An in‐depth characterization of the incidence, morphology, and onset of COVID‐19‐vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID‐19 vaccination‐related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID‐19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine‐related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID‐19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID‐19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID‐19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.

SummaryPortal thrombosis may complicate the clinical course of cirrhosis, but the pathophysiologic mechanism is unclear. Aim of the study was to evaluate the behavior of clotting system and endotoxemia in portal vein and in peripheral circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt (TIPS).Portal blood showed higher values of Fl+2 [Median (range): 2.5 (1.1-5.3) vs. 1.1 (0.6-2.1) nM, p <0.01], D-dimer [765 (184-1713) vs. 192 (64-813) ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p <0.01] than peripheral circulation. In the portal vein, all but one sample had Fl+2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper limit of control values). Fibrinogen was lower in the portal circulation compared to peripheral circulation but the difference was not significant [85 (58-195) vs. 134 (75-244) mg/dl, p > 0.05].Endotoxemia was directly correlated with Fl+2 (Rho = 0.92 p <0.006) and D-dimer (Rho = 0.93, p <0.005).This study shows that an ongoing prothrombotic state is present in the portal circulation of cirrhotic patients and may play a pivotal role in the thrombotic episodes occurring in this clinical setting.

The Coronavirus Disease (COVID-19) pandemic imposed a high burden of morbidity and mortality. In COVID-19, direct lung parenchymal involvement and pulmonary microcirculation dysfunction may entail pulmonary hypertension (PH). PH and direct cardiac injury beget right ventricular dysfunction (RVD) occurrence, which has been frequently reported in COVID-19 patients; however, the prevalence of RVD and its impact on outcomes during COVID-19 are still unclear. This study aims to evaluate the prevalence of RVD and associated outcomes in patients with COVID-19, through a Systematic Review and Meta-Analysis. MEDLINE and EMBASE were systematically searched from inception to 15th July 2021. All studies reporting either the prevalence of RVD in COVID-19 patients or all-cause death according to RVD status were included. The pooled prevalence of RVD and Odds Ratio (OR) for all-cause death according to RVD status were computed and reported. Subgroup analysis and meta-regression were also performed. Among 29 studies (3813 patients) included, pooled prevalence of RVD was 20.4% (95% CI 17.1–24.3%; 95% PI 7.8–43.9%), with a high grade of heterogeneity. No significant differences were found across geographical locations, or according to the risk of bias. Severity of COVID-19 was associated with increased prevalence of RVD at meta-regression. The presence of RVD was found associated with an increased likelihood of all-cause death (OR 3.32, 95% CI 1.94–5.70). RVD was found in 1 out of 5 COVID-19 patients, and was associated with all-cause mortality. RVD may represent one crucial marker for prognostic stratification in COVID-19; further prospective and larger are needed to investigate specific management and therapeutic approach for these patients.

Manuscript Word Count: 3210 Tables: 3 Figures: 2 References: 36 FUNDING No funding was provided for this project. DISCLOSURES MP reports consultant activity for Boehringer Ingelheim. PMM reports honoraria for lectures as speaker or chair symposia organized by Bayer, Grifols, Kedrion, LFB, Novo Nordisk and Pfizer; scientific consultant for Bayer, Baxalta and Kedrion. GB reports small speaker's fee from Medtronic, Boston, Boehringer and Bayer. GYHL reports consultant activity for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife and Daiichi-Sankyo. Speaker activity for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo. No fees are received personally. All relationship disclosed are related to activities performed outside the submitted work. All other authors have no disclosures to declare.

SummarySince there is some clinical evidence that the clinical course of patients with chronic obstructive pulmonary disease (COPD) may be complicated by thrombosis in the pulmonary vessels, we studied whether a hypercoagulability state (HS) does occur in COPD. Plasma levels of prothrombin F1+2 fragment, a marker of thrombin generation, D-dimer, a marker of in vivo thrombin and plasmin activation, and fibrinogen were measured in 37 COPD patients and in 30 controls matched for sex and age. COPD patients had significantly higher values of F1+2 (p = 0.0001) and fibrinogen (p = 0.0005) than healthy subjects. The difference persisted after excluding smoking patients. F1+2 was not correlated with PaO2 (r = 0.02, p >0.05) and PaCO2 (p = 0.12, p >0.05). In six patients with stable COPD and F1+2 greater than 1.65 nM (mean + 2SD of controls) subcutaneous calcium-heparin therapy (5000 IU t.i.d. for 15 days) significantly reduced F1+2 (p = 0.03) and PaCO2 (p = 0.01). This study shows that COPD patients have an ongoing prothrombotic state which could potentially account for thrombosis occurring in pulmonary vessels. The effect of calcium-heparin treatment on clotting system activation and blood gas may suggest this treatment as potential candidate for prospective study in COPD patients.