ATTITUDES and HESITANCY in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES TOWARDS SARS-COV-2 VACCINATION: A SINGLE-CENTER STUDY from BULGARIA

Background: Bulgaria is among the countries with the lowest vaccination rate of adult population in Europe. The presence of autoimmune rheumatic disease could further contribute to vaccine hesitancy and skepticism and influence patients' attitudes towards vaccination [1, 2]. However, little is still known about the willingness and particular causes of hesitancy in patients with infammatory joint diseases in the skeptical part of adult population across Europe. Objectives: Our goal was to assess the rate of SARS-CoV-2 vaccination among patients with immune-mediated rheumatic joint diseases receiving biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) and to determine the modifable predictors of vaccination hesitancy. Methods: Patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis undergoing biological or targeted synthetic DMARDs therapy were consecutively selected and included in this single-center cross-sectional study. Excluding criteria in patients were psychiatric or neurological disease preventing understanding or responding to the questions, being illiterate, or not willing to participate in the study. Various demographic, anthropometric, and clinical data were collected. Disease activity was determined using DAS28-CRP for rheumatoid arthritis and peripheral psoriatic arthritis and ASDAS for ankylosing spondy-litis and psoriatic spondylitis. All patients were given a questionnaire assessing their vaccination status, hesitancy, and attitude towards vaccination. Binary logistic regression analysis was used to analyze the relationship between self-reported modifable parameters and vaccination status for SARS-CoV-2. Results: Two hundred and one participants were eligible for participating in the study with mean age and BMI of 54.6 years and 28.2, respectively. Of these, 40.3% were women;30.3% had rheumatoid arthritis, 17.9%-psoriatic arthritis, and 51.7%-ankylosing spondylitis. 29.4 % of all participants had already survived a COVID-19 infection with a mean time of 8.4 months since the COVID-19 onset. Only slightly above 1/3 (35.8%) of the study group was fully vaccinated and the majority of them were vaccinated with BNT162b2 (68.1%). Among the modifable factors, we identifed preceding discussion with a rheumatologist, hesitancy due to autoimmune disease presence and (un)awareness of vaccine safety and efficacy as signifcant predictors of vaccination status Conclusion: Our data suggest that there are still possibilities to influence rheumatic patients on their decision to vaccinate against SARS-CoV-2 in Bulgaria. Raising the awareness of the safety and efficacy of the SARS-CoV-2 vaccines and spending more time on the education of patients with rheumatic diseases may positively affect their attitude towards vaccination.

MUSCULOSKELETAL PAIN AS A PART of the RHEUMATIC SPECTRUM in COVID-19

Background: Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) (1), our understanding of the underlying pathophysiology is constantly evolving in order to explain the wide range of heterogenic clinical manifestations (2). Nevertheless, limited data are available for the severity and multifactorial causality of musculoskeletal pain in COVID-19 patients (3). Objectives: This study aimed to evaluate the prevalence and intensity of rheumatic pain symptoms-arthralgia and myalgia and their association with anxiety and depression in a cohort of COVID-19 patients, hospitalized at the COVID-19 rheumatology department of the University Hospital St. Marina, Varna, Bulgaria. Methods: In the present single-center cohort study, a prospective analysis was performed among COVID-19 patients who were hospitalized from 1 Oct 2021 to 20 Jan 2022 and self-reported for new-onset of musculoskeletal pain. All 226 patients (age 26-91 years) were treated for moderate or severe SARS-CoV-2 infection confrmed by laboratory tests, including positive antigen test or polymer-ase chain reaction (PCR) test, and imaging modality. Detailed disease history and clinical examination were carried out by a fully certifed rheumatologist. All patients who reported new-onset of musculoskeletal pain during the acute phase of the infection, participated on a voluntary basis in a questionnaire survey, by completed Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS) and visual analogue scale (VAS) for arthralgia and myalgia. The questionnaire form also elicited information on sociodemographic characteristics of the patients. In all patients, infammation and thrombotic biomarkers were assessed. The level of signifcance was set to 0.05. Results: Among all 226 COVID-19 patients with musculoskeletal pain, 46.5% (n =105) were women and 53.5% (n = 121), were men. Mean age was 65.6 years. We found a signifcant correlation of depression and anxiety scales scores with pain intensity (both arthralgia and myalgia), all < 0.001. A multiple regression analysis found that SDS and SAS accounted for signifcant variance in the prediction of muscle pain (β = 0.441, p < 0.001;β = 0.293, p = 0.003, respectively) while SDS signifcantly predicted joint pain (β = 0.341, p = 0.043). On the other hand, musculoskeletal pain does not correlate with any of infammation and thrombotic biomarkers assessed in SARS-CoV-2 patients (p > 0.05). Conclusion: Rheumatic pain manifestations are part of the heterogeneous spectrum of COVID-19 disease. The pain intensity is signifcantly associated with anxiety and depression symptoms and does not correlate with infammation and thrombotic biomarkers.

COVID-19-induced sarcoidosis granulomas

Sarcoidosis is a heterogeneous inflammatory disease of unknown cause. The main symptom of the disease are noncaseating granulomas. Regardless of the unknown etiology, the trigger may be cross-reactions to an infectious antigen. As such, COVID-19 infection may also be considered. Although the virus mainly affects the lungs, we are increasingly confronted with its extrapulmonary manifestations. Several cases of sarcoidosis-like manifestations associated with COVID-19 have been described in the literature to date. A 52-year-old man was admitted to the Clinic of Rheumatology at MHAT "Sv. Marina "-Varna with joint pain syndrome, swelling of the wrists, the presence of rapidly growing, painless tumors on the extensor surfaces of the right wrist and forearm, as well as in the left knee. Complaints appeared two months after suffering from COVID-19 viral infection. The patient underwent a number of studies that proved the presence of a pathological process in soft tissues. Histopathological examinations proved the presence of a noncaseating granulomatous process. Despite the lack of complaints from the respiratory system, a CT scan of the chest was performed, which revealed hilar lymphadenopathy. In recent months we have witnessed the appearance of various pathological conditions that develop after suffering from COVID-19 viral infection. Only a few cases of sarcoid-like granulomas have been reported in the literature. Due to the short time from disease to granuloma, noncaseating granulomas are thought to be a sarcoid-like immune response to SARS-CoV-2.

Clinical manifestations of COVID-19 concerning the rheumatlogist

Over the last year, the concept of coronavirus disease 2019 (COVID-19) has undergone a major shift. Our initial understanding of COVID-19 as a flu-like illness was rethought as a polysyndromic inflammatory disease involving not only the respiratory system but also the musculoskeletal system, the skin, the cardiovascular system, and the genitourinary system. Within this inflammatory condition, the tissue damage is immunemediated, resembling the exacerbations of a full-blown rheumatic disease. Our aim was to describe the frequency and type of rheumatic manifestations in a cohort of patients with COVID-19 hospitalized in the Rheumatology Department for COVID-19 at Sv. Marina University Hospital, Varna, Bulgaria. In the current single-center cohort study, a retrospective database analysis was performed among all COVID-19 patients hospitalized from 1 December 2020 to 22 January 2021. All 243 patients (aged 19-93 years) were treated for moderate or severe SARS-CoV-2 infection confirmed by laboratory tests, including a positive polymerase chain reaction (PCR) test and imaging. Inpatient treatment includes dexamethasone, anticoagulants, antibiotics and the antiviral drug remdesevir (at clinical judgment). A detailed medical history and clinical examination were performed by a rheumatologist and/or internal medicine specialist. Among all 243 patients with COVID-19, those with a history of myalgia and arthralgia were 26% (n = 63) and 21.3% (n = 52), respectively. We found 4 (1.6%) cases of emerging cutaneous vasculitis and 2 (0.8%) cases of severe Raynaud's phenomenon after the onset of SARS-CoV-2 infection. Two patients had severe muscle weakness, elevated creatine phosphokinase, and were diagnosed with inflammatory myopathy caused by COVID-19. Lupus-like syndrome was observed in 2 (0.8%) patients. Rheumatic manifestations are part of the heterogeneous spectrum of COVID-19 disease. Amidst the COVID-19 pandemic, any newly onset rheumatic manifestation requires the exclusion of SARS-CoV-2 infection. Therefore, the rheumatologist should be a part of a multidisciplinary approach to the treatment of COVID-19.

Eosinophils and COVID-19-clinical case of COVID-19 infection in a patient with eosinophilic granulomatosis with polyangiitis

Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. COVID-19 is caused by a virus called severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. The impact of the pandemic has led to significant research on all aspects of the disease, including diagnostic biomarkers, related risk factors and strategies that could be used for its treatment and prevention. To this end, eosinopenia has been identified as one of many factors that could facilitate diagnosis and have prognostic value in cases of severe COVID-19. While eosinophil-associated conditions have been misdiagnosed as COVID-19 and others are among the reported complications, patients with pre-existing eosinophil-associated diseases (e.g. asthma, eosinophilic gastrointestinal diseases) do not appear to be at increased risk of severe disease. Interestingly, several recent studies have shown that a diagnosis of asthma may be associated with some degree of protection. We present a 42-year-old patient with eosinophilic granulomatosis with polyangiitis (Church-Strauss vasculitis) known for 4 years, who in March 2021 was diagnosed with COVID-19 infection. The disease was presented with manifestations of acute viral infection, with observed post-COVID transient migrating nodules of subcutaneous adipose tissue on the limbs, percentage of eosinophils over 50 and complete recovery.

Structural and Biochemical Rationale for Enhanced Spike Protein Fitness in Delta and Kappa SARS-CoV-2 Variants (preprint)

The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a novel head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant.

Rheumatic manifestations in COVID-19 patients-single-center experience amidst the pandemic

Background: Recently evolved from a monochromic flu-like disease to a polysyndromic “spectrum of disease”, our understanding of coronavirus disease 2019 (COVID-19) is still far from being complete [1]. Hyperinflammation involving not only the lungs but also the musculoskeletal system, skin, cardiovascular, genitourinary systems is immune-mediated resembling the flares of a full-blown rheumatic disease [2,3]. Objectives: To describe the prevalence and type of rheumatic manifestations in a cohort of COVID-19 patients hospitalized in the COVID-19 rheumatology department in University Hospital St. Marina, Varna, Bulgaria. Methods: In the present single-center cohort study, a retrospective database analysis was performed among all COVID-19 patients hospitalized from 1 Dec 2020 to 22 Jan 2021. All 243 patients (age 19 -93 years) were treated for moderate or severe SARS-CoV-2 infection confirmed by laboratory tests, including positive polymerase chain reaction (PCR) test, and imaging modality. Inpatient treatment included antibiotics, dexamethasone, anticoagulants, and antiviral drug remdesevir (optional). Detailed disease history and clinical examination were carried out by a fully certified rheumatologist and/or specialist in internal medicine. Results: Among all 243 COVID-19 patients, those with prominent self-reported myalgia and arthralgia were 26% (n = 63) and 21.3 (n = 52), respectively. We had 4 (1.6%) cases of newly developed cutaneous vasculitis and 2 (0.8%) cases of severe Raynaud's phenomenon after SARS-CoV-2 infection onset. Two patients experienced severe muscle weakness, had elevated creatine phosphokinase, and were diagnosed with inflammatory myopathy secondary to COVID-19. Lupus-like syndrome was observed in 2 (0.8%) patients. Conclusion: Rheumatic manifestations are part of the heterogeneous spectrum of COVID-19 disease. Amidst the COVID-19 crisis, each newly onset rheumatic manifestation warrants exclusion of SARS-CoV-2 infection. Therefore, a rheumatologist should be a part of a multidisciplinary approach towards the COVID-19 treatment.