Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

Lumley, Sheila F; O’Donnell, Denise; Stoesser, Nicole; Matthews, Philippa C.; Howarth, Alison; Hatch, Stephanie B.; Marsden, Brian D.; Cox, Stuart; James, Tim; Warren, Fiona C; Peck, Liam J; Ritter, Thomas G.; Toledo, Zoe de; Warren, Laura; Axten, David; Cornall, Richard J.; Jones, Elizabeth; Stuart, D.I.; Screaton, Gavin; Ebner, Daniel; Hoosdally, Sarah; Chand, Meera; Crook, Derrick W.; A-M., O'Donnell; Conlon, Christopher P.; Pouwels, Koen B; Walker, A Sarah; Tea., Peto; Hopkins, Susan; Walker, Tim; Jeffery, Katie; Eyre, David W

doi:10.1056/nejmoa2034545

Cited by 896 publications

(897 citation statements)

References 24 publications

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“…The copyright holder for this preprint this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.08.21251362 doi: medRxiv preprint 8 individuals, our study extends this knowledge by data from a much larger population based survey using solely PCR-confirmed SARS-CoV-2 infection cases. 13 Importantly, a recent study using SARS-CoV-2 PCR and antibody test data from 66,001 patients from a laboratory in south-west London documented 8 patients with evidence of re-infections, and calculated a relative risk of re-infections versus first infections of 0.0578 (95% CI: 0.0288 to 0.1160) 18 which is also compatible with our estimate.…”

Section: Discussionsupporting

confidence: 87%

“…[3][4][5] Importantly, the study by Lumley et al in 12,541 healthcare workers documented protection against reinfection for those who had anti-SARS-CoV-2 antibodies with a rate ratio (0.11) very similar to what we observed. 13 While the investigation by Lumley et al was restricted to a specific population of predominantly healthy adult health care workers 65 years of age or younger, and was based on only two re-infections in seronegative All rights reserved. No reuse allowed without permission.…”

Section: Discussionmentioning

confidence: 99%

“…13 After a follow-up of up to 31 weeks, they calculated a rate ratio of 0.11 (95% confidence interval (CI): 0.03 to 0.44; p=0.002) for re-infections in seropositive healthcare workers versus first infections in health care workers with negative antibody status. 13 Similarly, another recent study among health care workers from the UK reported no re-infection case in 1038 individuals with evidence of previous SARS-CoV-2 infection based on PCR tests and/or antibody status. 10 While these studies suggest a high protection against SARS-CoV-2 re-infections in health care workers, the risk of re-infections in the general population remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 re-infection risk in Austria

Pilz

Chakeri

Ioannidis

et al. 2021

Preprint

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Background: A key question concerning coronavirus disease 2019 (COVID-19) is how effective and long lasting immunity against this disease is in individuals who were previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the risk of SARS-CoV-2 re-infections in the general population in Austria. Methods: This is a retrospective observational study using national SARS-CoV-2 infection data from the Austrian epidemiological reporting system. As the primary outcome, we aim to compare the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February to April 30, 2020) versus the odds of first infections in the remainder general population by tracking polymerase chain reaction (PCR)-confirmed infections of both groups during the second wave from September 1 to November 30, 2020. Re-infection counts are tentative, since it cannot be excluded that the positive PCR in the first and/or second wave might have been a false positive. Results: We recorded 40 tentative re-infections in 14,840 COVID-19 survivors of the first wave (0.27%) and 253,581 infections in 8,885,640 individuals of the remaining general population (2.85%) translating into an odds ratio (95% confidence interval) of 0.09 (0.07 to 0.13). Conclusions: We observed a relatively low re-infection rate of SARS-CoV-2 in Austria. Protection against SARS-CoV-2 after natural infection is comparable to the highest available estimates on vaccine efficacies. Further well-designed research on this issue is urgently needed for improving evidence-based decisions on public health measures and vaccination strategies.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 re-infection risk in Austria

Pilz

Chakeri

Ioannidis

et al. 2021

Preprint

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“…In conclusion, despite the large heterogeneity in antibody levels induced by SARS-CoV-2 infection, the majority of HCW patients remained seropositive for anti-S antibodies up to nine months after COVID-19. The ndings that after PCR reversion, 2 out of 13 seronegatives had another symptomatic episode, and that one low responder had a second (asymptomatic) infection, are consistent with a protective role for antibodies 2 . Data suggest that immune memory induced by rst generation vaccines could also be long-lasting, therefore reducing the probability that periodical boosters might be required to sustain protective immunity.…”

Section: Main Textmentioning

confidence: 55%

Persistence and baseline determinants of seropositivity in health care workers up to nine months after COVID-19

Dobaño

Ramírez

Alonso

et al. 2021

Preprint

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We determined the duration and baseline determinants of antibody responses to SARS-CoV-2 up to nine months after COVID-19 symptoms onset in 173 primary health care worker patients from Spain. Seropositivity to SARS-CoV-2 spike and RBD antigens was 92.49% (60.69% IgM, 76.3% IgA, 90.17% IgG), with four suspected reinfection cases. Antibody levels significantly correlated with fever, hospitalization, anosmia/hypogeusia, allergies, smoking and occupation, and persisted 149-270 days in this cohort of patients

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“…Classically, neutralization by antibody, measured by reduction in plaque or infectious foci by authentic virus in vitro is considered a major component of protection, though indirect effects of antibody, such as complement activation and opsonization may also play a role in vivo. Recent studies have demonstrated that symptomatic re-infection within six months after the first wave in the UK was very rare in the presence of anti-S or anti-N IgG antibodies 7,8 . Virus-specific lymphocytes may play an important direct role in protection, in addition to their indirect effect mediated through help to antibody-producing cells.…”

Section: Introductionmentioning

confidence: 99%

Natural and vaccine-induced antibody and cellular responses against emerging SARS-CoV-2 variants of concern

Dt¹,

Ac²,

Gilbert‐Jaramillo³

et al. 2021

Preprint

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Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020. We tested antibody and T cell responses against a reference isolate (VIC001) representing the original circulating lineage B and the impact of sequence variation in these two VOCs. We identified a reduction in antibody neutralization against the VOCs which was most evident in the B1.351 variant. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced than in naturally-induced immune responses and could be largely explained by the potency of the homotypic antibody response. However, after a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOCs was completely abrogated in the majority of vaccinees. These data indicate that VOCs may evade protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine, but the impact of the VOCs on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants. We observed that two doses of vaccine also induced a significant increase in binding antibodies to spike of both SARS-CoV-1 & MERS, in addition to the four common coronaviruses currently circulating in the UK. The impact of antigenic imprinting on the potency of humoral and cellular heterotypic protection generated by the next generation of variant-directed vaccines remains to be determined.

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Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

Cited by 896 publications

References 24 publications

SARS-CoV-2 re-infection risk in Austria

SARS-CoV-2 re-infection risk in Austria

Persistence and baseline determinants of seropositivity in health care workers up to nine months after COVID-19

Natural and vaccine-induced antibody and cellular responses against emerging SARS-CoV-2 variants of concern

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