Omicron variant dominance and anti-SARS-CoV-2 vaccination are key determinants for a milder course of COVID-19 in patients with systemic autoimmune rheumatic diseases.

INTRODUCTION: This study aimed to determine whether the introduction of anti-SARS-CoV-2 vaccines and the dominance of the omicron variant had a significant impact on the outcome of COVID-19 in patients with systemic autoimmune rheumatic diseases (SAIRDs). METHODS: Using data entered to the Greek Rheumatology Society COVID-19 registry, we investigated the incidence of hospitalization and death due to COVID-19, during the successive periods of the pandemic according to the prevalent strain (wild-type, Alpha, Delta, Omicron) in vaccinated and unvaccinated patients. Variables independently associated with hospitalization and death were explored using multivariate regression analyses, while Kaplan-Meier curves were used to depict survival data. RESULTS: From August 2020 until June 30, 2022, 456 cases (70.2% females) of COVID-19 with a mean age (± SD) of 51.4 ± 14.0 years were reported. In unvaccinated patients, the proportions of hospitalization and death were 24.5% and 4%, compared to 12.5% and 0.8% in the vaccinated group (p < 0.001 for both comparisons). The rates of hospitalization for the wild-type, Alpha, Delta, and Omicron periods were 24.7%, 31.3%, 25.9%, and 8.1% respectively (p < 0.0001), while the case fatality rates were 2.7%, 4%, 7%, and 0%, respectively (p = 0.001). Using multivariable regression analysis, factors independently associated with hospitalization were infection by a non-Omicron variant, being non-vaccinated, exposure to rituximab, older age, and respiratory and cardiovascular disease. Independent predictors for death were contracting COVID-19 during the Alpha or Delta period, pulmonary disease, and older age, while being vaccinated was protective. CONCLUSIONS: In this 2-year analysis, the rates of hospitalization and death among patients with SAIRDs have declined significantly. Vaccination and the dominance of the Omicron variant appear to be the major determinants for this shift. Key points • During the late phase of the pandemic, the proportion of severe COVID-19 cases, defined as requiring hospitalization or resulting in death, in patients with systemic autoimmune rheumatic diseases has declined. • Anti-SARS-CoV-2 vaccination and the dominance of the Omicron strain are the key factors that have independently contributed to this shift.

Oral Antiviral Treatment for COVID-19 in Patients With Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: To describe data on the safety and efficacy of molnupiravir (MP) and nirmatrelvir/ritonavir (NM/R) in patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: Among patients with SARD being followed in 2 tertiary outpatient rheumatology clinics, we retrospectively identified those infected with SARS-CoV-2 between February and August 2022 who received MP or NM/R. Patients' medical files were reviewed for demographics and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, antiviral treatment, side effects, and COVID-19 outcomes. RESULTS: Seventy-four patients with SARD (52 females) were identified who had been infected with SARS-CoV-2 and received MP (n = 26, 35.1%) or NM/R (n = 48, 64.9%). Most patients were vaccinated against SARS-CoV-2 (n = 62, 83.8%). Among frequently used regimens were glucocorticoids (n = 43, 58.1%), mycophenolate mofetil (n = 26, 35.1%), tumor necrosis factor inhibitors (n = 14, 18.9%), methotrexate (n = 13, 17.6%), and rituximab (n = 12, 16.2%). Common adverse events were reported only by 4 patients receiving NM/R (metallic taste, gastrointestinal upset, hypertension), not leading to drug discontinuation. During follow-up, all but 2 patients (n = 72, 97.3%) recovered at home without COVID-19-related complications. Nonetheless, we describe 2 presumptive cases of COVID-19 rebound who progressed to severe COVID-19. CONCLUSION: These data show a favorable outcome and acceptable safety profile of the 2 oral antiviral therapies MP and NM/R among a high-risk SARD population. However, cases of COVID-19 rebound are being increasingly identified. These findings call for continuous surveillance to capture the real-world efficacy and safety profiles in our subpopulations of interest.

Clinical, Serological, and Immunological Characteristics of Greek Patients with Polymyalgia Rheumatica and/or Giant Cell Arteritis: A Research Protocol.

Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) are chronic inflammatory disorders that usually affect older people. Although the aetiology of these diseases remains unknown, genetic, environmental, and immune factors have been implicated. Specific cytokines such as the IL-6, IL-1ß, IL-12, IL-17, and interferon -γ seem to play an essential role. The diagnosis of the disease is usually based on clinical manifestations and the use of histology or imaging, while disease monitoring is based on physical examination, laboratory, and imaging findings. However, there is the unmet need in identifying possible biomarkers that could help the diagnosis and the monitoring as well. The present study aims to investigate the epidemiological, clinical, and immunological characteristics of PMR and/or GCA patients in the region of northwest Greece and to evaluate the role of specific molecules associated with the pathogenesis of the diseases, giving evidence to possible future biomarkers.

COVID-19: Clinical features and outcomes in unvaccinated 2-dose and 3-dose vaccinated against SARS-CoV-2 patients with systemic autoimmune and autoinflammatory rheumatic diseases.

Clinical data on vaccinated patients with coronavirus disease 2019 (COVID-19) who have systemic autoimmune and autoinflammatory rheumatic diseases (SAARD) are limited. This observational study aimed to report the clinical features and outcomes of COVID-19 among cases with SAARD that were unvaccinated or were 2- and 3-dose vaccinated against SARS-CoV-2 and were consecutively recorded by the treating physician. Unvaccinated and 2- and 3-dose vaccinated patients were compared in terms of COVID-19 symptomatology, hospitalizations, oxygen supplementation requirements, and death rates. From the beginning of the pandemic to February 15, 2022, 134 vaccine-naïve COVID-19 cases were recorded among our study cohort. From March 1, 2021 to February 15, 2022, 89 2-dose vaccinated and 105 3-dose vaccinated patients who were infected with SARS-CoV-2 ≥14 days after the second dose were included. The hospitalization rate was higher in the unvaccinated (n = 36, 26.9%) than in the 2-dose (n = 13, 14.6%, p = 0.03) or 3-dose (n = 5, 4.8%, p < 0.001) vaccinated patients. Severe/critical COVID-19 cases requiring oxygen supplementation were the least among 3-dose vaccinated (n = 4, 3.8%) compared to both 2-dose vaccinated (n = 12, 13.5%, p = 0.018) and unvaccinated (n = 25, 18.7%, p < 0.001) patients. ICU admission and death rates were similar among unvaccinated (n = 5, 3.7% and n = 3, 2.2%, respectively) and 2-dose vaccinated patients (n = 4, 4.5%; and n = 2, 2.2%, respectively), while no 3-dose vaccinated patients died or required ICU admission. Logistic regression analysis revealed a significant inverse association between 3-dose vaccination and severe/critical COVID-19 (OR = 0.078, 95% CI: 0.022-0.273, p < 0.001). In conclusion, these findings argue in favor of booster vaccination against SARS-CoV-2 in patients with SAARD.

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases.

OBJECTIVE: Τo report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs). METHODS: Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients. RESULTS: Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients. CONCLUSIONS: Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics.

Calcified constrictive pericarditis resulting in tamponade in a patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan involvement, including heart. Pericarditis-the most common cardiac manifestation-occurs in up to 50% of cases, resulting in positive treatment outcomes. Rarely, it evolves to hazardous complications. A 50-year-old woman with SLE in clinical remission, receiving hydroxychloroquine 400 mg/day, presented to us with severe chest pain and low-grade fever. Physical examination revealed a friction rub and decreased breath sounds at the right lung base. Laboratory evaluation demonstrated leukopenia, thrombocytopenia, low C4 levels, and high acute phase reactants. Chest X-ray exhibited cardiomegaly, calcified pericardium, and right pleural effusion, confirmed by CT scan. PPD skin test and IGRA were both negative. Pericardial fluid, blood, and urine cultures for bacteria and fungi, as well as Gram and Ziehl-Neelsen stains were negative. Serological tests for viruses were also negative. The patient was diagnosed with calcified constrictive pericarditis (CP) due to SLE. She was treated with cyclophosphamide and methylprednisolone pulses, without improvement. Her clinical condition deteriorated, developing signs and symptoms compatible with cardiac tamponade (TMP), which was confirmed by Doppler echocardiography. The patient underwent pericardiectomy. A dramatic response was noted and she was discharged with prednisone 50 mg/day and azathioprine 100 mg/day. Thus, we review and discuss the relevant literature of SLE cases with CP or TMP. When an SLE patient presents with CP, infectious causes should be excluded first. To the best of our knowledge, this is the only case of SLE and calcified CP leading to TMP, hence physicians should be aware of this complication.

Functional connectivity and microstructural changes of the brain in primary Sjögren syndrome: the relationship with depression.

BACKGROUND: Fatigue and depression are among the most common manifestations of primary Sjögren syndrome (pSS), but information is lacking on the relationship with brain function and microstructural changes. PURPOSE: To investigate microstructural changes and brain connectivity in pSS, and to evaluate their relationship with fatigue and depression. MATERIAL AND METHODS: The study included 29 patients with pSS (mean age 61.2 ± 12.1 years; disease duration 10.5 ± 5.9 years) and 28 controls (mean age 58.4 ± 9.2 years). All the patients completed the Beck's depression and Fatigue Assessment Scale questionnaires. The imaging protocol consisted of: (i) standard magnetic resonance imaging (MRI) pulse sequences (FLAIR, 3D T1W); (ii) a diffusion tensor imaging pulse sequence; and (iii) a resting state functional MRI pulse sequence. Resting state brain networks and maps of diffusion metrics were calculated and compared between patients and controls. RESULTS: Compared with the controls, the patients with pSS and depression showed increased axial, radial, and mean diffusivity and decreased fractional anisotropy; those without depression showed decreased axial diffusivity in major white matter tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, anterior thalamic radiation, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, and forceps minor-major). Decreased brain activation in the sensorimotor network was observed in the patients with pSS compared with the controls. No correlation was found between fatigue and structural or functional changes of the brain. CONCLUSION: pSS is associated with functional connectivity abnormalities of the somatosensory cortex and microstructural abnormalities in major white matter tracts, which are more pronounced in depression.