Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 21;27(1):255.
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  1 , Vera Balz  1 , Danny Jazmati  2 , Edwin Bölke  3 , Noemi F Freise  4 , Verena Keitel  4 , Torsten Feldt  4 , Björn-Erik Ole Jensen  4 , Johannes Bode  4 , Tom Lüdde  5 , Dieter Häussinger  4 , Ortwin Adams  5 , E Marion Schneider  6 , Jürgen Enczmann  1 , Jutta M Rox  1 , Derik Hermsen  7 , Karin Schulze-Bosse  7 , Detlef Kindgen-Milles  8 , Wolfram Trudo Knoefel  9 , Martijn van Griensven  10 , Jan Haussmann  2 , Balint Tamaskovics  2 , Christian Plettenberg  11 , Kathrin Scheckenbach  11 , Stefanie Corradini  12 , Alessia Pedoto  13 , Kitti Maas  2 , Livia Schmidt  2 , Olaf Grebe  14 , Irene Esposito  15 , Anja Ehrhardt  16 , Matthias Peiper  17 , Bettina Alexandra Buhren  2 , Christian Calles  18 , Andreas Stöhr  18 , Peter Arne Gerber  2 , Artur Lichtenberg  19 , Hubert Schelzig  20 , Yechan Flaig  2 , Amir Rezazadeh  2 , Wilfried Budach  2 , Christiane Matuschek  2
Affiliations

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

Johannes C Fischer et al. Eur J Med Res. .

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: CCR5; COVID-19; Chemokine receptor; Clinical course of the disease; HLA haplotypes; Neutralizing antibodies; Persistence; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Univariate association of HLA haplotypes with mild/moderate disease (relative risk, OR, log rank (LR)) in females (A) and males (B) and for disease duration (hazard ratio, (Cox)) in females (C) and males (D). Haplotype frequency within the group is plotted on the x-axis and the y-axis shows the significance levels of the OR for moderate disease / HR for disease duration. The size of the spheres indicates the effect size and was calculated as absolute value of the logarithms of OR/HR. Full spheres represent a favorable association with OR or HR, and empty spheres represent an association with a higher RR or HR. The 0.05 significance level is shown as parallel to the x-axis. Alleles/haplotypes which were either significant in females or males for OR (panel A and B) are denoted in both panels. Same applies for HR (panel C and D). *Note that the sphere for the HLA-Class II haplotype DRB_DQA_DQB_15 in panel A is not on scale, since all females homozygous for this haplotype had had a mild course of disease (n = 8)
Fig. 2
Fig. 2
Multivariate association of age, gender, and HLA haplotypes as risk factors for disease severity (WHO° I & IIa (mild) vs WHO° IIb & III). A shows results for the whole group, B for females, C for males.*Note that for the HLA-Class II haplotype DRB_DQA_DQB_15 in panel B whisker is not on scale, since all females homozygous for this haplotype had had a mild course of disease (n = 8)
Fig. 3
Fig. 3
Multivariate association of age, gender, and HLA haplotypes as risk factors for disease duration (longer disease (HR < 1) vs. shorter disease duration (HR > 1). A shows results for the whole group, B for females, C for males
Fig. 4
Fig. 4
Kaplan–Meier estimates for the impact of disease specific favorable or unfavorable HLA haplotypes on duration of the disease when coded for significant alleles in females (A&C) or males (B&D)
Fig. 5
Fig. 5
Kaplan–Meier estimates for the impact of CCR5 wt and CCR5Δ32 on disease duration in females (A) and males (B)
See this image and copyright information in PMC

References

    1. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99–111. doi: 10.1016/s0140-6736(20)32661-1. - DOI - PMC - PubMed
    1. Yarmarkovich M, Warrington JM, Farrel A, Maris JM. Identification of SARS-CoV-2 vaccine epitopes predicted to induce long-term population-scale immunity. Cell Rep Med. 2020;1(3):100036. doi: 10.1016/j.xcrm.2020.100036. - DOI - PMC - PubMed
    1. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020 doi: 10.1056/NEJMoa2035389. - DOI - PMC - PubMed
    1. Bhatnager R, Bhasin M, Arora J, Dang AS. Epitope based peptide vaccine against SARS-COV2: an immune-informatics approach. J Biomol Struct Dyn. 2020 doi: 10.1080/07391102.2020.1787227. - DOI - PubMed
    1. BionTech Pa. Vaccines and Related Biological Products Advisory Committee Meeting. FDA Briefing Document Pfizer-BioNTech COVID-19 Vaccine 2020.