Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

ABSTRACT

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants’ PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

Related collections

Most cited references 17

Record: found
Abstract: found
Article: found

Is Open Access

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

Jennifer M. Dan, Jose Mateus, Yu Kato … (2021)

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

0 comments Cited 1311 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Humoral Immune Response to SARS-CoV-2 in Iceland

Daniel Gudbjartsson, Gudmundur L Norddahl, Páll Melsted … (2020)

Abstract Background Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. Results Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. Conclusions Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

0 comments Cited 538 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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

Sheila Lumley, Denise O’Donnell, Nicole Stoesser … (2020)

Abstract Background The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear. Methods We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time. Results A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status. Conclusions The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.)

0 comments Cited 471 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Susanne Dam Nielsen:

ORCID: https://orcid.org/0000-0001-6391-7455

Ujjwal Neogi: Role: Editor

Journal

Journal ID (nlm-ta): Microbiol Spectr

Journal ID (iso-abbrev): Microbiol Spectr

Journal ID (publisher-id): spectrum

Title: Microbiology Spectrum

Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )

ISSN (Electronic): 2165-0497

Publication date (Electronic, pub): 20 October 2021

Publication date (Electronic, collection): Sep-Oct 2021

Publication date PMC-release: 20 October 2021

Volume: 9

Issue: 2

Electronic Location Identifier: e00904-21

Affiliations

[a ] Department of Clinical Research, Nordsjaellands Hospital, Hilleroed, Denmark

[b ] Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

[c ] Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark

[d ] Department of Cardiology, Herlev og Gentofte Hospital, University of Copenhagen, Herlev, Denmark

[e ] Department of Emergency Medicine, Herlev og Gentofte Hospital, University of Copenhagen, Herlev, Denmark

[f ] Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

[g ] Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

[h ] Department of Emergency, Copenhagen University Hospitalgrid.4973.9, – Amager og Hvidovre, Hvidovre, Denmark

[i ] Department of Clinical Research, Copenhagen University Hospitalgrid.4973.9, – Amager og Hvidovre, Hvidovre, Denmark

[j ] Department of Clinical Biochemistry, Copenhagen University Hospitalgrid.4973.9, – Nordsjællands Hospital, Hillerød, Denmark

[k ] Department of Cardiology and Clinical Research, Nordsjællands Hospital, Hillerød, Denmark

[l ] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark

[m ] Department of Public Health, University of Copenhagen, Copenhagen, Denmark

[n ] Department of Endocrinology, Copenhagen University Hospitalgrid.4973.9, – Bispebjerg and Frederiksberg, Bispebjerg, Copenhagen, Denmark

[o ] Copenhagen Center for Translational Research, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Bispebjerg, Copenhagen, Denmark

[p ] Department of Pulmonary Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Bispebjerg, Copenhagen, Denmark

[q ] Mental Health Services-The Capital Region of Denmark, Copenhagen, Denmark

[r ] Department of Clinical Microbiology, Zealand University Hospital–Slagelse, Slagelse, Denmark

[s ] Department of Regional Health Research, University of Southern Denmark, Odense, Denmark

[t ] Copenhagen University Hospitalgrid.4973.9, –Copenhagen Emergency Medical Services, Copenhagen, Denmark

[u ] Diagnostisk Enhed, Copenhagen University Hospitalgrid.4973.9, , Bornholm, Denmark

[v ] Department of Infectious Disease, Copenhagen University Hospitalgrid.4973.9, –Amager and Hvidovre, Hvidovre, Denmark

[w ] Statens Serum Institutgrid.6203.7, , Copenhagen, Denmark

[x ] Department of Public Health, Global Health Section, University of Copenhagen, Denmark

Karolinska Institutet

Author notes

Caroline Klint Johannesen and Omid Rezahosseini contributed equally, and Thea Kølsen Fischer and Susanne Dam Nielsen contributed equally to this article. The order of names was determined according to the criteria for authorship of the International Committee of Medical Journal Editors (ICMJE).

Citation Johannesen CK, Rezahosseini O, Gybel-Brask M, Kristensen JH, Hasselbalch RB, Pries-Heje MM, Nielsen PB, Knudsen AD, Fogh K, Norsk JB, Andersen O, Jensen CAJ, Torp-Pedersen C, Rungby J, Ditlev SB, Hageman I, Møgelvang R, Dessau RB, Sørensen E, Harritshøj LH, Folke F, Sten C, Møller MEE, Engsig FN, Ullum H, Jørgensen CS, Ostrowski SR, Bundgaard H, Iversen KK, Fischer TK, Nielsen SD. 2021. Risk factors for being seronegative following SARS-CoV-2 infection in a large cohort of health care workers in Denmark. Microbiol Spectr 9:e00904-21. https://doi.org/10.1128/Spectrum.00904-21.

Author information

Omid Rezahosseini https://orcid.org/0000-0003-2198-1904

Mikkel Gybel-Brask https://orcid.org/0000-0002-5716-5899

Kamille Fogh https://orcid.org/0000-0002-6669-6894

Ram B. Dessau https://orcid.org/0000-0002-1497-6309

Lene Holm Harritshøj https://orcid.org/0000-0003-3100-6256

Susanne Dam Nielsen https://orcid.org/0000-0001-6391-7455

Article

Publisher ID: 00904-21 Publisher ID: spectrum.00904-21

DOI: 10.1128/Spectrum.00904-21

PMC ID: 8528102

PubMed ID: 34668738

SO-VID: 1b433d7b-147e-44aa-9a6f-8cbc4352ad57

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

History

Date received : 15 July 2021

Date accepted : 16 September 2021

Page count

supplementary-material: 1, Figures: 1, Tables: 2, Equations: 0, References: 18, Pages: 7, Words: 4393

Funding

Funded by: Lundbeckfonden (Lundbeck Foundation), FundRef https://doi.org/10.13039/501100003554;

Award ID: R349-2020-731

Award Recipient : Kasper K. Iversen

Funded by: Novo Nordisk Fonden (NNF), FundRef https://doi.org/10.13039/501100009708;

Award Recipient : Susanne Dam Nielsen

Funded by: Rigshospitalet, FundRef https://doi.org/10.13039/501100005111;

Award Recipient : Omid Rezahosseini

Custom metadata

cover-date September/October 2021

Keywords: asymptomatic infections,body mass index,health care workers,risk factor,sars-cov-2,seroconversion

Data availability:

Keywords: asymptomatic infections, body mass index, health care workers, risk factor, sars-cov-2, seroconversion

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark

Read this article at

ABSTRACT

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 17

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

Humoral Immune Response to SARS-CoV-2 in Iceland

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

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 195

Cited by 7

Most referenced authors 541