ABSTRACT
Background: A novel viral infection known as COVID-19 (Coronavirus-19 disease) spread up in Wuhan (China) in December 2019, but rapidly diffused worldwide and nowadays it remains an international health problem. Because of its impact on immunologic system, immunomodulating therapies have been studied as possible treatments for severe cases of COVID-19. In that context, patients affected by from rheumatic musculoskeletal disorders (RMD) under disease modifying anti-rheumatic drugs (DMARDs) have been observed in several studies to evaluate the impact of COVID-19 on these subjects, well known to be at higher risk of infection. Objectives: The primary objective of this study is to assess prevalence and severity of COVID-19 in patients with RMD under treatment with biologic (b-DMARDs) or targeted synthetic (ts-DMARDs) DMARDs, before the vaccination campaign. The second aim is to compare those data with that in general population of the same Area (Province of Udine, Friuli Venezia Giulia Region, Italy,). Methods: A cohort of RMD patients treated with b-DMARDs or ts-DMARDs was observed from September 2019 to November 2020. Both pandemic waves have been considered, until the start of vaccination (since current variants can overcome vaccine protection), between February 2020 and April 2020 (first wave) and between September 2020 and November 2020 (second one). Results: Among 1051 RMD patients treated with b-or ts-DMARDs COVID-19 prevalence was 3.5% (37 cases) without significant differences compared to general population of the same Region (Table 1). Infected patients were 18 men and 19 women, with a median age of 60 years (IQR 49-68). Notably, the infection rate of RMD patients was significantly lower compared to the general population of the same province, particularly during the second wave (p<0.001, Table 1). Almost all patients reported fever (70%). Gastro-intestinal symptoms (nausea, vomit and diarrhoea) have been recorded in 10 subjects (27%) and resulted significantly associated with longer swab pos-itivity (p<0.05) (Figure 1). Only a small percentage of patients with COVID-19 infection was receiving corticosteroids (8%), and the doses were low (3.5 or 5 mg per day of prednisone equivalents). The most used b-DMARDs were anti-TNFs (24/37, 65%), while just 4/37 (11%) employed JAK inhibitors. A small percentage of patients (6/37, 16%) continued ongoing treatment, with no worsened outcomes, while none preventively suspended the immuno-suppressant. The course of infection was generally benign with a mortality rate of 2.6% (1 patient, with several risk factors) and only 9 patients needed to be hospitalized (24%). After COVID-19 infection, 12 subjects (32%) had RMD flare and 5 of them subsequently needed to change the immunosup-pressive drug. Conclusion: The prevalence of COVID-19 in RMD patients has been confrmed low in both waves and it could be partially explained by the great awareness about preventive strategies by the patients. The benign course of COVID-19 in our patients may be linked to the very low amount of chronic corticosteroids used and the possible protective effect of anti-TNF agents, which were the main class of biologics herein employed. Gastro-intestinal symptoms might be a predictor of viral persistence in immunosuppressed patients. This fnding could be useful to identify earlier COVID-19 carriers with uncommon symptoms (without respiratory manifestations), eventually eligible for antiviral drugs.
ABSTRACT
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.
ABSTRACT
Background:COVID-19 is an emerging infectious disease caused by SARS-CoV-2. Risk factors for the worst outcome in COVID-19 are pre-existing pulmonary and cardiovascular disease, while the impact of chronic immunosuppression has not yet completely been clarified (1).Currently, there is no clinical evidence that chronically immunosuppressed rheumatic patients under biologic agent or a small molecule may have a higher risk of COVID-19 or a worse prognosis(2). However, the anti-CD20 antibody monoclonal rituximab may contribute to severe consequences, inhibiting the humoral response to SARS-CoV-2 and capacity to produce efficient antibodies against it (3,4). Rituximab is widely use in the treatment of ANCA-associated vasculitis (AAV). Nowadays, the incidence and impact of COVID-19 in AAV-patients are still unknown and, in particular, in AAV-patients who have been exposed to rituximab since the outbreak (5).Objectives:Herein we evaluate the incidence and outcome of SARS-CoV-2 infection in our cohort of AAV-patients who had at least one visit in the year 2020.Methods:We collected clinical data of 100 AAV-patients who had at least one visit in our Centre from February 2020 to December 2020, and we described cases of COVID-19 infection among them. The COVID-19 was proved by detection of SARS-CoV-2 RNA in nose-pharyngeal swabs. In case of infection, anti-SARS-CoV-2 IgM or IgG production was then investigated.Results:Among 100 patients (53 females;47 males) regularly followed, the median age was 65, and the mean (SD) duration of disease was 8.8 (6.8) years. The most frequent diagnosis was granulomatosis with polyangiitis (GPA) (56%), followed by granulomatosis eosinophilic with polyangiitis (EGPA) (31%), and microscopic polyangiitis (MPA) (13%). The mean (SD) BVASv3 at the onset of disease was 12.6 (5.6). More than half of the patients (59%) have had lung and/or ENT involvement at the onset of disease. Overall, 84% of our patients received immunosuppressive agents and 45% also received glucocorticoids (GC). Rituximab was administered in 15% of patients during the pandemic. COVID-19 was diagnosed in 2 cases (2%). Both patients have received rituximab as maintenance: the last rituximab infusion was on November 9, 2020 for patient 1 (female, 73 years old, GPA ANCA-PR3+) and was on August 17, 2020 for patient 2 (female, 74 years old, MPA ANCA-MPO+). Both patients had a BVAS 0 and negative ANCA antibodies at the time of the first positive nose-pharyngeal swab RT-PCR test, on December 24 and on November 25, respectively. Both patients were B-cell depleted and IgG levels were 455 mg/dL and 866 mg/dL, respectively. While patient 1 died due to critically ill COVID-19 pneumonia 25 days after the COVID-19 disease onset, patient 2 remained asymptomatic with nose-pharyngeal swab still positive on day 56 after the first detection. Anti-SARS-CoV-2 IgM or IgG antibodies above the cut-off (cut-off value 10 AU/mL) were absent in patient 1, while in patient 2 a low level of anti-SARS-CoV-2 IgG (39 AU/mL, cut-off value 10 AU/mL) was documented.Conclusion:Prevalence of COVID-19 in AAV seems lower than in general population (prevalence of 29582/466700, 6.3%, in the same geographical area). Rituximab compromises the B-cells function and can lead to humoral immunodeficiency, causing the inability to produce anti-SARS-CoV-2 IgG antibodies. The timing of the last rituximab infusion and the levels of IgG can greatly affect the outcome. Patients who underwent anti-CD20 therapy are at higher risk of severe outcome in case of infection (3), and require prioritization for SARS-CoV-2 vaccination.References:[1]Guilpain P, et al. Ann Rheum Dis. 2021;80(1):e10.[2]Quartuccio L, et al. Joint Bone Spine. 2020;87(5):439–43.[3]Benucci M, et al. Ann Rheum Dis. 2020;Aug 4:annrheumdis-2020-218590.[4]Tepasse P-R, et al. Br J Haematol. 2020;190(2):185–8.[5]Kant S, et al. J Nephrol. 2020;J Nephrol. 2020 Oct 8:1-6.Disclosure of Interests:None declared.
ABSTRACT
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.
ABSTRACT
The concluding chapter outlines the main findings of the book concerning the analysis and discussion of new workplaces, specifically, CSs and MSs, in different geographical contexts, by: (i) providing definitions, exploring their typologies, users, and location factors;(ii) investigating the effects on the local context;(iii) exploring urban planning and policies. Several case studies in Europe (Italy, UK, and France) and in the USA have been explored. The results show that the phenomenon is mainly urban, but even suburban and peripheral areas are becoming attractive to new working spaces. Although the book is concerned about the period before the Covid-19 pandemic, this chapter opens the discourse towards the immediate and future effects of the pandemic on the geography of work and new working spaces and suggests new avenues for future research. © 2021, Springer Nature Switzerland AG.