COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.4/5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history.

BACKGROUND: SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC). METHODS: In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests. RESULTS: 563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (ß = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or BA.4/5 infections. CONCLUSION: Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults. TRIAL REGISTRATION: NCT04750356.

Image challenge: A diabetic man with facial swelling following recent Covid-19 infection.

A 68-year-old man with diabetes presented with shortness of breath, left sided facial swelling, and nasal discharge. He had recently returned from India and PCR was positive for SARS-CoV-2 Delta variant. CT head and diffusion-weighted MRI sinuses were performed and the patient underwent endoscopic sinus surgery before being transferred to a specialist skull base centre.

A case report of ChAdOx1 nCoV-19 vaccine-associated encephalitis.

BACKGROUND: Vaccination against COVID-19 continues apace, but side-effects, both common and severe, continue to be reported. We report here the first published case of COVID-19 vaccine-related encephalitis. CASE PRESENTATION: A young woman presented with acute neuropsychiatric symptoms following recent ChAdOx1 nCoV-19 vaccination. Extensive investigation did not identify alternative causes. CONCLUSIONS: This difficult case is here described, including presentation, investigation, and management. Further study on neuropsychiatric side-effects of COVID-19 vaccination, including investigation as to whether there may be a causal link, is required.

Failure of rapid diagnostic tests in Plasmodium falciparum malaria cases among travelers to the UK and Ireland: Identification and characterisation of the parasites.

OBJECTIVES: Our objective was to systematically investigate false-negative histidine-rich protein 2 rapid diagnostic tests (HRP2-RDT) in imported Plasmodium falciparum malaria cases from travelers to the UK and the Republic of Ireland (RoI). METHODS: Five imported malaria cases in travellers returning to the UK and RoI from East Africa were reported to the PHE Malaria Reference Laboratory as negative according to histidine-rich protein (HRP2)-RDT. The cases were systematically investigated using microscopic, RDT, molecular, genomic, and in in vitro approaches. RESULTS: In each case, HRP2-RDT was negative, whereas microscopy confirmed the presence of P. falciparum. Further analysis revealed that the genes encoding HRP2 and HRP3 were deleted in three of the five cases. Whole-genome sequencing in one of these isolates confirmed deletions in P. falciparum chromosomes 8 and 13. Our study produced evidence that the fourth case, which had high parasitemia at clinical presentation, was a rare example of antigen saturation ('prozone-like effect'), leading to a false negative in the HRP2-RDT, while the fifth case was due to low parasitemia. CONCLUSIONS: False-negative HRP2-RDT results with P. falciparum are concerning. Our findings emphasise the necessity of supporting the interpretation of RDT results with microscopy, in conjunction with clinical observations, and sets out a systematic approach to identifying parasites carrying pfhrp2 and pfhrp3 deletions.

A simple measure to improve sepsis documentation and coding.

INTRODUCTION: Sepsis incidence and mortality are increasing, yet sepsis appears to be under-recognised and under-reported. Accurate recognition and coding of sepsis allows for appropriate funding and accurate epidemiological representation. METHODS: We implemented a discharge summary template for all patients discharged from our infectious diseases service and analysed sepsis documentation and coding before and after its introduction. RESULTS: Beforehand, we found that 59% of 29 patients had sepsis, yet only 10% had it documented on their discharge summary, and 17% had it coded. Following implementation of the template, 38% of 52 patients had sepsis documented, yet only 20% of these had it coded. After delivery of a training session to the coders regarding the importance of sepsis, 38% of patients with a diagnosis of sepsis had it coded. DISCUSSION: Despite requiring ongoing education and encouragement of clinicians and coders, implementation of the template was quick, cheap and easy and improved sepsis coding.

False-negative RT-PCR for COVID-19 and a diagnostic risk score: a retrospective cohort study among patients admitted to hospital.

OBJECTIVE: To describe the characteristics and outcomes of patients with a clinical diagnosis of COVID-19 and false-negative SARS-CoV-2 reverse transcription-PCR (RT-PCR), and develop and internally validate a diagnostic risk score to predict risk of COVID-19 (including RT-PCR-negative COVID-19) among medical admissions. DESIGN: Retrospective cohort study. SETTING: Two hospitals within an acute NHS Trust in London, UK. PARTICIPANTS: All patients admitted to medical wards between 2 March and 3 May 2020. OUTCOMES: Main outcomes were diagnosis of COVID-19, SARS-CoV-2 RT-PCR results, sensitivity of SARS-CoV-2 RT-PCR and mortality during hospital admission. For the diagnostic risk score, we report discrimination, calibration and diagnostic accuracy of the model and simplified risk score and internal validation. RESULTS: 4008 patients were admitted between 2 March and 3 May 2020. 1792 patients (44.8%) were diagnosed with COVID-19, of whom 1391 were SARS-CoV-2 RT-PCR positive and 283 had only negative RT-PCRs. Compared with a clinical reference standard, sensitivity of RT-PCR in hospital patients was 83.1% (95% CI 81.2%-84.8%). Broadly, patients with false-negative RT-PCR COVID-19 and those confirmed by positive PCR had similar demographic and clinical characteristics but lower risk of intensive care unit admission and lower in-hospital mortality (adjusted OR 0.41, 95% CI 0.27-0.61). A simple diagnostic risk score comprising of age, sex, ethnicity, cough, fever or shortness of breath, National Early Warning Score 2, C reactive protein and chest radiograph appearance had moderate discrimination (area under the receiver-operator curve 0.83, 95% CI 0.82 to 0.85), good calibration and was internally validated. CONCLUSION: RT-PCR-negative COVID-19 is common and is associated with lower mortality despite similar presentation. Diagnostic risk scores could potentially help triage patients requiring admission but need external validation.

Experience of a novel community testing programme for COVID-19 in London: Lessons learnt.

We describe the London community testing programme developed for COVID-19, audit its effectiveness and report patient acceptability and patient adherence to isolation guidance, based upon a survey conducted with participants.Any patients meeting the Public Health England (PHE) case definition for COVID-19 who did not require hospital admission were eligible for community testing. 2,053 patients with suspected COVID-19 were tested in the community between January and March 2020. Of those tested, 75 (3.6%) were positive. 88% of patients that completed a patient survey felt safe and 82% agreed that community testing was preferable to hospital admission. 97% were able to remain within their own home during the isolation period but just 41% were able to reliably isolate from other members of their household.The London community testing programme allowed widespread testing for COVID-19 while minimising patient transport, hospital admissions and staff exposures. Community testing was acceptable to patients and preferable to admission to hospital. Patients were able to reliably isolate in their home but not from household contacts. The authors believe in the importance, feasibility and acceptability of community testing for COVID-19 as a part of a package of interventions to mitigate a second wave of infection.

Time to diagnosis of tuberculosis is greater in older patients: a retrospective cohort review.

INTRODUCTION: Age-related immunosenescence influences the presentation of tuberculosis (TB) in older patients. Here, we explore the clinical and radiological presentation of TB in the elderly and the factors associated with time to treatment for TB. METHODS: This is a retrospective cohort study comparing the clinical, radiological and demographic characteristics of TB patients aged ≥65 years with TB patients aged 18-64 years in a large cohort of TB patients in the UK. Factors associated with the time to presentation and time to treatment were identified using a multivariable analysis model. RESULTS: 1023 patients were included in the analyses: 679 patients aged 18-64 years and 344 patients aged ≥65 years. "Classical" symptoms of TB (cough, haemoptysis, fever, nights sweats and weight loss) were less common among older patients with pulmonary TB (PTB) (p<0.05), but dyspnoea was more common among older patients (p=0.001). Time from presenting in secondary care to starting treatment was shorter in younger compared with older patients: 3 versus 15 days (p=0.001). When adjusted for age, factors associated with shorter time to treatment from symptom onset include sex (male versus female) (hazard ratio (HR) 1.23 (95% CI 1.05-1.46)), UK born (HR 1.23 (95% CI 1.05-1.46)) and HIV (HR 2.07 (95% CI 1.30-3.29)). Only age remained an independent predictor of time to treatment in a multivariable model (HR 0.98 (95% CI 0.98-0.99)). For those with PTB, chest radiography findings showed that cavitation and lymphadenopathy were more common among younger patients (p=0.001). CONCLUSIONS: Older patients aged ≥65 years with TB had fewer "classical" clinical and radiological presentations of TB, which may explain longer times to starting treatment from symptom onset compared with younger patients aged <65 years.

Screening contacts of patients with extrapulmonary TB for latent TB infection.

2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply that contacts of extrapulmonary TB do not require screening for latent TB infection. At our high TB prevalence site, we identified 189 active cases of TB for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and 10.7% of the contacts of extrapulmonary TB had active or latent TB infection. This supports screening contacts of extrapulmonary TB at our site and presents a way to access high-risk individuals. We propose to continue to screen the contacts of our patients with extrapulmonary TB and recommend other TB units audit their local results.

Management of Necrotizing Otitis Externa: Our Experience with Forty-Three Patients.

OBJECTIVE: To assess the impact of the introduction of a dedicated management protocol of necrotizing otitis externa patients with joint care between otorhinolaryngology and infectious diseases. MATERIALS AND METHODS: Retrospective review of case notes and the otorhinolaryngology department database of all adults admitted with necrotizing otitis externa at our teaching hospital over a 5-year period. The patients were split into two groups (first group of 10 patients prior to the introduction of the dedicated management protocol, and a second group of 33 patients managed after the introduction of this protocol). RESULTS: Of the 43 patients included in the study, diabetes mellitus was present in 83.7%. Pseudomonas aeruginosa was grown in 67.4% of patients. All 43 patients underwent computed tomography and magnetic resonance imaging (with contrast) scans. Surgical intervention was undertaken in 25.6% of patients. Mean follow-up was 10 months (SD, ±7 months). Of the 43 patients, 79.1% made a full recovery and were discharged. Relapse occurred in 9.3% of patients. One patient died because of a myocardial infarction 4 months after treatment. The mean length of stay was significantly lower after the protocol was introduced (25.6±5.3 vs. 14.2±3.8 days, p=0.001), and the duration of treatment was also significantly lower after the protocol (21.2±6.8 vs. 14.3±4.3 weeks, p=0.01). CONCLUSION: The introduction of a dedicated management protocol and joint care with otorhinolaryngology and infectious diseases resulted in improved care and decreased length of stay in patients. Early diagnosis and involvement with the relevant teams as well as prompt intervention are the key factors that reduce morbidity and mortality.

Communicable disease surveillance and control in the context of conflict and mass displacement in Syria.

OBJECTIVES: To describe trends in major communicable diseases in Syria during the ongoing conflict, and the challenges to communicable disease surveillance and control in the context of dynamic, large-scale population displacement, unplanned mass gatherings, and disruption to critical infrastructure. METHODS: A rapid review of the peer-reviewed and non-peer-reviewed literature from 2005 to 2015 was performed, augmented by secondary analysis of monitoring data from two disease early warning systems currently operational in Syria, focusing mainly on three diseases: tuberculosis (TB), measles, and polio. RESULTS: Trend data show discrepancies in case report numbers between government and non-government controlled areas, especially for TB, but interpretation is hampered by uncertainties over sentinel surveillance coverage and base population numbers. Communicable disease control has been undermined by a combination of governance fragmentation, direct and indirect damage to facilities and systems, and health worker flight. CONCLUSIONS: Five years into the crisis, some progress has been made in disease surveillance, but governance and coordination problems, variable immunization coverage, and the dynamic and indiscriminate nature of the conflict continue to pose a serious threat to population health in Syria and surrounding countries. The risk of major cross-border communicable disease outbreaks is high, and challenges for health in a post-conflict Syria are formidable.

Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines.

Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required.

Towards host-directed therapies for tuberculosis.

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

Massive CD8 T cell response to primary HIV infection in the setting of severe clinical presentation.

Acute HIV-1 infection causes a rapid total body depletion of CD4(+) T cells in most individuals and HIV-1-specific CD8(+) T cell expansion in response to viral replication. A numerically high CD8 T cell response may indicate limited T cell repertoire against HIV and rapid progression. We present a detailed evaluation of an acutely infected individual with a strong HIV-1-specific CD8 T cell response targeting multiple epitopes demonstrating that the upper limit of CD8 expansion in this setting may be much higher than previously reported and was likely driven by the narrow HIV-specific response.