For public health planning we need scalable assays validated against large banks of samples from individuals who had proven seasonal (non-severe acute respiratory syndrome) coronaviruses and those ...who had well characterised symptomatic and asymptomatic confirmed SARS-CoV-2 infection. The expectation is that the best predictor of antibody-mediated protection will come from neutralisation assays, in which the ability of patient serum to prevent live virus infecting cell cultures is measured. Measuring the different antibodies might also have prognostic value; a report showed that a predominant humoral response to nucleoprotein is associated with poor outcome in patients admitted to hospital, compared with that of spike.10 Further investigation is required and the possibility of a one-size-fits-all immunological assay looks less and less likely.
Abstract
Coronavirus disease 2019 (COVID-19) can cause deadly healthcare-associated outbreaks. In a major London teaching hospital, 66 of 435 (15%) COVID-19 inpatient cases between 2 March and 12 ...April 2020 were definitely or probably hospital-acquired, through varied transmission routes. The case fatality was 36%. Nosocomial infection rates fell following comprehensive infection prevention and control measures.
Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to ...describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant.
In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths.
Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio PR 0·97 95% CI 0·72–1·31), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 0·76–1·38). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 SD 4·7 vs 32·0 4·8; p=0·0085) and genomic read depth (1280 1004 vs 831 682; p=0·0011).
Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort.
University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.
Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, ...spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy.
Display omitted
•SARS-CoV-2 pseudotypes produced by amino acids substitutions in SARS-CoV•SARS-CoV-2 pseudotyped virus that encodes the B.1.1.7 variant spike•Amino acid changes and B.1.1.7 can decrease monoclonal antibody neutralization•Minimal effect on sera with only 10% losing potency against the B.1.1.7 pseudotype
This study describes neutralization by antibodies and convalescent sera of SARS-CoV-2 spike mutants. Rees-Spear et al. show that SARS-CoV amino acid substitutions and the B.1.1.7 variant can block monoclonal antibody neutralization and that serum samples collected following mild illness are less resilient to spike variation than those following severe illness.
Most reported cases of human monkeypox occur in Central and West Africa, where the causing virus is endemic. We describe the identification and public health response to an imported case of West ...African monkeypox from Nigeria to the United Kingdom (UK) in May 2021. Secondary transmission from the index case occurred within the family to another adult and a toddler. Concurrent COVID-19-related control measures upon arrival and at the hospital, facilitated detection and limited the number of potential contacts.
The COVID-19 pandemic has emphasised the need to rapidly assess infection risks for healthcare workers within the hospital environment. Using data from the first year of the pandemic, we investigated ...whether an individual's COVID-19 test result was associated with behavioural markers derived from routinely collected hospital data two weeks prior to a test. The temporal and spatial context of behaviours were important, with the highest risks of infection during the first wave, for staff in contact with a greater number of patients and those with greater levels of activity on floors handling the majority of COVID-19 patients. Infection risks were higher for BAME staff and individuals working more shifts. Night shifts presented higher risks of infection between waves of COVID-19 patients. Our results demonstrate the epidemiological relevance of deriving markers of staff behaviour from electronic records, which extend beyond COVID-19 with applications for other communicable diseases and in supporting pandemic preparedness.
PURPOSE OF REVIEWCentral nervous system (CNS) infections present an ongoing diagnostic challenge for clinicians, with an aetiological agent remaining unidentified in the majority of cases even in ...high-income settings. This review summarizes developments in a range of diagnostic methods published in the past 18 months.
RECENT FINDINGSSeveral commercial assays exist for the detection of viral, bacterial and fungal pathogens using single multiplex PCR. Multicentre validation of the Biofire FilmArray panel illustrated high sensitivity for bacterial and fungal pathogens, but poor results for Cryptococcus species detection. The development of microarray cards for bacterial CNS pathogens shows promise but requires further validation. Few developments have been made in proteomics and transcriptomics, contrasted with significant increase in the use of metagenomic (or unbiased) sequencing. Novel viruses causing CNS infection have been described using this technique but contamination, cost, expertise and turnaround time requirements remain restrictive. Finally, the development of Gene Xpert and Ultra has revolutionized tuberculosis meningitis diagnostics with newly released recommendations for their use from the WHO.
SUMMARYProgress has been made in the clinical validation and international recommendation of PCR-based tests for CNS infections. Sequencing techniques present the most dynamic field, although significant ongoing challenges persist.
Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who ...are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding.
There are over 200 herpesvirus species, of which 10 affect humans. Each of these 10 herpesviruses has a unique clinical syndrome, but common to all is their ability to cause infection and pathology ...in the central nervous system. In this article, we discuss the epidemiology, clinical presentation, diagnostic modalities, treatment, sequelae, and availability of vaccination of each of the following herpesviruses: herpes simplex virus 1 and 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6A, 6B, and 7, Epstein-Barr virus, human herpesvirus 8, and simian herpesvirus B.
PDF
