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"Cox, Stuart"
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Stringent thresholds in SARS-CoV-2 IgG assays lead to under-detection of mild infections
Background
Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. In this setting the sensitivity and specificity of the best performing assays can both exceed 98%. However, antibody assay performance following mild infection is less clear.
Methods
We assessed quantitative IgG responses in a cohort of healthcare workers in Oxford, UK, with a high pre-test probability of Covid-19, in particular the 991/11,475(8.6%) who reported loss of smell/taste. We use anosmia/ageusia and other risk factors as probes for Covid-19 infection potentially undiagnosed by immunoassays by investigating their relationship with antibody readings either side of assay thresholds.
Results
The proportion of healthcare workers reporting anosmia/ageusia increased at antibody readings below diagnostic thresholds using an in-house ELISA (
n
= 9324) and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA;
n
= 11,324): 426/906 (47%) reported anosmia/ageusia with a positive ELISA, 59/449 (13.1%) with high-negative and 326/7969 (4.1%) with low-negative readings. Similarly, by CMIA, 518/1093 (47.4%) with a positive result reported anosmia/ageusia, 106/686 (15.5%) with a high-negative and 358/9563 (3.7%) with a low-negative result. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays in mild infection is lower than previously reported: Oxford ELISA 89.8% (95%CI 86.6–92.8%) and Abbott CMIA 79.3% (75.9–82.7%).
Conclusion
Following mild SARS-CoV-2 infection 10–30% of individuals may have negative immunoassay results. While lowered diagnostic thresholds may result in unacceptable specificity, our findings have implications for epidemiological analyses and result interpretation in individuals with a high pre-test probability. Samples from mild PCR-confirmed infections should be included in SARS-CoV-2 immunoassay evaluations.
Journal Article
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers
In a longitudinal study of seropositive and seronegative health care workers undergoing asymptomatic and symptomatic SARS-CoV-2 testing, the presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months.
Journal Article
Identification of undetected SARS-CoV-2 infections by clustering of Nucleocapsid antibody trajectories
During the COVID-19 pandemic, numerous SARS-CoV-2 infections remained undetected. We combined results from routine monthly nose and throat swabs, and self-reported positive swab tests, from a UK household survey, linked to national swab testing programme data from England and Wales, together with Nucleocapsid (N-)antibody trajectories clustered using a longitudinal variation of K-means (N = 185,646) to estimate the number of infections undetected by either approach. Using N-antibody (hypothetical) infections and swab-positivity, we estimated that 7.4% (95%CI: 7.0–7.8%) of all true infections (detected and undetected) were undetected by both approaches, 25.8% (25.5–26.1%) by swab-positivity-only and 28.6% (28.4–28.9%) by trajectory-based N-antibody-classifications-only. Congruence with swab-positivity was respectively much poorer and slightly better with N-antibody classifications based on fixed thresholds or fourfold increases. Using multivariable logistic regression N-antibody seroconversion was more likely as age increased between 30–60 years, in non-white participants, those less (recently/frequently) vaccinated, for lower cycle threshold values in the range above 30, and in symptomatic and Delta (vs. BA.1) infections. Comparing swab-positivity data sources showed that routine monthly swabs were insufficient to detect infections and incorporating national testing programme/self-reported data substantially increased detection. Overall, whilst N-antibody serosurveillance can identify infections undetected by swab-positivity, optimal use requires fourfold-increase-based or trajectory-based analysis.
Many SARS-CoV-2 infections may go undetected through conventional PCR or lateral flow tests. Here, the authors analyse the utility of analysing longitudinal nucleocapsid antibody trajectories to improve identification of prior SARS-CoV-2 infections using surveillance data from the UK.
Journal Article
COVID-19 vaccination, risk-compensatory behaviours, and contacts in the UK
The physiological effects of vaccination against SARS-CoV-2 (COVID-19) are well documented, yet the behavioural effects not well known. Risk compensation suggests that gains in personal safety, as a result of vaccination, are offset by increases in risky behaviour, such as socialising, commuting and working outside the home. This is potentially important because transmission of SARS-CoV-2 is driven by contacts, which could be amplified by vaccine-related risk compensation. Here, we show that behaviours were overall unrelated to personal vaccination, but—adjusting for variation in mitigation policies—were responsive to the level of vaccination in the wider population: individuals in the UK were risk compensating when rates of vaccination were rising. This effect was observed across four nations of the UK, each of which varied policies autonomously.
Journal Article
Estimating the prevalence of problem drug use in inner London: a discussion of three capture-recapture studies
Aims. To provide an evidence base of estimates of the prevalence of problem drug use in inner London. Design. Re‐analysis of three capture‐recapture studies using subjects aged 15‐49 years, that aim to estimate the hidden population from analysing the overlaps between three data sources. Setting. Newham (1995) Camden and Islington (C&I) (1993/4) and Lambeth, Southwark and Lewisham (LSL) (1992). Participants. Each study collected data from three sources of problem drug users including: the Regional Drug Misuse Database, specialist drug agencies, HIV tests, social services, police arrests and court records. In LSL opiate users were analysed separately. The studies identified 1832 individuals in LSL, 543 in Newham, and 1321 in C&I. Measurements. Poisson models were fitted to the data testing different interactions between the data sources representing potential dependencies. The simplest model was selected on the basis of its AIC score and log‐likelihood ratio tests. Findings. The number of hidden problem drug users were estimated to be 12 500 (95% CI 9600‐16100) in LSL with 4400 (3200‐6100) opiate users; 7000 (5000‐10000) in C&I and 3800 (2000‐7200) in Newham. The prevalence of problem drug use in those aged 15‐49 was estimated to be 3.1% (2.5‐3.9%) in LSL with 1.3% (1.0‐1.6%) opiate users; and 3.6% (2.7‐4.9%) and 3.3% (1.9‐5.7%) in C&I and Newham, respectively. Conclusions. Despite the inherent problems with capture‐recapture methods, our three studies establish an evidence base for estimates of problem drug use in London. It is important that a larger study is carried out in London.
Journal Article