You have accessJournal of UrologyCME1 Apr 2023MP15-01 THE NEW PANDEMIC: MONKEYPOX AND ITS UROLOGICAL PRESENTATIONS Alex Murray, Piotr Śluzar, Anna Daunt, Aatish Patel, Nori Achyuta, Geraldine O'Hara, and Tet Yap Alex MurrayAlex Murray More articles by this author , Piotr ŚluzarPiotr Śluzar More articles by this author , Anna DauntAnna Daunt More articles by this author , Aatish PatelAatish Patel More articles by this author , Nori AchyutaNori Achyuta More articles by this author , Geraldine O'HaraGeraldine O'Hara More articles by this author , and Tet YapTet Yap More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003235.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Monkeypox (MPX) is a zoonotic virus, endemic to Central and Western Africa. Since early May 2022, there has been an outbreak of the virus with 3,548 confirmed cases in the UK for 2022, predominantly affecting men who have sex with men (MSM). Due to the virus’ capacity to transmit via exchange of bodily fluids, colonisation of the genitalia is not uncommon. Despite this, there is a paucity of available literature concerning urological manifestations. This case series seeks to elucidate the natural history of MPX from a urological perspective. METHODS: We reviewed all MPX antigen-positive cases at Guy’s & St Thomas’ NHS Trust, and affiliated sexual health centres in south London, between May and October 2022. Patients that presented with penile lesions were identified — of those, cases that required specialist urological input were selected. RESULTS: 199 men with Monkeypox were identified. Of those, 10% (19/199) presented with penile lesions and required treatment in an isolation ward with full personal protection equipment; 4% (8/199) required input from the urology team. Their average age was 41.6 (±7.1) years. 62.5% (5/8) of these patients were HIV positive but only one was poorly controlled (>200 copies/mL). 75% (6/8) of patients experienced penile oedema and 50% (3/6) of these patients experienced paraphimosis. One patient experienced paraphimosis without oedema, another experienced penile cyanosis concomitant with severe distal oedema. Rarely, urinary insufficiency will develop. The average number of penile lesions was 6 (range: 1-14, s.d. ±5.4). Lesions demonstrated a range of presentations — some initially appeared as pustules and papules, while more severe cases developed extensive, wet ulcerations; in some cases secondary infections were superimposed on the lesions, leading to necrosis. All lesions, however, were painful and required analgesia. On average, patients would present to health services 5.4 (±1.6) days after onset of symptoms, and would take 21 (±7.9) days for all lesions to heal. CONCLUSIONS: MPX urological presentations seem to observe a continuum of severity. Currently, the long-term urological sequelae of MPX are unknown but small lesions seem to heal without issue. By assessing the number of penile lesions and the presence of/potential for superimposed infections, a clinical picture for the course of the infection can be constructed and be used to inform management. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e191 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alex Murray More articles by this author Piotr Śluzar More articles by this author Anna Daunt More articles by this author Aatish Patel More articles by this author Nori Achyuta More articles by this author Geraldine O'Hara More articles by this author Tet Yap More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023MP15-03 MONKEYPOX AND THE PENIS: AN EMPIRICAL CARE PATHWAY Piotr Sluzar, Alex Murray, Anna Daunt, Aatish Patel, Achyuta Nori, Geraldine O'Hara, and Tet Yap Piotr SluzarPiotr Sluzar More articles by this author , Alex MurrayAlex Murray More articles by this author , Anna DauntAnna Daunt More articles by this author , Aatish PatelAatish Patel More articles by this author , Achyuta NoriAchyuta Nori More articles by this author , Geraldine O'HaraGeraldine O'Hara More articles by this author , and Tet YapTet Yap More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003235.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Monkeypox is a viral illness affecting predominantly gay, bisexual and other men having sex with men. The rapid progression of the recent outbreak meant genital manifestations preceded any guidelines for cases with urological symptoms. This study aims to develop an empirical care pathway for patients presenting with penile and scrotal symptoms secondary to monkeypox. METHODS: From May to September 2022, 198 patients with monkeypox who presented to a tertiary referral hospital were assessed for genital involvement by the infectious disease team, with the involvement of a urologist. Of these, 19 patients (10%) were admitted with genital lesions and were treated in an isolation ward with full personal protection equipment (PPE) in use. Symptoms requiring urological input were present in 8 individuals (4%). The mean time from the onset of symptoms to resolution was 25.3 (range 9-63) days. Based on the management of these patients, an empirical care pathway for genital monkeypox was developed. RESULTS: Four stages of genital monkeypox were observed (Figure 1). Limited penile oedema and discrete lesions should be managed conservatively with analgesia, cold compresses and elevation for swelling control. Patients with moderate oedema, paraphimosis and large coalescing ulcers should be considered for a topical 1% hydrocortisone cream to reduce the inflammation. In severe oedema with necrotic ulcers glyceryl trinitrate (GTN) patches are crucial to improve the vascularization of the necrotic ulcers on the penis. Cases of widespread necrosis and oedema may require imaging to assess the need for surgical debridement. GTN patches require daily changes for tissue salvage. Catheterization should be guided by the extent of oedema, the presence of paraphimosis and lesions close to the external urethral orifice. CONCLUSIONS: Monkeypox cases presenting through lesions on the penis and scrotum often require urological management to reduce penile oedema and prevent catheterisation. All admitted patients require isolation with full PPE. The initial stages of the infection should be managed conservatively with cold compresses, elevation and analgesia. Patients with advanced genital symptoms can benefit from the early use of topical steroid creams and GTN patches applied over the necrotic areas to reduce swelling and aid perfusion. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e192 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Piotr Sluzar More articles by this author Alex Murray More articles by this author Anna Daunt More articles by this author Aatish Patel More articles by this author Achyuta Nori More articles by this author Geraldine O'Hara More articles by this author Tet Yap More articles by this author Expand All Advertisement PDF downloadLoading ...

Objective To characterise the clinical features of monkeypox infection in humans. Design Descriptive case series. Setting A regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022. Participants 197 patients with polymerase chain reaction confirmed monkeypox infection. Results The median age of participants was 38 years. All 197 participants were men, and 196 identified as gay, bisexual, or other men who have sex with men. All presented with mucocutaneous lesions, most commonly on the genitals (n=111 participants, 56.3%) or in the perianal area (n=82, 41.6%). 170 (86.3%) participants reported systemic illness. The most common systemic symptoms were fever (n=122, 61.9%), lymphadenopathy (114, 57.9%), and myalgia (n=62, 31.5%). 102/166 (61.5%) developed systemic features before the onset of mucocutaneous manifestations and 64 (38.5%) after (n=4 unknown). 27 (13.7%) presented exclusively with mucocutaneous manifestations without systemic features. 71 (36.0%) reported rectal pain, 33 (16.8%) sore throat, and 31 (15.7%) penile oedema. 27 (13.7%) had oral lesions and 9 (4.6%) had tonsillar signs. 70/195 (35.9%) participants had concomitant HIV infection. 56 (31.5%) of those screened for sexually transmitted infections had a concomitant sexually transmitted infection. Overall, 20 (10.2%) participants were admitted to hospital for the management of symptoms, most commonly rectal pain and penile swelling. Conclusions These findings confirm the ongoing unprecedented community transmission of monkeypox virus among gay, bisexual, and other men who have sex with men seen in the UK and many other non-endemic countries. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema. These presentations should be included in public health messaging to aid early diagnosis and reduce onward transmission.

We report the successful use of combination therapy with two direct acting antivirals for treatment of chronic COVID-19. An immunocompromised 60 year old male with persistent SARS-CoV-2 infection over 4 months had chronic, progressive COVID-19 requiring mechanical ventilation. After failing monotherapy with two antivirals and neutralising monoclonal antibodies, he was treated with a 10 day course of intravenous remdesivir and crushed nirmatrelvir/ritonavir (Paxlovid) administered through a nasogastric tube. Following treatment, SARS-CoV-2 RNA became undetectable, with resolution of supplemental oxygen requirement and acute inflammatory changes on computed tomography. This case demonstrates potential synergy between remdesivir and nirmatrelvir/ritonavir in treating persistent, symptomatic SARS-CoV-2 infection.

Cases of monkeypox, a double-stranded DNA virus that is closely related to smallpox, have recently increased in non-endemic countries, prompting fears of a new health emergency. Tens of thousands of cases have now been reported globally, with the majority of locations not having historically reported monkeypox. Here we review the epidemiology, transmission, diagnosis, management and prevention of monkeypox.

Background. Emerging evidence suggests ethnic minorities are disproportionately affected by coronavirus disease 2019 (COVID-19). Detailed clinical analyses of multicultural hospitalized patient cohorts remain largely undescribed. Methods. We performed regression, survival, and cumulative competing risk analyses to evaluate factors associated with mortality in patients admitted for COVID-19 in 3 large London hospitals between 25 February and 5 April, censored as of 1 May 2020. Results. Of 614 patients (median age, 69 [interquartile range, 25] years) and 62% male), 381 (62%) were discharged alive, 178 (29%) died, and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (adjusted odds ratio [aOR], 4.25 [95% confidence interval {CI}, 2.36-7.64]), leukocytosis (aOR, 2.35 [95% CI, 1.35-4.11]), thrombocytopenia (aOR [1.01, 95% CI, 1.00-1.01], increase per 109 decrease), severe renal impairment (aOR, 5.14 [95% CI, 2.65-9.97]), and low albumin (aOR, 1.06 [95% CI, 1.021.09], increase per gram decrease) were associated with death. Forty percent (n = 244) were from black, Asian, and other minority ethnic (BAME) groups, 38% (n = 235) were white, and ethnicity was unknown for 22% (n = 135). BAME patients were younger and had fewer comorbidities. Although the unadjusted odds of death did not differ by ethnicity, when adjusting for age, sex, and comorbidities, black patients were at higher odds of death compared to whites (aOR, 1.69 [95% CI, 1.00-2.86]). This association was stronger when further adjusting for admission severity (aOR, 1.85 [95% CI, 1.06-3.24]). Conclusions. BAME patients were overrepresented in our cohort; when accounting for demographic and clinical profile of admission, black patients were at increased odds of death. Further research is needed into biologic drivers of differences in COVID-19 outcomes by ethnicity.

BACKGROUND:The time-concentrated nature of the first wave of the COVID-19 epidemic in England in March and April 2020 provides a natural experiment to measure changes in antibody positivity at the population level before onset of the second wave and initiation of the vaccination programme. METHODS:Three cross-sectional national surveys with non-overlapping random samples of the population in England undertaken between late June and September 2020 (REACT-2 study). 365,104 adults completed questionnaires and self-administered lateral flow immunoassay (LFIA) tests for IgG against SARS-CoV-2. FINDINGS:Overall, 17,576 people had detectable antibodies, a prevalence of 4.9% (95% confidence intervals 4.9, 5.0) when adjusted for test characteristics and weighted to the adult population of England. The prevalence declined from 6.0% (5.8, 6.1), to 4.8% (4.7, 5.0) and 4.4% (4.3, 4.5), over the three rounds of the study a difference of -26.5% (-29.0, -23.8). The highest prevalence and smallest overall decline in positivity was in the youngest age group (18-24 years) at -14.9% (-21.6, -8.1), and lowest prevalence and largest decline in the oldest group (>74 years) at -39.0% (-50.8, -27.2). The decline from June to September 2020 was largest in those who did not report a history of COVID-19 at -64.0% (-75.6, -52.3), compared to -22.3% (-27.0, -17.7) in those with SARS-CoV-2 infection confirmed on PCR. INTERPRETATION:A large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first wave. Widespread vaccination is needed to confer immunity and control the epidemic at population level. FUNDING:This work was funded by the Department of Health and Social Care in England.

Patients with strong clinical features of COVID-19 with negative real time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing are not currently included in official statistics. The scale, characteristics and clinical relevance of this group are not well described. We performed a retrospective cohort study in two large London hospitals to characterize the demographic, clinical, and hospitalization outcome characteristics of swab-negative clinical COVID-19 patients. We found 1 in 5 patients with a negative swab and clinical suspicion of COVID-19 received a clinical diagnosis of COVID-19 within clinical documentation, discharge summary or death certificate. We compared this group to a similar swab positive cohort and found similar demographic composition, symptomology and laboratory findings. Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for > 60% supplementary oxygen and reduced mortality. Patients with strong clinical features of COVID-19 that are swab-negative are a common clinical challenge. Health systems must recognize and plan for the management of swab-negative patients in their COVID-19 clinical management, infection control policies and epidemiological assessments.

OBJECTIVE To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2-React 2). DESIGN Diagnostic accuracy study. SETTING Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London. Research clinics for finger prick sampling were run in two affiliated NHS trusts. PARTICIPANTS Sensitivity analyses were performed on sera stored from 320 previous participants in the React 2 programme with confirmed previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specificity analyses were performed on 1000 prepandemic serum samples. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger prick testing. INTERVENTIONS Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 serum samples from participants with confirmed SARS-CoV-2 infection and 500 prepandemic serum samples, respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger prick sensitivity of the LFIA currently used in React 2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger prick testing on participants with confirmed previous SARS-CoV-2 infection: two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July 2020 and the third LFIA (AbC-19) in September 2020. A spike protein enzyme linked immunoassay and hybrid double antigen binding assay were used as laboratory reference standards. MAIN OUTCOME MEASURES The accuracy of LFIAs in detecting immunoglobulin G (IgG) antibodies to SARS-CoV-2 compared with two reference standards. RESULTS The sensitivity and specificity of seven new LFIAs that were analysed using sera varied from 69% to 100%, and from 98.6% to 100%, respectively (compared with the two reference standards). Sensitivity on finger prick testing was 77% (95% confidence interval 61.4% to 88.2%) for Panbio, 86% (72.7% to 94.8%) for Surescreen, and 69% (53.8% to 81.3%) for AbC-19 compared with the reference standards. Sensitivity for sera from matched clinical samples performed on AbC-19 was significantly higher with serum than finger prick at 92% (80.0% to 97.7%, P=0.01). Antibody titres varied considerably among cohorts. The numbers of positive samples identified by finger prick in the lowest antibody titre quarter varied among LFIAs. CONCLUSIONS One new LFIA was identified with clinical performance suitable for potential inclusion in seroprevalence studies. However, none of the LFIAs tested had clearly superior performance to the LFIA currently used in React 2 seroprevalence surveys, and none showed sufficient sensitivity and specificity to be considered for routine clinical use.

Abstract Background England has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers. Methods A cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later. Results The survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of Pfizer-BioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups. Conclusions There is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.

WHO Collaborating Centre for Infectious Disease Modelling MRC Centre for Global Infectious Disease Analysis Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA) Division of Digestive Diseases, Department of Metabolism Digestion and Reproduction Department of Infectious Diseases Department of Primary Care and Public Health NIHR Imperial Biomedical Research Centre Imperial College Healthcare NHS Trust Imperial College London

In May 9, 2020, a study published in this journal by Chen et al. described the symptoms and investigations of eleven patients requiring re-hospitalisation, after an index admission for COVID-19 disease. This article is protected by copyright. All rights reserved.

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) released its Early Access to Medicines Scheme (EAMS) criteria for the use of Remdesivir in patients with COVID-19 on May 26th, 2020.1UK Department of Health & Social Care. Early Access to Medicines Scheme for remdesivir in the treatment of COVID-19. 2020; published online May 26. https://www.gov.uk/government/publications/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirmed (Accessed 25 May 2020).Google Scholar The MHRA Scientific Opinion supports the use of Remdesivir in patients with severe disease. However, given current limitations in drug supply, an interim risk score has been proposed to identify those patients thought most likely to benefit from the drug. The score includes eight variables: radiographic severity score > 3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 10/L, age >40 and CRP >40.1UK Department of Health & Social Care. Early Access to Medicines Scheme for remdesivir in the treatment of COVID-19. 2020; published online May 26. https://www.gov.uk/government/publications/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirmed (Accessed 25 May 2020).Google Scholar It seems to have first been developed for a recently launched COVID-19 immune modulator therapy trial (TACTIC-R),2Hall F., Jayne D.Multi-Arm Therapeutic Study in Pre-ICU Patients Admitted with COVID-19. 2020. https://cctu.org.uk/portfolio/COVID-19/TACTIC/TACTIC-R (Accessed 26 May 2020).Google Scholar based on an initial unpublished cohort of 200 patients.3Sneep R., Cantle F., Brookes A. et al. Early Epidemiological and Clinical Analysis of the First 200 Patients with COVID-19 Admitted via the Emergency Department in King's College Hospital, London: a Retrospective Cohort Stodu (4/9/20). Available at SSRN:https://ssrn.com/abstract=3576791 / http://dx.doi.org/10.2139/ssrn.3576791 (Accessed 9 April 2020)Google Scholar An adapted version of the risk score, with twelve variables, was used to predict clinical deterioration (i.e. death or admission to critical care) in a cohort of 1157 confirmed COVID-19 patients in one London NHS Trust.4Galloway J.B. Norton S. Barker R.D. et al.A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: an observational cohort study.J Infect. 2020; (S0163445320303145)Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar This score showed good performance, with an area under the receiver operating curve (AUROC) of 71.2% (test data).4Galloway J.B. Norton S. Barker R.D. et al.A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: an observational cohort study.J Infect. 2020; (S0163445320303145)Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar The findings were published in this journal, which we read with interest. However, how the score proposed by EAMS performs in front-line settings and its implications for how many patients will likely receive Remdesivir for COVID-19 is currently unknown. We evaluated the performance of the EAMS criteria in a cohort of 517 patients COVID-19 confirmed patients admitted to Imperial College Healthcare Trust between the start of the pandemic and 5th April 2020.5Perez Guzman P., Daunt A., Mukherjee S., et al. Report 17: clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study. Imperial College London, 2020 DOI:10.25561/78613.Google Scholar We found that 348 patients in our cohort would have met criteria to be considered for Remdesivir therapy (i.e. age > 12, weight > = 40 kg, creatinine clearance >50 ml/min and AST/ALT <5 x ULN or no history of Childs Pugh C liver cirrhosis). According to the EAMS score, 262 (75.3%) of the eligible patients in our cohort would have been classified as high-risk and 86 (24.7%%) as low-risk. The composite risk of death or ITU admission was 2.58 times greater (95%CI 1.56–4.25, p < 0.001) for the high- compared to the low-risk group (Fig. 1a). The performance of the score was reasonable when considering the AUROC of 71.1% (p < 0.001) (Fig. 1b). However, the overall misclassification of outcome was of 45.7%, with 14 (4.0%) patients who deteriorated classified as low-risk and 145 (41.7%) who did not deteriorate as high-risk, which has potential implications for allocation of a scarce resource. Common characteristics of those classified as low-risk that subsequently deteriorated included being female, white and having a non-severe appearance by chest X-ray (Table 1). Additionally, of the eight individual covariates in the full predictive model proposed by EAMS, only RALE score and CRP levels were statistically significant in predicting the composite outcome in our cohort (Table 2).Table 1Characteristics of patients who deteriorated by classification outcome by EAMS criteria.Patients scored as 'low-risk' who deteriorated*High- and low-risk as per EAMS criteria; deterioration defined as admission to ITU or death.Patients scored as 'high-risk' who did not deteriorate*High- and low-risk as per EAMS criteria; deterioration defined as admission to ITU or death.N = 14 (4.02%)N = 110 (31.61%)Age > 4012 (85.71%)103 (93.64%)Male sex4 (28.57%)83 (75.45%)Non-White ethnicity4 (28.57%)81 (73.64%)Diabetes1 (7.14%)23 (20.91%)Hypertension0 (0.00%)44 (40.00%)Neutrophils > 8 × 10/L4 (28.57%)28 (25.45%)CRP > 40 mg/L10 (71.43%)103 (93.64%)RALE score > 31 (7.14%)94 (85.45%) High- and low-risk as per EAMS criteria; deterioration defined as admission to ITU or death. Open table in a new tab Also of note, 169 patients in our cohort did not meet initial EAMS eligibility criteria for Remdesivir. The majority (n = 160) would have been excluded due to a creatinine clearance <50 mL/min, 1 based on age, 1 for weight and 7 for known cirrhotic liver disease. The crude incidence rate of deterioration in this group was of 47.9% and, if the EAMS score would have been applied, it would not have differentiated the risk of deterioration between those classified as high or low-risk (RR 1.43, 95%CI 0.87–2.36, p = 0.12). Worryingly, their crude incidence rate of deterioration was similar to the high-risk group meeting inclusion criteria, at 42.0%. This highlights an important group of patients with renal impairment with poor COVID-19 outcomes who are often excluded from clinical trials. We acknowledge the urgent need to be responsive to the rapidly changing context, given the enormous public health implications of treatment allocation decisions based on clinical criteria. Nevertheless, the release of the EAMS criteria based on a single cohort of patients seems premature. While reassuring that the scoring system seems to show reasonable performance in identifying most of those at high risk of adverse outcomes in our cohort, 11.3% of those who deteriorate and met inclusion criteria were missed by this score. Moreover, amongst those not meeting inclusion criteria, the score was not able to accurately predict outcome, highlighting the urgent need to identify safe treatments for use in those with renal and/or hepatic impairment. Importantly, in both the adapted risk criteria published previously in this journal and in that proposed by our group, hypalbuminaemia, reduced glomerular filtration and admission hypoxia (amongst other parameters) were also important predictors of worse hospitalisation outcomes.4Galloway J.B. Norton S. Barker R.D. et al.A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: an observational cohort study.J Infect. 2020; (S0163445320303145)Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar,5Perez Guzman P., Daunt A., Mukherjee S., et al. Report 17: clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study. Imperial College London, 2020 DOI:10.25561/78613.Google Scholar None of these parameters are included in the EAMS criteria, which could improve the misclassification issues observed. However, rationalising the number of parameters included for a scoring system intended for front-line clinical use should be carefully assessed to maximise its utility and limit increasing workload for already overstretched clinical teams. It has to be hoped that access to Remdesivir for all who may benefit from it will be achievable in coming months as manufacturing capacity expands. In the meantime, criteria for eligibility should be refined based on data from a wide range of clinical settings and shared as quickly as possible to ensure a finite resource is used as rationally as possible. None to declare. MRC Centre for Global Infectious Disease Analysis, NIHR Imperial BRC Centre.

Background & aims Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease (NAFLD). We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19. Methods This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD. Clinical data and early weaning score (EWS) were recorded. NAFLD diagnosis was based on imaging or past medical history and patients were stratified for Fibrosis-4 (FIB-4) index. Clinical endpoints were admission to intensive care unit (ICU)and in-hospital mortality. Results 561 patients were admitted. Overall, 193 patients were included in the study. Fifty nine patients (30%) died, 9 (5%) were still in hospital, and 125 (65%) were discharged. The NAFLD cohort (n = 61) was significantly younger (60 vs 70.5 years, p = 0.046) at presentation compared to the non-NAFLD (n = 132). NAFLD diagnosis was not associated with adverse outcomes. However, the NAFLD group had higher C reactive protein (CRP) (107 vs 91.2 mg/L, p = 0.05) compared to non-NAFLD(n = 132). Among NAFLD patients, male gender (p = 0.01), ferritin (p = 0.003) and EWS (p = 0.047) were associated with in-hospital mortality, while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not. Conclusion The presence of NAFLDper sewas not associated with worse outcomes in patients hospitalised for COVID-19. Though NAFLD patients were younger on admission, disease stage was not associated with clinical outcomes. Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.

Background Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required. Methods Sensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were ≥21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two ‘in-house’ ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum. Findings 95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%–99.8%). Interpretation LFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.

Background The prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity. Methods Prevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed. Results There were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, -23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: -14.9% [-21.6, -8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: -39.0% [-50.8, -27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]). The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (-64.0% [-75.6, -52.3]), compared to -22.3% ([-27.0, -17.7]) in those with SARS-CoV-2 infection confirmed on PCR. Discussion These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.

AIMS:For a group of medical students to design and deliver a mental health workshop in Cambridge secondary schools. Subsequently, to evaluate any improvements in pupils' knowledge of mental health issues, including knowledge of common mental illnesses, stigma and where to access help with mental health problems.METHOD:A group of three medical students undertook a five week Student Selected Component to develop a mental health workshop in Spring 2013. The workshop was designed to include interactive components, such as role play, models and video. It was delivered to eight classes of 12-13 year old pupils across two local secondary schools, a total of 230 students. Questionnaires were completed before and after each workshop to test knowledge acquisition of mental health issues, stigma and where pupils could get help with mental health problems. Comparisons between data from the pre- and post-workshop questionnaires were made to assess learning.RESULTS:The responses from the questionnaires showed a global improvement in knowledge of mental health. This is highlighted by the increase in awareness of the prevalence of mental health problems amongst young people from 47.0% before the workshops to 97.8% after the workshops. The ability to identify symptoms of anxiety rose from 21.7% to 44.8% and the ability to identify depression rose from 29.0% to 53.5% respectively. Whilst only 15.2% pupils disagreed with a stigmatising statement about mental illness before the workshops, 61.3% pupils disagreed afterwards. The students were also better informed about how to access help and identified areas that they found useful to learn about.CONCLUSION:Comparison of the pre- and post-workshop questionnaires indicate that medical student-led workshops are an effective method for improving knowledge of mental health topics amongst 12-13 year old school pupils, as well as encouraging positive attitudes towards mental health. The project highlights a demand for mental health education in schools and brings to light topics that could be covered in future sessions or similar projects.