ABSTRACT
Background. The overlapping clinical presentations of patients with acute respiratory disease can complicate disease diagnosis. Whilst PCR diagnostic methods to identify SARS-CoV-2 are highly sensitive, they have their shortcomings including false-positive risk and slow turnaround times. Changes in host gene expression can be used to distinguish between disease groups of interest, providing a viable alternative to infectious disease diagnosis. Methods. We interrogated the whole blood gene expression profiles of patients with COVID-19 (n=87), bacterial infections (n=88), viral infections (n=36), and not-infected controls (n=27) to identify a sparse diagnostic signature for distinguishing COVID-19 from other clinically similar infectious and non-infectious conditions. The sparse diagnostic signature underwent validation in a new cohort using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and then underwent further external validation in an independent in silico RNA-seq cohort. Findings. We identified a 10-gene signature (OASL, UBP1, IL1RN, ZNF684, ENTPD7, NFKBIE, CDKN1C, CD44, OTOF, MSR1) that distinguished COVID-19 from other infectious and non-infectious diseases with an AUC of 87.1% (95% CI: 82.6%-91.7%) in the discovery cohort and 88.7% and 93.6% when evaluated in the RT-qPCR validation, and in silico cohorts respectively. Interpretation. Using well-phenotyped samples collected from patients admitted acutely with a spectrum of infectious and non-infectious syndromes, we provide a detailed catalogue of blood gene expression at the time of hospital admission. The findings result in the identification of a 10-gene host diagnostic signature to accurately distinguish COVID-19 from other infection syndromes presenting to hospital. This could be developed into a rapid point-of-care diagnostic test, providing a valuable syndromic diagnostic tool for future early pandemic use.
Subject(s)
Communicable Diseases, Emerging , Infections , Severe Acute Respiratory Syndrome , Bacterial Infections , Communicable Diseases , Virus Diseases , COVID-19ABSTRACT
Background The programme to vaccinate adults in England has been rapidly implemented since it began in December 2020. The community prevalence of SARS-CoV-2 anti-spike protein antibodies provides an estimate of total cumulative response to natural infection and vaccination. We describe the distribution of SARS-CoV-2 IgG antibodies in adults in England in May 2021 at a time when approximately 7 in 10 adults had received at least one dose of vaccine. Methods Sixth round of REACT-2 (REal-time Assessment of Community Transmission-2), a cross-sectional random community survey of adults in England, from 12 to 25 May 2021; 207,337 participants completed questionnaires and self-administered a lateral flow immunoassay test producing a positive or negative result. Results Vaccine coverage with one or more doses, weighted to the adult population in England, was 72.9% (95% confidence interval 72.7-73.0), varying by age from 25.1% (24.5-25.6) of those aged 18 to 24 years, to 99.2% (99.1-99.3) of those 75 years and older. In adjusted models, odds of vaccination were lower in men (odds ratio [OR] 0.89 [0.85-0.94]) than women, and in people of Black (0.41 [0.34-0.49]) compared to white ethnicity. There was higher vaccine coverage in the least deprived and highest income households. People who reported a history of COVID-19 were less likely to be vaccinated (OR 0.61 [0.55-0.67]). There was high coverage among health workers (OR 9.84 [8.79-11.02] and care workers (OR 4.17 [3.20-5.43]) compared to non-key workers, but lower in hospitality and retail workers (OR 0.73 [0.64-0.82] and 0.77 [0.70-0.85] respectively) after adjusting for age and key covariates. The prevalence of antibodies (weighted to the adult population of England and adjusted for test characteristics) was 61.1% (95% CI 60.9-61.4), up from 6.6% (5.4-5.7) in round 4 (27 October to 10 November 2020) and 13.9% (13.7-14.1) in round 5 (26 January to 8 February 2021). Prevalence (adjusted and weighted) increased with age, from 35.8% (35.1-36.5) in those aged 18 to 24 years, to 95.3% (94.6-95.9) in people 75 and over. Antibodies were 30% less likely to be detected in men than women (adjusted OR 0.69, 0.68-0.70), and were higher in people of Asian (OR 1.67 [1.58-1.77]), Black (1.55 [1.41-1.69]), mixed 1.17 [1.06-1.29] and other (1.37 [1.23-1.51]) ethnicities compared with white ethnicity. Workers in hospitality (OR 0.69 [0.63-0.74]) and retail (0.71 [0.67-0.75]) were less likely to have antibodies. Following two doses of Pfizer-BioNTech vaccine, antibody positivity (adjusted for test performance) was 100% (100-100) at all ages except 80 years and older when it was 97.8% (95.9-99.6). For AstraZeneca positivity was over 90% up to age 69, and then 89.2% (88.5-89.9) in 70-79 year olds and 83.6% (78.5-88.3) in those aged 80 and over. Following a single dose of Pfizer-BioNTech positivity ranged from 100.0% (91.1-100.0) in those aged 18-29 to 32.2% (18.2-51.1) in those aged 70-79 years. For AstraZeneca this was 72.2% (68.5-75.9) in the youngest and 46.2% (40.0-52.7) in the oldest age group. Discussion The successful roll out of the vaccination programme in England has led to a high proportion of individuals having detectable antibodies, particularly in older age groups and those who have had two doses of vaccine. This is likely to be associated with high levels of protection from severe disease, and possibly from infection. Nonetheless, there remain some key groups with a lower prevalence of antibody, notably unvaccinated younger people, certain minority ethnic groups, those living in deprived areas and workers in some public facing employment. Obtaining improved rates of vaccination in these groups is essential to achieving high levels of protection against the virus through population immunity.
Subject(s)
COVID-19ABSTRACT
Background Access to rapid diagnosis is key to the control and management of SARS-CoV-2. Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR) testing usually requires a centralised laboratory and significant infrastructure. We describe the development and diagnostic accuracy assessment of a novel, rapid point-of-care RT-PCR test, the DnaNudge platform CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods Nasopharyngeal swabs are inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as a positive control. Between April and May 2020, swab samples were tested in parallel using the CovidNudge direct-to-cartridge platform and standard laboratory RT-PCR using swabs in viral transport medium. Samples were collected from three groups: self-referred healthcare workers with suspected COVID-19 (Group 1, n=280/386; 73%); patients attending the emergency department with suspected COVID-19 (Group 2, n=15/386; 4%) and hospital inpatient admissions with or without suspected COVID-19 (Group 3, n=91/386; 23%). Results Of 386 paired samples tested across all groups, 67 tested positive on the CovidNudge platform and 71 with standard laboratory RT-PCR. The sensitivity of the test varied by group (Group 1 93% [84-98%], Group 2 100% [48-100%] and Group 3 100% [29-100%], giving an average sensitivity of 94.4% (95% confidence interval 86-98%) and an overall specificity of 100% (95%CI 99-100%; Group 1 100% [98-100%]; Group 2 100% [69-100%] and Group 3 100% [96-100%]). Point of care testing performance was comparable during a period of high (25%) and low (3%) background prevalence. Amplification of the viral nucleocapsid (n1, n2, n3) targets were most sensitive for detection of SARS-CoV2, with the assay able to detect 1x104 viral particles in a single swab. Conclusions The CovidNudge platform offers a sensitive, specific and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The implementation of such a device could be used to enable rapid decisions for clinical care and testing programs.
Subject(s)
COVID-19ABSTRACT
Background Emergency Department (ED) attendances have fallen across the UK since the "lockdown" introduced on 23rd March 2020 to limit the spread of coronavirus disease 2019 (COVID-19). We hypothesised that reductions would vary by patient age and disease type. We examined pre- and in-lockdown ED attendances for two COVID-19 unrelated diagnoses; one likely to be affected by lockdown measures (gastroenteritis) and one likely to be unaffected (appendicitis). Methods Retrospective cross-sectional study conducted across two EDs in one London hospital Trust. We compared all adult and paediatric ED attendances, before (January 2020) and during lockdown (March/April 2020). Key patient demographics, method of arrival and discharge location were compared. We used SNOMED codes to define attendances for gastroenteritis and appendicitis. Results ED attendances fell from 1129 per day before lockdown to 584 in-lockdown; 51.7% of pre-lockdown rates. In-lockdown attendances were lowest for under-18s (16.0% of pre-lockdown). The proportion of patients admitted to hospital increased from 17.3% to 24.0% and the proportion admitted to intensive care increased four-fold. Attendances for gastroenteritis fell from 511 to 103; 20.2% of pre-lockdown rates. Attendances for appendicitis also decreased, from 144 to 41; 28.5% of pre-lockdown rates. Conclusion ED attendances fell substantially following lockdown implementation. The biggest reduction was for under-18s. We observed reductions in attendances for gastroenteritis and appendicitis. This may reflect lower rates of infectious disease transmission, though the fall in appendicitis-related attendances suggests that behavioural factors are also important. Larger studies are urgently needed to understand changing patterns of ED use and access to emergency care during the COVID-19 pandemic.