Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4 + T-Cell Responses.
(2021) In Frontiers in Immunology 12. p.1-12- Abstract
BACKGROUND: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.
METHOD: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive... (More)
BACKGROUND: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.
METHOD: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4 + T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.
FINDINGS: Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4 + T-cell reactivity to S1 or SMN. Pre-existing CD4 + T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.
CONCLUSIONS: HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4 + T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
(Less)
- author
- Marklund, Emelie ; Leach, Susannah ; Nyström, Kristina ; Lundgren, Anna ; Liljeqvist, Jan-Åke ; Nilsson, Staffan ; Yilmaz, Aylin ; Andersson, Lars-Magnus ; Bemark, Mats LU and Gisslén, Magnus
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- keywords
- Adult, Aged, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, CD4-Positive T-Lymphocytes/immunology, COVID-19/immunology, Female, Follow-Up Studies, Health Personnel, Humans, Immunity/immunology, Immunoglobulin G/immunology, Male, Middle Aged, Pandemics/prevention & control, SARS-CoV-2/immunology, Seroepidemiologic Studies, Sweden, Young Adult
- in
- Frontiers in Immunology
- volume
- 12
- article number
- 750448
- pages
- 1 - 12
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85119335202
- pmid:34795668
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2021.750448
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2021 Marklund, Leach, Nyström, Lundgren, Liljeqvist, Nilsson, Yilmaz, Andersson, Bemark and Gisslén.
- id
- 1b988635-20dc-449c-96c7-08bb6852413b
- date added to LUP
- 2023-11-16 12:41:28
- date last changed
- 2024-04-14 17:00:01
@article{1b988635-20dc-449c-96c7-08bb6852413b, abstract = {{<p>BACKGROUND: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.</p><p>METHOD: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4 + T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools. </p><p>FINDINGS: Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4 + T-cell reactivity to S1 or SMN. Pre-existing CD4 + T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not. </p><p>CONCLUSIONS: HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4 + T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals. </p>}}, author = {{Marklund, Emelie and Leach, Susannah and Nyström, Kristina and Lundgren, Anna and Liljeqvist, Jan-Åke and Nilsson, Staffan and Yilmaz, Aylin and Andersson, Lars-Magnus and Bemark, Mats and Gisslén, Magnus}}, issn = {{1664-3224}}, keywords = {{Adult; Aged; Antibodies, Neutralizing/immunology; Antibodies, Viral/immunology; CD4-Positive T-Lymphocytes/immunology; COVID-19/immunology; Female; Follow-Up Studies; Health Personnel; Humans; Immunity/immunology; Immunoglobulin G/immunology; Male; Middle Aged; Pandemics/prevention & control; SARS-CoV-2/immunology; Seroepidemiologic Studies; Sweden; Young Adult}}, language = {{eng}}, pages = {{1--12}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4 + T-Cell Responses.}}, url = {{http://dx.doi.org/10.3389/fimmu.2021.750448}}, doi = {{10.3389/fimmu.2021.750448}}, volume = {{12}}, year = {{2021}}, }