HLA-DRB1* Alleles and Long COVID: A Mediation Analysis of Anti-RBD IgG, CRP, and Anti-β2GPI IgG
-
Ensiye Torki
,
Nahid Eskandari
,
Kiana Sami
,
Arezou Gharezadeh
,
Mark J. M. Sullman
,
Shakiba Soltani Shiraz
,
Hamed Fouladseresht
Abstract
Long COVID syndrome (LCS) is characterized by persistent multi-system manifestations with an unclear underlying pathophysiology. Identifying the genetic and immunological factors associated with LCS is essential for improved risk stratification and clinical management. This study investigated whether incorporating HLA-DRB1* and HLA-DQB1* genotyping data could enhance the predictive value of laboratory parameters for identifying individuals at higher risk of developing LCS.
Demographic characteristics and relevant clinical history data were extracted from the medical records of 88 individuals diagnosed with LCS (LCS+) and 96 individuals without LCS (LCS−). Serum levels of anti-receptor binding domain IgG (anti-RBD IgG), anti-β2-glycoprotein I IgG (anti-β2GPI IgG), and C-reactive protein (CRP) were measured. Low-resolution genotyping was performed to identify HLA-DRB1* and HLA-DQB1* alleles. Logistic regression analysis was employed to examine the associations between HLA alleles and LCS status. Subsequently, mediation analysis was conducted to explore the potential mechanistic roles of anti-RBD IgG, CRP, and anti-β2GPI IgG in these observed relationships.
The LCS+ group exhibited a significantly higher frequency of the HLA-DRB1*01 allele and a lower frequency of the HLA-DRB1*11 than the LCS− cohort. Serum levels of both CRP and anti-β2GPI IgG were substantially higher in the LCS+ cohort, whereas anti-RBD IgG levels were significantly lower. After adjusting for key variables, HLA-DRB1*01 and HLA-DRB1*11 remained significantly associated with LCS. Mediation analysis suggested that these HLA associations might be partially mediated by CRP, anti-RBD IgG, and anti-β2GPI IgG levels.
Our findings indicate that the combination of HLA-DRB1*01 and HLA-DRB1*11 allele screening with serological profiling (anti-RBD IgG, CRP, and anti-β2GPI IgG) may contribute to refining predictive models of LCS susceptibility, though clinical utility requires validation in larger, independent cohorts.
Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e7.
2. Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026.
3. Torki E, Hoseininasab F, Moradi M, Sami R, Sullman MJM, Fouladseresht H. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case-control study. Clin Exp Med. 2024;24(1):1.
4. Torki E, Gharezade A, Doroudchi M, Sheikhi S, Mansury D, Sullman MJM, Fouladseresht H. The kinetics of inhibitory immune checkpoints during and post-COVID-19: the knowns and unknowns. Clin Exp Med. 2023;23(7):3299-319.
5. Chen B, Julg B, Mohandas S, Bradfute SB. Viral persistence, reactivation, and mechanisms of long COVID. Elife. 2023;12.
6. Augusto DG, Hollenbach JA. HLA variation and antigen presentation in COVID-19 and SARS-CoV-2 infection. Curr Opin Immunol. 2022;76:102178.
7. Troshina E, Yukina M, Nuralieva N, Vasilyev E, Rebrova O, Akhmatova R, et al. Association of Alleles of Human Leukocyte Antigen Class II Genes and Severity of COVID-19 in Patients of the 'Red Zone' of the Endocrinology Research Center, Moscow, Russia. Diseases. 2022;10(4).
8. Langton DJ, Bourke SC, Lie BA, Reiff G, Natu S, Darlay R, et al. The influence of HLA genotype on the severity of COVID-19 infection. HLA. 2021;98(1):14-22.
9. Naemi FMA, Al-Adwani S, Al-Khatabi H, Al-Nazawi A. Association between the HLA genotype and the severity of COVID-19 infection among South Asians. J Med Virol. 2021;93(7):4430-7.
10. Novelli A, Andreani M, Biancolella M, Liberatoscioli L, Passarelli C, Colona VL, et al. HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients. HLA. 2020;96(5):610-4.
11. Lorente L, Martín MM, Franco A, Barrios Y, Cáceres JJ, Solé-Violán J, et al. HLA genetic polymorphisms and prognosis of patients with COVID-19. Med Intensiva (Engl Ed). 2021;45(2):96-103.
12. Fischer JC, Schmidt AG, Bölke E, Uhrberg M, Keitel V, Feldt T, et al. Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19. Eur J Med Res. 2021;26(1):107.
13. Pang NY, Pang AS, Chow VT, Wang DY. Understanding neutralising antibodies against SARS-CoV-2 and their implications in clinical practice. Mil Med Res. 2021;8(1):47.
14. Carrillo J, Izquierdo-Useros N, Ávila-Nieto C, Pradenas E, Clotet B, Blanco J. Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Biochem Biophys Res Commun. 2021;538:187-91.
15. Lier J, Stoll K, Obrig H, Baum P, Deterding L, Bernsdorff N, et al. Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients. Front Neurol. 2022;13:988359.
16. Zhan Y, Zhu Y, Wang S, Jia S, Gao Y, Lu Y, et al. SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection. Signal Transduct Target Ther. 2021;6(1):368.
17. Malik P, Patel U, Mehta D, Patel N, Kelkar R, Akrmah M, et al. Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis. BMJ Evid Based Med. 2021;26(3):107-8.
18. Bivona G, Agnello L, Ciaccio M. Biomarkers for Prognosis and Treatment Response in COVID-19 Patients. Ann Lab Med. 2021;41(6):540-8.
19. Gameil MA, Marzouk RE, Elsebaie AH, Rozaik SE. Long-term clinical and biochemical residue after COVID-19 recovery. Egypt Liver J. 2021;11(1):74.
20. Durstenfeld MS, Peluso MJ, Kelly JD, Win S, Swaminathan S, Li D, et al. Role of antibodies, inflammatory markers, and echocardiographic findings in postacute cardiopulmonary symptoms after SARS-CoV-2 infection. JCI Insight. 2022;7(10).
21. Liao B, Liu Z, Tang L, Li L, Gan Q, Shi H, et al. Longitudinal clinical and radiographic evaluation reveals interleukin-6 as an indicator of persistent pulmonary injury in COVID-19. Int J Med Sci. 2021;18(1):29-41.
22. Wieczfinska J, Kleniewska P, Pawliczak R. Oxidative Stress-Related Mechanisms in SARS-CoV-2 Infections. Oxid Med Cell Longev. 2022;2022:5589089.
23. Passam FH, Giannakopoulos B, Mirarabshahi P, Krilis SA. Molecular pathophysiology of the antiphospholipid syndrome: the role of oxidative post-translational modification of beta 2 glycoprotein I. J Thromb Haemost. 2011;9 Suppl 1:275-82.
24. Nocella C, Bartimoccia S, Cammisotto V, D'Amico A, Pastori D, Frati G, et al. Oxidative Stress in the Pathogenesis of Antiphospholipid Syndrome: Implications for the Atherothrombotic Process. Antioxidants (Basel). 2021;10(11).
25. McDonnell T, Wincup C, Buchholz I, Pericleous C, Giles I, Ripoll V, et al. The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS. Blood Rev. 2020;39:100610.
26. Del Papa N, Sheng YH, Raschi E, Kandiah DA, Tincani A, Khamashta MA, et al. Human beta 2-glycoprotein I binds to endothelial cells through a cluster of lysine residues that are critical for anionic phospholipid binding and offers epitopes for anti-beta 2-glycoprotein I antibodies. J Immunol. 1998;160(11):5572-8.
27. Rahgozar S. Revisiting beta 2 glycoprotein I, the major autoantigen in the antiphospholipid syndrome. Iran J Immunol. 2012;9(2):73-85.
28. on K, Jamil R, Chowdhury A, Mukherjee M, Venegas C, Miyasaki K, et al. Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms. Eur Respir J. 2023;61(1).
29. Wallukat G, Hohberger B, Wenzel K, Fürst J, Schulze-Rothe S, Wallukat A, et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms. Journal of Translational Autoimmunity. 2021;4:100100.
30. Chen H-J, Appelman B, Willemen H, Bos A, Prado J, Geyer CE, et al. Transfer of IgG from Long COVID patients induces symptomology in mice. BioRxiv. 2024:2024.05. 30.596590.
31. Santos Guedes de Sa K, Silva J, Bayarri-Olmos R, Brinda R, Alec Rath Constable R, Colom Diaz PA, et al. A causal link between autoantibodies and neurological symptoms in long COVID. medRxiv. 2024.
32. O'Mahoney LL, Routen A, Gillies C, Ekezie W, Welford A, Zhang A, et al. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis. EClinicalMedicine. 2023;55:101762.
33. Casanova JL, Abel L. The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity? Hum Genet. 2020;139(6-7):681-94.
34. Su Y, Yuan D, Chen DG, Ng RH, Wang K, Choi J, et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185(5):881-95.e20.
35. Fouladseresht H, Safa A, Khosropanah S, Doroudchi M. Increased frequency of HLA-A*02 in patients with atherosclerosis is associated with VZV seropositivity. Arch Physiol Biochem. 2021;127(4):351-8.
36. Khan T, Rahman M, Ahmed I, Al Ali F, Jithesh PV, Marr N. Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens. Front Immunol. 2022;13:856497.
37. Yao Y, Yang H, Shi L, Liu S, Li C, Chen J, et al. HLA Class II Genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 Are Associated With the Antibody Response to Inactivated Japanese Encephalitis Vaccine. Front Immunol. 2019;10:428.
38. Detsika MG, Giatra C, Kitsiou V, Jahaj E, Athanassiades T, Kouniaki D, et al. Demographic, Clinical and Immunogenetic Profiles of a Greek Cohort of COVID-19 Patients. Life (Basel). 2021;11(10).
39. Farahani RH, Esmaeilzadeh E, Asl AN, Heidari MF, Hazrati E. Frequency of HLA Alleles in a Group of Severe COVID-19 Iranian Patients. Iran J Public Health. 2021;50(9):1882-6.
40. Ouedraogo AR, Traoré L, Ouattara AK, Ouedraogo AR, Zongo SV, Savadogo M, et al. Association of HLA-DRB1*11 and HLA-DRB1*12 gene polymorphism with COVID-19 in Burkina Faso. BMC Med Genomics. 2023;16(1):246.
41. Ebrahimi S, Ghasemi-Basir HR, Majzoobi MM, Rasouli-Saravani A, Hajilooi M, Solgi G. HLA-DRB1*04 may predict the severity of disease in a group of Iranian COVID-19 patients. Hum Immunol. 2021;82(10):719-25.
42. Wolday D, Fung CYJ, Morgan G, Casalino S, Frangione E, Taher J, Lerner-Ellis JP. HLA Variation and SARS-CoV-2 Specific Antibody Response. Viruses. 2023;15(4).
43. Crocchiolo R, Gallina AM, Pani A, Campisi D, Cento V, Sacchi N, et al. Polymorphism of the HLA system and weak antibody response to BNT162b2 mRNA vaccine. Hla. 2022;99(3):183-91.
44. Weidner L, Kalser J, Kreil TR, Jungbauer C, Mayr WR. Neutralizing Antibodies against SARS-CoV-2 and HLA Class I and II Polymorphism. Transfus Med Hemother. 2021;48(3):173-4.
45. Astbury S, Reynolds CJ, Butler DK, Muñoz-Sandoval DC, Lin KM, Pieper FP, et al. HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19. Immunology. 2022;166(1):68-77.
46. Molnar T, Varnai R, Schranz D, Zavori L, Peterfi Z, Sipos D, et al. Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms. J Clin Med. 2021;10(19).
47. García-Abellán J, Padilla S, Fernández-González M, García JA, Agulló V, Andreo M, et al. Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study. J Clin Immunol. 2021;41(7):1490-501.
48. Fouladseresht H, Ghamar Talepoor A, Farjadian S, Khosropanah S, Doroudchi M. Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis. Iran J Allergy Asthma Immunol. 2019;18(5):543-53.
49. Harrison M. Erythrocyte sedimentation rate and C-reactive protein. Aust Prescr. 2015;38(3):93-4.
50. Eggleton P, Haigh R, Winyard PG. Consequence of neo-antigenicity of the 'altered self'. Rheumatology (Oxford). 2008;47(5):567-71.
51. López-Pedrera C, Barbarroja N, Jimenez-Gomez Y, Collantes-Estevez E, Aguirre MA, Cuadrado MJ. Oxidative stress in the pathogenesis of atherothrombosis associated with anti-phospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches. Rheumatology (Oxford). 2016;55(12):2096-108.
52. Acosta-Ampudia Y, Monsalve DM, Rojas M, Rodríguez Y, Zapata E, Ramírez-Santana C, Anaya JM. Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome. J Infect Dis. 2022;225(12):2155-62.
53. Torki E, Hoseininasab F, Moradi M, Sami R, Sullman MJM, Fouladseresht H. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study. Clin Exp Med. 2024;24.
2. Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026.
3. Torki E, Hoseininasab F, Moradi M, Sami R, Sullman MJM, Fouladseresht H. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case-control study. Clin Exp Med. 2024;24(1):1.
4. Torki E, Gharezade A, Doroudchi M, Sheikhi S, Mansury D, Sullman MJM, Fouladseresht H. The kinetics of inhibitory immune checkpoints during and post-COVID-19: the knowns and unknowns. Clin Exp Med. 2023;23(7):3299-319.
5. Chen B, Julg B, Mohandas S, Bradfute SB. Viral persistence, reactivation, and mechanisms of long COVID. Elife. 2023;12.
6. Augusto DG, Hollenbach JA. HLA variation and antigen presentation in COVID-19 and SARS-CoV-2 infection. Curr Opin Immunol. 2022;76:102178.
7. Troshina E, Yukina M, Nuralieva N, Vasilyev E, Rebrova O, Akhmatova R, et al. Association of Alleles of Human Leukocyte Antigen Class II Genes and Severity of COVID-19 in Patients of the 'Red Zone' of the Endocrinology Research Center, Moscow, Russia. Diseases. 2022;10(4).
8. Langton DJ, Bourke SC, Lie BA, Reiff G, Natu S, Darlay R, et al. The influence of HLA genotype on the severity of COVID-19 infection. HLA. 2021;98(1):14-22.
9. Naemi FMA, Al-Adwani S, Al-Khatabi H, Al-Nazawi A. Association between the HLA genotype and the severity of COVID-19 infection among South Asians. J Med Virol. 2021;93(7):4430-7.
10. Novelli A, Andreani M, Biancolella M, Liberatoscioli L, Passarelli C, Colona VL, et al. HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients. HLA. 2020;96(5):610-4.
11. Lorente L, Martín MM, Franco A, Barrios Y, Cáceres JJ, Solé-Violán J, et al. HLA genetic polymorphisms and prognosis of patients with COVID-19. Med Intensiva (Engl Ed). 2021;45(2):96-103.
12. Fischer JC, Schmidt AG, Bölke E, Uhrberg M, Keitel V, Feldt T, et al. Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19. Eur J Med Res. 2021;26(1):107.
13. Pang NY, Pang AS, Chow VT, Wang DY. Understanding neutralising antibodies against SARS-CoV-2 and their implications in clinical practice. Mil Med Res. 2021;8(1):47.
14. Carrillo J, Izquierdo-Useros N, Ávila-Nieto C, Pradenas E, Clotet B, Blanco J. Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Biochem Biophys Res Commun. 2021;538:187-91.
15. Lier J, Stoll K, Obrig H, Baum P, Deterding L, Bernsdorff N, et al. Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients. Front Neurol. 2022;13:988359.
16. Zhan Y, Zhu Y, Wang S, Jia S, Gao Y, Lu Y, et al. SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection. Signal Transduct Target Ther. 2021;6(1):368.
17. Malik P, Patel U, Mehta D, Patel N, Kelkar R, Akrmah M, et al. Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis. BMJ Evid Based Med. 2021;26(3):107-8.
18. Bivona G, Agnello L, Ciaccio M. Biomarkers for Prognosis and Treatment Response in COVID-19 Patients. Ann Lab Med. 2021;41(6):540-8.
19. Gameil MA, Marzouk RE, Elsebaie AH, Rozaik SE. Long-term clinical and biochemical residue after COVID-19 recovery. Egypt Liver J. 2021;11(1):74.
20. Durstenfeld MS, Peluso MJ, Kelly JD, Win S, Swaminathan S, Li D, et al. Role of antibodies, inflammatory markers, and echocardiographic findings in postacute cardiopulmonary symptoms after SARS-CoV-2 infection. JCI Insight. 2022;7(10).
21. Liao B, Liu Z, Tang L, Li L, Gan Q, Shi H, et al. Longitudinal clinical and radiographic evaluation reveals interleukin-6 as an indicator of persistent pulmonary injury in COVID-19. Int J Med Sci. 2021;18(1):29-41.
22. Wieczfinska J, Kleniewska P, Pawliczak R. Oxidative Stress-Related Mechanisms in SARS-CoV-2 Infections. Oxid Med Cell Longev. 2022;2022:5589089.
23. Passam FH, Giannakopoulos B, Mirarabshahi P, Krilis SA. Molecular pathophysiology of the antiphospholipid syndrome: the role of oxidative post-translational modification of beta 2 glycoprotein I. J Thromb Haemost. 2011;9 Suppl 1:275-82.
24. Nocella C, Bartimoccia S, Cammisotto V, D'Amico A, Pastori D, Frati G, et al. Oxidative Stress in the Pathogenesis of Antiphospholipid Syndrome: Implications for the Atherothrombotic Process. Antioxidants (Basel). 2021;10(11).
25. McDonnell T, Wincup C, Buchholz I, Pericleous C, Giles I, Ripoll V, et al. The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS. Blood Rev. 2020;39:100610.
26. Del Papa N, Sheng YH, Raschi E, Kandiah DA, Tincani A, Khamashta MA, et al. Human beta 2-glycoprotein I binds to endothelial cells through a cluster of lysine residues that are critical for anionic phospholipid binding and offers epitopes for anti-beta 2-glycoprotein I antibodies. J Immunol. 1998;160(11):5572-8.
27. Rahgozar S. Revisiting beta 2 glycoprotein I, the major autoantigen in the antiphospholipid syndrome. Iran J Immunol. 2012;9(2):73-85.
28. on K, Jamil R, Chowdhury A, Mukherjee M, Venegas C, Miyasaki K, et al. Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms. Eur Respir J. 2023;61(1).
29. Wallukat G, Hohberger B, Wenzel K, Fürst J, Schulze-Rothe S, Wallukat A, et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms. Journal of Translational Autoimmunity. 2021;4:100100.
30. Chen H-J, Appelman B, Willemen H, Bos A, Prado J, Geyer CE, et al. Transfer of IgG from Long COVID patients induces symptomology in mice. BioRxiv. 2024:2024.05. 30.596590.
31. Santos Guedes de Sa K, Silva J, Bayarri-Olmos R, Brinda R, Alec Rath Constable R, Colom Diaz PA, et al. A causal link between autoantibodies and neurological symptoms in long COVID. medRxiv. 2024.
32. O'Mahoney LL, Routen A, Gillies C, Ekezie W, Welford A, Zhang A, et al. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis. EClinicalMedicine. 2023;55:101762.
33. Casanova JL, Abel L. The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity? Hum Genet. 2020;139(6-7):681-94.
34. Su Y, Yuan D, Chen DG, Ng RH, Wang K, Choi J, et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185(5):881-95.e20.
35. Fouladseresht H, Safa A, Khosropanah S, Doroudchi M. Increased frequency of HLA-A*02 in patients with atherosclerosis is associated with VZV seropositivity. Arch Physiol Biochem. 2021;127(4):351-8.
36. Khan T, Rahman M, Ahmed I, Al Ali F, Jithesh PV, Marr N. Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens. Front Immunol. 2022;13:856497.
37. Yao Y, Yang H, Shi L, Liu S, Li C, Chen J, et al. HLA Class II Genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 Are Associated With the Antibody Response to Inactivated Japanese Encephalitis Vaccine. Front Immunol. 2019;10:428.
38. Detsika MG, Giatra C, Kitsiou V, Jahaj E, Athanassiades T, Kouniaki D, et al. Demographic, Clinical and Immunogenetic Profiles of a Greek Cohort of COVID-19 Patients. Life (Basel). 2021;11(10).
39. Farahani RH, Esmaeilzadeh E, Asl AN, Heidari MF, Hazrati E. Frequency of HLA Alleles in a Group of Severe COVID-19 Iranian Patients. Iran J Public Health. 2021;50(9):1882-6.
40. Ouedraogo AR, Traoré L, Ouattara AK, Ouedraogo AR, Zongo SV, Savadogo M, et al. Association of HLA-DRB1*11 and HLA-DRB1*12 gene polymorphism with COVID-19 in Burkina Faso. BMC Med Genomics. 2023;16(1):246.
41. Ebrahimi S, Ghasemi-Basir HR, Majzoobi MM, Rasouli-Saravani A, Hajilooi M, Solgi G. HLA-DRB1*04 may predict the severity of disease in a group of Iranian COVID-19 patients. Hum Immunol. 2021;82(10):719-25.
42. Wolday D, Fung CYJ, Morgan G, Casalino S, Frangione E, Taher J, Lerner-Ellis JP. HLA Variation and SARS-CoV-2 Specific Antibody Response. Viruses. 2023;15(4).
43. Crocchiolo R, Gallina AM, Pani A, Campisi D, Cento V, Sacchi N, et al. Polymorphism of the HLA system and weak antibody response to BNT162b2 mRNA vaccine. Hla. 2022;99(3):183-91.
44. Weidner L, Kalser J, Kreil TR, Jungbauer C, Mayr WR. Neutralizing Antibodies against SARS-CoV-2 and HLA Class I and II Polymorphism. Transfus Med Hemother. 2021;48(3):173-4.
45. Astbury S, Reynolds CJ, Butler DK, Muñoz-Sandoval DC, Lin KM, Pieper FP, et al. HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19. Immunology. 2022;166(1):68-77.
46. Molnar T, Varnai R, Schranz D, Zavori L, Peterfi Z, Sipos D, et al. Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms. J Clin Med. 2021;10(19).
47. García-Abellán J, Padilla S, Fernández-González M, García JA, Agulló V, Andreo M, et al. Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study. J Clin Immunol. 2021;41(7):1490-501.
48. Fouladseresht H, Ghamar Talepoor A, Farjadian S, Khosropanah S, Doroudchi M. Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis. Iran J Allergy Asthma Immunol. 2019;18(5):543-53.
49. Harrison M. Erythrocyte sedimentation rate and C-reactive protein. Aust Prescr. 2015;38(3):93-4.
50. Eggleton P, Haigh R, Winyard PG. Consequence of neo-antigenicity of the 'altered self'. Rheumatology (Oxford). 2008;47(5):567-71.
51. López-Pedrera C, Barbarroja N, Jimenez-Gomez Y, Collantes-Estevez E, Aguirre MA, Cuadrado MJ. Oxidative stress in the pathogenesis of atherothrombosis associated with anti-phospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches. Rheumatology (Oxford). 2016;55(12):2096-108.
52. Acosta-Ampudia Y, Monsalve DM, Rojas M, Rodríguez Y, Zapata E, Ramírez-Santana C, Anaya JM. Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome. J Infect Dis. 2022;225(12):2155-62.
53. Torki E, Hoseininasab F, Moradi M, Sami R, Sullman MJM, Fouladseresht H. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study. Clin Exp Med. 2024;24.
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| Beta 2-glycoprotein I C-reactive protein Human leukocyte antigen Post-acute COVID-19 syndrome Receptor binding domain | ||
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How to Cite
1.
Torki E, Eskandari N, Sami K, Gharezadeh A, Sullman M, Soltani Shiraz S, Fouladseresht H. HLA-DRB1* Alleles and Long COVID: A Mediation Analysis of Anti-RBD IgG, CRP, and Anti-β2GPI IgG. Iran J Allergy Asthma Immunol. 2026;:1-15.
