Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Background
There is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection.
Methods
A large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis.
Findings
Between 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days.
Interpretation
A prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included.
Funding
Department of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.
Article activity feed
-
SciScore for 10.1101/2021.01.13.21249642: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: 34 Participants: All healthcare workers, support staff and administrative staff working at hospital sites participating in SIREN, who could provide informed consent and anticipated remaining engaged in follow-up for 12 months were eligible to join SIREN. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Variables: Questionnaires on symptoms and exposures were sent electronically at baseline and every two weeks (Supplementary appendix); SARS-CoV-2 antibody (using the Roche cobas® or Abbott immunoassay®) and Nucleic Acid Amplification Testing … SciScore for 10.1101/2021.01.13.21249642: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: 34 Participants: All healthcare workers, support staff and administrative staff working at hospital sites participating in SIREN, who could provide informed consent and anticipated remaining engaged in follow-up for 12 months were eligible to join SIREN. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Variables: Questionnaires on symptoms and exposures were sent electronically at baseline and every two weeks (Supplementary appendix); SARS-CoV-2 antibody (using the Roche cobas® or Abbott immunoassay®) and Nucleic Acid Amplification Testing (NAAT), generally RT-PCR, was conducted at enrolment and at regular intervals (PCR every two weeks, antibody every four weeks). SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources Variables: Questionnaires on symptoms and exposures were sent electronically at baseline and every two weeks (Supplementary appendix); SARS-CoV-2 antibody (using the Roche cobas® or Abbott immunoassay®) and Nucleic Acid Amplification Testing (NAAT), generally RT-PCR, was conducted at enrolment and at regular intervals (PCR every two weeks, antibody every four weeks). Abbottsuggested: (Abbott, RRID:SCR_010477)37 Analysis was conducted in STATA v15.1 (College Station, STATAsuggested: (Stata, RRID:SCR_012763): StataCorp LLC). StataCorpsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Another limitation is measurement error capturing the primary infection onset date for positive cohort participants without a PCR positive test associated with their primary episode. This introduces imprecision into both our person time at risk, and consequently reinfection rates, and our estimated intervals between primary infection episodes and reinfections. For those who were symptomatic in their primary episode we have used their self-reported COVID-19 symptom onset date as a proxy, which may be subject to recall bias. We have introduced validation rules here to reduce this, excluding onset dates before March 2020. However, for participants with asymptomatic or non-COVID-19 symptomatic primary infections, we are reliant on using their first antibody positive date. We are therefore not capturing all the time they were susceptible to reinfection, reducing our overall follow-up time for this cohort, and thus inflating our reinfection rates and reducing our intervals between infection episodes. As the cohort assignment has been determined by testing at SIREN sites, which use a range of testing platforms and assays, there is the possibility of misclassification bias. We have included participants in the positive cohort who had a prior positive PCR test, irrespective of their antibody status. Some of those PCR results, especially early in the epidemic, may have been false positives or laboratory contamination episodes, particularly given Ct/RLU values are not available. We aim ...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title ISRCTN11041050 NA NA 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.
-
SciScore for 10.1101/2021.01.13.21249642: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement METHODS Study design and setting The SIREN study is a prospective cohort study among staff working in the publicly funded hospitals (the National Health Service (NHS)) across the UK. described elsewhere.34 The SIREN protocol is Participants All healthcare workers, support staff and administrative staff working at hospital sites participating in SIREN, who could provide informed consent and anticipated remaining engaged in follow-up for 12 months were eligible to join SIREN. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable 35 Table 1 describes the SIREN participants by their baseline cohort assignment; in … SciScore for 10.1101/2021.01.13.21249642: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement METHODS Study design and setting The SIREN study is a prospective cohort study among staff working in the publicly funded hospitals (the National Health Service (NHS)) across the UK. described elsewhere.34 The SIREN protocol is Participants All healthcare workers, support staff and administrative staff working at hospital sites participating in SIREN, who could provide informed consent and anticipated remaining engaged in follow-up for 12 months were eligible to join SIREN. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable 35 Table 1 describes the SIREN participants by their baseline cohort assignment; in summary the cohort was predominately female (n=17,487; 84%), white (n=18,304; 88%), middle-aged (median age 45.9, interquartile range 35.8-53.6) and from clinical occupations with representation from all English regions and two-thirds of acute hospital trusts. Table 2: Resources
Antibodies Sentences Resources Variables Questionnaires on symptoms and exposures were sent electronically at baseline and every two weeks (Supplementary appendix); SARS-CoV-2 antibody (using the Roche cobas® or Abbott immunoassay® ) and Nucleic Acid Amplification Testing (NAAT), generally RT-PCR, was conducted at enrolment and at regular intervals (PCR every two weeks, antibody every four weeks). SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources Variables Questionnaires on symptoms and exposures were sent electronically at baseline and every two weeks (Supplementary appendix); SARS-CoV-2 antibody (using the Roche cobas® or Abbott immunoassay® ) and Nucleic Acid Amplification Testing (NAAT), generally RT-PCR, was conducted at enrolment and at regular intervals (PCR every two weeks, antibody every four weeks). Abbottsuggested: (Abbott, RRID:SCR_010477)37 Analysis was conducted in STATA v15.1 (College Station, TX: StataCorp LLC). 3. RESULTS From 18 June to 09 November 2020, 20,787 enrolled participants, with linked data on antibody and PCR testing, were included in this analysis (figure 1). STATAsuggested: (Stata, RRID:SCR_012763)StataCorpsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
Another limitation is measurement error capturing the primary infection onset date for positive cohort participants without a PCR positive test associated with their primary Investigations have been restricted by the limited availability of data and episode. This introduces imprecision into both our person time at risk, and consequently reinfection rates, and our estimated intervals between primary infection episodes and reinfections. For those who were symptomatic in their primary episode we have used their self-reported COVID-19 symptom onset date as a proxy, which may be subject to recall bias. We have introduced validation rules here to reduce this, excluding onset dates before March 2020. However, for participants with asymptomatic or non-COVID-19 symptomatic primary infections, we are reliant on using their first antibody positive date. We are therefore not capturing all the time they were susceptible to reinfection, reducing our overall follow-up time for this cohort, and thus inflating our reinfection rates and reducing our intervals between infection episodes. As the cohort assignment has been determined by testing at SIREN sites, which use a range of testing platforms and assays, there is the possibility of misclassification bias. We have included participants in the positive cohort who had a prior positive PCR test, irrespective of their antibody status. Some of those PCR results, especially early in the epidemic, may have been false positives or laboratory contami...
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.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
-
