SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)
Summary
Background
Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection.
Methods
A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts.
Findings
From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days.
Interpretation
A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals.
Funding
Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.
Introduction
Reinfection with SARS-CoV: considerations for public health response.
,
Establishing whether reinfection is typically symptomatic or asymptomatic, whether reinfected individuals are infectious to others, and the expected duration of SARS-CoV-2 immunity from infection and vaccination are key components of determining the future dynamics of SARS-CoV-2 circulation.
,
- Colson P
- Finaud M
- Levy N
- et al.
,
- Selhorst P
- Van Ierssel S
- Michiels J
- et al.
,
- Tillett RL
- Sevinsky JR
- Hartley PD
- et al.
,
- Abu-Raddad LJ
- Chemaitelly H
- Malek JA
- et al.
,
,
- Goldman JD
- Wang K
- Roltgen K
- et al.
,
- Gupta V
- Bhoyar RC
- Jain A
- et al.
,
- Larson D
- Brodniak Sl
- Voegtly LJ
- et al.
,
- Mulder M
- van der Vegt DSJM
- Munnink BBO
- et al.
,
- Munoz Mendoza J
- Alcaide ML
,
- Prado-Vivar B
- Becerra-Wong M
- Guadalupe JJ
- et al.
,
- To KK
- Hung IF
- Ip JD
- et al.
,
- Van Elslande J
- Vermeersch P
- Vandervoort K
- et al.
,
- Zhang K
- Lau JY
- Yang L
- et al.
,
- Bonifácio LP
- Pereira APS
- de Almeida E Araújo DC
- et al.
,
- Nachmias V
- Fusman R
- Mann S
- et al.
,
- Ozaras R
- Ozdogru I
- Yilmaz AA
,
- Selvaraj V
- Herman K
- Dapaah-Afriyie
,
- Tomassini S
- Kotecha D
- Bird PW
- et al.
Large longitudinal cohort studies with regular testing are needed to understand the rates of reinfection and their implications for policy by providing systematic epidemiological, virological, immunological, and clinical data.
Evidence before this study
Added value of this study
In comparison, by Jan 11, 2021, SIREN had detected two cases meeting probable and 153 cases meeting possible SARS-CoV-2 reinfection definition from a cohort of 8278 participants that have previously been infected with SARS-CoV-2. Although the report and study of individual cases of SARS-CoV-2 reinfection is important to build our understanding of the body’s response to reinfection, large cohort studies are essential to gain more information about reinfection rate and the characteristics that predispose to reinfection. The SARS-CoV-2 Immunity and Reinfection Evaluation study is powered to achieve such objectives, with a large proportion of seropositive participants from enrolment, and provide robust answers to drive policy.
Implications of all the available evidence
We are at a precarious point of the SARS-CoV-2 epidemic in the UK, with cases due to new strains emerging across the nation while social restrictions are in the process of being lifted. Although vaccines have started to become more widely available, there are several difficult months ahead and the longevity of natural and vaccine-associated immunity is uncertain, particularly in emerging strains. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. The importance of understanding the nature and rate of SARS-CoV-2 reinfection to guide non-pharmaceutical interventions and public health control measures is essential in this evolving pandemic.
- Wajnberg A
- Amanat F
- Firpo A
- et al.
,
- Gudbjartsson DF
- Helgason A
- Jonsson H
- et al.
High concentrations of neutralising antibodies targeting the SARS-CoV-2 spike protein offer considerable protection against SARS-CoV-2 reinfection, supported by data from common human coronaviruses and non-human primate models and vaccine studies.
- Muecksch F
- Wise H
- Batchelor B
- et al.
,
- Huang AT
- Garcia-Carreras B
- Hitchings MD
- et al.
,
- Yu J
- Tostanoski LH
- Peter L
- et al.
,
- Voysey M
- Clemens SAC
- Madhi SA
- et al.
,
- Polack FP
- Thomas SJ
- Kitchin N
- et al.
Although the exact length of immunity conferred by natural infection is still unknown, titres of neutralising antibodies against the SARS-CoV-2 spike protein were detectable for at least 5 months after primary infection.
- Wajnberg A
- Amanat F
- Firpo A
- et al.
- Wajnberg A
- Amanat F
- Firpo A
- et al.
,
- Lumley SF
- O’Donnell D
- Stoesser NE
- et al.
,
- Addetia A
- Crawford KH
- Dingens A
- et al.
,
- Houlihan CF
- Vora N
- Byrne T
- et al.
However, given the relatively small size of some of these cohorts and the lack of systematic SARS-CoV-2 molecular testing, the true population effect remains unknown.
The SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study is a large, national, multicentre prospective cohort study of hospital health-care workers across the National Health Service (NHS) in the UK, which investigated whether the presence of antibodies against SARS-CoV-2 was associated with a reduction in the subsequent risk of symptomatic and asymptomatic reinfection over the 12 months of follow-up. This Article presents an interim analysis of the primary study objective, with data collected up to Jan 11, 2021.
Methods
Study design and participants
- Wallace S
- Hall V
- Charlett A
- et al.
Ethical approval was granted by Berkshire Research Ethics Committee, and Health Research Authority and Health and Care Research Wales.
Procedures
Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01, technical briefing 3.
The SGTF PCR testing was introduced to specific laboratories in England only, termed Pillar 2 laboratories, which are large hospital laboratories established specifically for the COVID-19 response for the purpose of community testing.
Participants were assigned to the positive cohort if they met one of the following criteria: antibody positive on enrolment or antibody positive from previous clinical laboratory samples, with or without a previous positive PCR test; antibody negative on enrolment with a positive PCR result before enrolment. Participants were assigned to the negative cohort if they had a negative antibody test and no documented previous positive PCR or antibody test. Participants with linked negative PCR tests but no linked antibody data were excluded from this analysis because data were insufficient to assign them to a cohort.
- Voysey M
- Clemens SAC
- Madhi SA
- et al.
,
- Lumley SF
- O’Donnell D
- Stoesser NE
- et al.
Participants reporting cough, fever, anosmia, or dysgeusia 14 days before or after their positive PCR result were defined as having COVID-19 symptoms, and if patients reported a sore throat, runny nose, headache, muscle aches, fatigue, diarrhoea, vomiting, or itchy red patches they were defined as having other potential COVID-19 symptoms.
For data management and linkage, personal identifiable information collected via the enrolment survey completed by all SIREN participants was used to match participants to their NHS numbers, which were obtained through the Demographic Batch Service. This information (forename, surname, date of birth, and NHS number) was used to link the SIREN survey data (enrolment and follow-up survey) to results from all laboratory investigations (PCR and antibody data) held at Public Health England. Automated data linkage was developed and run daily to extract new test results. All SIREN data (survey and laboratory extracts) were sorted and matched in the SIREN Structured Query Language (SQL) database.
An SQL query was run on the SIREN database daily, to identify any participants who might be categorised as a potential reinfection. This included participants who had two positive PCR tests 90 days apart or antibody-positive participants with a positive PCR test 4 weeks after their first antibody-positive date. Sites were advised to report potential reinfections.
Data were collected on potential confounders, including site and participant demographics, to permit adjustment in analysis. Questionnaires were piloted and formatted to reduce misclassification bias. Recall bias was limited once participants were enrolled by asking them to complete surveys every 2 weeks for exposures and symptoms. Verification that sites were using validated testing platforms and standardised criteria for reporting into the national laboratory surveillance system was obtained during site initiation.
For the quantitative variable person-time at risk, data were censored at the date of a participant’s last PCR date up to Jan 11, 2021, with the following cohorts assigned. (1) The cohort susceptible to primary infection: from first antibody-negative date to first positive PCR date or seroconversion (if no positive PCR test had been reported before seroconversion); or if neither of these occurred, to censor date. (2) The cohort with previous infection: the earliest date for previous infection was taken as whichever was first of the positive PCR result or the onset of COVID-19 typical symptoms (if there was no positive PCR test result), or if neither was available, the first positive antibody test.
The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. No secondary outcomes were analysed.
Statistical analysis
- Wallace S
- Hall V
- Charlett A
- et al.
The interim analysis was done as the cumulative incidence in the total cohort reached 7%.
The cohort was described by their baseline cohort allocation. Participants with positive PCR results during follow-up in both negative and positive cohorts were described in more detail. Cumulative incidence (using the total number of participants in each cohort) and incidence density (using the total person-time at risk) were calculated for both cohorts and subcategories and plotted over time using PCR confirmation only.
The model fitting approach also provided estimates of the baseline IRRs. The hospital site was added into models as a random effect to account for the extra variation and associated correlation that was not explained by risk and covariate variables. The fixed covariates included in the model were age, gender, ethnicity, region, staff group, and index of multiple deprivation. Time varying covariates included in the model were 21 days after COVID-19 vaccination and regional prevalence of the B.1.1.7 variant. We ran five separate models using the following outcomes: probable reinfections versus all primary infections, infections (reinfection and primary infections) with COVID-19 symptoms, infections with other symptoms, asymptomatic infections, and all infections.
- Diggle PJ
- Heagerty P
- Liang K-Y
- Zeger SL
We investigated the association between protection and SGTF, introducing an interaction term into the model; however, the interaction term was not found to be strongly associated and, therefore, was not included in the final model.
All participants meeting the inclusion criteria were included in the analysis, regardless of their testing frequency, with data censored accordingly. The category “unknown” was introduced for variables with missing values, such as symptom status or index of multiple deprivation.
Analyses were done with STATA version 15.1. The trial was registered with ISRCTN, ISRCTN11041050.
Role of the funding source
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Results
Figure 1Study profile
Participants were enrolled June 18–Dec 31, 2020. SIREN=The SARS-CoV-2 Immunity and Reinfection Evaluation study.
The baseline cohorts assigned 8278 (32·3%) of 25 661 participants to the positive cohort and 17 383 (67·7%) to the negative cohort. 7551 (91·2%) of the 8278 participants in the positive cohort were antibody positive at enrolment, 582 (7·0%) were antibody negative at enrolment but had a previous antibody positive result or positive PCR result (of which 108 also had a previous positive PCR result), and 145 (1·8%) had a previous PCR positive result but no linked antibody data.
Table 1Demographics of study participants by baseline cohort allocation
Data are n (%), unless otherwise indicated.
The cohort had 220 484 PCR tests (23 321 before SIREN enrolment and 197 163 after enrolment) and 135 890 antibody tests (16 862 before SIREN enrolment and 119 028 after enrolment). A median of eight post-enrolment PCR tests (IQR 6–11) and five post-enrolment antibody tests (3–7) were done. The PCR test density during follow-up was 64 per 1000 days of participant follow-up in the positive cohort and 70 per 1000 days of participant follow-up in the negative cohort.
13 401 (52·2%) participants of the cohort were vaccinated during the follow-up period (between Dec 8, 2020, and Jan 11, 2021), 9468 in the negative cohort and 3933 in the positive cohort. Vaccine roll-out accelerated in January, 2021, and peaked during the week commencing Jan 11, 2021. The number of participants who contributed follow-up time to this analysis who had been vaccinated for 21 days or more, the period at which a protective effect from vaccination would be expected, was 833 from the positive cohort, contributing 4941 days of follow-up, and 2279 from the negative cohort, contributing 12 839 days of follow-up. In total 0·4% of the study’s person-time of follow-up included participants 21 days or more following vaccination.
Figure 2Weekly frequency of SIREN participants with a first positive PCR test result by baseline cohort assignment, from March, 2020, to January, 2021
Table 2Characteristics of reinfections and new infections detected in SIREN participants up to Jan 11, 2021, stratified by case definition
Data are n, n (%), or median (range), unless otherwise indicated. SIREN=The SARS-CoV-2 Immunity and Reinfection Evaluation study. Ct=cycle threshold. RLU=relative light unit.
Table 3Frequency of new infections and reinfections by cohort, characterised by case definitions and symptoms 14 days before and after date of positive PCR test
Both probable cases had COVID-19 symptoms and one reinfection case did not provide details on symptoms so the results for this participant are unknown.
IRR unadjusted model was adjusted for period and site. IRR adjusted model included fixed effects (adjusted for week group, age group, gender, ethnicity, staff role, index of multiple deprivation, region); time-varying effects (adjusted for vaccination and B.1.1.7 variant prevalence); and random effect (adjusted for site). SIREN=The SARS-CoV-2 Immunity and Reinfection Evaluation study. IRR=incidence rate ratio. aIRR=adjusted incidence rate ratio.
We did not find any evidence that increased prevalence of the B.1.1.7 variant adversely affected reinfection rates in our cohort during this follow-up period. Our models suggested that the protective effect of previous infection increased when the variant was dominant (IRR 0·18, 95% CI 0·15–0·23) compared with IRR 0·13 (0·10–0·17), although the formal test of interaction between cohort and SGTF did not reach conventional levels of statistical significance (p=0·05). Additionally, the ecological nature of the SGTF data available to use precludes the ability to definitively answer the question of protection conferred to new variants.
Discussion
We have presented the interim findings after 7 months of follow-up from the SIREN study, a unique, large-scale, multicentre, prospective cohort study of health-care staff undergoing frequent asymptomatic testing, powered to detect and characterise reinfections and estimate the protective effect of SARS-CoV-2 antibodies.
We have detected two probable reinfections and 153 possible reinfections in our positive cohort. 50 of the reinfections were symptomatic with typical COVID-19 symptoms, 28 with other symptoms, and 76 were asymptomatic. By contrast, we identified 1704 new PCR positive infections in patients, 1126 of whom had COVID-19 symptoms, 243 with other symptoms, and 293 were asymptomatic in our negative cohort. Using a COVID-19 symptomatic case definition aligned with positive PCR results, previous infection reduced the incidence of infection by at least 90% (aIRR 0·07, 95% CI 0·06 to 0·10) and even when we included all possible and probable reinfections reduced the incidence of reinfection by at least 84% (aIRR 0·159, 0·13–0·19).
Coronavirus (COVID-19) infection survey, UK: 8 January 2021.
Additionally, we did not include 864 seroconversions in the negative cohort, because these seroconversions were not detected by PCR and whether a similar rate of undetected infections occurred in the positive cohort remains unknown.
None of the reinfections we have identified are confirmed by our stringent case definitions, most reinfections we only consider possible and are undergoing further serological investigation. Investigations have been restricted by the scarce data and samples from historic infections, with most swabs discarded without sequencing, preventing the genomic comparison between infection episodes required to confirm a reinfection. This finding emphasises the importance of SIREN, through which we are ensuring the data collection and characterisation of new infections, to build a stronger base to investigate and confirm future reinfections. Our use of hierarchical case definitions identifies cases with stronger evidence and allows us to present the range of potential reinfection scenarios.
Another limitation is measurement error when capturing the primary infection onset date for positive cohort participants without a positive PCR test associated with their primary episode. This limitation introduces imprecision into 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 could be subject to recall bias. However, we have introduced validation rules to reduce the recall bias, excluding onset dates before March, 2020. We used the first antibody positive date for participants with asymptomatic or non-COVID-19 symptomatic primary infections. Therefore, we did not capture the entire time period during which participants 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.
Because the cohort assignment was determined by testing at SIREN sites, which use a range of testing platforms and assays, misclassification bias might have occurred. We have included participants in the positive cohort who had a previous positive PCR test, irrespective of their antibody status, although these participants account for less than 4% of the positive cohort. Some of those PCR results, especially early in the epidemic, might have been false positives or laboratory contamination episodes, particularly when considering that cycle threshold/relative light unit values are not available. We aim to retest all baseline serum samples within Public Health England, using both S and N target assays to give each participant a validated quantitative baseline antibody result. This testing will inform future analyses and might lead to changes to the cohort assignment presented.
Although COVID-19 vaccines were introduced to our cohort from Dec 8, 2020, onwards, the effect on the follow-up time in this analysis was modest and has been adjusted for, therefore our finding on the durability of protection following previous infection is independent of the vaccine effect. However, we note that given the high vaccination coverage in the SIREN cohort, future analyses will need to estimate both the protective effect of previous infections and vaccine effectiveness simultaneously.
Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01, technical briefing 3.
,
- Dd Volz E
- Mishra S
- Chand M
- et al.
,
Previous studies have shown that commercially available vaccines in the UK are still effective against this new variant, inducing a neutralising antibody response and offering similar protection when compared with other lineages.
- Emary KR
- Golubchik T
- Aley P
- et al.
,
- Muik A
- Wallisch AK
- Sänger B
- et al.
,
- Wu K
- Werner AP
- Moliva JI
- et al.
We have shown in this analysis that immunity from previous infection is protective against reinfection with the B.1.1.7 variant.
- Lumley SF
- O’Donnell D
- Stoesser NE
- et al.
,
- Houlihan CF
- Vora N
- Byrne T
- et al.
Another prospective cohort of health-care workers previously reported the incidence of new positive PCR-confirmed infections to be lower among seropositive than seronegative participants (three of 1246 vs 165 of 11 052, an incidence density of 2·1 per 100 000 days at risk for seropositive participants and 8·6 per 100 000 days at risk for seronegative participants).
- Lumley SF
- O’Donnell D
- Stoesser NE
- et al.
However, this study did not routinely do PCR tests on all individuals in the cohort and the three potential reinfections were asymptomatic.
- Voysey M
- Clemens SAC
- Madhi SA
- et al.
,
- Polack FP
- Thomas SJ
- Kitchin N
- et al.
Another phase 3 trial of the mRNA-1273 vaccine showed 94·1% efficacy against symptomatic (COVID-19 typical symptoms) SARS-CoV-2 infection, including severe illness, over a median of 2 months of follow-up.
- Baden LR
- El Sahly HM
- Essink B
- et al.
In a separate analysis on the SIREN cohort, we showed that the BNT162b2 vaccine offered 70% protection from both symptomatic and asymptomatic infection, 21 days after the first dose, which increased to 85% 7 days after the second dose.
- Hall V
- Foulkes S
- Saei A
- et al.
Our findings of a 93% lower risk of COVID-19 symptomatic infection, after a longer period of follow-up, show equal or higher protection from natural infection, both for symptomatic and asymptomatic infection.
Sixty-third SAGE meeting on Covid-19, 22nd October 2020.
Our findings increase the likelihood that this protection could also be attainable by vaccine-induced immunity, which a separate analysis on the SIREN cohort previously demonstrated.
- Hall V
- Foulkes S
- Saei A
- et al.
Further detailed studies on the longevity of antibody responses, assessment of reinfection rates under the challenge of the new lineages, and the effect of all COVID-19 vaccines introduced in the UK are underway in this cohort.
Contributors
VJH, SF, and SH designed the analysis plan and wrote the paper. SF and VJH cleaned and finalised the dataset for analysis and did the descriptive analyses. AC and AS planned and did the statistical analysis. RS, EW, PDK, SF, KM, and AV set up and ran the data collection systems and linkage of participant records. AV, MK, PDK, VJH, and SH designed, piloted, and built the online questionnaires. MAC, CSB, SH, TB, MZ, MJC, AA, EJMM, SR, BO, SW, MS, VJH, MR, and RS designed the reinfection investigation pathways and investigated reinfections. AA, EJMM, BO, SW, MS, SR, and MJC led onsite recruitment and initiation. VJH, SF, AC, AS, and AA verified the data in the study. All authors reviewed and approved the manuscript for publication. All authors had full access to all the data in the study and accept responsibility to submit for publication.
Data sharing
The metadata will be available through the Health Data Research UK Co-Connect platform and will be available for secondary analysis once the study has completed reporting.
Declaration of interests
We declare no competing interests.
Acknowledgments
The study is funded by the UK Department of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh, and Northern Irish governments. Funding was also provided by the National Institute for Health Research (NIHR) as an Urgent Public Health Priority Study. SH and VJH are supported by the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (NIHR200915). We would like to thank all the staff supporting study delivery at participating sites and all participants for their ongoing commitment and contributions to this study. We also thank all staff undertaking COVID-19 testing within Public Health England Reference Microbiology.
Supplementary Materials
References
- 1.
Reinfection with SARS-CoV: considerations for public health response.
- 2.
What reinfections mean for COVID-19.
Lancet Infect Dis. 2020; 21: 3-5
- 3.
Evidence of SARS-CoV-2 re-infection with a different genotype.
J Infect. 2020; ()
- 4.
Symptomatic SARS-CoV-2 re-infection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response.
medRxiv. 2020; ()
- 5.
Genomic evidence for reinfection with SARS-CoV-2: a case study.
Lancet Infect Dis. 2021; 21: 52-58
- 6.
Assessment of the risk of SARS-CoV-2 reinfection in an intense re-exposure setting.
medRxiv. 2020; ()
- 7.
COVID-19 re-infection in an healthcare worker.
J Med Virol. 2020; ()
- 8.
Reinfection with SARS-CoV-2 and failure of humoral immunity: a case report.
medRxiv. 2020; ()
- 9.
Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2.
Clin Infect Dis. 2020; ()
- 10.
A case of early re-infection with SARS-CoV-2.
Clin Infect Dis. 2020; ()
- 11.
Reinfection of SARS-CoV-2 in an immunocompromised patient: a case report.
Clin Infect Dis. 2020; ()
- 12.
COVID-19 in a patient with end-stage renal disease on chronic in-center hemodialysis after evidence of SARS-CoV-2 IgG antibodies. Reinfection or inaccuracy of antibody testing.
IDCases. 2020; 22e00943
- 13.
COVID-19 re-infection by a phylogenetically distinct SARS-CoV-2 variant, first confirmed event in South America.
SSRN. 2020; ()
- 14.
COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing.
Clin Infect Dis. 2020; ()
- 15.
Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain.
Clin Infect Dis. 2020; ()
- 16.
SARS-CoV-2 reinfection in two patients who have recovered from COVID-19.
Precis Clin Med. 2020; 3: 292-293
- 17.
Are SARS-CoV-2 reinfection and Covid-19 recurrence possible? A case report from Brazil.
Rev Soc Bras Med Trop. 2020; 53e20200619
- 18.
The first case of documented Covid-19 reinfection in Israel.
IDCases. 2020; 22e00970
- 19.
Coronavirus disease 2019 re-infection: first report from Turkey.
New Microbes New Infect. 2020; 38100774
- 20.
Severe, symptomatic reinfection in a patient with COVID-19.
R I Med J (2013). 2020; 103: 24-26
- 21.
Setting the criteria for SARS-CoV-2 reinfection – six possible cases.
J Infect. 2021; 82: 282-327
- 22.
Understanding protection from SARS-CoV-2 by studying reinfection.
Nat Med. 2020; 26: 1680-1681
- 23.
Robust neutralizing antibodies to SARS-CoV-2 infection persist for months.
Science. 2020; 370: 1227-1230
- 24.
Spread of SARS-CoV-2 in the Icelandic population.
N Engl J Med. 2020; 382: 2302-2315
- 25.
Longitudinal analysis of serology and neutralizing antibody levels in coronavirus disease 2019 convalescent patients.
J Infect Dis. 2021; 223: 389-398
- 26.
A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity.
Nat Commun. 2020; 114704
- 27.
DNA vaccine protection against SARS-CoV-2 in rhesus macaques.
Science. 2020; 369: 806-811
- 28.
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
Lancet. 2021; 397: 99-111
- 29.
Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.
N Engl J Med. 2020; 383: 2603-2615
- 30.
Antibodies to SARS-CoV-2 are associated with protection against reinfection.
medRxiv. 2020; ()
- 31.
Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate.
J Clin Microbiol. 2020; 58: e02107-e02120
- 32.
Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers.
Lancet. 2020; 396: e6-e7
- 33.
SIREN protocol: impact of detectable anti-SARS-CoV-2 on the subsequent incidence of COVID-19 in 100,000 healthcare workers: do antibody positive healthcare workers have less reinfection than antibody negative healthcare workers?.
medRxiv. 2020; ()
- 34.
Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01, technical briefing 3.
- 35.
The analysis of rates and of survivorship using log-linear models.
Biometrics. 1980; 36: 299-305
- 36.
Analysis of longitudinal data.
2nd edn. Oxford University Press,
Oxford2002 - 37.
Coronavirus (COVID-19) infection survey, UK: 8 January 2021.
- 38.
Transmission of SARS-CoV-2 lineage B.1.1.7 in England: insights from linking epidemiological and genetic data.
medRxiv. 2021; ()
- 39.
Covid-19: new UK variant may be linked to increased death rate, early data indicate.
BMJ. 2021; 372: n230
- 40.
Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7).
SSRN. 2021; ()
- 41.
Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine–elicited human sera.
Science. 2021; 371: 1152-1153
- 42.
mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants.
bioRxiv. 2021;
- 43.
Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.
N Engl J Med. 2021; 384: 403-416
- 44.
Effectiveness of BNT162b2 mRNA vaccine against infection and COVID-19 vaccine coverage in healthcare workers in England, multicentre prospective cohort study (the SIREN Study).
SSRN. 2021; ()
- 45.
Sixty-third SAGE meeting on Covid-19, 22nd October 2020.
Article Info
Publication History
Published: April 09, 2021
Identification
Copyright
Crown Copyright © 2021 Published by Elsevier Ltd. All rights reserved.
ScienceDirect
Linked Articles
- Correlates of protection from SARS-CoV-2 infection
-
Since the beginning of the COVID-19 pandemic, many scientists and public health officials assumed that infection with SARS-CoV-2 would protect from reinfection and that neutralising antibodies would correlate with protection or would be at least one of the protective immune mechanisms.1 Early on, these assumptions were supported by non-human primate data showing protection from reinfection, a correlation between neutralising antibodies protection, and protection afforded by passive transfer of neutralising antibodies.
- Full-Text
-
- Department of Error
-
The SIREN Study Group. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN). Lancet 2021; 397: 1459–69—For this Article, Mariyam Mirfenderesky and Thushan De Silva should have been included in the SIREN Study Group, and author EJM Monk’s initials have been corrected. These corrections have been made to the online version as of May 6, 2021.
- Full-Text
-