Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England

Krutikov, Maria; Palmer, Tom; Tut, Gokhan; Fuller, Christopher; Azmi, Borscha; Giddings, Rebecca; Shrotri, Madhumita; Kaur, Nayandeep; Sylla, Panagiota; Lancaster, Tara L.; Irwin-Singer, Aidan; Hayward, Andrew; Moss, Paul; Copas, Andrew J.; Shallcross, Laura J.

doi:10.1016/S2666-7568(21)00282-8

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Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England

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Author(s): Maria Krutikov , MRCP ^a ^, ^* , Tom Palmer , MSc ^b , Gokhan Tut , PhD ^d , Christopher Fuller , MSc ^a , Borscha Azmi , MSc ^a , Rebecca Giddings , MFPH ^a , Madhumita Shrotri , MFPH ^a , Nayandeep Kaur , MSc ^d , Panagiota Sylla , MSc ^d , Tara Lancaster , PhD ^d , Aidan Irwin-Singer , MA ^f , Andrew Hayward , Prof, MD ^c ^, ^e , Paul Moss , Prof, PhD ^d , Andrew Copas , Prof, PhD ^b , Laura Shallcross , Prof, PhD ^a

Publication date (Electronic): 16 December 2021

Journal: The Lancet. Healthy Longevity

Publisher: The Author(s). Published by Elsevier Ltd.

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Abstract

Background

Long-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England.

Methods

This was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves.

Findings

9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6–40·0) in residents and 26·1% (23·0–29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107–169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days.

Interpretation

At least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed.

Funding

UK Government Department of Health and Social Care.

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Most cited references 25

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Antibody responses to SARS-CoV-2 in patients with COVID-19

Quan-Xin Long, Bai-Zhong Liu, Hai-Jun Deng … (2020)

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

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Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Jeffrey Seow, Carl Graham, Blair Merrick … (2021)

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

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Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19

F. Ibarrondo, Jennifer A. Fulcher, David Goodman-Meza … (2020)

To the Editor: A recent article suggested the rapid decay of anti–SARS-CoV-2 IgG in early infection, 1 but the rate was not described in detail. We evaluated persons who had recovered from Covid-19 and referred themselves to our institution for observational research. Written informed consent was obtained from all the participants, with approval by the institutional review board. Blood samples were analyzed by enzyme-linked immunosorbent assay (ELISA) to detect anti–SARS-CoV-2 spike receptor-binding domain IgG. 2 The ELISA was further modified to precisely quantify serum anti–receptor-binding domain activity in terms of equivalence to the concentration of a control anti–receptor-binding domain monoclonal IgG (CR3022, Creative Biolabs). Infection had been confirmed by polymerase-chain-reaction assay in 30 of the 34 participants. The other 4 participants had had symptoms compatible with Covid-19 and had cohabitated with persons who were known to have Covid-19 but were not tested because of mild illness and the limited availability of testing. Most of the participants had mild illness; 2 received low-flow supplemental oxygen and leronlimab (a CCR5 antagonist), but they did not receive remdesivir. There were 20 women and 14 men. The mean age was 43 years (range, 21 to 68) (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). A total of 31 of the 34 participants had two serial measurements of IgG levels, and the remaining 3 participants had three serial measurements. The first measurement was obtained at a mean of 37 days after the onset of symptoms (range, 18 to 65), and the last measurement was obtained at a mean of 86 days after the onset of symptoms (range, 44 to 119). The initial mean IgG level was 3.48 log10 ng per milliliter (range, 2.52 to 4.41). On the basis of a linear regression model that included the participants’ age and sex, the days from symptom onset to the first measurement, and the first log10 antibody level, the estimated mean change (slope) was −0.0083 log10 ng per milliliter per day (range, −0.0352 to 0.0062), which corresponds to a half-life of approximately 36 days over the observation period (Figure 1A). The 95% confidence interval for the slope was −0.0115 to −0.0050 log10 ng per milliliter per day (half-life, 26 to 60 days) (Figure 1B). The protective role of antibodies against SARS-CoV-2 is unknown, but these antibodies are usually a reasonable correlate of antiviral immunity, and anti–receptor-binding domain antibody levels correspond to plasma viral neutralizing activity. Given that early antibody decay after acute viral antigenic exposure is approximately exponential, 3 we found antibody loss that was quicker than that reported for SARS-CoV-1, 4,5 and our findings were more consistent with those of Long et al. 1 Our findings raise concern that humoral immunity against SARS-CoV-2 may not be long lasting in persons with mild illness, who compose the majority of persons with Covid-19. It is difficult to extrapolate beyond our observation period of approximately 90 days because it is likely that the decay will decelerate. 3 Still, the results call for caution regarding antibody-based “immunity passports,” herd immunity, and perhaps vaccine durability, especially in light of short-lived immunity against common human coronaviruses. Further studies will be needed to define a quantitative protection threshold and rate of decline of antiviral antibodies beyond 90 days.

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Author and article information

Journal

Journal ID (nlm-ta): Lancet Healthy Longev

Journal ID (iso-abbrev): Lancet Healthy Longev

Title: The Lancet. Healthy Longevity

Publisher: The Author(s). Published by Elsevier Ltd.

ISSN (Electronic): 2666-7568

Publication date PMC-release: 16 December 2021

Publication date (Electronic): 16 December 2021

Affiliations

[a ]UCL Institute of Health Informatics, London, UK

[b ]UCL Institute for Global Health, London, UK

[c ]UCL Institute of Epidemiology & Health Care, London, UK

[d ]Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

[e ]Health Data Research, London, UK

[f ]Department of Health and Social Care, London, UK

Author notes

[* ]Correspondence to: Dr Maria Krutikov, UCL Institute of Health Informatics, London, NW1 2DA, UK

Article

Publisher Item ID: S2666-7568(21)00282-8

DOI: 10.1016/S2666-7568(21)00282-8

PMC ID: 8676418

PubMed ID: 34935001

SO-VID: 72a18230-0cb2-48fd-9bf2-0cb603bd5d5e

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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.

Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England

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UCL: UN SDG 03 Good Health and Well-Being

Most cited references 25

Antibody responses to SARS-CoV-2 in patients with COVID-19

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19

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