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The aim of the paper is twofold: first, to examine the hedging effectiveness of cryptocurrencies and cryptocurrency portfolios for European equities in bearish and bullish market conditions, and second, to contrast cryptocurrencies with gold as a safe haven asset. To this end, daily data from 2018 to 2022 were employed in a linear and nonlinear Autoregressive Distributed Lag (ARDL) framework. The findings have significant implications for investors, financial intermediaries and regulators. © 2023 Elsevier B.V.
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Background: Patients with autoimmune systemic diseases have an increased risk to contract infections and develop severe complications;infections in turn can reactivated and worsen the disease itself in a vicious circle. Thus, vaccination is the main weapon to prevent infectious diseases and represents an important and safe instrument of care for rheumatic patients that needs to be further promoted. However, the immunosuppressive drugs used to treat rheumatic diseases may impair response to vaccines, in particular those targeting B or T cells directly (1). Objectives: The aim of this study is to evaluate the B and T-cell mediated immune response to mRNA vaccination in patients with systemic autoimmune diseases, such as vasculitis or systemic connective tissue diseases, early or continuously treated with B-cell targeting therapies, rituximab (RTX) or beli-mumab (BEL), by comparing with controls and each other. Secondary we evaluated the in vitro effective neutralizing capacity in belimumab-exposed patients. Methods: Twenty-eight consecutive patients under treatment with rituximab (RTX, n=11) or belimumab (BEL, n=17) and 13 age/sex matched controls (non-rheumatic healthcare personnel) were enrolled in the study. Nobody presented anti-SARS-CoV2 antibodies related to previous viral contact and all were always negative at the molecular swab monthly control. All patients and controls received mRNA vaccines and were tested three to four weeks after complete vaccination. All RTX patients started vaccination within 5 months from the last infusion, and all but one of them were B-cell depleted. Anti-SARS-CoV-2 RBD total antibodies were analysed by a diagnostic assay (Elecsys, Roche) while T-cell response was evaluated using the IGRA test (Euroimmun). A subgroup of BEL-patients was tested with pseudovirus neutralization assay. Results: Detectable anti-SARS-CoV2 RBD antibodies were documented in 1/11 RTX patients versus 16/17 BEL patients (p<0.0001). The median concentration was signifcantly lower than that observed in controls (39.6 AU/ml vs 1133 AU/ml, p<0.0001). A very low titer of anti-RBD antibodies were documented only in 1 out of 11 patients in the RTX subgroup (0.93 U/ml, positive if >0,79 U/ml) and the patient was the only one who showed an initial B-cell recovery (CD19+ B-cell 5 cells/microL). Anti-RBD antibodies were documented in 16 out 17 of patients in the BEL subgroup. The median anti-RBD antibody titer in patients receiving BEL was 243 [77.55-744.0] U/ml, and it was signifcantly lower compared to the controls (p=0.002). The IGRA test was positive in 8/11 (72.7%) RTX patients vs 16/17 (94.1%) BEL patients (p=0.7), with interferon release comparable to control subjects (p=0.2). Six patients with BEL were also stratifed according to total antibodies (IgG+I-gA+IgM) against-RBD into high responders (>800 AU/mL, n=3) and low responders (≤45 AU/mL, n=3) and tested with pseudovirus neutralization assay. Two thirds of low titer group of patients neutralized the Wuhan-Hu1 strain at medium-low titer (IC50 ≈102) but were almost ineffective in inhibiting the B.1.1.7 entry into target cells (IC50 =10). Regarding high responders, while two patients were able to inhibit both the strains at medium-high titer (approximately IC50 ≈103 for Wuhan-Hu1 and B.1.1.7), one patient neutralized only the WT strain. Conclusion: B-cell targeting therapies do not preclude SARS-CoV-2 vaccination since a cellular immunity can raise even in the absence of circulating B cells. Most importantly, the immunogenicity of COVID-19 vaccination in SLE patients treated with belimumab is supported. However, patients showing the lowest humoral response to vaccine could remain at higher risk of infections, due to low neutralizing capacity.
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Background: COVID-19 is a systemic viral disease currently spreading as a pandemic. A more severe course and prognosis of COVID-19 in systemic lupus erythematosus (SLE) and vasculitis has been reported (1). Several papers have focused on the concerns, healthcare-related behaviors and psychological impact of COVID-19 pandemic among patients with rheumatic diseases, and specifically on SLE patients, showing a trend towards remarkable psychological distress (2-4). To date, no investigation on the psychological effects of quarantine strategy on SLE patients has been carried out. Objectives: To investigate the psychological impact of the lockdown measures adopted in Italy to contrasting the COVID-19 outbreak, on patients with SLE as compared to the general population. Methods: Patients affected by SLE were given an online questionnaire focused on psychological impact and self-perception during the lockdown measures contrasting the COVID-19 outbreak. The survey was focused on COVID-19 concerns, emotional impact, self-perception and changes in daily living activities and relationships. Results were compared with those of PRESTO (imPact of quaRantine mEasures againST cOvid19) project, an Italian survey, which used the same questionnaire, directed to the general population, with or without chronic diseases. A propensity matching procedure has been applied to LEPRE (Lupus Erythematosus PRESTO project) cases and the PRESTO responders with a ratio of 2 versus 1. Results: 64 patients and 1114 unselected people completed the survey. After the matching procedure, patients were compared to 128 matched adults. Missing data were below 6%. The median age among patients was 43 years (I-III interquartile range 35-54.5), 88% were female and 100% Caucasian. The SLE subjects live mainly in detached houses (38/64 vs 348/1114, p<0.0001), having access to a private garden (52/64 vs 625/1112, p<0.0001) and also owning a pet (43/64 vs 508/1114, p<0.001), in comparison with the PRESTO sample living mainly in flats. The psychological impact measured by IES-R, GHQ.12, and CEDS scores were not statistically different between patients and the general population, such as globally COVID-19 concerns and feelings. However, patients perceived more difficulty to find some free time and enjoy it (13/60 vs 48/121, p=0.01) and to be able to solve own problems (47/61 vs 71/120, p=0.02). On the contrary, patients felt more able to cope with the problem and less sad or depressed in comparison with the PRESTO group (17/61 vs 13/120, p=0.003). Moreover, patients missed playing sports/exercise less than general population (12/63 vs 46/128, p=0.02), while they felt more the distance from family and relatives (45/63 vs 42/86, p<0.0001). Conclusion: the COVID-19 pandemic didn't unveil a greater psychological fragility of people living with SLE than the others. By contrast, a coping strategy, including the role of the family and the lifestyle, contributes to resilience of SLE in difficult scenarios such as those presented by the pandemic.
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Aim: To describe the standardized methodology of the clinical-functional-radiological pulmonary follow-up (F-up) planned for COVID-19 patients discharged from the Pisa University Hospital, Italy. Methods: COVID-19 patients are identified by Hospital Discharge Form code. One month after discharge (T1), symptoms are assessed through a telephone questionnaire. Three months after discharge (T3), patients are proposed to undergo: pulmonary visit, spirometry, plethysmography, DLCO, ABG analysis (if SpO2<95%), chest CT, chest ultrasound, blood test, salivary test. Subsequent F-up for individual patients is based on the combination of standardized comparisons of chest CT (T3 vs. baseline), lung function (presence/absence of spirometric and/or DLCO abnormalities at T3) and respiratory symptoms (T3 vs. T1), as follows: (A) worsening/occurrence of COVID-19 pneumonia chest CT signs, regardless of functional abnormalities and/or respiratory symptoms;F-up is planned at 6 months (T6), with chest CT and clinical-functional evaluation. (B) stability/improvement of COVID-19 pneumonia, with (B1) or without (B2) functional abnormalities and/or respiratory symptoms;F-up is planned at 12 months (T12) with chest CT for both (B1) and (B2), and at T6 with clinical-functional evaluation for (B1). (C) complete resolution of COVID-19 pneumonia, regardless of functional abnormalities and/or respiratory symptoms;F-up is planned at T12, with clinical-functional evaluation. Results: Up to 08/10/2020, n=316 patients were discharged (17% hospitalized ≥3 days in ICU). Up to 01/12/2020, n=162/316 (51,3%) underwent T3-F-up;n=60/316 patients (18.9%) waiting for T3-F-up;n=38/316 (18%) lost to F-up;n=31/316 (9.8%) refusing F-up;n=20/316 (6.3%) died after discharge. Among patients who completed T3-F-up, n=12/162 (7,4%), n=33/162 (20,4%), n=32/162 (19,7%), and n=85/162 (52,5%) were assigned to F-up (A), (B1), (B2), and (C), respectively. The worse the radiological imaging, the higher the median age of the patients (74-, 67-, 68-, and 56-years median age, respectively). In n=65/162 (40,1%) patients, chest CT detected collateral findings (e.g., pulmonary nodules). 57,4% of patients showed normal lung function tests, while 24.5% showed a reduction of DLCO. 64,1% of patients were asymptomatic, 32.7% showed improved/stable, and 3% showed worsening respiratory symptoms. Conclusions: More than half hospitalized COVID-19 patients shows complete resolution of pneumonia chest CT signs and normal lung function at T3-F-up. For a disease whose natural history is yet unknown, a standardized clinical-functional-radiological pulmonary evaluation may serve as tentative guideline for planning F-up. To date such an approach is ongoing and under evaluation.