Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust
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Abstract
Background
We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity.
Methods
HCWs at Sheffield Teaching Hospitals NHS Foundation Trust (STH) were prospectively enrolled and sampled at two time points. SARS-CoV-2 antibodies were tested using an in-house assay for IgG and IgA reactivity against Spike and Nucleoprotein (sensitivity 99·47%, specificity 99·56%). Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model.
Findings
As of 12th June 2020, 24·4% (n=311/1275) HCWs were seropositive. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0–52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4–56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years.
Interpretation
HCWs in acute medical units working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals.
Research in context
Evidence before this study
We searched PubMed for studies published up to March 6th 2021, using the terms “COVID”, “SARS-CoV-2”, “seroprevalence”, and “healthcare workers”, and in addition for articles of antibody titres in different age groups against coronaviruses using “coronavirus”, “SARS-CoV-2, “antibody”, “antibody tires”, “COVID” and “age”. We included studies that used serology to estimate prevalence in healthcare workers. SARS-CoV-2 seroprevalence has been shown to be greater in healthcare workers working on acute medical units or within domestic services. Antibody levels against seasonal coronaviruses, SARS-CoV and SARS-CoV-2 were found to be higher in older adults, and patients who were hospitalised.
Added value of this study
In this healthcare worker seroprevalence modelling study at a large NHS foundation trust, we confirm that those working on acute medical units, COVID-19 “Red Zones” and within domestic services are most likely to be seropositive. Furthermore, we show that physiotherapists and occupational therapists have an increased risk of COVID-19 infection. We also confirm that antibody titres are greater in older individuals, even in the context of non-hospitalised cases. Importantly, we demonstrate that this can result in age-specific sensitivity in serological assays, where lower antibody titres in younger individuals results in lower assay sensitivity.
Implications of all the available evidence
There are distinct occupational roles and locations in hospitals where the risk of COVID-19 infection to healthcare workers is greatest, and this knowledge should be used to prioritise infection prevention control and other measures to protect healthcare workers. Serological assays may have different sensitivity profiles across different age groups, especially if assay validation was undertaken using samples from older and/or hospitalised patients, who tend to have higher antibody titres. Future seroprevalence studies should consider adjusting for age-specific assay sensitivities to estimate true seroprevalence rates.
Author Contributions
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SciScore for 10.1101/2021.07.07.21260151: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Immediately following electronic informed consent, participants received a study email with a link to an online questionnaire which used a unique study number and retrospectively collected self-reported data on age, gender, ethnicity, job role, and working environment since start of pandemic (to stratify risk of direct contact with COVID-19 patients; including “COVID-19 zone” - defined in Supplementary Information). Sex as a biological variable Age group categories considered were <30, 30-39, 40-49, 50-59, and 60 years plus; gender categories considered included Female and Male, and Ethnicity categories included White, Black, Asian and Other (which includes “Prefer not to say”). Rando… SciScore for 10.1101/2021.07.07.21260151: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Immediately following electronic informed consent, participants received a study email with a link to an online questionnaire which used a unique study number and retrospectively collected self-reported data on age, gender, ethnicity, job role, and working environment since start of pandemic (to stratify risk of direct contact with COVID-19 patients; including “COVID-19 zone” - defined in Supplementary Information). Sex as a biological variable Age group categories considered were <30, 30-39, 40-49, 50-59, and 60 years plus; gender categories considered included Female and Male, and Ethnicity categories included White, Black, Asian and Other (which includes “Prefer not to say”). Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources For the IgG assay, this calibration curve was later run in parallel with the WHO International Standard for anti-SARS-CoV-2 immunoglobulin when this became available (NIBSC, 20/136), to allow conversion of our antibody units to the WHO-recommended universal antibody units (Supplementary Information). anti-SARS-CoV-2 immunoglobulinsuggested: NoneResults from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Using an assay which detects spike IgG, that has been validated using serum samples from a broader population, with antibody kinetics modelling and/or with age adjusted cut offs could overcome these limitations. However, with increasing vaccine coverage, use of spike IgG to determine seroprevalence becomes more problematic when distinguishing whether an individual is seropositive from vaccination or previous infection. Assays which combine antibody responses to membrane protein with NCP antibodies may overcome these challenges.35,36 We note the limitations of our study, which include a potential for selection bias due to participants self-enrolling for convenience, rather than using systematic sampling. Reassuringly, our seroprevalence rates are similar to those seen in other UK based seroprevalence studies.5,30 In addition, we recognise that our cohort has relatively low numbers of HCWs from minority ethnic backgrounds (∼10%), compared to the Sheffield general population (19%).37 With the ongoing global devastation due to the COVID-19 pandemic, knowledge of HCW exposure risk factors is vital, given the possibility of reinfection with immune-escape variants, and that future re-vaccination programmes are likely on the horizon. Our real-world data demonstrate that HCWs are at high risk of exposure, particularly those who work on AMU or as PT/OT as well as domestic services personnel. Measuring and correctly interpreting population seroprevalence data can help guide decision mak...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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