Impact of mental disorders on COVID-19 outcomes

Objective: to analyze clinical and follow-up indicators in patients with mental disorders and COVID-19 and to identify on their basis predictors of poor outcomes associated with mental state.

Patients and methods. We conducted a prospective study in a multidisciplinary hospital. The severity of coronavirus infection was determined according to the temporary guidelines. Data collection was carried out using a patient chart consisting of 109 variables. Predictors of poor outcomes were determined using predictive models (logit regression, Cox model). The study included 97 patients: 41 men (42.3%) and 56 (57.7%) women, mean age – 62.3±15.3 years. 26 patients died; 71 patients recovered.

Results and discussion. The death occurred on 11.5 day. The mental state of these patients was severe, with a predominance of delirium cases. With increasing age, the probability of non-lethal outcome decreases [hazard ratio (HR) 1.03; 95% confidence interval (CI) 1.00–1.06; p=0.037]. The risk of death increased by 1.03 (p=0.037) for each year of life. An improvement in the mental state of patients during psychotropic therapy is associated with an 11.11-fold decrease in the risk of poor outcome of coronavirus infection (HR 0.09; 95% CI 0.01–0.76; p=0.027). Delirium is a predictor of low patient survival, especially in prolonged hospitalizations (HR 4.55; 95% CI 1.66–12.48; p=0.003). The severity of coronavirus infection makes the greatest contribution to the poor outcome: the risk of death increases by 33.17 times (CR 33.17; 95% CI 4.01–274.65; p<0.001). The severity of the mental disorder had a greater impact on the risk of death compared with age, increasing it by 4.55 times (p=0.003).

Conclusion. We found significant differences between the groups of deceased and surviving patients with COVID-19 concerning the variables related to certain mental disorders, their severity and dynamics, and the severity of coronavirus infection. In addition, the age of the patients had a significant impact on the prognosis of COVID-19. The results reflect the special prognostic significance of delirium in the structure of mental disorders developing in patients with coronavirus infection.

1. Ulumbekova GE, Khudova IYu. The technologies of Health Care Management During COVID-19. Byulletin’ VShOUZ. 2020;6(4):4-22. doi: 10.24411/2411-8621-2020-14001 (In Russ.).

2. Xiong J, Lipsitz O, Nasri F, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020 Dec 1;277:55-64. doi: 10.1016/j.jad.2020.08.001. Epub 2020 Aug 8.

3. Zhou J, Liu L, Xue P, et al. Mental Health Response to the COVID-19 Outbreak in China. Am J Psychiatry. 2020;177(7):574-5. doi: 10.1176/appi.ajp.2020.20030304

4. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry. 2020 Oct;7(10):875-82. doi: 10.1016/S2215-0366(20)30287-X. Epub 2020 Jun 25. Erratum in: Lancet Psychiatry. 2020 Oct;7(10):e64. doi: 10.1016/S2215-0366(20)30320-5. Epub 2020 Jul 14.

5. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020 Jul;7(7):611-27. doi: 10.1016/S2215-0366(20)30203-0. Epub 2020 May 18.

6. Mazza MG, De Lorenzo R, Conte C, et al. Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun. 2020 Oct;89:594-600. doi: 10.1016/j.bbi.2020.07.037. Epub 2020 Jul 30.

7. Martin Gimenez VM, Inserra F, Tajer CD, et al. Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment. Life Sci. 2020 Aug 1;254:117808. doi: 10.1016/j.lfs.2020.117808. Epub 2020 May 15.

8. Berenguer J, Ryan P, Rodriguez-Bano J, et al. Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain. Clin Microbiol Infect. 2020 Nov;26(11):1525-36. doi: 10.1016/j.cmi.2020.07.024. Epub 2020 Aug 4.

9. Benedetti F, Poletti S, Hoogenboezem TA, et al. Higher Baseline Proinflammatory Cytokines Mark Poor Antidepressant Response in Bipolar Disorder. J Clin Psychiatry. 2017;78(8):986-93. doi: 10.4088/JCP.16m11310

10. Mendes A, Serratrice C, Herrmann FR, et al. Predictors of In-Hospital Mortality in Older Patients With COVID-19: The COVIDAge Study. J Am Med Dir Assoc. 2020 Nov;21(11):1546-1554.e3. doi: 10.1016/j.jamda.2020.09.014. Epub 2020 Sep 15.

11. Lee SW, Yang JM, Moon SY, et al. Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study. Lancet Psychiatry. 2020 Dec;7(12):1025-31. doi: 10.1016/S2215-0366(20)30421-1. Epub 2020 Sep 17.

12. Vremennyye metodicheskiye rekomendatsii «Profilaktika, diagnostika i lecheniye novoy koronavirusnoy infektsii (COVID-19)». Versiya 10 (08.02.2021) [Temporary guidelines «Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)». Version 10 (02/08/2021)]. Available from: http://www.consultant.ru/document/cons_doc_LAW_376205/ (In Russ.).

13. Fischetti T, Mayor E, Forte RM. R: predictive analysis: master the art of predictive modeling: Birmingham, UK: Packt Publishing; 2017. Available from: http://proquest.safaribooksonline.com/?fpi=9781788290371

14. Moore DF. Applied Survival Analysis Using R. Springer International Publishing Switzerland; 2016. doi: 10.1007/978-3-319-31245-3

15. Therneau TM. A Package for Survival Analysis in R. R package version 3.2-10, 2021. Available from: https://CRAN.Rproject.org/package=survival

16. Portet S. A primer on model selection using the Akaike Information Criterion. Infect Dis Model. 2020 Jan 7;5:111-28. doi: 10.1016/j.idm.2019.12.010. eCollection 2020.

17. Nakagawa S, Johnson PCD, Schielzeth H. The coefficient of determination R2 and intraclass correlation coefficient from generalized linear mixed-effects models revisited and expanded. J R Soc Interface. 2017 Sep;14(134):20170213. doi: 10.1098/rsif.2017.0213. Epub 2017 Sep 13.

18. Lüdecke D. ggeffects: Tidy Data Frames of Marginal Effects from Regression Models. J Open Source Softw. 2018;3(26):772. doi: 10.21105/joss.00772

19. Chen Y, Li T, Ye Y, et al. Impact of Fundamental Diseases on Patients With COVID-19. Disaster Med Public Health Prep. 2020;14(6):776-81. doi: 10.1017/dmp.2020.139

20. Steardo L, Verkhratsky А. Psychiatric face of COVID-19. Transl Psychiatry. 2020 Jul 30;10(1):261. doi: 10.1038/s41398-020-00949-5

21. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753

22. Vasilevskis EE, Chandrasekhar R, Holtze CH, et al. The cost of ICU delirium and coma in the intensive care unit patient. Med Care. 2018 Oct;56(10):890-7. doi: 10.1097/MLR.0000000000000975

23. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.

24. Jacomy H, Talbot PJ. Vacuolating encephalitis in mice infected by human coronavirus OC43. Virology. 2003 Oct 10;315(1):20-33. doi: 10.1016/s0042-6822(03)00323-4

25. Kotfis К, Roberson SW, Wilson JE. COVID-19: What do we need to know about ICU delirium during the SARS-CoV-2 pandemic? Anaesthesiol Intensive Ther. 2020;52(2):132-8. doi: 10.5114/ait.2020.95164

26. Kotfis К, Roberson SW, Wilson JЕ, et al. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020 Apr 28;24(1):176. doi: 10.1186/s13054-020-02882-x

27. Pranata R, Huang I, Lim MA, et al. Delirium and Mortality in Coronavirus Disease 2019 (COVID-19) – A Systematic Review and Meta-analysis. Arch Gerontol Geriatr. 2021 Mar 5;95:104388. doi: 10.1016/j.archger.2021.104388. Epub ahead of print.

28. Garcez FB, Aliberti MJR, Poco PCE, et al. Delirium and Adverse Outcomes in Hospitalized Patients with COVID-19. J Am Geriatr Soc. 2020 Nov;68(11):2440-6. doi: 10.1111/jgs.16803. Epub 2020 Sep 5.

29. O’Hanlon S, Inouye SK. Delirium: a missing piece in the COVID-19 pandemic puzzle. Age Ageing. 2020 Jul 1;49(4):497-8. doi: 10.1093/ageing/afaa094

30. Hawkins M, Sockalingam S, Bonato S. A rapid review of the pathoetiology, presentation, and management of delirium in adults with COVID-19. J Psychosomat Res. 2021 Feb;141:110350. doi: 10.1016/j.jpsychores.2020.110350. Epub 2020 Dec 25.

31. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038.

32. Grasselli G, Greco M, Zanella A, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. 2020 Oct 1;180(10):1345-55. doi: 10.1001/jamainternmed.2020.3539

33. Yahya AS, Khawaja S, Chukwuma J. The use of «novel pharmacology» in the treatment of COVID- 19 and potential psychiatric risks. Prim Care Companion CNS Disord. 2020 May 21;22(3):20com02638. doi: 10.4088/PCC.20com02638