Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay.

Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D3 (25(OH)D3)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D3 followed by treatment as usual (TAU) of daily vitamin D3 daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D3-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups, p = 0.920). We adjusted the length of stay for COVID-19 risk factors (ß = 0.44; 95% CI: -2.17-2.22), and center (ß = 0.74; 95% CI: -1.25-2.73). The subgroup analysis in patients with severe 25(OH)D3-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days, p = 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62-1.48, p = 0.850). Serum 25(OH)D3 level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: -2.73, p < 0.001). The intervention with 140,000 IU vitamin D3 + TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D3 levels.

Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial.

BACKGROUND: Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS. METHODS: This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 µg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization. DISCUSSION: Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04536350 . Registered 02 September 2020.

Myocarditis and pericarditis in association with COVID-19 mRNA-vaccination: cases from a regional pharmacovigilance centre.

In this article we summarize suspected adverse events following immunization (AEFI) of pericarditis, myocarditis and perimyocarditis that were reported by our regional pharmacovigilance centre after COVID-19 mRNA-vaccination and discuss their association with these vaccines. Seventeen cases were reported between March and July 2021. Of these, nine had perimyocarditis, five myocarditis and three pericarditis. Twelve patients were male (71%). The median age was 38 years (range 17-88). The most commonly observed presenting symptom was acute chest pain (65%). While 47% of the patients were previously healthy, 53% had at least one pre-existing comorbidity, with hypertension being the most prevalent (24%). The European Society of Cardiology diagnostic criteria for the reported AEFIs were fulfilled in twelve cases (71%). The AEFIs occurred after the first vaccine dose in six cases (35%), after the second vaccine dose in ten cases (59%) and after both doses in one case (6%). The median latency of all AEFIs taken together was 14 days (range 1-28) after the first vaccination and 3 days (range 1-17) after the second one. All patients except one were hospitalized (94%) with a median length of stay of 7.5 days (range 3-13). The majority of patients (n = 11, 65%) did not experience any complications, and 13 (77%) of the patients had recovered or were recovering at the time of discharge. In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible by the pharmacovigilance centre.

High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study-VitCov Trial.

BACKGROUND: The coronavirus disease 19 (COVID-19) pandemic has caused millions of deaths, and new treatments are urgently needed. Factors associated with a worse COVID-19 prognosis include old age (> 65 years), ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19. METHODS: As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000 IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency. DISCUSSION: Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made. TRIAL REGISTRATION: ClinicalTrials.gov NCT04525820 and SNCTP 2020-01401.

Immune thrombocytopenia associated with COVID-19 mRNA vaccine tozinameran - a clinical case and global pharmacovigilance data.

We report the occurrence of immune thrombocytopenia (ITP) in a 77-year-old man a few days after receiving the first dose of the COVID-19 mRNA vaccine tozinameran (Comirnaty®). The patient was treated with systemic corticosteroids, intravenous immunoglobulins and eltrombopag. He elected to proceed with the second dose of tozinameran 14 weeks after the first and his platelet count remained stable under a tapered eltrombopag dose. To our knowledge, this is the first case in which a second tozinameran dose has been administered to a patient who developed presumed secondary ITP after the first vaccination. We also report global pharmacovigilance data for the occurrence of ITP after vaccination with tozinameran.

Cardiovascular adverse effects of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients: Cases from a single pharmacovigilance centre.

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients.