Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics:A Systematic Review and Network Meta-Analysis

ObjectiveAnterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.MethodsWe conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin-17 (anti–IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsForty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL-17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL-17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti-TNF mAb, anti–IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL-17, and etanercept. All treatments were ranked superior to placebo.ConclusionAnti-TNF mAbs, JAKi, and anti–IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.<p/

No Waning of Pneumococcal Vaccine Responses over Time in People with Inflammatory Arthritis:Findings from a Single Centre Cohort

Background: Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time. Methods: This was a single centre, retrospective cohort study of individuals with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis who had previously received the PPSV23 polysaccharide pneumococcal vaccine (Pneumovax). Data were retrieved between January 2021 to August 2023. Dates of previous pneumococcal vaccination were identified using linked primary care records. Serum serotype levels were collected. The primary outcome was serological response defined as a titre ≥0.35 mcg/mL in at least five from a total of 12 evaluated pneumococcal serovars, examined using a Luminex platform. Multivariate logistic regression models adjusting for age, gender, ethnicity, co-morbidities, and the use of prednisolone, conventional synthetic and biological DMARDs were used to determine the odds of a sustained serological response according to time categorised into ≤5 years, 5–10 years, and ≥10 years since vaccination. Results: Serological response was measured in 296 individuals with inflammatory arthritis, with rheumatoid arthritis the most common diagnosis (74% of patients). The median time between pneumococcal vaccine administration and serological assessment was 6 years (interquartile range 2.4 to 9.9). A positive serological response to at least 5 serovars was present in 195/296 (66%) of patients. Time since vaccination did not significantly associate with serological protection compared with those vaccinated &lt;5 years, the adjusted ORs of vaccine response was 1.15 (95% CI 0.64 to 2.07) in those 5–10 years and 1.26 (95% CI: 0.64 to 2.48) in those vaccinated over 10 years ago. No individual variable from the multivariate model reached statistical significance as an independent predictor of vaccine response, although steroid use at the time of vaccine had a consistent detrimental impact on serological immunity. Conclusions: We demonstrated that antibody titres following vaccination against pneumococcal serovars do not appear to wane over time. It appears more critical to focus on maximising the initial vaccine response, which is known to be diminished in this patient population.<p/

Risk of infection in patients with early inflammatory arthritis:results from a large UK prospective observational cohort study

OBJECTIVE: To identify risk of serious infections-(SI) according to initial conventional synthetic disease modifying anti-rheumatic drugs-(csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit.METHODS: An observational cohort study was used, including adults in England and Wales with new diagnoses of rheumatoid arthritis-(RA) between 2018-2023. Main outcome was SI-events, defined as infections requiring hospitalisation/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios-(HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments.RESULTS: 17 472 patients were included, of whom 10 997 on methotrexate-based strategies; 4,540 on other csDMARDs; 13 680 received corticosteroids. There were 1307 SI-events, corresponding to incidence rates per 100 person-years of 3.02 (95% CI: 2.86-3.19) and 311 SI-related mortality (IR 0.69, 95% CI: 0.61-0.77). Methotrexate-based strategies were associated with reduced risk of SI-events compared with other csDMARDs (adjusted HR 0.72, 95% CI: 0.63-0.82). In unadjusted models, corticosteroid was associated with higher risk of SI-events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI: 0.87-1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive, and having high DAS28 all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI-event by 10%.CONCLUSION: Methotrexate-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.</p

Gout incidence and management during the COVID-19 pandemic in England, UK: a nationwide observational study using OpenSAFELY

BackgroundGout is the most prevalent inflammatory arthritis, yet one of the worst managed. Our objective was to assess how the COVID-19 pandemic impacted incidence and quality of care for people with gout in England, UK.MethodsWith the approval of National Health Service England, we did a population-level cohort study using primary care and hospital electronic health record data for 17·9 million adults registered with general practices using TPP health record software, via the OpenSAFELY platform. The study period was from March 1, 2015, to Feb 28, 2023. Individuals aged 18–110 years were defined as having incident gout if they were assigned index diagnostic codes for gout, were registered with TPP practices in England for at least 12 months before diagnosis, did not receive prescriptions for urate-lowering therapy more than 30 days before diagnosis, and had not been admitted to hospital or attended an emergency department for gout flares more than 30 days before diagnosis. Outcomes assessed were incidence and prevalence of people with recorded gout diagnoses, incidence of gout hospitalisations, initiation of urate-lowering therapy, and attainment of serum urate targets (≤360 μmol/L).FindingsFrom a reference population of 17 865 145 adults, 246 695 individuals were diagnosed with incident gout. The mean age of individuals with incident gout was 61·3 years (SD 16·2). 66 265 (26·9%) of 246 695 individuals were female, 180 430 (73·1%) were male, and 189 035 (90·9%) of 208 050 individuals with available ethnicity data were White. Incident gout diagnoses decreased by 30·9% in the year beginning March, 2020, compared with the preceding year (1·23 diagnoses vs 1·78 diagnoses per 1000 adults). Gout prevalence was 3·07% in 2015–16, and 3·21% in 2022–23. Gout hospitalisations decreased by 30·1% in the year commencing March, 2020, compared with the preceding year (9·6 admissions vs 13·7 admissions per 100 000 adults). Of 228 095 people with incident gout and available follow-up, 66 560 (29·2%) were prescribed urate-lowering therapy within 6 months. Of 65 305 individuals who initiated urate-lowering therapy with available follow-up, 16 790 (25·7%) attained a serum urate concentration of 360 μmol/L or less within 6 months of urate-lowering therapy initiation. In interrupted time-series analyses, urate-lowering therapy prescribing improved modestly during the pandemic, compared with pre-pandemic, whereas urate target attainment was similar.InterpretationUsing gout as an exemplar disease, we showed the complexity of how health care was impacted during the COVID-19 pandemic. We observed a reduction in gout diagnoses but no effect on treatment metrics. We showed how country-wide, routinely collected data can be used to map disease epidemiology and monitor care quality

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

EP18 Testicular sarcoidosis: a challenging diagnosis

Abstract Case report - Introduction Sarcoidosis is an inflammatory systemic disorder that is characterised by the formation of immune granulomas. Lung involvement is seen in about 90% of patients but extrapulmonary sarcoidosis can be a clinically challenging manifestation. Despite the majority remitting in three years, a considerable proportion (10-30%) develop chronic disease requiring continuous treatment. The development of extrapulmonary disease can be prior to, after or concomitant with pulmonary disease. Although cardiac, ophthalmic, neurological, and musculoskeletal manifestations have been described elsewhere, testicular involvement remains a rare phenotype of the disease which is poorly understood. Case report - Case description A 36-year old male patient born in Jamaica, presented in 2017 with unilateral left-sided testicular pain and enlargement measuring 20 x 16 x 18mm on ultrasound. This was initially suspected of malignancy or an atypical infection. A subsequent CT chest, abdomen and pelvis demonstrated nodal evidence of hilar, internal mammary and mediastinum involvement. Blood tests were unremarkable other than a raised lactate dehydrogenase (248 IU. mL (NR &amp;lt; 240)), low testosterone (5.2nmol/L (NR 10-30)) and androgen index (11.6 (NR 25-90). The patient underwent an orchidectomy and prosthesis, histological sampling demonstrated idiopathic granulomatous orchitis with features consistent of sarcoidosis. Malignancy could be excluded, and the absence of characteristic histochemical staining patterns favoured sarcoid to other differential diagnoses. He was efficaciously treated after a year’s interval with prednisolone, which was gradually weaned from 40mg. However, eighteen months later, the patient returned complaining of right testicular pain. Ultrasound showed inflammation and enlargement of the testicle. PET-CT supported a recurrence of testicular involvement along with systemic disease involvement including neuropathy. His serum angiotensin-converting enzyme was raised at 118 IU/L (NR8-52) and responded similarly to high dose corticosteroid treatment. Additionally, an MRI brain showed neurosarcoid in the superior sagittal sinus tracking along the right transverse sinus. Currently the patient is maintained on subcutaneous methotrexate 25mg disease modifying anti-rheumatic drug (DMARD) monotherapy. He has diabetes attributed to prolonged corticosteroid use over the last three years. As a result of his testicular involvement, the patient suffers from erectile dysfunction and hypogonadism with low testosterone production. Chronic pain and neuro-sagittal involvement have contributed to difficulties in achieving treatment targets with increased malaise, fatigue and poor cognition all compounding his disease further. This has posed a challenge as to whether this is due to the disease or the patients use of cannabis or a combination of the two. Case report - Discussion Testicular sarcoid is a rare presentation in which only around 0.2% of all sarcoidosis cases are diagnosed. The epididymis, vas deferens and testis can all be involved. Presentation can mimic that of infections such as tuberculosis mycobacterium and malignancy with uni- or bilateral testicular involvement. Challenges arise, as in this case, when the patient presents with genito-urinary involvement in the absence of more systemic features which may favour extra-pulmonary manifestations. The diagnosis and treatment can be difficult, as corticosteroid response tends to be most effective at high doses and disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate have evidence for pulmonary and extra-pulmonary sites. Our patient developed more systemic features at a later stage. The diagnosis was challenging and there was an interval of a year between the orchidectomy and commencement of steroids. This shows the ongoing difficulties in diagnosing patients with sarcoidosis and the delays that occur in treatment initiation. Testicular involvement has created debilitating symptoms for the patient with chronic pain affecting his ability to sit and ride his bike for extended periods. Involvement of the other testicle, ongoing low testosterone production and erectile dysfunction have posed difficult discussions around future fertility. It is encouraging that he has managed to wean from corticosteroid and methotrexate seems to be controlling the disease quite well. The evidence relating to best possible DMARD treatment in testicular sarcoid is still scarce and is an interesting point of discussion. There have been co-existent reports of testicular tumours in sarcoid, and as most of these patients are seen by surgical specialties, further work must heighten awareness of sarcoid in this cohort of patients. Case report - Key learning points We feel this is an unusual presentation of sarcoidosis; a patient who presented with primary testicular involvement and is pertinent to the topic of extrapulmonary disease manifestation. Despite appropriate treatment, he developed recurrence within the other testis two years later. Testicular involvement as a manifestation of extra-pulmonary sarcoidosis is rare and difficult to treat. There are limitations in treatment beyond corticosteroid, although DMARD therapy with methotrexate being favoured in case reports listed elsewhere. It is difficult to differentiate from malignancy and infection, and as a result often requires complete removal of the testis for histological interpretation. This can lead to hypogonadism and may affect long-term fertility which has significant psychosocial impacts for patients. There is an association between sarcoidosis and the development of co-morbidities which carries significant long-term complications. The relationship between long-term corticosteroid use and ethnicity in the development of co-morbidities in patients with sarcoidosis is poorly understood. Medical and surgical specialties that manage most cases involving testicular masses may not be aware of the differentials such as sarcoid; clinicians may therefore be exposed to a degree of cognitive bias in these cases. We propose this as an example to improve framing of similar cases for clinicians in the future. From a patient’s perspective, similar cases require careful discussion to explore potential management options and their outcomes as the impact may be life changing. </jats:sec

EP21 Tumour necrosis factor inhibitor for the treatment of refractory extra-pulmonary disease including sarcoid arthritis and myositis

Abstract Case report - Introduction Sarcoid myositis is a rare extrapulmonary manifestation of sarcoid, histologically characterised by non-caseating granuloma in the perimysial connective tissue. Muscle involvement is often asymptomatic but can cause weakness, myalgia, or muscle nodules. The first line treatment for sarcoid myositis is steroids. This case report details a case of sarcoid myositis and multi-system disease refractory to both steroids and mycophenolate mofetil. The use of infliximab, a Tumour Necrosis Factor α inhibitor (TNFi) resulted in drastic clinical and radiological resolution of sarcoid myositis. The patient is still on the TNFi and his sarcoid remains relatively well controlled. Case report - Case description A 33-year old Afro-Caribbean gentleman with a 10-year history of sarcoid (biopsy confirmed, affecting lymph nodes, lung) presented in May 2017 with joint pain, weakness, difficulty walking and cognitive impairment. At the time of the original diagnosis of sarcoid, he had concurrently been diagnosed with schizophrenia and steroids had been avoided. His only medication was olanzapine 5mg. Due to declining cognitive function, his psychiatrists arranged an MRI brain which showed extensive leptomeningeal disease. Lumbar puncture excluded infection and neurosarcoid was diagnosed. Prednisolone resulted in partial improvement in cognition, however joint symptoms and weakness persisted. On rheumatologic assessment there was an asymmetric inflammatory arthropathy, with small joint synovitis as well as large volume joint effusions of elbows and knees. Radiologic investigations showed characteristic lattice bony destruction, consistent with osseous sarcoid. His gait was waddling, and muscle strength was reduced symmetrically in the proximal groups. His creatinine kinase was 865, myositis specific antibody screen was negative although U1RNP was equivocal. Serum ACE was 102, CRP 17, ESR 25. CT-PET demonstrated FDG avidity in lymph nodes, lung parenchyma, bones, muscles, and testes. The muscle involvement was typical of nodular sarcoid and did not correlate with his weakness. The disease failed to respond adequately to either methotrexate or mycophenolate. He started Infliximab (5mg/kg). There was remarkable resolution of symptoms, including improvement in cognition. Follow up CT-PET confirmed response. Three years on he remains well, and no longer takes olanzapine. Case report - Discussion Muscle involvement occurs in 50-80% of sarcoidosis patients. Symptomatic myositis is rare (0.5-2.5%). There are three types of sarcoid myositis: nodular form, chronic myopathy, and acute myositis. Nodular involvement, as seen in our patient, usually occurs in young adults who experience palpable, painless nodules which may occur in any muscle. Nodules are not usually associated with weakness or limitation of movement. EMG and CK are usually normal. Chronic myopathy is rarely observed. It is characterised by a slowly progressive, symmetrical proximal myopathy with myopathic EMG changes but normal muscle enzymes, usually in women aged 50-60. Acute myositis typically affects younger patients (&amp;lt;40 years old) with diffuse muscle swelling, pain and proximal weakness which may progress to hypertrophy and contractures. Fatigue, fever, joint symptoms, and erythema nodosum are frequently seen. Inclusion Body Myositis is another granulomatous myopathy and should be considered as a differential, particularly in cases of treatment failure. The patient has had several episodes of psychosis and confusion which were previously diagnosed as schizophrenia and corticosteroid induced psychosis, meaning the team used steroids cautiously. MRI brain imaging revealed the presence of extensive neurosarcoidosis, and the neurocognitive improvement with treatment of a TNF inhibitor, suggested that the underlying pathology was sarcoidosis. Steroids could therefore be utilised appropriately for ongoing management. This case illustrates the difficulty of teasing out the underlying aetiology of neurocognitive dysfunction in patients with extensive sarcoidosis. TNFα released by alveolar macrophages is implicated in the induction and maintenance of sarcoid granulomas. Limited data from small randomised controlled trials and increasing data from non-randomised studies have led to consensus-based recommendations for TNFi use in pulmonary, ocular, cutaneous, neurological, and multi-system sarcoidosis. To our knowledge, this case is the first documented example of rapid clinical and radiological resolution of sarcoid myositis with an anti-TNF agent. Case report - Key learning points There are three important points to take away from this case. First, this case highlights the importance of a PET scan in demonstrating multi-system involvement in sarcoidosis. The PET scan was key in highlighting the extent of disease including sarcoid myositis. MRI scans of the brain were also important in highlighting the extent of neurosarcoidosis. Second, the patient presented with psychosis in 2013. This was thought to be corticosteroid-induced at the time. However, since treatment with the TNF inhibitor the patient experienced a significant neurocognitive improvement. The drastic improvement undermines the diagnosis of primary psychosis and suggests that the psychosis may have been due to neurosarcoidosis. In the context of patients with multi-organ sarcoidosis, psychosis secondary to neurosarcoid should be considered as a differential, even in the context of an earlier diagnosis of schizophrenia pre-dating the diagnosis of sarcoid. Third, the drastic resolution of sarcoid myositis and arthritis with a TNF inhibitor suggests that TNF inhibitors should be considered as treatment for cases of sarcoid myositis or sarcoid arthritis refractory to steroids. Whilst TNF inhibitors are currently unlicensed for this use in the UK, there is a growing body of evidence for their effectiveness in treating refractory extra-pulmonary sarcoidosis. </jats:sec

P022 Audit of vitamin D and calcium level monitoring in sarcoidosis patients taking calcium and/or vitamin D supplements

Abstract Background/Aims Sarcoidosis is a chronic inflammatory disorder, for which steroids are a common treatment. A side effect of long-term steroid therapy is an increased risk of osteoporosis, and calcium and/or vitamin D supplementation may be indicated. In sarcoidosis patients, increased expression of 1α-hydroxylase triggers the conversion of 25(OH)D3 to 1,25(OH)2D3 (calcitriol). Therefore, monitoring of calcium and vitamin D levels are recommended for patients taking supplementation, as they are at increased risk of hypercalcemia. Methods We conducted a retrospective analysis on community measurements of serum calcium and vitamin D levels, in sarcoidosis patients, who were prescribed calcium and/or vitamin D supplementation. Patients with biopsy confirmed sarcoidosis were identified using the King’s College Hospital sarcoidosis database and electronic primary care records were reviewed for each patient. Results The database identified 431 patients with biopsy confirmed sarcoidosis, of whom 102 patients (24%) had been prescribed calcium and/or vitamin D supplementation and were further evaluated. Of these 102 patients, 63 (62%) were taking calcium and vitamin D supplementation simultaneously; and 39 (38%) were taking vitamin D supplementation alone. In the last 12 months, 46 patients (45%) had measurements of serum calcium and vitamin D levels taken in the community. One patient taking vitamin D supplementation was identified as having hypercalcemia. Conclusion This audit has found infrequent monitoring of serum calcium and vitamin D levels over the last 12 months, in sarcoidosis patients, who were prescribed calcium and/or vitamin D supplementation. A Clinical Commissioning Group wide prescribing alert has been implemented to alert primary care physicians to the importance of monitoring these levels, to reduce the risk of hypercalcemia. Disclosure S. Gunawardana: None. D. Nagra: None. K. Bechman: None. S. Birring: None. J. Galloway: None. A. Patel: None. </jats:sec

EP13 A case of candida albicans septic sacroiliitis complicating severe COVID-19 infection

Abstract Case report - Introduction Bacterial and fungal infections are recognised complications of viral pneumonia, particularly in patients who are critically ill. We describe a case of fungal sacroiliitis complicating severe COVID-19 pneumonia following a prolonged intensive care unit (ICU) admission. Candida albicans sacroilitis is a rarely reported infection with few case reports in the literature. Candida osteoarticular infections can present as septic arthritis, with knee involvement in 75% of cases, or osteomyelitis. The latter presentation differs based on age - vertebral involvement (51%) is more common in adults while children are more likely to present with infection in the long bones, ribs, or sternum. Case report - Case description A 48-year-old Afro-Caribbean gentleman with a history of hypertension and obesity was admitted to the ICU with clinical, laboratory and radiographic features of COVID-19 infection despite persistently negative swabs. Whilst in ICU he required mechanical ventilation. His stay was further complicated by multiple infections, pulmonary emboli, and the presence of a cavitating lesion in the left lung. Cultures from bronchoalveolar lavage and a central venous catheter line grew Serratia Mascense, candida glabrata and pseudomonas were isolated from his urine. He was treated with multiple antibiotics including meropenem, tazocin, ceftazidime and avibactam. After 61 days in the ICU he was transferred to the ward. He developed severe pain in his right hip which was worse on movement. This was followed by urinary incontinence and sensory deficit in the right L2/L3 dermatome. He underwent magnetic resonance imaging (MRI) of his spine and sacroiliac joints which showed right sided sacroiliitis and oedema around the iliopsoas muscle. He was started on vancomycin, later changed to ceftazidime avibactam and metronidazole. An echocardiogram did not show any vegetations. He underwent a biopsy of his sacroiliac joints which confirmed the presence of leucocytes, extended cultures yielded candida albicans in one out of two biopsy specimens. Considering ongoing pyrexia, pain and inflammatory markers, intravenous fluconazole was added to his antibiotic regimen which resulted in a marked improvement in mobility. After four weeks, ceftazidime, metronidazole and avibactam were stopped, and fluconazole was administered as oral tablets. 6 days later he became febrile and IV fluconazole was restarted. A repeat chest CT showed resolution of the cavity but ongoing changes suggestive of organising pneumonia. A repeat MRI of the sacroiliac joints revealed minor improvement. Intravenous Fluconazole was continued for a total of 8 weeks and was changed to tablets for complete a total of 12 weeks. Case report - Discussion This is a severe case of COVID-19 infection who despite 9 negative PCR tests, on day 53, had positive IgG for SARS-CoV-2 infection, confirming our clinical suspicion. Particularly in the ICU setting, individuals are approximately ten times more likely to have secondary bacterial/fungal infections with more frequent detection of multidrug-resistant Gram- negative pathogens. This case highlights several difficulties. Urine cultures had confirmed candida albicans, likely to be related to catheter related urinary tract infections, and a possible source for our patient but also a resistant pseudomonas aeruginosa species. Furthermore, cultures were positive for Serratia Mascense, candida glabrata. He had also already been treated with prolonged, broad spectrum antimicrobial treatment. Considering this, establishing the aetiology of the septic sacroiliitis was challenging. The rarity of candida sacroiliitis and presence of the organism in just one specimen made this more difficult. This led to the decision of a repeat sacroiliac biopsy to supply sufficient samples for further microbial analyses such as 16S, 18S and mycobacteria culture, all of which were negative. He became febrile after the discontinuation of antimicrobials and a switch to oral fluconazole therapy. He was extensively re-investigated and despite resolution of the lung cavity, there were changes which could have been consistent with an organising pneumonia. At this point he was neutropenic, mildly eosinophilic, and therefore a drug reaction was also considered. Repeat MRI revealed resolving muscle inflammation and minimal change at the bone site, with erosions and possible reactive bone marrow oedema. Following discussion with microbiology the decision was made to persist with intravenous Fluconazole. He continued to improve, and his inflammatory markers normalised after 8 weeks of treatment. Prednisolone was started for COVID-19 related pneumonitis. Long-term antifungal treatment is advisable, and we aim to complete 12 weeks of treatment. Case report - Key learning points  Patients with SARS-CoV-2 infection, particularly those requiring ICU admission were at risk of developing superinfections with multidrug-resistant Gram-negative bacteria or fungal infections.Candida albicans sacroiliitis is rare therefore early aspiration/biopsy is essential for the management.Longer treatment is needed in osteoarticular candida infections, even up to 6 or 12 months, therefor long-term close monitoring of this patients is essential.The utility and timing of reimaging patients following such infections is still unclearClose multidisciplinary and interdisciplinary team collaboration is essential in the management of this complex patients </jats:sec