOAC) use. RESULTS: Median age was 72 years, median Charlson comorbidity index (CCI) was 4 points. There were 56.2% male patients. Majority of patients had severe (70.5%) or critical (15.8%) COVID-19 on admission. A total of 84.8% patients did not receive prior OAC, 9% were previously anticoagulated with warfarin and 6.2% were previously anticoagulated with DOACs. In the multivariate regression analyses, prior warfarin use was associated increased in-hospital mortality (OR 1.24, P = 0.048) independently of older age (OR 2.12, P < 0.001), male sex (OR 1.27, P < 0.001), higher CCI (OR 1.26, P < 0.001) and severe or critical COVID-19 on admission (OR 22.66, P < 0.001). Prior DOAC use was associated with higher occurrence of major bleeding (OR 1.72, P = 0.045) independently of higher CCI (OR 1.08, P = 0.017). CONCLUSION: Prior OAC use could be associated with worse clinical outcomes during COVID-19 hospitalization. These phenomena might be OAC type specific and persist after multivariate adjustments.

Clinical and prognostic significance of C-reactive protein to albumin ratio in hospitalized coronavirus disease 2019 (COVID-19) patients : Data on 2309 patients from a tertiary center and validation in an independent cohort.

C­reactive protein (CRP) and albumin are inflammation sensitive parameters that are regulated by interleukin­6 inflammatory pathways. The CRP to albumin ratio (CAR) integrates these two into a potent clinical parameter whose clinical and prognostic association in the context of coronavirus disease 2019 (COVID-19) have not been well defined. We aimed to investigate the clinical and prognostic significance of CAR in the context of COVID-19 infection.We retrospectively analyzed 2309 consecutive COVID-19 patients hospitalized at a tertiary level hospital in the period from March 2020 to March 2021 who had baseline data for a CAR assessment. Findings were validated in an independent cohort of 1155 patients hospitalized from March 2021 to June 2021.The majority of patients (85.8%) had severe or critical COVID-19 on admission. Median CRP, albumin and CAR levels were 91 mg/L, 32 g/L and 2.92, respectively. Higher CAR was associated with a tendency for respiratory deterioration during hospitalization, increased requirement of high-flow oxygen treatment and mechanical ventilation, higher occurrence of bacteriemia, higher occurrence of deep venous thrombosis, lower occurrence of myocardial infarction, higher 30-day mortality and higher postdischarge mortality rates. We defined and validated four CAR prognostic categories (< 1.0, 1.0-2.9, 3.0-5.9 and ≥ 6.0) with distinct 30-day survival. In the series of multivariate Cox regression models we could demonstrate robust prognostic properties of CAR that was associated with inferior 30-day survival independently of COVID-19 severity, age and comorbidities and additionally independently of COVID-19 severity, CURB-65 and VACO index in both development and validation cohorts.The CAR seems to have a good potential to improve prognostication of hospitalized COVID-19 patients.

Effects of Long-Term Multimodal Psychosocial Treatment on Antipsychotic-Induced Metabolic Changes in Patients With First Episode Psychosis.

Background: Antipsychotic-induced weight gain and metabolic abnormalities are one of the major challenges in the treatment of psychosis, contributing to the morbidity, mortality and treatment non-adherence. Different approaches were used to counteract these side effects but showed only limited or short-term effects. This study aims to analyse the effects of a long-term multimodal treatment program for first episode psychosis on antipsychotic-induced metabolic changes. Methods: We enrolled 71 patients with first episode psychosis treated at the Zagreb University Hospital Centre from 2016 until 2018. Participants were assigned to one of the two groups: day hospital program vs. treatment as usual (TAU). Outcomes were: body weight, blood glucose, lipids and cholesterol, psychopathology and global level of functioning during the 18-months follow-up. Results: Although the TAU group gained more weight and had higher increase of blood glucose, while the day hospital group had a higher increase in total cholesterol at 18th month follow-up, after the adjustment for age, gender and baseline measures, the type of treatment was not significantly associated with any of the primary outcome measures. Patients' psychopathology measures significantly decreased and their functional level significantly increased at month 18th in both groups. Conclusion: While both types of treatment were effective in reducing psychopathology and restoring the patients' level of functioning, both were relatively ineffective in counteracting antipsychotic-induced metabolic abnormalities and antipsychotic-induced weight gain.