The impact of the COVID-19 pandemic and stringent social distancing measures on health-related quality of life and COVID-19 infection rates in patients with rheumatic disease: a longitudinal analysis through the pandemic.

Objective: The aim was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and stringent social isolation measures on patients with rheumatic disease (RD) from the beginning of the pandemic (April 2020). Methods: In this UK-based single-centre, prospective, observational cohort study, all RD follow-up patients at our centre were invited by SMS text message in April 2020 to participate in the study. Participants completed questionnaires at four time points between April 2020 and December 2021. We collected demographics, clinically extremely vulnerable (CEV) status, short form 12 mental (MCS) and physical health component scores (PCS) for health-related quality of life, vaccination status, COVID-19 infection rates and incidence of long COVID. Results: We enrolled 1605 patients (female, 69.0%; CEV, 46.5%); 906 of 1605 (56.4%) completed linked responses to our final questionnaire. MCS improved (+0.6, P < 0.05), whereas PCS scores deteriorated (-1.4, P < 0.001) between April 2020 and December 2021. CEV patients had worse mental and physical health scores than non-CEV patients at entry (PCS, 36.7 and 39.3, respectively, P < 0.001; MCS, 40.9 and 43.0, respectively, P < 0.001) and at each time point throughout the study; both mental and physical health outcomes were worse in CEV compared with non-CEV patients (P < 0.001 and P = 0.004, respectively). At study close, 148 of 906 (16.3%) reported COVID infection, with no difference in infection, vaccination or long COVID rates between CEV and non-CEV patients. Conclusions: Mental and physical health in RD patients has changed throughout the pandemic; outcomes for both metrics of health were worse in CEV patients, although there were no differences in infection rates between the groups. These data might assist the understanding and planning of future health-care policy and social restrictions in RD patients. Trial registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT04542031.

Developing immortal cell lines from Xenopus embryos, four novel cell lines derived from Xenopus tropicalis.

The diploid anuran Xenopus tropicalis has emerged as a key research model in cell and developmental biology. To enhance the usefulness of this species, we developed methods for generating immortal cell lines from Nigerian strain (NXR_1018, RRID:SCR_013731) X. tropicalis embryos. We generated 14 cell lines that were propagated for several months. We selected four morphologically distinct lines, XTN-6, XTN-8, XTN-10 and XTN-12 for further characterization. Karyotype analysis revealed that three of the lines, XTN-8, XTN-10 and XTN-12 were primarily diploid. XTN-6 cultures showed a consistent mixed population of diploid cells, cells with chromosome 8 trisomy, and cells containing a tetraploid content of chromosomes. The lines were propagated using conventional culture methods as adherent cultures at 30°C in a simple, diluted L-15 medium containing fetal bovine serum without use of a high CO2 incubator. Transcriptome analysis indicated that the four lines were distinct lineages. These methods will be useful in the generation of cell lines from normal and mutant strains of X. tropicalis as well as other species of Xenopus.

Complete persistent remission of rheumatoid arthritis after COVID-19 infection - A rare case and literature review.

A 55-year-old man was admitted to a hospital in Northeast India with fever, cough and breathlessness and was diagnosed with severe COVID-19 pneumonia. He was a known case of seropositive, erosive rheumatoid arthritis (RA) and was taking disease-modifying anti-rheumatic drugs (DMARDs). The patient was treated with remdesivir, heparin and a short course of corticosteroids for COVID-19 pneumonia. With the improvement of COVID-19 pneumonia, the patient also noticed a marked improvement in his joint symptoms despite not taking any DMARDs for RA. The temporal relationship between the time of disappearance of all signs and symptoms of RA within a few days after COVID-19 pneumonia and maintenance of RA remission for over one year of follow up to date suggests that COVID-19 likely caused the remission of RA. This case highlights the need for larger studies to understand the COVID-19 effects on RA remission and their potential link if any. However, the evidence of worse outcome with COVID-19 in immunosuppression which is common in RA cannot be overlooked.

Nanotechnology applications in rheumatology.

Nanomedicine (NM) is the medical use of nanotechnology (NT). NT is the study and control of nanoscale structures (between approximately 1 and 100 nm). Nanomaterials are created by manipulating atoms and molecules at the nanoscale, resulting in novel physical and chemical properties. With its targeted tissue delivery capabilities, NT has enabled molecular modulation of the immune response and underlying inflammatory responses in individuals with rheumatic diseases (RD). NM has enabled targeted drug delivery, reduced adverse effects on non-target organs, raised drug concentration in synovial tissue, and slowed the progression of immune-mediated RD such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Thus, NM has evolved in rheumatology prevention, diagnosis, and therapy. Animal models have proven superior outcomes to conventional techniques of treating specific illnesses. Nanodiamond (ND) immunomodulatory applications have been proposed as an alternative to traditional nanoparticles in the diagnosis and treatment of RA due to their small size and ability to be removed from the body without causing harm to the patient's organs, such as the liver. However, human clinical NM needs more research. We conducted a literature review to assess the present role of NM in clinical rheumatology, describing its current and future applications in the diagnosis and treatment of rheumatic diseases.

Long COVID from rheumatology perspective - a narrative review.

Long-term sequel of acute COVID-19, commonly referred to as long COVID, has affected millions of patients worldwide. Long COVID patients display persistent or relapsing and remitting symptoms that include fatigue, breathlessness, cough, myalgia, arthralgia, sleep disturbance, cognitive impairment and skin rashes. Due to the shared clinical features, laboratory and imaging findings, long COVID could mimic rheumatic disease posing a diagnostic challenge. Our comprehensive literature review will help rheumatologist to be aware of long COVID manifestations and differentiating features from rheumatic diseases to ensure a timely and correct diagnosis is reached.

Incidence and risk factors of long COVID in the UK: a single-centre observational study.

BACKGROUND: Studies to evaluate long COVID symptoms and their risk factors are limited. We evaluated the presence of long COVID and its risk factors in patients discharged from a hospital with COVID-19 illness. METHODS: This observational study included 271 COVID-19 patients admitted between February and July 2020 in a hospital in the UK. The primary outcome measure was to assess the duration and severity of long COVID and its predictors at 3, 6 and 9 months. Logistic regression was performed to assess the potential risk factors for long COVID. RESULTS: Out of 89 patients interviewed, 55 (62%) had long COVID for 3 months, 46 (52%) for 6 months and 37 of the 75 patients admitted to the hospital with acute COVID-19 had long COVID for 9 months (49%). The most common long COVID symptoms were fatigue and breathlessness. CONCLUSION: Nearly two-thirds of patients at 3 months and a half at 9 months had long COVID. COVID-19 pneumonia was the strongest predictor of long COVID in Caucasians at 3 months.

Impact of COVID-19 on rheumatology practice in the UK-a pan-regional rheumatology survey.

The COVID-19 pandemic has disrupted healthcare services and rheumatology staff were redeployed to the frontline. The purpose of this survey was to evaluate the impact of the COVID-19 pandemic on the provision of rheumatology services as viewed by rheumatologists in the UK. Survey monkey questionnaire weblink was sent to 804 clinicians including consultant rheumatologists, speciality trainees, nurse specialists, and allied health professionals in 4 regions of the UK to evaluate personal effects of COVID-19 and redeployment, impact on current out-patient clinic activity, immunosuppressive drug use, and future rheumatology care. Response rate was 21%. One-fifth of the responders reported that their rheumatology departments were functioning less than 50% capacity during the pandemic. Two-third of responders felt anxious about the ill-effects of COVID-19 on their health and well-being, and one-third of them were redeployed. During the peak of the pandemic, 75% of clinicians stopped intravenous biologics. Although access to video consultation was available for up to three-fourths of the clinicians, the majority (90%) used this modality in less than 1 in 4 consultations. This survey highlights rheumatologists' perception in the delivery of future care and anxiety they faced. As demonstrated by this survey, the National Institute for Health and Care Excellence (NICE) guidance did not influence clinician decision making in some aspects of patient care. Underutilization of tele-rheumatology in this survey should be considered whilst planning the restoration of rheumatology services in the post-COVID era. Key points • COVID-19 has generated significant concerns among rheumatology community about their mental well-being. • In over 50% of cases, rheumatologists stopped IV biologic drugs as per patients' wishes during the first wave of the pandemic. • Tele-rheumatology has been used more widely during the pandemic, but the extent of its use in the post-COVID era is less clear. Evolving evidence will determine its future wider use.

Statin-induced autoimmune necrotizing myositis-A single-center case series highlighting this potentially life-threatening but treatable condition.

Statin-induced autoimmune necrotizing myositis is a rare but important cause muscle weakness. Withdrawal of the statin and steroid treatment alone may be insufficient treatment for SIANM. Targeted immunosuppression may be needed and can be effective.

CSAG1 maintains the integrity of the mitotic centrosome in cells with defective p53.

Centrosomes focus microtubules to promote mitotic spindle bipolarity, a critical requirement for balanced chromosome segregation. Comprehensive understanding of centrosome function and regulation requires a complete inventory of components. While many centrosome components have been identified, others yet remain undiscovered. We have used a bioinformatics approach, based on 'guilt by association' expression to identify novel mitotic components among the large group of predicted human proteins that have yet to be functionally characterized. Here, we identify chondrosarcoma-associated gene 1 protein (CSAG1) in maintaining centrosome integrity during mitosis. Depletion of CSAG1 disrupts centrosomes and leads to multipolar spindles, particularly in cells with compromised p53 function. Thus, CSAG1 may reflect a class of 'mitotic addiction' genes, whose expression is more essential in transformed cells.

Multiple determinants and consequences of cohesion fatigue in mammalian cells.

Cells delayed in metaphase with intact mitotic spindles undergo cohesion fatigue, where sister chromatids separate asynchronously, while cells remain in mitosis. Cohesion fatigue requires release of sister chromatid cohesion. However, the pathways that breach sister chromatid cohesion during cohesion fatigue remain unknown. Using moderate-salt buffers to remove loosely bound chromatin cohesin, we show that "cohesive" cohesin is not released during chromatid separation during cohesion fatigue. Using a regulated protein heterodimerization system to lock different cohesin ring interfaces at specific times in mitosis, we show that the Wapl-mediated pathway of cohesin release is not required for cohesion fatigue. By manipulating microtubule stability and cohesin complex integrity in cell lines with varying sensitivity to cohesion fatigue, we show that rates of cohesion fatigue reflect a dynamic balance between spindle pulling forces and resistance to separation by interchromatid cohesion. Finally, while massive separation of chromatids in cohesion fatigue likely produces inviable cell progeny, we find that short metaphase delays, leading to partial chromatid separation, predispose cells to chromosome missegregation. Thus, complete separation of one or a few chromosomes and/or partial separation of sister chromatids may be an unrecognized but common source of chromosome instability that perpetuates the evolution of malignant cells in cancer.

Spatio-temporal regulation of RAG2 following genotoxic stress.

V(D)J recombination of lymphocyte antigen receptor genes occurs via the formation of DNA double strand breaks (DSBs) through the activity of RAG1 and RAG2. The co-existence of RAG-independent DNA DSBs generated by genotoxic stressors potentially increases the risk of incorrect repair and chromosomal abnormalities. However, it is not known whether cellular responses to DSBs by genotoxic stressors affect the RAG complex. Using cellular imaging and subcellular fractionation approaches, we show that formation of DSBs by treating cells with DNA damaging agents causes export of nuclear RAG2. Within the cytoplasm, RAG2 exhibited substantial enrichment at the centrosome. Further, RAG2 export was sensitive to inhibition of ATM, and was reversed following DNA repair. The core region of RAG2 was sufficient for export, but not centrosome targeting, and RAG2 export was blocked by mutation of Thr(490). In summary, DNA damage triggers relocalization of RAG2 from the nucleus to centrosomes, suggesting a novel mechanism for modulating cellular responses to DSBs in developing lymphocytes.