The Association of Prolactin and CRP Biomarkers with the Severity of COVID-19 in Thumbay Hospital, Ajman, UAE

Aisha Abdulkrim Nur, Ahmed L. Osman, Praveen Kumar Kandakurti, Marwan Ismail, Abdelgdair A. Altoum

International Journal of Biomedicine. 2023;13(4):286-295.
DOI: 10.21103/Article13(4)_OA9
Originally published December 5, 2023


Background: This study aimed to estimate the levels of CRP and PRL in SARS-CoV2 infection and their association with the severity of COVID-19 among patients in Ajman, UAE.
Methods and Results:  This cross-sectional study was conducted in Thumbay Hospital from 2020 to 2021. The study included 71 patients (55 males and 16 females) with positive SARS-CoV-2 test results. Nasal swab specimens were collected for the COVID-19 test on the day of admission or after one day of admission. COVID-19 diagnoses and severity levels were determined according to the New Coronavirus Pneumonia Prevention and Control Program (7th edition) published by the National Health Commission of China (2020).
Serum samples were collected from the patients upon admission. The PRL level was determined using the immune chemiluminescent method by the DXI 800 Beckman Coulter analyzer. The CRP level was determined using the immunoturbidimetric method by the DXC 700 AU chemistry analyzer.
Among 71 COVID-19 patients, the great majority were men 55(77.5%), 38(53.5%) being of Indian nationality. In this study, most participants (50.7%) had no history of chronic illnesses. In terms of COVID-19 severity, 24(33.8%) of patients had mild cases, 27(38.0%) had moderate cases, and 20(28.2%) had severe cases. Twenty (28.2%) patients were transferred to the ICU, and 19(26.8%) were intubated. The patients' average age was 47.58±13.63, CRP level - 74.30±71.46 mg/L, and PRL level - 205.1946±168.52 ng/mL. The mean CRP level was highest in severe cases, compared to mild and moderate cases, with a statistically significant difference between mild and severe groups (P=0.000) and mild and moderate groups (P=0.004). The mean PRL level was highest in severe cases compared to mild and moderate cases; however, the differences between the groups were not significant. CRP and PRL levels were greater in the ICU patients than non-ICU patients, with statistically significant differences only for CRP. We found a moderate positive correlation between CRP level and age (r=0.458, P=0.000); a weak positive correlation between PRL level and age was not statistically significant (r=0.201, P=0.093). A moderate positive correlation between CRP level and PRL level (r=0.461, P=0.03) was statistically significant.
Conclusion: The current study implies that serum CRP levels might be an important indication of COVID-19 development and severity. A more extensive study with a larger sample size is needed to validate the significance of PRL in disease severity.

COVID-19 • prolactin • C-reactive protein
  1. WHO: Weekly epidemiological update on COVID-19 - 25 August 2023. Available from:
  2. Picchianti Diamanti A, Rosado MM, Pioli C, Sesti G, Laganà B. Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity. Int J Mol Sci. 2020 May 8;21(9):3330. doi: 10.3390/ijms21093330.
  3. Ali N. Elevated level of C-reactive protein may be an early marker to predict risk for severity of COVID-19. J Med Virol. 2020 Nov;92(11):2409-2411. doi: 10.1002/jmv.26097.
  4. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018 Apr 13;9:754. doi: 10.3389/fimmu.2018.00754. 
  5. Ahnach M, Zbiri S, Nejjari S, Ousti F, Elkettani C. C-reactive protein as an early predictor of COVID-19 severity. J Med Biochem. 2020 Oct 2;39(4):500-507. doi: 10.5937/jomb0-27554.
  6. Kermali M, Khalsa RK, Pillai K, Ismail Z, Harky A. The role of biomarkers in diagnosis of COVID-19 - A systematic review. Life Sci. 2020 Aug 1;254:117788. doi: 10.1016/j.lfs.2020.117788.
  7. Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and autoimmunity: The hormone as an inflammatory cytokine. Best Pract Res Clin Endocrinol Metab. 2019 Dec;33(6):101324. doi: 10.1016/j.beem.2019.101324.
  8. Zaid D, Greenman Y. Human Immunodeficiency Virus Infection and the Endocrine System. Endocrinol Metab (Seoul). 2019 Jun;34(2):95-105. doi: 10.3803/EnM.2019.34.2.95.
  9. Williams LM, Sarma U, Willets K, Smallie T, Brennan F, Foxwell BM. Expression of constitutively active STAT3 can replicate the cytokine-suppressive activity of interleukin-10 in human primary macrophages. J Biol Chem. 2007 Mar 9;282(10):6965-75. doi: 10.1074/jbc.M609101200. 
  10. Tripathi A, Sodhi A. Prolactin-induced production of cytokines in macrophages in vitro involves JAK/STAT and JNK MAPK pathways. Int Immunol. 2008 Mar;20(3):327-36. doi: 10.1093/intimm/dxm145. 
  11. Abramicheva PA, Smirnova OV. Prolactin Receptor Isoforms as the Basis of Tissue-Specific Action of Prolactin in the Norm and Pathology. Biochemistry (Mosc). 2019 Apr;84(4):329-345. doi: 10.1134/S0006297919040011.
  12. Del Vecchio Filipin M, Brazão V, Santello FH, da Costa CMB, Paula Alonso Toldo M, Rossetto de Morais F, do Prado Júnior JC. Does Prolactin treatment trigger imunoendocrine alterations during experimental T. cruzi infection? Cytokine. 2019 Sep;121:154736. doi: 10.1016/j.cyto.2019.154736. 
  13. Pinoli M, Marino F, Cosentino M. Dopaminergic Regulation of Innate Immunity: a Review. J Neuroimmune Pharmacol. 2017 Dec;12(4):602-623. doi: 10.1007/s11481-017-9749-2. 
  14. Sen A. Repurposing prolactin as a promising immunomodulator for the treatment of COVID-19: Are common Antiemetics the wonder drug to fight coronavirus? Med Hypotheses. 2020 Nov;144:110208. doi: 10.1016/j.mehy.2020.110208. 
  15. Gong N, Ferreira-Martins D, McCormick SD, Sheridan MA. Divergent genes encoding the putative receptors for growth hormone and prolactin in sea lamprey display distinct patterns of expression. Sci Rep. 2020 Feb 3;10(1):1674. doi: 10.1038/s41598-020-58344-5.
  16. Liu Y, Jiang J, Lepik B, Zhang Y, Zinn KR, Frank SJ. Subdomain 2, Not the Transmembrane Domain, Determines the Dimerization Partner of Growth Hormone Receptor and Prolactin Receptor. Endocrinology. 2017 Oct 1;158(10):3235-3248. doi: 10.1210/en.2017-00469. 
  17. Ihedioha O, Blanchard AA, Balhara J, Okwor I, Jia P, Uzonna J, Myal Y. The human breast cancer-associated protein, the prolactin-inducible protein (PIP), regulates intracellular signaling events and cytokine production by macrophages. Immunol Res. 2018 Apr;66(2):245-254. doi: 10.1007/s12026-018-8987-6. 
  18. Ochoa-Amaya JE, Malucelli BE, Cruz-Casallas PE, Nasello AG, Felicio LF, Carvalho-Freitas MI. Acute and chronic stress and the inflammatory response in hyperprolactinemic rats. Neuroimmunomodulation. 2010;17(6):386-95. doi: 10.1159/000292063.
  19. Al-Kuraishy HM, Al-Gareeb AI, Butnariu M, Batiha GE. The crucial role of prolactin-lactogenic hormone in Covid-19. Mol Cell Biochem. 2022 May;477(5):1381-1392. doi: 10.1007/s11010-022-04381-9. 
  20. Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, et al. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Rep Med. 2021 May 18;2(5):100288. doi: 10.1016/j.xcrm.2021.100288.
  21. Lennartsson AK, Jonsdottir IH. Prolactin in response to acute psychosocial stress in healthy men and women. Psychoneuroendocrinology. 2011 Nov;36(10):1530-9. doi: 10.1016/j.psyneuen.2011.04.007.
  22. Wang S, Zhang A, Pan Y, Liu L, Niu S, Zhang F, Liu X. Association between COVID-19 and Male Fertility: Systematic Review and Meta-Analysis of Observational Studies. World J Mens Health. 2023 Apr;41(2):311-329. doi: 10.5534/wjmh.220091.
  23. Tomaszewska-Zaremba D, Haziak K, Tomczyk M, Herman AP. Inflammation and LPS-Binding Protein Enable the Stimulatory Effect of Endotoxin on Prolactin Secretion in the Ovine Anterior Pituitary: Ex Vivo Study. Mediators Inflamm. 2018 Aug 14;2018:5427089. doi: 10.1155/2018/5427089. 
  24. Sanli DET, Altundag A, Kandemirli SG, Yildirim D, Sanli AN, Saatci O, Kirisoglu CE, Dikensoy O, Murrja E, Yesil A, Bastan S, Karsidag T, Akinci IO, Ozkok S, Yilmaz E, Tuzuner F, Kilercik M, Ljama T. Relationship between disease severity and serum IL-6 levels in COVID-19 anosmia. Am J Otolaryngol. 2021 Jan-Feb;42(1):102796. doi: 10.1016/j.amjoto.2020.102796. 
  25. Al-Kuraishy HM, Al-Gareeb AI, Qusti S, Alshammari EM, Atanu FO, Batiha GE. Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective. Biomed Pharmacother. 2021 Nov;143:112193. doi: 10.1016/j.biopha.2021.112193.
  26. Vilar L, Vilar CF, Lyra R, Freitas MDC. Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia. Neuroendocrinology. 2019;109(1):7-19. doi: 10.1159/000499694.
  27. Nehring SM, Goyal A, Patel BC. C Reactive Protein. 2023 Jul 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 28722873.
  28. Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition). Available from:
  29. Mirzaei F, Tavilani A, Asefy Z, Abbasi E. Prolactin and susceptibility to COVID-19 infection. Medical Hypotheses. 2021;155:110662.
  30. Zare-Zardini H, Soltaninejad H, Ferdosian F, Hamidieh AA, Memarpoor-Yazdi M. Coronavirus Disease 2019 (COVID-19) in Children: Prevalence, Diagnosis, Clinical Symptoms, and Treatment. Int J Gen Med. 2020 Jul 28;13:477-482. doi: 10.2147/IJGM.S262098.
  31. Li Y, Jerkic M, Slutsky AS, Zhang H. Molecular mechanisms of sex bias differences in COVID-19 mortality. Crit Care. 2020 Jul 9;24(1):405. doi: 10.1186/s13054-020-03118-8. 
  32. Mirzaei F, Tavilani A, Asefy Z, Abbasi E. Prolactin and susceptibility to COVID-19 infection. Med Hypotheses. 2021 Oct;155:110662. doi: 10.1016/j.mehy.2021.110662.
  33. Liu H, Wang LL, Zhao SJ, Kwak-Kim J, Mor G, Liao AH. Why are pregnant women susceptible to COVID-19? An immunological viewpoint. J Reprod Immunol. 2020 Jun;139:103122. doi: 10.1016/j.jri.2020.103122. 
  34. Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, Zheng C. Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis. AJR Am J Roentgenol. 2020 Jul;215(1):127-132. doi: 10.2214/AJR.20.23072. 
  35. Jin JM, Bai P, He W, Wu F, Liu XF, Han DM, Liu S, Yang JK. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health. 2020 Apr 29;8:152. doi: 10.3389/fpubh.2020.00152. 
  36. Sawin CT, Carlson HE, Geller A, Castelli WP, Bacharach P. Serum prolactin and aging: basal values and changes with estrogen use and hypothyroidism. J Gerontol. 1989 Jul;44(4):M131-5. doi: 10.1093/geronj/44.4.m131. 
  37. Yamaji T, Shimamoto K, Ishibashi M, Kosaka K, Orimo H. Effect of age and sex on circulating and pituitary prolactin levels in human. Acta Endocrinol (Copenh). 1976 Dec;83(4):711-9. doi: 10.1530/acta.0.0830711. 
  38. Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME. Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers. Psychopharmacology (Berl). 1982;78(4):305-8. doi: 10.1007/BF00433730.
  39. Chen W, Zheng KI, Liu S, Yan Z, Xu C, Qiao Z. Plasma CRP level is positively associated with the severity of COVID-19. Ann Clin Microbiol Antimicrob. 2020 May 15;19(1):18. doi: 10.1186/s12941-020-00362-2
  40. Smilowitz NR, Kunichoff D, Garshick M, Shah B, Pillinger M, Hochman JS, Berger JS. C-reactive protein and clinical outcomes in patients with COVID-19. Eur Heart J. 2021 Jun 14;42(23):2270-2279. doi: 10.1093/eurheartj/ehaa1103. 
  41. Pepys MB. C-reactive protein predicts outcome in COVID-19: is it also a therapeutic target? Eur Heart J. 2021 Jun 14;42(23):2280-2283. doi: 10.1093/eurheartj/ehab169. 
  42. Benito N, Filella D, Mateo J, Fortuna AM, Gutierrez-Alliende JE, Hernandez N, Gimenez AM, Pomar V, Castellvi I, Corominas H, Casademont J, Domingo P. Pulmonary Thrombosis or Embolism in a Large Cohort of Hospitalized Patients With Covid-19. Front Med (Lausanne). 2020 Aug 25;7:557. doi: 10.3389/fmed.2020.00557.
  43. Zhang JJ, Cao YY, Tan G, Dong X, Wang BC, Lin J, Yan YQ, Liu GH, Akdis M, Akdis CA, Gao YD. Clinical, radiological, and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients. Allergy. 2021 Feb;76(2):533-550. doi: 10.1111/all.14496. 
  44. Li X, Xu S, Yu M, Wang K, Tao Y, Zhou Y, Shi J, Zhou M, Wu B, Yang Z, Zhang C, Yue J, Zhang Z, Renz H, Liu X, Xie J, Xie M, Zhao J. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 2020 Jul;146(1):110-118. doi: 10.1016/j.jaci.2020.04.006.
  45. Luan YY, Yin CH, Yao YM. Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections. Front Immunol. 2021 Aug 10;12:720363. doi: 10.3389/fimmu.2021.720363.
  46. Li Y, Li H, Song C, Lu R, Zhao Y, Lin F, Han D, Chen L, Pan P, Dai M. Early Prediction of Disease Progression in Patients with Severe COVID-19 Using C-Reactive Protein to Albumin Ratio. Dis Markers. 2021 Dec 3;2021:6304189. doi: 10.1155/2021/6304189. 
  47. Luo X, Zhou W, Yan X, Guo T, Wang B, Xia H, Ye L, Xiong J, Jiang Z, Liu Y, Zhang B, Yang W. Prognostic Value of C-Reactive Protein in Patients With Coronavirus 2019. Clin Infect Dis. 2020 Nov 19;71(16):2174-2179. doi: 10.1093/cid/ciaa641. 
  48. Bouayed MZ, Laaribi I, Chatar CEM, Benaini I, Bouazzaoui MA, Oujidi Y, Berrichi S, El Aidouni G, Bkiyar H, Abda N, Housni B. C-Reactive Protein (CRP): A poor prognostic biomarker in COVID-19. Front Immunol. 2022 Nov 14;13:1040024. doi: 10.3389/fimmu.2022.1040024. 
  49. Stringer D, Braude P, Myint PK, Evans L, Collins JT, Verduri A, Quinn TJ, Vilches-Moraga A, Stechman MJ, Pearce L, Moug S, McCarthy K, Hewitt J, Carter B; COPE Study Collaborators. The role of C-reactive protein as a prognostic marker in COVID-19. Int J Epidemiol. 2021 May 17;50(2):420-429. doi: 10.1093/ije/dyab012.
  50. Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect. 2020 Jun;50(4):332-334. doi: 10.1016/j.medmal.2020.03.007. 
  51. Zhang JN, Gao Y, Wang XT, Li NN, Du X, Tang YJ, Lai QQ, Chen PF, Yue CS, Wu JH, Kang K, Zhao MY. Lymphocyte-C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission. Front Immunol. 2022 Sep 23;13:957407. doi: 10.3389/fimmu.2022.957407. 
  52. Rizzi M, D'Onghia D, Tonello S, Minisini R, Colangelo D, Bellan M, Castello LM, Gavelli F, Avanzi GC, Pirisi M, Sainaghi PP. COVID-19 Biomarkers at the Crossroad between Patient Stratification and Targeted Therapy: The Role of Validated and Proposed Parameters. Int J Mol Sci. 2023 Apr 12;24(8):7099. doi: 10.3390/ijms24087099.
  53. Obaid KG, Hussein SEO, Osman AL, Abdmomen NK, Ismail M, Kandakurti PK, Altoum AA. The Association of C-Reactive Protein and Ferritin Levels with the Severity of COVID-19 in Ajman, UAE. International Journal of Biomedicine. 2022;12(2):237-241. doi:10.21103/Article12(2)_OA6

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Received August 28, 2023.
Accepted September 25, 2023.
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