Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses
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Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses. / Schlickeiser, Stephan; Schwarz, Tatjana; Steiner, Sophie; Wittke, Kirsten; Al Besher, Nabeel; Meyer, Oliver; Kalus, Ulrich; Pruß, Axel; Kurth, Florian; Zoller, Thomas; Witzenrath, Martin; Sander, Leif Erik; Müller, Marcel A; Scheibenbogen, Carmen; Volk, Hans-Dieter; Drosten, Christian; Corman, Victor M; Hanitsch, Leif G.
In: FRONT IMMUNOL, Vol. 11, 2021, p. 628971.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses
AU - Schlickeiser, Stephan
AU - Schwarz, Tatjana
AU - Steiner, Sophie
AU - Wittke, Kirsten
AU - Al Besher, Nabeel
AU - Meyer, Oliver
AU - Kalus, Ulrich
AU - Pruß, Axel
AU - Kurth, Florian
AU - Zoller, Thomas
AU - Witzenrath, Martin
AU - Sander, Leif Erik
AU - Müller, Marcel A
AU - Scheibenbogen, Carmen
AU - Volk, Hans-Dieter
AU - Drosten, Christian
AU - Corman, Victor M
AU - Hanitsch, Leif G
N1 - Copyright © 2021 Schlickeiser, Schwarz, Steiner, Wittke, Al Besher, Meyer, Kalus, Pruß, Kurth, Zoller, Witzenrath, Sander, Müller, Scheibenbogen, Volk, Drosten, Corman and Hanitsch.
PY - 2021
Y1 - 2021
N2 - Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and -IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 ≥ 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 ≥ 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79-0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 ≥ 1:320).
AB - Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and -IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 ≥ 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 ≥ 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79-0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 ≥ 1:320).
KW - Adolescent
KW - Adult
KW - Age Factors
KW - Aged
KW - Antibodies, Neutralizing/immunology
KW - Antibodies, Viral/immunology
KW - Blood Donors
KW - COVID-19/immunology
KW - Convalescence
KW - Female
KW - Fever
KW - Humans
KW - Immunization, Passive
KW - Male
KW - Middle Aged
KW - SARS-CoV-2/immunology
KW - Severity of Illness Index
KW - Sex Factors
KW - Young Adult
U2 - 10.3389/fimmu.2020.628971
DO - 10.3389/fimmu.2020.628971
M3 - SCORING: Journal article
C2 - 33584731
VL - 11
SP - 628971
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -