How to optimize recruitment strategies of patients with rheumatic and musculoskeletal diseases for online surveys: experience from an international study.

The use of online surveys as a recruitment tool for clinical research has recently expanded; nevertheless, optimal recruitment strategies remain poorly identified. Objectives. The study aimed to identify the most effective recruitment strategies for online research studies and to determine the optimal survey channels for obtaining patients' responses. This is a post-hoc analysis of the ARCOVAX (ArLAR COVID Vaccination) study. Multiple recruitment strategies were disseminated in Arabic, English, and French. The proportion of enrolled patients was correlated with each strategy. Channels used by patients to complete the survey were divided into three categories (social media (SoMe), doctor, and patients' associations). These channels were correlated with the patients' characteristics and the country's Gross Domestic Product (GDP). A total of 1595 patients from 19 Arab countries completed the survey. Patients' mean age was 39 years, 73.2% (1159) were females, 17.8% (284) had a university education level and 93.1% (1468) answered the survey in Arabic. The most effective recruitment strategies were personalized WhatsApp reminders to recruiters (30% of enrolled patients), technical support in response to access issues (27%) and sharing recruitment status by country on a WhatsApp group (24%). The channels used to complete the survey were: SoMe in 45% (711), doctor in 40% (647), and patients' associations in 8.5% (233), and correlated with age and GDP. To optimize recruitment, it is recommended to combine multiple strategies and channels, use the native language and be active (mobilize teams), reactive (provide prompt technical support), and proactive (share regular updates and reminders).

Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ's effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

Difficulties and Psychological Impact of the SARS-CoV-2 Pandemic in Patients with Systemic Lupus Erythematosus: A Nationwide Patient Association Study.

OBJECTIVES: We aimed to evaluate the difficulties encountered by systemic lupus erythematosus (SLE) patients during the early COVID-19 pandemic and to evaluate their impact on patient mental health. METHODS: We conducted a nationwide survey including SLE patients from France, recruited by their treating specialist or through a patient association. The survey was administered online or in paper form between November 2020 and April 2021 and included questions aiming at evaluating the difficulties encountered during the early COVID-19 pandemic (March to August 2020). The impact on mental health was evaluated using the Hospital Anxiety and Depression Scale (HADS) and the Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5). RESULTS: 536 SLE patients (91.9% women) of mean age 50 (±14.1) years responded to the survey. The main reported difficulties were issues regarding access to medical care (n = 136, 25.4%) or hydroxychloroquine treatment (n = 98/389, 25.2%), the loss of employment (n = 85/349, 24.4%), and financial difficulties (n = 75/536, 11%). In 328 patients with complete mental health assessments, 161 (47.2%) screened positive for anxiety, 141 (41.2%) screened positive for depressive syndrome, and 128 (38.7%) screened positive for PTSD. The multivariate analysis showed that female sex (OR = 4.29 [95%CI: 1.39-13.24]), financial issues (OR = 2.57 [1.27-5.22]), and difficulties accessing medical care (OR = 2.15 [1.26-3.69]) or hydroxychloroquine treatment (OR = 1.90 [1.06-3.40]) were independently associated with a positive screening for PTSD. CONCLUSIONS: The COVID-19 pandemic resulted in a severe burden in SLE patients, including difficulties accessing care and treatment along with high psychological distress. Better understanding these difficulties will allow for better prevention and care in times of crisis.

Effect of SARS-CoV-2 Vaccination on Symptoms from Post-Acute Sequelae of COVID-19: Results from the Nationwide VAXILONG Study.

INTRODUCTION: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute sequelae of COVID-19 (PASC). PATIENTS AND METHODS: We conducted a nationwide online study among adult patients with PASC as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PASC symptoms, vaccine type and scheme and its effect on PASC symptoms were studied. RESULTS: 620 questionnaires were completed and 567 satisfied the inclusion criteria and were analyzed. The respondents' median age was 44 (IQR 25-75: 37-50) and 83.4% were women. The initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. A total of 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 (198-431) days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported a global effect on symptoms following the injection, corresponding to an improvement in 21.8% and a worsening in 31%. There were no differences based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. A total of 170 PASC patients had not been vaccinated. The most common reasons for postponing the SARS-CoV-2 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%). CONCLUSION: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PASC patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increasing vaccine coverage in patients with PASC.

Cluster analysis reveals three main patterns of beliefs and intention with respect to SARS-CoV-2 vaccination in patients with autoimmune and inflammatory diseases.

INTRODUCTION: Given the COVID-19 pandemic, it is crucial to understand the underlying behavioural determinants of SARS-CoV-2 vaccine hesitancy in patients with autoimmune or inflammatory rheumatic diseases (AIIRDs). We aimed to analyse patterns of beliefs and intention regarding SARS-CoV-2 vaccination in AIIRD patients, as a mean of identifying pragmatic actions that could be taken to increase vaccine coverage in this population. METHODS: Data relating to 1258 AIIRD patients were analysed using univariate and multivariate logistic regression models, to identify variables associated independently with willingness to get vaccinated against SARS-CoV-2. Subsets of patients showing similar beliefs and intention about SARS-CoV-2 vaccination were characterized using cluster analysis. RESULTS: Hierarchical cluster analysis identified three distinct clusters of AIIRD patients. Three predominant patient attitudes to SARS-COV-2 vaccination were identified: voluntary, hesitant and suspicious. While vaccine willingness differed significantly across the three clusters (P < 0.0001), there was no significant difference regarding fear of getting COVID-19 (P = 0.11), the presence of comorbidities (P = 0.23), the use of glucocorticoids (P = 0.21), or immunocompromised status (P = 0.63). However, patients from cluster #2 (hesitant) and #3 (suspicious) were significantly more concerned about vaccination, the use of a new vaccine technology, lack of long-term data in relation to COVID-19 vaccination, and potential financial links with pharmaceutical companies (P < 0.0001 in all) than patients from cluster #1 (voluntary). DISCUSSION: Importantly, the differences between clusters in terms of patient beliefs and intention was not related to the fear of getting COVID-19 or to any state of frailty, but was related to specific concerns about vaccination. This study may serve as a basis for improved communication and thus help increase COVID-19 vaccine coverage among AIIRD patients.

Incidence and predictors of COVID-19 and flares in patients with rare autoimmune diseases: a systematic survey and serological study at a national reference center in France.

BACKGROUND: The risk of severe COVID-19 and its determinants remain largely unknown in patients with autoimmune and inflammatory rheumatic diseases. The objective of this study was to assess the prevalence of COVID-19 infection in patients followed for rare autoimmune diseases as well as the predictors of COVID-19 and disease flare-ups. METHODS: Cross-sectional phone survey from April 9, 2020, to July 2, 2020, during which patients with autoimmune diseases followed at the National Reference Center for Rare Autoimmune diseases of Strasbourg were systematically contacted by phone and sent a prescription for a SARS-CoV-2 serology. RESULTS: One thousand two hundred thirty-two patients were contacted. One thousand fifty-five patients with a confirmed diagnosis of systemic autoimmune disease were included (4 unreachable, 4 moves abroad, 5 deaths before pandemic, 50 without consent, and 114 without autoimmune disease). Among them, 469 (44.5%) patients were tested for SARS-CoV-2 serology. Thirty-nine patients (7.9%) had SARS-CoV-2 infection (either through chest CT-scan [n = 5], RT-PCR on nasopharyngeal swab [n = 14], or serology [n = 31]) among the 496 who underwent at least one of those 3 diagnosis modalities. Of the 39 proven cases, 33 had clinical manifestations (6 asymptomatic patients were diagnosed through systematic serology testing), 31 were managed by home care, 3 were hospitalized due to a need for oxygenation, two required admission to an intensive care unit, and one died. Among patients with confirmed SARS-CoV-2 infection, reported flares were more frequent than in uninfected patients (26.3% [10/38] vs. 7.0% [32/457], p < 0.0001). Preventive sick leave had no significant impact on the prevalence of SARS-CoV-2 infection (5.8% [3/53]) compared to work continuation (7.6% [30/397], p = 0.64). Overall, the seroprevalence of SARS-CoV-2 was 6.6% (31/469) which was numerically lower to the Grand-Est general population estimated to be 9.0%. CONCLUSIONS: This systematic survey of more than 1000 patients with rare systemic autoimmune diseases reports a low prevalence of proven SARS-CoV-2 infection and very rare severe infections, probably related to good compliance with prophylactic measures in these patients.

Refining "Long-COVID" by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection.

INTRODUCTION: COVID-19 long-haulers, also decribed as having "long-COVID" or post-acute COVID-19 syndrome, represent 10% of COVID-19 patients and remain understudied. METHODS: In this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation, including clinical, psychologic, virologic and specific immunologic assays and were followed longitudinally. A group of 17 convalescent COVID-19 individuals without persistent symptoms were included as a comparison group. RESULTS: The median age was 40 [interquartile range: 35-54] years and 18 (60%) were female. At a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients, although the median fatigue and pain visual analog scales were 7 [5-8] and 5 [2-6], respectively. Extensive biologic studies were unremarkable, and multiplex cytokines and ultra-sensitive interferon-α2 measurements were similar between long-haulers and convalescent COVID-19 individuals without persistent symptoms. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with evidence of a lack of immune response, or a waning immune response, in two patients. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively. CONCLUSIONS: Half of patients seeking medical help for post-acute COVID-19 syndrome lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity, or not, had no consequence on the clinical or biologic characteristics of post-acute COVID-19 syndrome patients, all of whom reported severe fatigue, altered quality of life and psychologic distress.

Hydroxychloroquine dans les maladies systémiques et auto-immunes : où en sommes-nous ?

Résumé L’hydroxychloroquine (HCQ), l’un des plus anciens médicaments utilisés en rhumatologie, a récemment été placée sur le devant de la scène comme l’une des thérapies testées dans le contexte de la maladie du syndrome respiratoire aigu sévère à coronavirus 2 (COVID-19). Utilisée dans un premier temps comme antipaludéen puis dans les maladies rhumatismales, l’HCQ a été employée dans diverses affections parmi lesquelles des maladies infectieuses, des troubles de l’immunité, le diabète, la dyslipidémie ou les néoplasies. Sur le plan des maladies systémiques, l’HCQ est le traitement de référence du lupus érythémateux systémique (LES) et les dernières directives européennes préconisent son utilisation chez tous les patients ne présentant pas de contre-indications ou d’effets indésirables. Les effets positifs de l’HCQ dans le LES ont été démontrés pour des critères robustes tels que l’accumulation de dommages, l’activité de la maladie et la survie. Des effets pléiomorphiques ont également été observés : moindre besoin de glucocorticoïdes, risque réduit de lupus néonatal, diminution de la glycémie à jeun et protection contre le diabète, le risque thrombotique, la dyslipidémie, les infections, etc. L’HCQ peut en outre être utilisée pendant la grossesse et l’allaitement. En dehors du LES, le rôle de l’HCQ dans le syndrome des antiphospholipides (SAPL) et le syndrome de Gougerot-Sjögren (SGS) est encore controversé. En revanche, de récentes études n’ont fait apparaître qu’un intérêt limité dans la polyarthrite rhumatoïde, en particulier parce que l’HCQ ne prévient pas les dommages structuraux. Il n’existe pas à ce jour de données solides en faveur de l’utilisation de l’HCQ dans d’autres maladies systémiques. Dans cette revue, nous résumons les données sur l’utilité et l’efficacité de l’HCQ dans différentes affections cliniques pertinentes pour la pratique rhumatologique.

Hydroxychloroquine in systemic and autoimmune diseases: Where are we now?

Hydroxychloroquine (HCQ), one of the oldest drugs used in rheumatology, came recently into attention as one of the potential therapies tested for the severe acute respiratory syndrome coronavirus-2 disease treatment. Used initially as an antimalarial, then translated to rheumatic diseases, HCQ has been used in a wide range of pathologies, including infectious diseases, immune disorders, diabetes, dyslipidemia, or neoplasia. Regarding systemic diseases, HCQ is the mainstay treatment for systemic lupus erythematosus (SLE), where, according to last European guidelines, it is proposed to all SLE patients unless contraindicated or with side effects. HCQ proved positive impact in SLE on robust outcomes, such as accrual damage, disease activity and survival, but also pleiomorphic effects, including decrease in the need for glucocorticoids, reduction in the risk of neonatal lupus, lower fasting glucose and protection against diabetes, thrombotic risk, dyslipidemia, infections, etc. Moreover, HCQ can be used during pregnancy and breast-feeding. Besides SLE, the role for HCQ in the anti-phospholipid syndrome and Sjögren's disease is still under debate. On the contrary, recent advances showed only limited interest for rheumatoid arthritis, especially due the lack of structural damage prevention. There are still no strong data to sustain the HCQ use in other systemic diseases. In this review, we summarised the utility and efficacy of HCQ in different clinical conditions relevant for rheumatology practice.

Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19.

Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.