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1.
Diagnostics ; 12(5):1263, 2022.
Article in English | MDPI | ID: covidwho-1857054

ABSTRACT

The COVID-19 pandemic has unveiled a pressing need to expand the diagnostic landscape to permit high-volume testing in peak demand. Rapid nucleic acid testing based on isothermal amplification is a viable alternative to real-time reverse transcription polymerase chain reaction (RT-PCR) and can help close this gap. With the emergence of SARS-CoV-2 variants of concern, clinical validation of rapid molecular tests needs to demonstrate their ability to detect known variants, an essential requirement for a robust pan-SARS-CoV-2 assay. To date, there has been no clinical validation of reverse transcription recombinase polymerase amplification (RT-RPA) assays for SARS-CoV-2 variants. We performed a clinical validation of a one-pot multi-gene RT-RPA assay with the E and RdRP genes of SARS-CoV-2 as targets. The assay was validated with 91 nasopharyngeal samples, with a full range of viral loads, collected at University College London Hospitals. Moreover, the assay was tested with previously sequenced clinical samples, including eleven lineages of SARS-CoV-2. The rapid (20 min) RT-RPA assay showed high sensitivity and specificity, equal to 96% and 97%, respectively, compared to gold standard real-time RT-PCR. The assay did not show cross-reactivity with the panel of respiratory pathogens tested. We also report on a semi-quantitative analysis of the RT-RPA results with correlation to viral load equivalents. Furthermore, the assay could detect all eleven SARS-CoV-2 lineages tested, including four variants of concern (Alpha, Beta, Delta, and Omicron). This variant-proof SARS-CoV-2 assay offers a significantly faster and simpler alternative to RT-PCR, delivering sensitive and specific results with clinical samples.

2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327612

ABSTRACT

Introduction: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48h) and 4 weeks of 'longer-turnaround' (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs;detected ≥48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated. Results A total of 2170 HOCI cases were recorded from October 2020-April 2021, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (IRR 1.60, 95%CI 0.85-3.01;P=0.14) or rapid (0.85, 0.48-1.50;P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a per-protocol sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Conclusion While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322658

ABSTRACT

Background: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. Little is known about the impact their increased infectivity has on transmission within hospitals.Methods: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences.Findings: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages.Interpretation: Notwithstanding evidence from community studies that the Alpha variant is more transmissible, we find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.Funding Information: COG-UK HOCI funded by COG-UK consortium. The COG-UK consortium is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute.Declaration of Interests: None to declare. Ethics Approval Statement: Ethical approval for the HOCI study was provided by REC 20/EE/0118.

4.
J Infect ; 83(6): 693-700, 2021 12.
Article in English | MEDLINE | ID: covidwho-1446866

ABSTRACT

OBJECTIVES: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals. METHODS: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. RESULTS: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. CONCLUSIONS: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.


Subject(s)
COVID-19 , Cross Infection , Cross Infection/epidemiology , Hospitals , Humans , SARS-CoV-2 , United Kingdom/epidemiology
5.
Elife ; 102021 07 29.
Article in English | MEDLINE | ID: covidwho-1332333

ABSTRACT

Background: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood. Methods: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity. Results: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection. Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric. Funding: This work was supported by the Francis Crick Institute and the Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , COVID-19/epidemiology , Cross Reactions , Humans , Parents , South Africa/epidemiology , Spike Glycoprotein, Coronavirus , United Kingdom/epidemiology
6.
Lancet Infect Dis ; 21(9): 1246-1256, 2021 09.
Article in English | MEDLINE | ID: covidwho-1180123

ABSTRACT

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.


Subject(s)
COVID-19/virology , Genome, Viral , SARS-CoV-2/genetics , Severity of Illness Index , Whole Genome Sequencing , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , London , Male , Middle Aged , Phylogeny , United Kingdom , Viral Load , Virus Shedding
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