ABSTRACT
Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.
ABSTRACT
Background: Patients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments. Objectives: Our long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the frst 3 pandemic waves. Methods: A large series of 3,918 ASD patients (815 M, 3103 F;mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1). Results: A signifcantly increased prevalence of COVID-19 (8.37% vs 6.49%;p<0.0001) was observed in our ASD patients, while the cumulative death rate revealed statistically comparable to the Italian general population (3.65% vs 2.95%;p: ns). In particular, among the 328 ASD patients complicated by COVID-19, 57 (17%) needed hospitalization, while mild-moderate manifestations were observed in the large majority of individuals (83%). In addition, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular manifestations. Interestingly, a signifcantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%;p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients' older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a signifcantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%;p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%;p=0.000). Conclusion: The cumulative impact of COVID-19 on ASD patients after the frst 3 pandemic waves revealed less severe than that observed during the frst phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series. Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients' population. Of note, a signifcantly increased COVID-19-related mortality was recorded in only SSc patients' subgroup, possibly favored by pre-existing lung fbrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy. Besides SSc, the patients' subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.
ABSTRACT
Background: SARS-CoV-2 infection poses a serious challenge for patients with rheumatic autoimmune systemic diseases (ASD), characterized by marked immune-system dysregulation and frequent visceral organ involvement. Objectives: To evaluate the impact of COVID-19 pandemic in a large series of Italian patients with ASD. Methods: Our multicenter telephone survey (8-week period, March-April 2020) included a large series of 2,994 patients (584 M, 2,410 F, mean age 58.9±13.4SD years) with ASD followed at 34 tertiary referral centers of 14 regions of northern, central, and southern Italian macro areas, characterized by different prevalence of SARS-CoV-2 infection. According to currently used criteria, COVID-19 was classified as definite COVID-19 (signs or symptoms of COVID-19 confirmed by positive oral/nasopharyngeal swabs at PCR testing) or highly suspected COVID-19 (signs or symptoms highly suggestive of Covid-19, but not confirmed by PCR testing due to limited availability of virological tests in that period). The results were analyzed performing the Odds Ratio by Java-Stat 2-way Contingency Table Analysis. Results: The main findings of the survey study revealed a significantly increased prevalence of COVID-19 in: a.the whole series of ASD patients (definite Covid-19: 22/2994, 0.73%;p=0.0007;definite COVID-19 plus highly suspected Covid-19: 74/2,994, 2.47%;p<0.0001) when compared to Italian general population of COVID-19 infected individuals (349/100000 = 0.34%;data from Italian Superior Institute of Health;h t t p s : / / w w w . e p i c e n t r o . i s s . i t / e n / c o r o n a v i r u s / sars-cov-2-national-surveillance-system). b.the subgroup of patients with connective tissue diseases or systemic vasculitis (n = 1,901) compared to the subgroup of inflammatory arthritis (n = 1,093), namely rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (definite Covid-19: 19/1,901, 0.99%, vs 3/1,093, 0.27%;p=0.036;definite COVID-19 plus highly suspected Covid-19: 69/1,901, 3.6%, vs 5/1,093, 0.45%;p<0.0001) c.the subgroup of patients with pre-existing interstitial lung involvement (n = 526) compared to those without (n = 2,468) (definite Covid-19: 10/526, 1.90%, vs 12/2,468, 0.48%;p=0.0015;definite COVID-19 plus highly suspected Covid-19: 33/526, 6.27%, vs 41/2,468, 1.66%;p<0.0001). Of interest, the prevalence of COVID-19 did not correlate with presence/absence of different comorbidities, mainly diabetes, cardio-vascular and/or renal disorders, as well as of ongoing treatments with biological DMARDs;while patients treated with conventional DMARDs showed a significantly lower prevalence of COVID-19 compared to those without. COVID-19 was more frequently observed in the patients' populations from northern and central compared to southern Italian macro area with lower diffusion of pandemic. Clinical manifestations of Covid-19, observed in 74 patients, were generally mild or moderate;4/9 individuals requiring hospital admission died for severe pneumonia. Conclusion: The prevalence of COVID-19 observed in ASD patients during the first wave of pandemic was significantly higher than that observed in Italian general population;moreover, the actual prevalence of COVID-19 might be underestimated due to the high number of mild variants as well as the possible clinical overlapping between these two conditions. Patients with ASD should be invariably regarded as 'frail patients' during the pandemic course, considering the risk of worse outcome in the acute phase of Covid-19, as well as the potential long-term effects of viral infection. The statistically significant association of COVID-19 with connective tissue diseases/ systemic vasculitis, as well as with pre-existing interstitial lung involvement, suggests the presence of distinct clinico-pathological ASD subsets, characterized by markedly different patients' vulnerability to SARS-CoV-2 infection.
ABSTRACT
Background: Coronavirus disease-19 (COVID-19) has been a major clinical challenge worldwide. Sex, age and comorbidities have been associated with worse outcome in the general population. Systemic sclerosis (SSc) is a severe, autoimmune disease with frequent multi-organ involvement. Objectives: To assess the impact of COVID-19 and to determine factors associated with worse outcome in SSc patients from the European Scleroderma Trial and Research (EUSTAR) database. Methods: SSc patients from the EUSTAR database with COVID-19 were prospectively collected between 15.03.-31.12.2020. Two outcomes were chosen: (1) hospitalization;and (2) severe outcome defined as either non-invasive ventilation, mechanical ventilation/extracorporeal membrane oxygenation (ECMO) or death. General risk factors assessed were sex, age and number of comorbidities. SSc related risk factors were SSc subtype, autoantibodies, disease duration, SSc associated organ manifestations including interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac, gastrointestinal (GI), and musculoskeletal involvement;digital ulcers (DU), CRP at last visit, renal disease (scleroderma renal crisis and SSc associated renal insufficiency), modified Rodnan skin score (mRSS) and immunosuppressive treatment. Descriptive statistics and logistic regression models were applied. Results: In total, 178 European SSc patients with COVID-19 were registered with a median observation time of 5.5 weeks (Table 1). 95 patients (53%) could recall SAR-Cov-2 contact, while 47 (26%) had no contact. 156 (88%) were symptomatic at COVID-19 onset with fever, cough, malaise and dyspnea being most prevalent. Over the disease course, 63 (36%) developed pneumonia. In total, 67/176 (38%) were hospitalized which were in 84% due to COVID-19. 41/170 (24%) had a severe outcome including 21 (12%) deaths. 128 (72%) recovered completely, while 14 (8%) complained of sequela, with 7 (50%) stating respiratory complications. Age, non-SSc comorbidities, presence of ILD, PAH and SSc associated renal or cardiac disease were numerically associated with hospitalization and severe outcome (Table 1). Univariable logistic analyses for hospitalization and severe outcome are shown in Figure 1. In multivariable logistic regression, age (OR 1.03, 95%CI 1.01-1.07, p=0.019), presence of non-SSc comorbidities (OR 2.52, 95%CI 1.16-5.47, p=0.019) and SSc-related renal disease (predicting success perfectly) were associated with hospitalization and for severe outcome age (OR 1.05, 95%CI 1.01-1.08). Conclusion: SSc patients at older age, with non-SSc comorbidities, SSc related renal disease or ILD are at risk of a more severe outcome and should follow precautions to avoid COVID-19 infections and need careful monitoring in case of COVID-19.
ABSTRACT
BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.