Risk of vaso-occlusive episodes in patients with sickle cell disease exposed to systemic corticosteroids: a comprehensive review.

INTRODUCTION: Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is caused by a single amino acid mutation on the beta-globin chain, which lead to red blood cell deformation, haemolysis, and chronic inflammation. Clinical consequences are vaso-occlusives crisis, acute chest syndrome, thrombosis, infection, and chronic endothelial injury. AREAS COVERED: Corticosteroids are an old therapeutic class, that are inexpensive and widely available, which can be administered in different forms. Their adverse effects are numerous and well-known. This class could appear to be useful in SCD treatment due to its anti-inflammatory effect. Moreover, corticosteroids remain an essential therapeutic class for many indications, besides SCD. Although specific adverse effects of corticosteroids have been suspected in SCD patients for decades, recent papers has reported strong evidence of specific and severe adverse effects in this population. Based on a literature review, we will discuss pathophysiological considerations, consequences, and practical use of corticosteroids in SCD. EXPERT OPINION: High corticosteroid doses, for any indication , induce vaso-occlusive crises, acute chest syndrome, and re-hospitalization in patients with SCD. There is no evidence of any benefits of corticosteroid use in the SCD acute events. Prevention by hydroxyurea and/or red blood cell transfusion or exchange should be discussed when corticosteroid use is indispensable.

Increased Reporting of Venous and Arterial Thromboembolic events reported with Tixagevimab-Cilgavimab for COVID-19.

OBJECTIVES: Since in two phase 3 clinical trials, there were a disproportion of number of thromboembolic events in the tixagevimab/cilgavimab group than in placebo group, there is a cardiovascular safety concerns with the use of this Anti-SARS-COV-2 Monoclonal Antibody. Whether tixagevimab/cilgavimab use in real life context increases the risk for of thromboembolic events is unclear. METHODS: We used VigiBase, the World Health Organization's individual case safety reports database, to assess the risk of reporting arterial or venous thromboembolic events in COVID-19 patients (≥12 years) exposed to tixagevimab/cilgavimab compared with COVID-19 patients exposed to other anti-SARS-CoV-2 mAbs, including casirivimab/imdevimab, bamlanivimab/etesevimab and sotrovimab. RESULTS: Among the 8,952 reports of patients with an anti-SARS-CoV-2 mAb, 31 reports of thromboembolic events associated with tixagevimab/cilgavimab, mainly deep vein thrombosis (10), pulmonary embolism (8) and myocardial infarction (7). Compared with other anti-SARS-CoV-2 mAbs, the use of tixagevimab/cilgavimab was associated with an increased risk of reporting arterial thromboembolic events (Reporting Odds Ratio (ROR) 3.25; 95%CI 1.73, 6.10). Concerning venous thromboembolic events, a significant increase in the risk of reporting was observed with use of tixagevimab/cilgavimab (ROR 3.59; 95%CI 2.16, 5.96). CONCLUSIONS: This observational study corroborate in a real-world setting, the cardiovascular safety signal already found with tixagevimab/cilgavimab in two clinical trials. Owing these thromboembolic safety concerns and considering the lack of clinical trials supporting a protection against the omicron variant, there is an urgent need to improve knowledge on the effectiveness of tixagevimab/cilgavimab with new COVID-19 variants.

IgA vasculitis following COVID-19 vaccination: A French multicentre case series including 12 patients.

OBJECTIVE: The worldwide COVID-19 vaccination campaign triggered several autoimmune diseases. We hereby aimed to describe IgA vasculitis (IgAV) following COVID- 19 vaccination. METHODS: We conducted a French national multi-centre, retrospective study of new onset adult IgAV diagnosis following COVID-19 vaccination. RESULTS: Twelve patients with a new onset IgAV were included. Five were women (41.6%), and the median age was 52,5 years IQR [30.75-60.5]. Ten received an mRNA vaccine. Two patients received a viral vector vaccine. The median time from vaccination to onset of symptoms was 11.5 days with an IQR of [4.25-21.25]. The vasculitis occurred after the first vaccine dose in most patients (n=8). All patients had skin involvement, with skin necrosis in four patients. Seven patients had joint involvement and 2 had arthritis. Four had non-severe gastrointestinal involvement. Two had non-severe renal involvement. Median C-reactive protein was 26 mg/l [10-66.75], median creatininaemia was 72 µmol/l [65-81], one patient had eGFR < 60 ml/min at management. All patients received a treatment, including glucocorticosteroids in 9 patients (75%). Five patients received a vaccine dose after developing IgAV, one of them experienced a minor cutaneous relapse. CONCLUSION: Baseline presentation of IgAV following COVID-19 vaccination was mild to moderate and outcomes were favourable. Thus, a complete COVID-19 vaccination regimen should be completed in this population. Of note, a fortuitous link cannot be ruled out requiring a worldwide pharmacovigilance search now to confirm these findings.

COVID-19 vaccines: A perspective from social pharmacology.

Social pharmacology is a branch of clinical pharmacology, which depicts relationships between society and drugs and in particular factors, reasons, social consequences of drug use as well as representations of drugs in the society. Recent development and marketing of coronavirus disease 2019 (COVID-19) vaccines raises a number of questions of social pharmacology: are vaccines drugs like any other? What is their perception at the individual, population and societal levels? How do individuals perceive the risks and benefits of these vaccines? What is the perception at the societal level? What is the individual and societal acceptability of these vaccines during a pandemic? All these questions are discussed in the light of recent data. A number of proposals, both at the individual and at the collective or population level, are formulated to help solve these problems of social pharmacology.

Impact of previous exposure to systemic corticosteroids on unfavorable outcome in patients hospitalized for COVID-19.

BACKGROUND: The impact of prior exposure to systemic corticosteroids on COVID-19 severity in patients hospitalized for a SARS-CoV-2 pneumonia is not known. The present study was designed to answer to this question. METHODS: The population study was the Covid-Clinic-Toul cohort which records data about all hospitalized patients with a positive reverse transcriptase polymerase chain reaction for a SARS-CoV-2 infection at Toulouse University hospital, France. Exposure to systemic corticosteroids was assessed at hospital admission. A propensity score (PS) according to corticosteroid exposure was calculated including comorbidities, clinical, radiological and biological variables that impact COVID-19 severity. The primary outcome was composite, including admission to intensive care unit, need of mechanical ventilation and death occurring during the 14 days after hospital admission. Logistic regression models adjusted for the PS (overlap weighting) provided odds ratios (ORs) and their 95% confidence intervals (95% CIs). RESULTS: Overall, 253 patients were included in the study. Median age was 64 years, 140 patients (59.6%) were men and 218 (86.2%) had at least one comorbidity. Seventeen patients (6.7%) were exposed to corticosteroids before hospital admission. Chronic inflammatory disease (n = 8) was the most frequent indication. One hundred and twenty patients (47.4%) met the composite outcome. In the crude model, the OR of previous exposure to systemic corticosteroids was 1.64; 95% CI: 0.60-4.44. In the adjusted model, it was 1.09 (95% CI: 0.65-1.83). CONCLUSION: Overall, this study provide some evidences for an absence of an increased risk of unfavorable outcome with previous exposure to corticosteroids in the general setting of patients hospitalized for COVID-19.

Outcome of patients hospitalized for COVID-19 and exposure to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in France: results of the ACE-CoV study.

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID-19 with hypertension/cardiovascular disease, particularly in Europe. The ACE-CoV study was designed to assess this question. The study was conducted in the Covid-Clinic-Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS-CoV-2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid-Clinic-Toul included 263 patients. Among them, 111 were included in the ACE-CoV study population. In OW-PS-adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73-3.33). It was 0.99 (95% CI: 0.68-1.45) for ACEIs and 1.64 (95% CI: 0.77-3.50) for ARBs. Analyses with weighting by the IPTW-PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE-CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID-19 with a history of cardiovascular disease/arterial hypertension.