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Background Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. Methods We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates. Results Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1). Conclusions While our findings may overestimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both living with HIV and having current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex, and other comorbidities and COVID-19 mortality were similar to those in other settings.

Additional file 1: Table S1. Core questions for the main systematic literature review.

Supplementary material, approximately 2.7 MB.

Immune-mediated inflammatory disorders include a clinically diverse group of conditions sharing similar pathogenic mechanisms. Conditions such as rheumatoid arthritis, psoriasis, spondyloarthropathy, inflammatory bowel disease and connective tissue diseases are characterised by immune dysregulation and chronic inflammation. This review will focus immuno-pathogenic mechanisms, aspects of early disease, co-morbidity and therapy in rheumatoid arthritis.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) are at increased risk of the metabolic syndrome (MetS) and its complications. In the absence of published studies from sub-Saharan Africa, we investigated the prevalence and associations of the MetS amongst recent-onset SLE patients. METHODS: A cross-sectional study of recent onset (

Appropriate use of laboratory investigations is increasingly important in resource-constrained environments. We receive the anti-neutrophil cytoplasmic antibody (ANCA) testing practices in a tertiary hospital in South Africa.

Introduction. The high cost and concern of adverse events, particularly infections, limit the use of biologic disease-modifying anti-rheumatic (bDMARD) therapies. We undertook this retrospective study to document their use for immune-mediated diseases (IMDs) and explore the efficacy, safety, adherence and screening practices prior to initiating bDMARDs in a tertiary referral hospital. Methods. A folder review of all adult and paediatric patients treated for IMDs with bDMARDs at Groote Schuur and Red Cross Hospitals between January 2013 and December 2019. Clinico-demographic particulars, details of bDMARD therapy, and adverse events were collated. Changes in disease activity were measured by diseasespecific tools at 6, 12, 24-months and at the last available visit, and patient adherence to bDMARDs was explored by folder and pharmacy record review. Results. We studied 151 folders, with 182 bDMARDs uses (29 patients used more than 1 bDMARD). Patients were from rheumatology (n= 38: 13 rheumatoid arthritis; 10 spondyloarthritis, 5 Systemic Lupus Erythematosus (SLE) , 5 inflammatory myositis and 5 other conditions); gastroenterology (n=31; 26 Crohn`s and 5 Ulcerative Colitis), dermatology (n=9; psoriasis), neurology (n=4, ophthalmology (n= 25; 6 scleritis, 18 uveitis, 1 optic neuritis), and paediatrics (n= 45, 26 juvenile idiopathic arthritis , 12 SLE, 7 other conditions). The bDMARDs used were TNF inhibitors (112), rituximab (55), tocilizumab (10), anakinra (3), abatacept (1), and tofacitinib (1). The vast majority of patients had an excellent response and were in low disease activity or remission at their last available visit. Adverse events included severe infection (4), tuberculosis (TB) (2), mild infection (4), severe allergic reaction (3), mild skin reaction (14), elevated liver enzymes (2), and worsening interstitial lung disease ILD (1). bDMARD Therapy was discontinued in 18 patients, most commonly due to adverse reaction (9), lack of response (3), poor adherence (2), or remission (1). bDMARD Therapy was changed to alternative therapy in 29 patients, most commonly because of poor response (14), or adverse effects (9) or poor adherence (3). Poor adherence or patients lost to follow-up was noted in 18/182 (9.9%). Complete latent TB infection screening with chest x-ray and TB skin test was performed in only 55 (36.4 %) but INH prophylaxis was given to 51/88 (57.9%) of patients prescribed TNFi therapy. Hepatitis B screening performed in 93 (61.6 %) patients, but most patients (72.2 %) were not tested for Hepatitis B core ab. Hepatitis C screening was performed in 81 (53.6 %) patients. Only 88 (58.3%) patients had a recent HIV test. The majority (17.2%) received the influenza vaccine, but only 24 (15.8 %) received pneumococcal vaccination. Discussion and Conclusion. bDMARD therapy was an effective treatment, and the most common adverse effect was infection (7.2%), with 2 TB infections. Vaccination and screening for TB, viral hepatitis and HIV was suboptimal. Of concern, poor adherence to bDMARDs was frequently encountered.

Introduction. Interstitial lung disease (ILD) is prevalent in patients with autoimmune rheumatic diseases (ARD), leads to significant morbidity and mortality and is poorly characterized in South Africa (SA). We undertook this study to describe the clinical, serological and radiological features of ILD associated with ARD in a tertiary referral hospital. Methods. A cross-sectional study of patients with ILD attending the rheumatology and respiratory outpatient clinics of Groote Schuur Hospital between October 2018 and September 2019. Clinical, serological and radiological features were documented. We compared features of 3 groups of patients: rheumatoid arthritis (RA), systemic sclerosis (SSc) and other autoimmune connective tissue diseases (OCTD) which included idiopathic inflammatory myopathies, mixed connective tissue disease, systemic lupus erythematosus, primary Sjogren's syndrome and overlap syndromes. Factors associated with usual interstitial pneumonia (UIP) subtype were assessed. Results. Of 124 patients, 37 (29.8%) had RA, 32 (25,8%) SSc and 55 (44.4%) OCTD. Most patients were female (86.3%), of mixed racial ancestry (75.0%), and the median (IQR) age was 55 (46-66). Over one-third were smokers, emphysema was diagnosed in 22.6%, and one-third had previous pulmonary tuberculosis (PTB) infection. Smoking, emphysema, and previous PTB were higher in RA group but the difference was not statistically significant. All SSc patients and more than two-thirds of RA and OCTD patients had gastroesophageal reflux disease (GORD). Nonspecific interstitial pneumonia (NSIP) was the commonest pattern of ILD (63.7%), followed by usual interstitial pneumonia (UIP) (26.6%) and other patterns (9.7%). RA patients had similar frequencies of NSIP and UIP. Patients with RA were significantly older (median (IQR)) at ILD onset (62 (55-68) years), compared to SSc (49 (38-56)) and OCTD (42 (33-56)) (p < 0.001). Pulmonary function tests (PFTs) were significantly worse in SSc and OCTD groups. Regarding MTX exposure, 37.1% patients has MTX prescribed before ILD diagnosis, 33.9% continued, started or restarted after ILD diagnosis. No case of acute pneumonitis was documented. Pulmonary function tests and high-resolution computer tomography severity correlated poorly, with PFTs underestimating the severity. In the analysis comparing patients with and without UIP, RA diagnosis (OR 3.8, 95% CI 1.5-9.5), older age (0R 1.1, 95% CI 1.0-1.1), COPD (OR 3.2, 95% CI 1.4-8.0), longer ARD-ILD interval, and higher FVC (OR 1.0, 95% CI 1.0-1.1) were significantly associated with UIP. Conclusions: ILD was most commonly diagnosed in RA and SSc patients, with NSIP seen most frequently overall. Smoking, GORD, and PTB were frequent comorbidities. Amongst RA patients, we observed older age of onset and, interestingly, similar frequencies of NSIP and UIP patterns. The use of MTX was not associated with the development of acute pneumonitis in patients with ILD.

Objective: Systemic Lupus Erythematosus (SLE) is a multi‐system disease that predominately affects women. Considering the lack of data on health related quality of life (HRQoL) especially in sub‐ Saharan Africa, we undertook a literature review on HRQoL of SLE patients in developing countries to collate the existing evidence and identify information gaps. A mixed methods qualitative and quantitative study of lived experiences of South African women with SLE was performed. Methods: A literature search was conducted on medical databases using MeSH terms pertaining to HRQoL amongst SLE patients in the developing or low income countries to identify articles published between January 1975 and February 2018. The main study included 25 consenting SLE patients attending two tertiary hospitals in Johannesburg and Cape Town. Individual in‐depth interviews, using a topic guide, were conducted and analysed using NVivo software. In addition, participants completed the Short Form‐36 (SF‐36), Functional Assessment Instrument (FAI) and functional assessment of chronic illness therapy (FACIT) for fatigue questionnaires. The questionnaires were analysed per each tool's scoring method and SPSS software was used to calculate mean, standard deviations and correlations. Results The review of 31 articles, from 11 countries indicated that SLE women have a poor general HRQoL. In addition, we found relationships between disease factors including disease activity, organ damage, functioning, and mental health. Poor socioeconomic status worsened SLE outcomes by limiting patients' access to health care and psychosocial services. In the main study, the majority (72.0%) were black Africans, unemployed (76.0%), with low formal educational level and singlehood status (72.0%). The mean (SD) mental and physical composite SF‐36 scores were poor (50.9 (22.1) and 49.1 (20.5) respectively), and 68.0% of women had FACIT scores of severe fatigue. The mean (SD) FAI was 1.33 (0.8), showing that activities of daily living (ADL) were performed with difficulty. Major themes expressed were fatigue, pain, impaired functioning, depression, pregnancy, aesthetic concerns and sexuality issues. Disease chronicity, fatigue and pain were described by many participants as ‘taking over life' and impacting on performing ADL and career opportunities contributing to indigence. Negative pregnancy outcomes were frequently exacerbated by poor sexual relationships and miscommunication between patient and health care workers. Lack of understanding of SLE by patients, community and family as well as suicidal ideations and depressive symptoms were expressed. Although the quantitative tools measured these aspects, they were unable to explore complexities such as limitations in job acquisition, suicidal ideations, disease understanding and support systems. Conclusion This study underscores the complex, chronic and challenging life experiences, often exacerbated by poverty, of SA women with SLE. Quantitative tools may be inadequate in capturing important aspects of HRQoL that emerged from the qualitive interviews. Awareness of these limitations, together with psycho‐social support and education, might improve HRQoL. This thesis recommends multi‐centred, interventional longitudinal studies that incorporate mixed methods and focus on strategies to improve the negative outcomes in SLE.

Impaired Health-Related Quality of Life and Work Productivity amongst South African patients with Axial Spondyloarthritis. Background: No studies have investigated health-related quality of life (HRQoL) or work productivity in patients with axial spondyloarthritides (axSpA) living in sub-Saharan Africa. Methods: This cross-sectional study of adults with axSpA collated demographic particulars and patient questionnaires: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); Bath Ankylosing Spondylitis Functional Index (BASFI); Bath Ankylosing Spondylitis Global Score (BASG); Medical Short Form (SF)-36; and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). Results: Of 36 patients, the mean (SD) age was 40.3 (13.3) years and mean (SD) diagnostic delay was 8.7 (8.4) years. Most patients were male (80.6%) and of mixed racial ancestry (69.4%). Most (66.7%) patients were smokers and only 5 (13.9%) patients received tumor necrosis factor inhibitor (TNFi) therapy. The mean (SD) BASDAI was 5.3 (2.1), and 72.2% had a BASDAI ≥ 4. Patients with a high BASDAI (i.e. BASDAI ≥ 4) had higher BASG scores (p=0.003), higher WPAI:SHP activity impairment scores (p=0.003), and poorer SF-36 scores, particularly in the role-physical, bodily pain, and social functioning domains (p=0.0001, 0.001 and 0.02 respectively). Activity impairment according to the WPAI:SPH was 57.4%, with the BASDAI and activity impairment correlating closely (p=0.006). The SF-36 scores were low in physical (particularly role-physical, bodily pain, and general health) and mental (notably vitality and role emotional) domains. 6 Conclusion: This study describes a cohort of South African patients with axSpA who have poor prognostic features including diagnostic delay and cigarette smoking. Active disease, impaired function, poor physical- and mental HRQoL, and work disability are unmet needs.