ABSTRACT
BackgroundHuman SARS-CoV-2 infection is responsible for a large variety of clinical manifestations related to Coronavirus disease-19 (COVID-19) [1]. SARS-CoV-2 can induce microvascular damage, that can be safely detected by nailfold videocapillaroscopy (NVC), as recently demonstrated [2-4]. Virus-induced endothelial dysfunction has been implicated in the pathogenesis of both active infection and long-COVID clinical manifestations (the last as persistence of disease symptoms after at least three months from onset) [5]. The study group on capillaroscopy and microcirculation in rheumatic diseases of the Italian Society of Rheumatology (CAPSIR) carried out an internal survey on the interest of the Italian Centers that perform NVC in participating in a detailed capillaroscopic and clinical data collection in long-COVID patients.ObjectivesTo carry out an Italian multicenter cognitive survey on the interest in collecting NVC and clinical data of patients affected by long-COVID with or without previous rheumatological diseases.MethodsThe steering committee of the CAPSIR study group formulated a cognitive questionnaire, entitled "Study on the role of capillaroscopy in patients with long-COVID” (CAPSIR_2 Study), consisting of 27 open or multiple-choice questions. A Google Form of the questionnaire was emailed to all the member of the study group between September and October 2022. Data are reported with a descriptive analysis.ResultsThe online questionnaire was completed by 41 CAPSIR members, belonging to 33 different Italian centers. Of note, 63% of participants had already experienced NVC in patients with long-COVID. The primary indication to perform the NVC was the onset of a new Raynaud's phenomenon (46% of cases) and the requests come mainly from General Practitioners (33% of cases). In 2/3 of the cases, patients with long-COVID and previous rheumatic diseases, who underwent NVC examination, represented less than 20% of the total. It should be noted that always in 2/3 of the cases there was no preferential channel for the study of the microcirculation in patients affected by long-COVID nor a NVC investigation prior to the SARS-CoV-2 infection. According to the previous experience of the participants in the interview, the most important NVC parameters considered to be evaluated in long-COVID patients were number of capillaries per linear millimeter (24% of cases), presence of hemorrhages (34% of cases) and giant capillaries (22% of capillaries). All participants (100%) therefore agreed to participate in a further collection of NVC and clinical data in this cohort of patients.ConclusionThis survey highlighted the interest of Italian Rheumatologists in assessing by NVC the COVID-related microvascular involvement. A consensus has emerged that future research is needed. After this pilot survey, the second part of the CAPSIR_2 Study will concern the collection/analysis before and after the SARS-CoV-2 infection of NVC and clinical data in patients with primary and secondary (to rheumatic diseases) Raynaud's phenomenon and affected by long-COVID versus adequate controls. The aim is to investigate if the presence/severity of the microvascular damage might be involved in the pathogenesis of the clinical manifestations observed in COVID-19 patients after the active infection. CAPSIR_2 Study will be open to all Italian rheumatological centers that participated in the previous national CAPSIR_1 Project [6].References[1]Fernandes Q et al. Ann Med. 2022;54:524-540.[2]Cutolo M et al. Nat Rev Rheumatol. 2021;17:665-677.[3]Sulli A et al. Microvasc Res 2022;142:104361.[4]Natalello G et al. Microvasc Res. 2021;133:104071.[5]Charfeddine S et al. Front Cardiovasc Med. 2021;8:745758.[6]Ingegnoli F et al. Reumatismo. 2022;74.AcknowledgementsAuthors wrote the on behalf of the study group on capillaroscopy and microcirculation in rheumatic diseases of the Italian Society of Rheumatology (SIR) - CAPSIR.CAPSIR Study Group thanks the EULAR Study Group of Microcirculation in Rheumatic Diseases for the continuous cultural support.Dis losure of InterestsNone Declared.
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.