Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19.

BACKGROUND: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials. METHODS: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality. RESULTS: The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine. CONCLUSIONS: Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).

Tuberculosis incidence in country of origin is a key determinant of the risk of active tuberculosis in people living with HIV: Data from a 30-year observational cohort study.

INTRODUCTION: People living with HIV (PLWH) are at high risk of active tuberculosis (TB) but this risk in the era of antiretroviral treatment (ART) remains unclear. It is critical to identify the groups who should be prioritised for latent TB (LTBI) screening. In this study we identified the risk factors associated with developing incident TB disease, by analysing a 30-year observational cohort. METHODS: We evaluated PLWH in Leicester, UK, between 1983 and 2017 to ascertain those who developed active TB and the timing of this in relation to HIV diagnosis; whether before, concurrently with, or more than 3 months after the diagnosis of HIV (incident TB). Predictors of incident TB were ascertained using Cox proportional hazards models. RESULTS: In all, 325 out of 2158 (15.1%) PLWH under care had had active TB; 64/325 (19.7%) prior to HIV diagnosis, 161/325 (49.5%) concurrently with/within 3 months of HIV diagnosis and 100/325 (30.8%) had incident TB. Incident TB risk was 4.57/1000 person-years. Increased TB incidence in the country of birth was associated with an increased risk of developing incident TB [50-149/100 000 population, adjusted hazard ratio (AHR) = 3.10, 95% CI: 0.94-10.20; 150-249/100 000 population, AHR = 7.14, 95% CI: 3.46-14.74; 250-349/100 000 population, AHR = 5.90, 95% CI: 2.32-14.99; ≥ 350/100 000 population, AHR = 3.96, 95% CI: 1.39-11.26]. CONCLUSIONS: Tuberculosis risk remains high among PLWH and is related to TB incidence in the country of birth. Further work is required to determine whether specific groups of PLWH should be targeted for programmatic LTBI screening, and whether it will result in high uptake and completion of chemoprophylaxis and is cost-effective for widespread implementation.

Clinical outcomes of patients with and without HIV hospitalized with COVID-19 in England during the early stages of the pandemic: a matched retrospective multi-centre analysis (RECEDE-C19 study).

BACKGROUND: The contribution of HIV to COVID-19 outcomes in hospitalized inpatients remains unclear. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV status. METHODS: HIV-negative patients were matched to people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS-CoV-2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two-point improvement or better on a seven-point ordinal scale) or hospital discharge by day 28, whichever was earlier. RESULTS: A total of 68 PLWH and 181 HIV-negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39-0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43-1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. Baseline frailty (aHR = 0.79, 95% CI: 0.65-0.95, p = 0.011), malignancy (aHR = 0.37, 95% CI 0.17, 0.82, p = 0.014) remained associated with poorer outcomes. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2-5 vs, 2 × IQR: 1-4, p = 0.0069), and to have a non-significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29). CONCLUSIONS: Adjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID-19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID-19.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment.

A nested case-control study of predictors for tuberculosis recurrence in a large UK Centre.

BACKGROUND: Tuberculosis (TB) recurrence represents a challenge to control programs. In low incidence countries, the prevailing risk factors leading to recurrence are poorly characterised. METHODS: We conducted a nested case-control study using the Leicester TB service TBIT database. Cases were identified from database notifications between 1994 and 2014. Controls had one episode and were matched to cases on a ratio of two to one by the date of notification. Multiple imputation was used to account for missing data. Multivariate conditional logistic regression analysis was employed to identify clinical, sociodemographic and TB specific risk factors for recurrence. RESULTS: From a cohort of 4628 patients, 82 TB recurrences occurred (1.8%). Nineteen of 82 patients had paired isolates with MIRU-VNTR strain type profiles available, of which 84% were relapses and 16% reinfections. On multivariate analysis, smoking (OR 3.8; p = 0.04), grade 3/4 adverse drug reactions (OR 5.6; p = 0.02), ethnicity 'Indian subcontinent' (OR 8.5; p = <0.01), ethnicity 'other' (OR 31.2; p = 0.01) and receipt of immunosuppressants (OR 6.8; p = <0.01) were independent predictors of TB recurrence. CONCLUSIONS: Within this UK setting, the rate of TB recurrence was low, predominantly due to relapse. The identification of an elevated recurrence risk amongst the ethnic group contributing most cases to the national TB burden presents an opportunity to improve individual and population health.

Latent tuberculosis infection screening and treatment in HIV: insights from evaluation of UK practice.

Latent TB infection (LTBI) screening and treatment in HIV-positive individuals in the UK is advocated by the British HIV Association (BHIVA) and National Institute for Health and Care Excellence (NICE), although each recommends differing strategies. We undertook an evaluation of UK practice, relating the responses to the local HIV/TB disease burden. 162 of 188 (86%) UK geographical areas responded; only 93/162 (57.4%) offer LTBI testing with considerable heterogeneity in practice, and no difference in HIV/TB burden between areas offering testing and those who do not. Only 33/93 (35.5%) and 6/93 (6.5%) reported full compliance with BHIVA and NICE guidance respectively. A uniform national guideline is required.

Toscana virus meningo-encephalitis: an important differential diagnosis for elderly travellers returning from Mediterranean countries.

BACKGROUND: Elderly patients have a long list of differentials for causes of acute confusion and altered consciousness levels, including infectious agents. In addition, elderly, retired patients often have more time to travel for tourism, particularly to exotic, warmer locations. Mediterranean countries such as Spain and Italy are popular holiday destinations for British and other tourists, especially during the winter months. However, these warm climates allow insect vectors to proliferate, increasing the risk of exposure to endemic vectorborne viral infections whilst on vacation. Such infections may not be routinely considered by geriatric medical teams. CASE PRESENTATION: An 87-year old gentleman presented with a three-day history of worsening confusion, lethargy, ataxia, and fevers following a trip to Spain, where he may have sustained a sandfly bite. By the time of admission, he had a reduced GCS, was hallucinating, and was incontinent of urine and faeces, though blood pressure and heart rate were normal. He also appeared hyperaesthetic, and found even capillary blood sugar testing extremely painful. He had no history of cognitive defect or other neurological conditions. He had been previously independently active, with frequent trips to Spain where he maintained a holiday home. He probably sustained a sandfly bite during this most recent trip, whilst cleaning out a shed. Acute and convalescent sera demonstrated IgG antibodies to Toscana virus at extremely high titres of ≥1:10,000 by immunofluorescence assay, though no Toscana virus RNA was detectable in these sera by the time of presentation. CONCLUSIONS: Toscana virus should be included in the differential diagnosis of any patients presenting with meningo-encephalitis who have recently returned from a Mediterranean country. Testing for Toscana virus infection is performed by serological testing on acute/convalescent paired sera, and/or a polymerase chain reaction (PCR) assay on blood or cerebrospinal fluid (CSF) if presenting within 5 days of illness onset. Making a diagnosis of Toscana virus meningitis/encephalitis (where no other pathogen is detected) has additional clinical utility in reducing or preventing unnecessary use of antibiotics, as well as reassuring the patient and family that generally, this illness is generally self-limiting and full recovery within a few weeks is expected, as in the case reported here.

Vitamin D deficiency and TB disease phenotype.

BACKGROUND: Extrapulmonary TB is increasingly common, yet the determinants of the wide clinical spectrum of TB are poorly understood. METHODS: We examined surveillance data (Birmingham, UK: 1980-2009 and USA Centers for Disease Control: 1993-2008) to identify demographic factors associated with extrapulmonary TB. We then directly tested association of these factors and serum 25-hydroxycholecalciferol (25(OH)D) concentration with extrapulmonary TB by multivariable analysis in a separate UK cohort. RESULTS: Data were available for 10,152 and 277,013 TB cases for Birmingham and US, respectively. Local-born individuals of white ethnicity had a lower proportion of extrapulmonary disease when compared with local-born non-whites (p<0.0001); both groups had a lower proportion of extrapulmonary disease when compared with foreign-born non-whites (p<0.0001). In a separate UK cohort (n=462), individuals with extrapulmonary TB had lower mean serum 25(OH)D concentration than those with pulmonary TB (11.4 vs 15.2 nmol/L, respectively, p=0.0001). On multivariable analysis, vitamin D deficiency was strongly associated with extrapulmonary TB independently of ethnicity, gender and other factors. Doubling in serum 25(OH)D concentration conferred substantially reduced risk of extrapulmonary disease (OR 0.55, 95% CI 0.41 to 0.73). CONCLUSIONS: We identify vitamin D deficiency as a probable risk factor for extrapulmonary dissemination in TB, which may account for the associations of dark-skinned ethnicity and female gender with extrapulmonary disease. Our findings implicate vitamin D status in Mycobacterium tuberculosis containment in vivo and, given the high prevalence of deficiency, may inform development of novel TB prevention strategies.

Risk of vaccine preventable diseases in UK migrants: A serosurvey and concordance analysis.

Background: Vaccine preventable diseases (VPDs) such as measles and rubella cause significant morbidity and mortality globally every year. The World Health Organization (WHO), reported vaccine coverage for both measles and rubella to be 71 % in 2019, indicating an immunity gap. Migrants in the EU/EEA may be at high risk of VPDs due to under-immunisation and poor living conditions. However, there are limited data on VPD seroprotection rates amongst migrants living in the United Kingdom (UK). Methods: We conducted an exploratory cross-sectional serosurvey amongst a sample of adult migrants living in Leicester, UK to: (a) determine seroprotection rates for measles, varicella zoster, and rubella in this group; (b) identify risk factors associated with seronegativity and, (c) understand if self-reported vaccine or diseases history is an effective measure of seroprotection. Participants gave a blood sample and completed a questionnaire asking basic demographic details and vaccine and disease history for the three VPDs. We summarised the data using median and interquartile range (IQR) for non-parametric continuous variables and count and percentage for categorical variables. We used logistic regression to establish predictors of seroprotection against these diseases. We examined the reliability of self-reported vaccination/disease history for prediction of seroprotection through a concordance analysis. Results: 149 migrants were included in the analysis. Seroprotection rates were: varicella zoster 98 %, rubella 92.6 % and measles 89.3 %. Increasing age was associated with seroprotection (OR 1.07 95 % CI 1.01-1.13 for each year increase in age). Migrants from Africa and the Middle East (aOR 15.16 95 % CI 1.31 - 175.06) and South/East Asia and Pacific regions (aOR 15.43 95 %CI 2.38 - 100.00) are significantly more likely to be seroprotected against measles as compared to migrants from Europe and Central Asia. The proportions of migrants unsure about their vaccination and disease history combined were 53.0 % for measles; 57.7 % for rubella; 43.0 % for varicella. There was no agreement between self-reported vaccination/disease history and serostatus. Conclusion: Our findings suggest lower levels of seroprotection against measles in migrants living in Leicester, UK, with younger migrants and those from Europe and Central Asia more likely to lack seroprotection. A high proportion of surveyed migrants were unaware of their vaccination/disease history and self-reported vaccine/disease was a poor predictor of seroprotection against VPDs which is important for clinical decision-making regarding catch-up vaccination in this population. Our results, although derived from a small sample, suggest that there may be gaps in seroimmunity for certain VPDs in particular migrant populations. These findings should inform future qualitative studies investigating barriers to vaccine uptake in migrants and population-level seroprevalence studies aimed at determining individualised risk profiles based on demographic and migration factors.

Single-step QuantiFERON screening of adult contacts: a prospective cohort study of tuberculosis risk.

BACKGROUND: The efffectiveness of tuberculosis (TB) contact screening programmes using interferon γ release assays remains uncertain as prospective contact TB risk is not well characterised. OBJECTIVES: To quantify 2-year TB risk and evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT) in adult contacts. To compare TB risk between QFT tested subgroups stratified by exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB) and age (younger (16-35 years) versus older (≥36 years)). METHODS: Screening involved QFT testing in older contacts of SP and all younger contacts, 8-12 weeks after index notification. Chemoprevention (3RH) was offered to QFT positive (+) younger adults. TB risk was determined in a prospective cohort study. RESULTS: 43 TB events occurred in 1769 adult contacts observed for median 717 days (2-year rate (95% CI)=2·5% (1.7 to 3.2)). Index-contact strain matching was demonstrable for 18 of 22 (82%) paired samples. No contacts (0/98) receiving 3RH developed TB. 215 of 817 appropriately tested adults (26.3%) were QFT+. 14 of 112 untreated QFT+ adults developed TB (2-year rate (95% CI)=13·4% (7.7 to 21.1)). The model required 35 contacts screened with QFT to identify one contact developing TB at 2 years. TB rates were comparable in QFT+ contacts of SP and NSP (rate ratio (RR)=0.98, p=0·962). For QFT+ older contacts, the disease rate was lower (8.9% (3.3 to 19.1)) and similar to the overall group rate (RR=1.4, p=0.503). CONCLUSIONS: QFT based single-step contact screening is effective in young adults.

Latent tuberculosis screening and treatment in HIV: highly acceptable in a prospective cohort study.

Background: People living with HIV (PLWH) are at increased risk of re-activation of latent tuberculosis infection (LTBI). Although UK and international guidelines identify this group as a priority for LTBI screening and treatment, data on attitudes of PLWH to this policy recommendation are lacking. Methods: A five-point, Likert-style questionnaire was administered to PLWH to assess views and intentions towards accepting LTBI screening and treatment. Subsequent interferon-γ release assay (IGRA) testing was offered, and chemoprophylaxis if required. Influencing demographic and psychological associations with planned, and actual, testing and treatment uptake were assessed using multivariable logistic regression. Results: 444 out of 716 (62%) patients responded. 417 out of 437 (95.4%) expressed intention to accept LTBI testing. The only significant association was the perceived importance of testing to the individual (adjusted odds ratio (aOR) 8.98, 95% CI 2.55-31.67). 390 out of 393 (99.2%) accepted appropriate IGRA screening; 41 out of 390 (10.5%) were positive. 397 out of 431 (92.1%) expressed intention to accept chemoprophylaxis, associated with perceived importance of treatment (aOR 3.52, 95% CI 1.46-8.51), a desire to have treatment for LTBI (aOR 1.77, 95% CI 0.99-3.15) and confidence in taking treatment (aOR 3.77, 95% CI 1.84-7.72). Of those offered chemoprophylaxis, 36 out of 37 (97.3%) accepted and 34 out of 36 (94.4%) completed treatment. There were no correlates with actual screening acceptance. Conclusions: LTBI is common amongst PLWH, highlighting the importance of robust screening and treatment programmes. This study shows that screening and treatment for LTBI is highly acceptable to PLWH and provides strong, objective evidence for policy-makers developing guidelines in this cohort.

The impact, effectiveness and outcomes of targeted screening thresholds for programmatic latent tuberculosis infection testing in HIV.

BACKGROUND: Screening and treatment for latent tuberculosis infection (LTBI) are key for TB control. In the UK, the National Institute for Health and Care Excellence (NICE) and the British HIV Association (BHIVA) give conflicting guidance on which groups of people with HIV (PWH) should be screened, and previous national analysis demonstrated heterogeneity in how guidance is applied. There is an urgent need for a firmer clinical effectiveness evidence base on which to build screening policy. METHODS: We conducted a systematic, programmatic LTBI-screening intervention for all PWH receiving care in Leicester, UK. We compared yields (percentage IGRA positive) and number of tests required when applying the NICE and BHIVA testing strategies, as well as strategies targeting screening by TB incidence in patients' countries of birth. RESULTS: Of 1053 PWH tested, 118 were IGRA-positive (11.2%). Positivity was associated with higher TB incidence in country-of-birth [adjusted odds ratio, 50-149 cases compared with <50 cases/100 000: 11.6; 95% confidence interval (CI) 4.79-28.10)]. There was high testing uptake (1053/1069, 98.5%). Appropriate chemoprophylaxis was commenced in 100 of 117 (85.5%) patients diagnosed with LTBI, of whom 96 of 100 (96.0%) completed treatment. Delivering targeted testing to PWH from countries with TB incidence greater than 150 per 100 000 population or any sub-Saharan African country, would have correctly identified 89.8% of all LTBI cases while cutting tests required by 46.1% compared with NICE guidance, performing as well as BHIVA 2018 guidance. CONCLUSION: Targeting screening to higher risk PWH increases yield and reduces the number requiring testing. Our proposed 'PWH-LTBI streamlined guidance' offers a simplified approach, with the potential to improve national LTBI-screening implementation.

Eumycetoma of the hand caused by Leptosphaeria tompkinsii and refractory to medical therapy with voriconazole.

We report on the first case of eumycetoma caused by the organism Leptosphaeria tompkinsii to be diagnosed and possibly acquired within the United Kingdom. Conventional culture of fungal grains and surgical tissue specimens was negative and the diagnosis was achieved using panfungal polymerase chain reaction and sequencing technology. Despite limited surgical resection and prolonged antifungal therapy with voriconazole, the patient developed progressive disease with mycetoma bone involvement. This case highlights the usefulness of molecular diagnostic techniques in eumycetoma where organisms may fail to grow with conventional culture or be difficult to identify morphologically. It also reminds us that eumycetoma is a difficult infection to treat and despite optimism regarding the efficacy of the newer triazole antifungals in this condition, treatment failures may still occur.

Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C.

Background: The world health organization (WHO) has identified the need for a better understanding of which patients with hepatitis C virus (HCV) can be cured with ultrashort course HCV therapy. Methods: A total of 202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1/2). Participants not cured following first-line treatment were retreated with 12 weeks' sofosbuvir/ledipasvir/ribavirin. The primary outcome was sustained virological response 12 weeks (SVR12) after first-line treatment and retreatment. Participants were factorially randomised to receive ribavirin with first-line treatment. Results: All evaluable participants achieved SVR12 overall (197/197, 100% [95% CI 98-100]) demonstrating non-inferiority between fixed-duration and variable-duration strategies (difference 0% [95% CI -3.8%, +3.7%], 4% pre-specified non-inferiority margin). First-line SVR12 was 91% [86%-97%] (92/101) for fixed-duration vs 48% [39%-57%] (47/98) for variable-duration, but was significantly higher for VUS2 (72% [56%-87%] (23/32)) than VUS1 (36% [25%-48%] (24/66)). Overall, first-line SVR12 was 72% [65%-78%] (70/101) without ribavirin and 68% [61%-76%] (69/98) with ribavirin (p=0.48). At treatment failure, the emergence of viral resistance was lower with ribavirin (12% [2%-30%] (3/26)) than without (38% [21%-58%] (11/29), p=0.01). Conclusions: Unsuccessful first-line short-course therapy did not compromise retreatment with sofosbuvir/ledipasvir/ribavirin (100% SVR12). SVR12 rates were significantly increased when ultrashort treatment varied between 4-7 weeks rather than 4-6 weeks. Ribavirin significantly reduced resistance emergence in those failing first-line therapy. ISRCTN Registration: 37915093 (11/04/2016).

Socio-demographic heterogeneity in the prevalence of COVID-19 during lockdown is associated with ethnicity and household size: Results from an observational cohort study.

BACKGROUND: Accumulating evidence indicates that COVID-19 causes adverse outcomes in ethnic minority groups. However, little is known about the impact of ethnicity and household size on acquiring infection with SARS-CoV-2. METHODS: We undertook a retrospective cohort study, in Leicester (UK), of all individuals assessed for COVID-19 with polymerase chain reaction (PCR) testing at University Hospitals of Leicester NHS Trust between 1st March and 28th April 2020. We used logistic regression to identify sociodemographic, clinical and temporal factors associated with SARS-CoV-2 PCR positivity before/after lockdown. FINDINGS: 971/4051 (24.0%) patients with suspected COVID-19 were found to be PCR positive for SARS-CoV-2. PCR positivity was more common amongst individuals from ethnic minortiy backgrounds than their White counterparts (White 20.0%, South Asian 37.5%, Black 36.1%, Other 32.2%; p<0.001 for all ethnic minority groups vs White). After adjustment, compared to White ethnicity, South Asian (aOR 2.44 95%CI 2.01, 2.97), Black (aOR 2.56 95%CI 1.71, 3.84) and Other (aOR 2.53 95%CI 1.74, 3.70) ethnicities were more likely to test positive, as were those with a larger estimated household size (aOR 1.06 95%CI 1.02, 1.11). We saw increasing proportions of positive tests in the three weeks post-lockdown amongst the ethnic minority , but not the White, cohort. Estimated household size was associated with PCR positivity after, but not before, lockdown (aOR 1.10 95%CI 1.03, 1.16). INTERPRETATION: In individuals presenting with suspected COVID-19, those from ethnic minority communities and larger households had an increased likelihood of SARS-CoV-2 PCR positivity. Pandemic control measures may have more rapid impact on slowing viral transmission amongst those of White ethnicity compared to ethnic minority groups, Research is urgently required to understand the mechanisms underlying these disparities and whether public health interventions have differential effects on individuals from ethnic minority groups. FUNDING: 10.13039/100006662 NIHR.

Olecranon bursitis secondary to Mycobacterium kansasii infection in a patient receiving infliximab for Behcet's disease.

We present a case of Mycobacterium kansasii olecranon bursitis in a woman with known immunosuppression secondary to the treatment received for her Behçet's disease. We found only one other case report of olecranon bursitis caused by M. kansasii in the literature, which, unlike our case, presented in an immunocompetent adult following trauma. This case extends the range of opportunistic mycobacterial infections that are associated with anti-tumour necrosis factor therapy.