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
Vitamin D is a hormone rather than a vitamin in the strict sense. In fact, the active form 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] exerts several effects on the inflammatory response of autoimmune rheumatic and infectious diseases. Low serum concentrations (less than 20 ng/ml) of 25-hydroxyvitamin D3 [25(OH)D3], the precursor of 1,25(OH)2D3, are common in COVID-19 patients and are associated with an impairment of the innate (neutrophils, monocytes/macrophages, dendritic cells) and adaptive (T and B lymphocytes, antibodies production) immune responses. Respiratory parameters (partial pressure of arterial oxygen-PaO2, partial pressure of arterial carbon dioxide-PaCO2, pressure of arterial oxygen to fractional inspired oxygen concentration-PaO2/FiO2), radiological pulmonary involvement, and serum concentrations of 25(OH)D3 were evaluated in sixty-five hospitalized COVID-19 patients (mean age 76 +/- 13 years) and sixty-five sex- and age-matched control subjects (CNT). COVID-19 patients showed significant lower 25(OH)D3 serum concentrations than CNT (median 8 ng/ml vs 16 ng/ml, p=0.001). 25(OH)D3 serum concentrations correlated positively with PaO2 (p=0.03) and PaO2/FiO2 (p=0.02). Moreover, 25(OH)D3 serum concentrations were significantly lower in COVID-19 patients with diffuse/severe radiological lung involvement (p=0.05) or multiple lung consolidations (p=0.0001) than in those with mild radiological lung involvement. Finally, significantly lower 25(OH)D3 serum concentrations were found in COVID-19 patients who died during hospitalization, compared to those who survived (p=0.05). In conclusion, vitamin D deficiency is associated with a more severe lung involvement and a higher risk of death in old COVID-19 patients.
ABSTRACT
The SARS-CoV-2 infection causing the Coronavirus disease-19 (COVID-19) is characterized by a broad range of clinical manifestations, implicating microvascular damage with endothelial dysfunction and different organ involvement.
Subject(s)
COVID-19 , Nails , Humans , Nails/blood supply , Capillaries , SARS-CoV-2 , SurvivorsABSTRACT
Background: Human SARS-CoV-2 infection can induce a wide spectrum of organ dysfunctions, including microvascular impairment [1]. S1 subunit of viral receptor-binding domain binds to the angiotensin-converting enzyme 2 receptor on endothelium and S2 subunit allows the virus to enter endothelial cells. The resulting breakdown of barrier integrity drives a cascade of infammatory and thrombotic events, that aggravate the course of COVID-19 together with other risk factors [2-4]. Up to date, a lower capillary density has been reported in several distinct body districts, using sublingual video microscopy, ocular optical coherence tomography angiography, skin functional laser Doppler perfusion imaging and nailfold videocapillaroscopy (NVC) [5-8]. NVC examination has been performed in adult COVID-19 patients, however, without a control group [8]. Objectives: To confrm the statistical signifcance of the reduction in capillary density per linear millimeter evaluated by NVC in comparison with primary Ray-naud's phenomenon (PRP) patients and control subjects (CNT) and to evaluate the impact of an aggressive therapy against COVID-19 on the sparing in the number of capillaries. Methods: Sixty-one COVID-19 survivors, thirty-one PRP patients and thirty CNT age and sex-matched underwent NVC analysis. Demographic and clinical data of COVID-19 survivors were collected with special regard to concomitant therapies, that included antivirals, antibiotics, anticoagulants and anti-infamma-tory/immunomodulant drugs (glucocorticoids, hydroxychloroquine, IL-6 receptor antagonist). COVID-19 survivors were divided in two subgroups according to the severity of the active infection: thirty-four survivors with past mild-moderate disease (either unneedy for oxygen supplementation or need for Venturi mask) and twenty-seven survivors with past severe disease (need for Continuous Positive Airways Pressure and/or mechanical ventilation). The same Rheumatologist performed NVC evaluations in all patients and controls, using an optical probe, equipped with a 200x magnifcation lens and connected to a picture analysis software (Videocap, DS Medica, Milan, Italy). Absolute capillary number per linear millimeter was counted. Results: COVID-19 survivors underwent NVC examination after a mean period of 126±53 days from the disease onset. Multivariate analysis showed differences in absolute capillary number per linear millimeter (p<0.001) after adjusting for age, sex, body mass index, comorbidities and concomitant drugs. The mean (± standard deviation) absolute nailfold capillary number per linear millimeter was signifcantly lower in severe (8.2±1.15) and mild-moderate (8.4±0.75) COVID-19 survivors than in both PRP (8.7±0.68) and CNT subjects (9.3±0.53) (p<0.001). The analysis of the impact of treatments on capillary density in the severe COVID-19 patients showed a positive trend (preservation of the capillary number) with antivirals (no: 7.8±1.53;yes: 8.5±0.64;p=0.35) and anti-IL-6 receptor antagonist administration (no: 7.8±1.36;yes: 8.6±0.74;p=0.16), while none of the other drugs was shown to be effective (glucocorticoids p = 0.46;antibiotics = 0.52;anticoagulants not evaluable as they were used in all COVID-19 patients). Conclusion: SARS-CoV-2 infection seems associated to a signifcant capillary loss as distinctive NVC feature and data concerning the comparison of capillary density pre COVID-19 and post COVID-19 are desirable to reinforce this observation. The positive trend in saving the number of capillaries induced by aggressive anti-infammatory therapies in COVID-19 survivors needs larger cohorts of patients.
ABSTRACT
Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.
ABSTRACT
Background: Vitamin D regulates the innate and adaptive immune system responses and low vitamin D levels have been associated with the increased risk of respiratory tract infections (1). Vitamin D deficiency has been recently reported to interfere with the prognosis of COVID-19 (2,3). Objectives: The aim of this study was to correlate the 25OH-vitamin D serum levels with lung involvement and disease severity, in a cohort of elderly patients hospitalized for SARS-CoV-2 infection. Methods: Sixty-five COVID-19 patients (mean age 76±13 years) and sixty-five sex-and age-matched control subjects (CNT) were included in the study. Respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), clinical and laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein) and type of radiological pulmonary involvement were collected at hospital admission. Statistical analysis was performed by non-parametric tests. Results: Vitamin D sufficiency (≥30 ng/ml), insufficiency (between 20 and 30 ng/ ml), deficiency (between 10 and 20 ng/ml) and severe deficiency (<10 ng/ml) were observed respectively in 11, 11, 21 and 57 % of COVID-19 patients. Vitamin D serum levels were found significantly lower in COVID-19 patients than in CNT (median 8 vs 16 ng/ml, p=0.001). A statistically significant positive correlation was observed between vitamin D serum levels and SO2 (p=0.05), PaO2 (p=0.03), PaO2/FiO2 (p=0.02). A statistically significant negative correlation was found between vitamin D serum levels and severity of radiologic pulmonary involvement: vitamin D was significantly lower in COVID-19 patients with either diffuse/ severe interstitial lung involvement (p=0.05) or multiple lung consolidations (p=0.0001) than in those with mild radiological lung involvement. Significantly lower vitamin D serum levels were found in COVID-19 patients who died during hospitalization, compared to those who survived (median 3 vs 8 ng/ml, p=0.05). Finally, a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p=0.04), C-reactive protein (p=0.04) and disease duration (p=0.05). Conclusion: This study confirms that severe vitamin D deficiency is associated with more severe lung involvement, longer disease duration and risk of death in elderly COVID-19 patients.
ABSTRACT
Background: COVID-19 is a multifaceted condition with a wide range of clinical manifestations, including microvascular/endothelial dysfunction, that starts in the early phase of the disease and may become dramatically harmful in the late stage, causing a massive pro-thrombotic state. Nailfold videocapillaroscopy (NVC) is the most used tool to identify microvascular status in a large spectrum in a cohort of COVID-19 patients (no controls used) [2]. Objectives: To assess microvascular damage in recovered COVID-19 patients (range of 40-270 days from recovery) by considering the previous severity of the disease, and, as mandatory, the comparison with matched individuals suffering from primary Raynaud's phenomenon (PRP) and healthy volunteers (HV). Methods: NVC investigations were performed during standard clinical assessments in forty-four recovered COVID-19 patients (mean age 58±14 years, mean days from disease onset 129±54, mean days from disease recovery 106±52), twenty-two patients with PRP (mean age 60±15 years, mean years from disease onset 11±10) and twenty-two HV (mean age 60±14 years). COVID-19 patients were divided into two subgroups, according to the need of oxygen supplementation: twenty-two patients with severe lung involvement (need of Continuous Positive Airways Pressure and/or mechanical ventilation, mean age 57±12 years) vs twenty-two patients with mild-moderate lung involvement (need of Venturi mask or no need of oxygen supplementation, mean age 59±15 years). Clinical and demographic data of all the enrolled subjects were collected, during NVC examination. The following capillaroscopic parameters were evaluated: capillary number, dilated capillaries, giant capillaries, microhemorrhages, angiogenesis, disorganization of the microvascular array. A validated semiquantitative scoring (0-3) was adopted for NVC abnormalities [3-5]. Statistical analysis was carried out by non-parametric tests. Results: After COVID-19 recovery, no statistically significant difference was observed between COVID-19 patients and control groups of subjects concerning the score for the following NVC parameters: dilated capillaries, giant capillaries, disorganization of the microvascular array, angiogenesis. However, the capillary number per linear millimeter was significantly lower in COVID-19 patients (8.3±0.9) than in PRP (8.8±0.7, p=0.05) and HV (9.3±0.6, p<0.0001). Surprisingly, recovered COVID-19 patients showed significantly less microhemorrhages (score 0.4±0.3) than subjects of the other groups (PRP 0.6±0.5, p=0.01;HV 0.6±0.6, p=0.05). In particular, recovered patients who had more severe COVID-19 showed less microhemorrhages than patients with mild/moderate disease (score 0.18±0.4 vs 0.36±0.5), but this didn't reach the statistical significance (p=0.18). On the other hand, patients recovered from severe SARS-CoV-2 infection also showed higher rate of angiogenesis (0.18±0.4) than patients with mild/ moderate disease (no case, p=0.04). Conclusion: COVID-19 doesn't seem to significantly induce, in short-term, specific alterations in peripheral microvascular array as evaluated by NVC, despite the severity of the disease, except for a significant reduction of the absolute number of nailfold capillaries. The topic needs longer time of evaluation and larger number of COVID-19 recovered cases to also assess the role of concomitant therapies.