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      Reinfection with new variants of SARS-CoV-2 after natural infection: a prospective observational cohort in 13 care homes in England

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          Abstract

          Background

          Understanding the duration of protection and risk of reinfection after natural infection is crucial to planning COVID-19 vaccination for at-risk groups, including care home residents, particularly with the emergence of more transmissible variants. We report on the duration, neutralising activity, and protection against the alpha variant of previous SARS-CoV-2 infection in care home residents and staff infected more than 6 months previously.

          Methods

          We did this prospective observational cohort surveillance in 13 care homes in Greater London, England. All staff and residents were included. Staff and residents had regular nose and throat screening for SARS-CoV-2 by RT-PCR according to national guidelines, with ad hoc testing of symptomatic individuals. From January, 2021, antigen lateral flow devices were also used, but positive tests still required RT-PCR confirmation. Staff members took the swab samples for themselves and the residents. The primary outcome was SARS-CoV-2 RT-PCR positive primary infection or reinfection in previously infected individuals, as determined by previous serological testing and screening or diagnostic RT-PCR results. Poisson regression and Cox proportional hazards models were used to estimate protective effectiveness of previous exposure. SARS-CoV-2 spike, nucleoprotein, and neutralising antibodies were assessed at multiple timepoints as part of the longitudinal follow-up.

          Findings

          Between April 10 and Aug 3, 2020, we recruited and tested 1625 individuals (933 staff and 692 residents). 248 participants were lost to follow-up (123 staff and 125 residents) and 1377 participants were included in the follow-up period to Jan 31, 2021 (810 staff and 567 residents). There were 23 reinfections (ten confirmed, eight probable, five possible) in 656 previously infected individuals (366 staff and 290 residents), compared with 165 primary infections in 721 susceptible individuals (444 staff and 277 residents). Those with confirmed reinfections had no or low neutralising antibody concentration before reinfection, with boosting of titres after reinfection. Kinetics of binding and neutralising antibodies were similar in older residents and younger staff.

          Interpretation

          SARS-CoV-2 reinfections were rare in older residents and younger staff. Protection from SARS-CoV-2 was sustained for longer than 9 months, including against the alpha variant. Reinfection was associated with no or low neutralising antibody before reinfection, but significant boosting occurred on reinfection.

          Funding

          Public Health England.

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          Most cited references37

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          Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

          Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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            Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

            Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.
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              Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington

              Abstract Background Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. Methods After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health–Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. Results As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. Conclusions In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.
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                Author and article information

                Journal
                Lancet Healthy Longev
                Lancet Healthy Longev
                The Lancet. Healthy Longevity
                Published by Elsevier Ltd.
                2666-7568
                1 December 2021
                December 2021
                1 December 2021
                : 2
                : 12
                : e811-e819
                Affiliations
                [a ]Virus Reference Department, Public Health England, London, UK
                [b ]Data and Analytical Sciences, Public Health England, London, UK
                [c ]London Coronavirus Response Cell, National Infection Service, Public Health England, London, UK
                [d ]Immunisation and Countermeasures Division, Public Health England, London, UK
                [e ]Blizard Institute, Queen Mary University of London, London, UK
                [f ]Paediatric Infectious Diseases Research Group, St. George's University of London, London, UK
                Author notes
                [* ]Correspondence to: Dr Anna Jeffery-Smith, Virus Reference Department, Public Health England, London NW9 5EQ, UK
                [*]

                Joint senior authors

                Article
                S2666-7568(21)00253-1
                10.1016/S2666-7568(21)00253-1
                8635459
                34873592
                b32d118a-eafe-411a-97c2-4e487895a25e
                © 2021 Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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