Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection

Johannes C Fischer; Vera Balz; Danny Jazmati; Edwin Bölke; Noemi F Freise; Verena Keitel; Torsten Feldt; Björn-Erik Ole Jensen; Johannes Bode; Tom Lüdde; Dieter Häussinger; Ortwin Adams; E Marion Schneider; Jürgen Enczmann; Jutta M Rox; Derik Hermsen; Karin Schulze-Bosse; Detlef Kindgen-Milles; Wolfram Trudo Knoefel; Martijn van Griensven; Jan Haussmann; Balint Tamaskovics; Christian Plettenberg; Kathrin Scheckenbach; Stefanie Corradini; Alessia Pedoto; Kitti Maas; Livia Schmidt; Olaf Grebe; Irene Esposito; Anja Ehrhardt; Matthias Peiper; Bettina Alexandra Buhren; Christian Calles; Andreas Stöhr; Peter Arne Gerber; Artur Lichtenberg; Hubert Schelzig; Yechan Flaig; Amir Rezazadeh; Wilfried Budach; Christiane Matuschek

doi:10.1186/s40001-022-00864-z

Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection

Johannes C Fischer, Vera Balz, Danny Jazmati, Edwin Bölke^*, Noemi F Freise, Verena Keitel, Torsten Feldt, Björn-Erik Ole Jensen, Johannes Bode, Tom Lüdde, Dieter Häussinger, Ortwin Adams, E Marion Schneider, Jürgen Enczmann, Jutta M Rox, Derik Hermsen, Karin Schulze-Bosse, Detlef Kindgen-Milles, Wolfram Trudo Knoefel, Martijn van GriensvenJan Haussmann, Balint Tamaskovics, Christian Plettenberg, Kathrin Scheckenbach, Stefanie Corradini, Alessia Pedoto, Kitti Maas, Livia Schmidt, Olaf Grebe, Irene Esposito, Anja Ehrhardt, Matthias Peiper, Bettina Alexandra Buhren, Christian Calles, Andreas Stöhr, Peter Arne Gerber, Artur Lichtenberg, Hubert Schelzig, Yechan Flaig, Amir Rezazadeh, Wilfried Budach, Christiane Matuschek

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent.

METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease.

RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males.

CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

Original language	English
Article number	255
Number of pages	12
Journal	European Journal of Medical Research
Volume	27
Issue number	1
DOIs	https://doi.org/10.1186/s40001-022-00864-z
Publication status	Published - 21 Nov 2022

Keywords

Humans
Male
Female
COVID-19/genetics
HLA-DQ Antigens/genetics
Prognosis
RNA, Viral
SARS-CoV-2
HLA-DRB1 Chains

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Cite this

Fischer, J. C., Balz, V., Jazmati, D., Bölke, E., Freise, N. F., Keitel, V., Feldt, T., Jensen, B.-E. O., Bode, J., Lüdde, T., Häussinger, D., Adams, O., Schneider, E. M., Enczmann, J., Rox, J. M., Hermsen, D., Schulze-Bosse, K., Kindgen-Milles, D., Knoefel, W. T., ... Matuschek, C. (2022). Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection. European Journal of Medical Research, 27(1), Article 255. https://doi.org/10.1186/s40001-022-00864-z

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title = "Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection",

abstract = "BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent.METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease.RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males.CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.",

keywords = "Humans, Male, Female, COVID-19/genetics, HLA-DQ Antigens/genetics, Prognosis, RNA, Viral, SARS-CoV-2, HLA-DRB1 Chains",

author = "Fischer, {Johannes C} and Vera Balz and Danny Jazmati and Edwin B{\"o}lke and Freise, {Noemi F} and Verena Keitel and Torsten Feldt and Jensen, {Bj{\"o}rn-Erik Ole} and Johannes Bode and Tom L{\"u}dde and Dieter H{\"a}ussinger and Ortwin Adams and Schneider, {E Marion} and J{\"u}rgen Enczmann and Rox, {Jutta M} and Derik Hermsen and Karin Schulze-Bosse and Detlef Kindgen-Milles and Knoefel, {Wolfram Trudo} and {van Griensven}, Martijn and Jan Haussmann and Balint Tamaskovics and Christian Plettenberg and Kathrin Scheckenbach and Stefanie Corradini and Alessia Pedoto and Kitti Maas and Livia Schmidt and Olaf Grebe and Irene Esposito and Anja Ehrhardt and Matthias Peiper and Buhren, {Bettina Alexandra} and Christian Calles and Andreas St{\"o}hr and Gerber, {Peter Arne} and Artur Lichtenberg and Hubert Schelzig and Yechan Flaig and Amir Rezazadeh and Wilfried Budach and Christiane Matuschek",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = nov,

day = "21",

doi = "10.1186/s40001-022-00864-z",

language = "English",

volume = "27",

journal = "European Journal of Medical Research",

issn = "0949-2321",

publisher = "BioMed Central",

number = "1",

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Fischer, JC, Balz, V, Jazmati, D, Bölke, E, Freise, NF, Keitel, V, Feldt, T, Jensen, B-EO, Bode, J, Lüdde, T, Häussinger, D, Adams, O, Schneider, EM, Enczmann, J, Rox, JM, Hermsen, D, Schulze-Bosse, K, Kindgen-Milles, D, Knoefel, WT, van Griensven, M, Haussmann, J, Tamaskovics, B, Plettenberg, C, Scheckenbach, K, Corradini, S, Pedoto, A, Maas, K, Schmidt, L, Grebe, O, Esposito, I, Ehrhardt, A, Peiper, M, Buhren, BA, Calles, C, Stöhr, A, Gerber, PA, Lichtenberg, A, Schelzig, H, Flaig, Y, Rezazadeh, A, Budach, W & Matuschek, C 2022, 'Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection', European Journal of Medical Research, vol. 27, no. 1, 255. https://doi.org/10.1186/s40001-022-00864-z

TY - JOUR

T1 - Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection

AU - Fischer, Johannes C

AU - Balz, Vera

AU - Jazmati, Danny

AU - Bölke, Edwin

AU - Freise, Noemi F

AU - Keitel, Verena

AU - Feldt, Torsten

AU - Jensen, Björn-Erik Ole

AU - Bode, Johannes

AU - Lüdde, Tom

AU - Häussinger, Dieter

AU - Adams, Ortwin

AU - Schneider, E Marion

AU - Enczmann, Jürgen

AU - Rox, Jutta M

AU - Hermsen, Derik

AU - Schulze-Bosse, Karin

AU - Kindgen-Milles, Detlef

AU - Knoefel, Wolfram Trudo

AU - van Griensven, Martijn

AU - Haussmann, Jan

AU - Tamaskovics, Balint

AU - Plettenberg, Christian

AU - Scheckenbach, Kathrin

AU - Corradini, Stefanie

AU - Pedoto, Alessia

AU - Maas, Kitti

AU - Schmidt, Livia

AU - Grebe, Olaf

AU - Esposito, Irene

AU - Ehrhardt, Anja

AU - Peiper, Matthias

AU - Buhren, Bettina Alexandra

AU - Calles, Christian

AU - Stöhr, Andreas

AU - Gerber, Peter Arne

AU - Lichtenberg, Artur

AU - Schelzig, Hubert

AU - Flaig, Yechan

AU - Rezazadeh, Amir

AU - Budach, Wilfried

AU - Matuschek, Christiane

PY - 2022/11/21

Y1 - 2022/11/21

N2 - BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent.METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease.RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males.CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

AB - BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent.METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease.RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males.CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

KW - Humans

KW - Male

KW - Female

KW - COVID-19/genetics

KW - HLA-DQ Antigens/genetics

KW - Prognosis

KW - RNA, Viral

KW - SARS-CoV-2

KW - HLA-DRB1 Chains

U2 - 10.1186/s40001-022-00864-z

DO - 10.1186/s40001-022-00864-z

M3 - Article

C2 - 36411478

SN - 0949-2321

VL - 27

JO - European Journal of Medical Research

JF - European Journal of Medical Research

IS - 1

M1 - 255

ER -