Risk Factors Associated With Post-COVID-19 Condition: A Systematic Review and Meta-analysis.

Importance: Post-COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support. Objective: To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC. Data sources: Medline and Embase databases were systematically searched from inception to December 5, 2022. Study Selection: The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients. Data Extraction and Synthesis: Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023. Main Outcomes and Measures: The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19. Results: The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76). Conclusions and Relevance: This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination. Trial Registration: PROSPERO Identifier: CRD42022381002.

Post-COVID-19 syndrome risk factors and further use of health services in East England.

Post-COVID syndrome, defined as symptoms persisting for more than twelve weeks after the diagnosis of COVID-19, has been recognised as a new clinical entity in the context of SARS-CoV-2 infection. This study was conducted to characterise the burden and predictors for post-COVID-19 syndrome in the local population. It was a community-based web-survey study conducted in Norfolk, East England, UK. We sent the survey to patients with confirmed COVID-19 infection by real-time polymerase chain reaction by December 6th, 2020. Questions related to the pre-COVID and post-COVID level of symptoms and further healthcare use. Baseline characteristics were collected from the primary care records. Logistic regression analysis was conducted to establish predictors for post-COVID-19 syndrome and further healthcare utilisation. Of 6,318 patients, survey responses were obtained from 1,487 participants (23.5%). Post-COVID-19 syndrome symptoms were experienced by 774 (52.1%) respondents. Male sex compared to female sex was a factor protective of post-COVID symptoms; relative risk (RR) 0.748, 95% confidence interval (CI), 0.605-0.924. Body mass index was associated with a greater risk of developing post-COVID-19 symptoms (RR 1.031, 95% CI, 1.016-1.047, for 1 kg/m2). A total of 378 (25.4%) people used further health services after their index COVID-19 infection, of whom 277 (73.2%) had post-COVID symptoms. Male sex was negatively associated with the use of further health services (RR 0.618, 95% CI, 0.464-0.818) whereas BMI was positively associated (RR 1.027, 95% CI, 1.009-1.046). Overall, post-COVID-19 symptoms increased the probability of using health services with RR 3.280, 95% CI, 2.540-4.262. This survey of a large number of people previously diagnosed with COVID-19 across East England shows a high prevalence of self-reported post-COVID-19 syndrome. Female sex and BMI were associated with an increased risk of post-COVID-19 syndrome and further utilisation of healthcare.

Comparative Assessment of Hand Joint Ultrasound Findings in Symptomatic Patients with Systemic Lupus Erythematosus and Sjögren's Syndrome: A Pilot Study.

Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) can be associated with inflammatory arthritis, which is underdiagnosed by clinical examination. The aim of this cross-sectional, observational study was to compare, for the first time, the ultrasound (US)-detected joint abnormalities in these two diseases and to define the role of US in patient management. Participants had SLE (n = 18) and SS (n = 23), symptoms of hand joint pain and no previous diagnosis of arthritis. Data on disease activity, duration, damage scores, inflammatory and serologic markers, treatment and clinical and ultrasound parameters (derived from the assessment of 902 joints) were analysed and correlated using descriptive statistics, correlation tests and regression models. Subclinical synovitis/tenosynovitis was detected in 44.4% of SLE patients and 21.7% of SS patients (p = 0.23). There was no significant correlation between either the total Power Doppler score or the total grey-scale score and disease activity scores (British Isles Lupus Assessment Group index and European League Against Rheumatism Sjögren's syndrome disease activity index). Both damage scores (Systemic Lupus International Collaborating Clinics index and Sjögren's syndrome disease damage index) correlated with the total grey-scale synovitis score. Significant proportions of the participants with SLE and SS had erosions (55.6% and 34.8%, respectively, p = 0.184) and osteophytes (61.1% vs. 60.9%, p = 0.98) in at least one joint. The lack of correlation between disease activity scores and US outcome measures indicated their limitations in diagnosing subclinical synovitis in SLE and SS patients. Future research is needed to determine if the development of erosions could be prevented by early diagnosis and prompt treatment of inflammatory arthritis associated with SLE and SS.

Osteoprotegerin and Myocardial Fibrosis in Patients with Aortic Stenosis.

Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).

Impact of pre-transplant time on dialysis on survival in patients with lupus nephritis.

Lupus nephritis (LN) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) often leading to end-stage renal failure (ESRF) and necessitating renal transplantation (rTp). Optimal timing of rTp in SLE patients with ESRF is uncertain and could potentially affect survival. We investigated the time spent on dialysis before rTp and survival following rTp in a cohort of SLE patients. Retrospective analysis of all adult SLE patients receiving rTp over a 40-year period (1975-2015) in two tertiary UK centres. Cox proportional hazard regression and receiver operator curves (ROC) were used to determine the risk associated with time on dialysis before rTp and other potential predictors. Forty patients (age 35 ± 11 years, 34 female, 15 Caucasian, 15 Afro-Caribbean and 10 South Asian) underwent rTp. During a median follow-up of 104 months (IQR 80,145), eight (20%) patients died and the 5-year survival was 95%. Univariate analysis identified time on dialysis prior to rTp as the only potentially modifiable risk predictor of survival with a hazard ratio of 1.013 for each additional month spent on dialysis (95% CI = 1.001-1.026, p = 0.03). ROC curves demonstrated that > 24 months on dialysis had an adverse effect with sensitivity of 0.875 and specificity 0.500 for death. No other modifiable predictors were significantly associated with mortality, indicating that time on dialysis had an independent effect. Increased time on dialysis pre-transplantation is an independent modifiable risk factor of mortality in this cohort of patients with lupus nephritis.

The safety of pharmacological treatment options for lupus nephritis.

INTRODUCTION: The management of lupus nephritis (LN) has changed significantly over the last 10 years due to emerging evidence from large randomised clinical trials that produced good quality data and guided the formulation of two key concepts: the induction of remission and the maintenance phase of immunosuppressive therapy. AREAS COVERED: Optimizing cyclophosphamide and glucocorticoid regimens and the introduction of mycophenolate mofetil for proliferative and membranous LN has been pivotal. Nevertheless, concerns remain about treatment toxicity especially long term glucocorticoid use and exposure to cumulative cyclophosphamide doses. Here we discuss the conventional and newer pharmacological options for managing LN focusing on drug safety and toxicity issues. EXPERT OPINION: The need for effective and less toxic treatments led to the development of the role of targeted biologic therapies in LN. However, evidence from the initial randomized controlled trials has been disappointing, although this reflects inadequate trial design rather than true lack of efficacy.

Risk factors for renal disease in systemic lupus erythematosus and their clinical implications.

Lupus nephritis is one of the most common severe manifestations of systemic lupus erythematosus and is associated with significant morbidity and mortality. Genetic, ethnic and hormonal factors may influence the presence and severity of renal involvement and therefore affect the outcome and overall prognosis of patients. In this review, we will discuss the association of known lupus risk factors in developing renal disease and explore the recent literature to identify potential risk factors and their clinical implications in terms of diagnostic vigilance, management and prognosis.

Systemic rheumatoid vasculitis in the era of modern immunosuppressive therapy.

OBJECTIVES: Systemic rheumatoid vasculitis (SRV) is a rare but potentially serious systemic disease manifestation of rheumatoid arthritis (RA) characterized by the development of necrotizing vasculitis. The incidence of SRV appears to be decreasing possibly reflecting progress in RA treatment. The aims of this study were to review the clinical manifestations of SRV in a stable well-defined population during 2001-10 and to compare with our previous cohort (1988-2000) and also a cohort from 1975 to 1981. METHODS: Using Norfolk Vasculitis Register, a prospective register of patients with systemic vasculitis since 1988, all patients with a diagnosis of SRV from 1 January 2001 until 31 December 2010 were identified. SRV was defined according to the Scott and Bacon criteria (1984). Clinical features were obtained by retrospective case note review. RESULTS: Eighteen patients with SRV were identified (10 male), median age at diagnosis was 72 years and average disease duration 15.6 years. The average annual incidence for 2001-10 was 3.9 per million. One-year mortality was 12% and 5-year mortality 60%. The clinical manifestations were similar apart from systemic and cutaneous features which were more common in the earlier cohorts. CONCLUSION: The incidence of SRV has declined significantly in the last 40 years; but the clinical manifestations remain similar. Systemic symptoms, and cutaneous manifestations such as infarcts and nodules, are slightly less common in the recent cohort. Despite modern immunosuppressive therapy the prognosis remains poor.

ANCA vasculitis: time for a change in treatment paradigm? Not yet.

The ANCA-associated vasculitides (AAVs) are conventionally treated with a strategy of remission induction followed by maintenance therapy using glucocorticoids combined with CYC during induction and AZA for maintenance. Recently, several randomized controlled trials have been published that question whether these drugs should remain those of choice. B-cell depletion using rituximab is at least as effective as CYC for remission induction in newly presenting patients, but long-term efficacy, safety and cost-effectiveness data are awaited, and thus rituximab should be reserved for patients at high risk of infertility. Rituximab seems to be effective at inducing remission in relapsing patients. Whether routine pre-emptive treatment with rituximab for remission maintenance is a better approach than waiting for relapse is unknown. MTX and LEF have similar efficacy to AZA, but are not significantly safer; while MMF is less effective. Thus, AZA remains the conventional maintenance drug of choice.

Epidemiology of ANCA-associated vasculitis.

The epidemiology of the antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), comprising Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, poses considerable challenges to epidemiologists. These challenges include the difficulty of defining a case with a lack of clear distinction between the different disorders, case capture, and case ascertainment. The AAV are rare and therefore a large population is required to determine the incidence and prevalence, and this poses questions of feasibility. Despite these difficulties a considerable body of data on the epidemiology of the AAV has been built in the past 20 years with an interesting age, geographic, and ethnic tropism gradually being revealed. Most of the data come from White populations of European descent, and the overall annual incidence is estimated at approximately 10-20/million with a peak age of onset in those aged 65 to 74 years.

Preliminary report: the effect of a 6-month dietary glycemic index manipulation in addition to healthy eating advice and weight loss on arterial compliance and 24-hour ambulatory blood pressure in men: a pilot study.

We aimed to determine whether altering dietary glycemic index (GI) in addition to healthy eating and weight loss advice affects arterial compliance and 24-hour blood pressure (BP), both coronary heart disease (CHD) risk factors. Middle-aged men with at least 1 CHD risk were randomized to a 6-month low-GI (LGI) or high-GI (HGI) diet. All were advised on healthy eating and weight loss. They were seen monthly to assess dietary compliance and anthropometrics. Carotid-femoral pulse wave velocity (PWV), fasting blood lipid profile, and glucose and insulin concentrations were measured at baseline and at months 3 and 6. Six-hour postprandial glucose and insulin responses and 24-hour ambulatory BP were also assessed at baseline and month 6. Thirty-eight subjects (HGI group, n = 16; LGI group, n = 22) completed the study. At month 6, groups differed in dietary GI, glycemic load, and carbohydrate intake (P < .001). Fasting insulin concentration and insulin resistance (calculated by homeostatic model assessment) were lower in the LGI than the HGI group (P < .01). The reduction in total cholesterol and 24-hour BP was bigger in the LGI than the HGI group (P < .05); and only the LGI group had significant reductions (P < .05) in PWV, low-density lipoprotein cholesterol, and triacylglycerol concentration. There were no differences in postprandial glucose or insulin responses between the groups. The results suggest that an LGI diet may be more beneficial in reducing CHD risk, including PWV and 24-hour BP, even in the setting of healthy eating and weight loss; and thus, further study is warranted.

Electroconvulsive treatment for a patient with psychotic depression and inclusion body myositis.

A patient with inclusion body myositis (IBM) and psychotic depression required inpatient psychiatric care. The patient's mental and physical health continued to deteriorate despite maximal treatment with medication. After careful consideration and psychiatric, neurological, and anesthetic review, electroconvulsive therapy was initiated. We present, what is to our knowledge, the first documented case of a patient with inclusion body myositis requiring a course of electroconvulsive therapy for psychotic depression.