TY - JOUR
T1 - High Titers of Low Affinity Antibodies in COVID-19 Patients Are Associated With Disease Severity
AU - Hendriks, Jan
AU - Schasfoort, Richard
AU - Koerselman, Michelle
AU - Dannenberg, Maureen
AU - Cornet, Alexander Daniel
AU - Beishuizen, Albertus
AU - van der Palen, Job
AU - Krabbe, Johannes
AU - Mulder, Alide H.L.
AU - Karperien, Marcel
N1 - Funding Information:
Nederlandse Organisatie voor Wetenschappelijk Onderzoek and ReumaNederland’s unrestricted research grant LL25 and TTW for the William Hunter perspective program. Both funding sources contributed equally to this work.
Funding Information:
We would like to thank ReumaNederland for the unrestricted research grant LL25 and TTW for the William Hunter perspective program.
Publisher Copyright:
Copyright © 2022 Hendriks, Schasfoort, Koerselman, Dannenberg, Cornet, Beishuizen, van der Palen, Krabbe, Mulder and Karperien.
Financial transaction number:
2500002412, 2500002413, 2500026019
PY - 2022/4/13
Y1 - 2022/4/13
N2 - Background: Almost 2 years from the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there is still a lot unknown how the humoral response affects disease progression. In this study, we investigated humoral antibody responses against specific SARS-CoV2 proteins, their strength of binding, and their relationship with COVID severity and clinical information. Furthermore, we studied the interactions of the specific receptor-binding domain (RBD) in more depth by characterizing specific antibody response to a peptide library. Materials and Methods: We measured specific antibodies of isotypes IgM, IgG, and IgA, as well as their binding strength against the SARS-CoV2 antigens RBD, NCP, S1, and S1S2 in sera of 76 COVID-19 patients using surface plasmon resonance imaging. In addition, these samples were analyzed using a peptide epitope mapping assay, which consists of a library of peptides originating from the RBD. Results: A positive association was observed between disease severity and IgG antibody titers against all SARS-CoV2 proteins and additionally for IgM and IgA antibodies directed against RBD. Interestingly, in contrast to the titer of antibodies, the binding strength went down with increasing disease severity. Within the critically ill patient group, a positive association with pulmonary embolism, d-dimer, and antibody titers was observed. Conclusion: In critically ill patients, antibody production is high, but affinity is low, and maturation is impaired. This may play a role in disease exacerbation and could be valuable as a prognostic marker for predicting severity.
AB - Background: Almost 2 years from the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there is still a lot unknown how the humoral response affects disease progression. In this study, we investigated humoral antibody responses against specific SARS-CoV2 proteins, their strength of binding, and their relationship with COVID severity and clinical information. Furthermore, we studied the interactions of the specific receptor-binding domain (RBD) in more depth by characterizing specific antibody response to a peptide library. Materials and Methods: We measured specific antibodies of isotypes IgM, IgG, and IgA, as well as their binding strength against the SARS-CoV2 antigens RBD, NCP, S1, and S1S2 in sera of 76 COVID-19 patients using surface plasmon resonance imaging. In addition, these samples were analyzed using a peptide epitope mapping assay, which consists of a library of peptides originating from the RBD. Results: A positive association was observed between disease severity and IgG antibody titers against all SARS-CoV2 proteins and additionally for IgM and IgA antibodies directed against RBD. Interestingly, in contrast to the titer of antibodies, the binding strength went down with increasing disease severity. Within the critically ill patient group, a positive association with pulmonary embolism, d-dimer, and antibody titers was observed. Conclusion: In critically ill patients, antibody production is high, but affinity is low, and maturation is impaired. This may play a role in disease exacerbation and could be valuable as a prognostic marker for predicting severity.
KW - antibodies
KW - COVID-19
KW - immunoassay
KW - infectious diseases
KW - SPRi (surface plasmon resonance imagery)
KW - viral infection
UR - http://www.scopus.com/inward/record.url?scp=85128838124&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.867716
DO - 10.3389/fimmu.2022.867716
M3 - Article
AN - SCOPUS:85128838124
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 867716
ER -