Relationship between Natural Killer Lymphocytes and Length of Stay in Patients with Depression admitted with Corona Virus-19
Main Article Content
Abstract
Introduction: The recent unexpected COVID-19 pandemic had a serious and sudden impact on the world population physically and mentally. In the current study, we collected data prospectively on COVID-19 infected patients with depression/anxiety admitted to the hospital to evaluate the effect of these illnesses on patient length of stay and the level of Natural Killer Lymphocytes.
Methods: This project was a prospective study of patients admitted between July 2021 - July 2022 with COVID-19 to our community hospital. Patients completed the PHQ-9 and GAD-7 questionnaires to assess levels of depression and anxiety. A blood draw was done to check levels of natural killer lymphocyte cells (NKL). Data collected included age, sex, race, history of diabetes, hypertension, chronic obstructive pulmonary disease, hyperlipidemia, chronic kidney disease, obesity, length of stay, and mortality. Student’s t-Test, Chi-square, and Pearson’s correlation were used to identify the relationship of these patients to their NKL response and length of stay.
Results: There were a total of 67 patients enrolled. Of those 67 patients, 49 (73.1%) had labs drawn to measure NKL levels and were included in the analysis. Mean age was 61.8 (SD: 11.4). Over half of the participants were female (n=26, 53.1%). There were 30 (61.2%) patients with depression and 22 (44.9%) with anxiety. There were 26 (53.1%) patients with hypertension, 16 (32.7%) with diabetes, and 14 (28.6%) patients with chronic obstructive pulmonary disease. The mean Natural Killer lymphocyte was 82.3% (SD ±12.1) (which includes (CD3-CD16+CD56 dim and CD3-CD16+CD56 bright). The overall relationship between length of stay and combined NKL demonstrated a nonsignificant weak negative correlation (n=45, r= -0.07, p=.65). Patients with pre-existing chronic kidney disease had the highest NKL cell level (88.2) and the lowest LOS (5.4 days), and patients with Hypertension and hyperlipidemia had the lowest natural killer lymphocyte cell level (80.2 and 80.1 respectively) had the highest length of stay (8.6 and 10.1 days respectively).
Conclusion: Depression and anxiety did not influence length of stay of COVID-19 patients. NKL response and its relation to length of stay largely dependent on the associated comorbid conditions. Diabetes mellitus in patients with COVID-19 is a significant predictor of length of stay.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Burvill PW. Physical illness in the elderly. A study of patients in mental hospitals, geriatric hospitals and nursing homes. Gerontol Clin (Basel). 1970;12(5):288-296. doi:10.1159/000245291
3. Yu L, McCracken LM. COVID-19 and the mental health in the UK: Depression, anxiety and insomnia and their associations with persistent physical symptoms and risk and vulnerability factors. Br J Clin Psychol. 2024;63(1):92-104. doi:10.1111/bjc.12446.
4. Bu F, Steptoe A, Fancourt D. Depressive and anxiety symptoms in adults during the COVID-19 pandemic in England: A panel data analysis over 2 years. PloS Med. 2023;20(4):e1004144. doi:10.1371/journal.pmed.1004144.
5. Zhu C, Zhang T, Li Q, Chen X, Wang K. Depression and anxiety during the COVID-19 pandemic: Epidemiology, mechanism, and treatment. Neurosci Bull. 2023;39(4):675-684. doi:10.1007/s12264-022-00970-2.
6. Czeisler MÉ, Tynan MA, Howard ME, et al. Public attitudes, behaviors, and beliefs related to COVID-19, stay-at-home orders, nonessential business closures, and public health guidance – United States, New York city, and Los Angeles, May 5-12, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(24):751-758. doi:10.15585/mmwr.mm6924e1.
7. Titus AR, Mezuk B, Hirschtick JL, McKane P, Elliot MR, Fleischer NL. Patterns and predictors of depressive and anxiety symptoms within a population-based sample of adults diagnosed with COVID-19 in Michigan. Soc Psychiatry Psychiatr Epidemiol. 2023;58(7):1099-1108. doi:10.1007/s00127-023-02453-9.
8. Westmeier J, Paniskaki K, Karaköse Z, et al. Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients. mBio. 2020;11(5):e02243-20. doi:10.1128/mBio.02243-20.
9. Cook KD, Waggoner SN, Whitmire JK. NK cells and their ability to modulate T cells during virus infections. Crit Rev Immunol. 2014;34(5):359-88. doi:10.1615/critrevimmunol.2014010604.
10. Vijayanand P, Seumois G, Pickard C, et al. Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease. N Engl J Med. 2007;356(14):1410-22. doi:10.1056/NEJMoa064691.
11. Rijavec M, Volarevic S, Osolnik K, Kosnik M, Korosec P. Natural killer T cells in pulmonary disorders. Respir Med. 2011;105 Suppl 1:S20-S25. doi: 10.1016/S0954-6111(11)70006-3.
12. Vai B, Mazza MG, Colli CD, et al. Mental disorders and risk of COVID-19-related mortality, hospitalization, and intensive care unit admissions: a systematic review and meta-analysis. Lancet Psychiatry. 2021;8(9):797-812. doi:10.1016/S2215-0366(21)00232-7.
13. Song H, Fall K, Fang F, et al. Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study. BMJ. 2019;367:I5784. doi:10.1136/bmj.l5784.
14. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130(4):601-30. doi:10.1037/0033-2909.130.4.601.
15. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self- report version of PRIME-MD: the PHQ primary care study. Primary care evaluation of mental disorders. Patient health questionnaire. JAMA. 1999;282(18):1737-44. doi:10.1001/jama.282.18.1737.
16. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-13. doi:10.1046/j.1525-1497.2001.016009606.x.
17. Löwe B, Decker O, Müller S, et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008;46(3):266-274. doi:10.1097/MLR.0b013e318160d093.
18. Schultze-Florey CR, Chukhno E, Goudeva L, et al. Distribution of major lymphocyte subsets and memory T-cell subpopulations in healthy adults emplying GLP-conforming multicolor flow cytometry. Leukemia. 2021;35(10):3021-3025. doi:10.1038/s41375-021-01348-5.
19. Hoffman RS, Koran LM. Detecting physical illness in patients with mental disorders. Psychosomatics. 1984;26(9):654-60. doi:10.1016/S0033-3182(84)72974-4.
20. Galić K, Dodaj A, Ćorluka-Čerkez V, et al. Study of depression and anxiety in patients with asthma and chronic obstructive pulmonary disease. Psychiatr Danub. 2019;31(Suppl 1):112-117.
21. Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol. 2005;5(3):243-51. doi:10.1038/nri1571.
22. Momen NC, Plana-Ripoll O, Agerbo E, et al. Association between mental disorders and subsequent medical conditions. N Eng J Med. 2020;382(18):1721-1731. doi:10.1056/NEJMoa1915784.
23. Matheson FI, Smith KLW, Moineddin R, Dunn JR, Glazier RH. Mental health status and gender as risk factors for onset of physical illness over 10 years. J Epidemiol Community Health. 2014;68(1):64-70. doi:10.1136/jech-2013-202838.
24. Fousteri G, Kuka M. The elusive identity of CXCR5+ CD8 T cells in viral infection and autoimmunity: Cytotoxic, regulatory, or helper cells? Mol Immunol. 2020;119:101-105. doi:10.1016/j.molimm.2020.01.007.
25. Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15(6):388-400. doi:10.1038/nri3839.
26. Katipoglu B, Naharci MI, Yurdakul ES. Risk factors predicting hospital length of stay in older patients with type 2 diabetes with Covid-19. J Diabetes Metab Disord. 2022;21(2):1443-1449. doi:10.1007/s40200-022-01078-0.
27. Ciric VM, Rancic NK, Pesic MM, Radojkovic DB, Milenkovic N. Factors associated with length of hospitalization in patients with diabetes and mild COVID-19: Experiences from a tertiary university center in Serbia. Medicina (Kaunas). 2024;60(5):788. doi:10.3390/medicina60050788.
28. Soff S, Yoo YJ, Bramante C, et al. Association of glycemic control with long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C). BMJ Open Diabetes Res Care. 2025;13(1):e004536. doi:10.1136/bmjdrc-2024-004536.
29. Zhang J, Ma Y, To WL, et al. Impact of COVID-19 infection on mortality, diabetic complications and haematological parameters in patients with diabetes mellitus: a systematic review and meta-analysis. BMJ Open. 2025;15(3):e090986. doi:10.1136/bmjopen-2024-090986.
30. Mannheim J, Johnson D. COVID-19 and diabetes: an epidemiologic overview. Pediatr Ann. 2024;53(7):E258-E263. doi:10.3928/19382359-20240502-07.
31. He Y, Zheng Q, Zhifang Z, et al. When COVID-19 meets diabetes: a bibliometric analysis. Diabetes Res Clin Pract. 2025;223:112118. doi:10.1016/j.diabres.2025.112118.
32. Fairclough L, Urbanowicz RA, Corne J, Lamb JR. Killer cells in chronic obstructive pulmonary disease. Clin Sci (Lond). 2008;114(8):533-41. doi:10.1042/CS20070356.
33. Rahi MS, Thilagar B, Balaji S, et al. The impact of anxiety and depression in chronic obstructive pulmonary disease. Adv Respir Med. 2023;91(2):123-134. doi:10.3390/arm91020011.