Method for predicting probability of developing cognitive impairment in patients with covid-19

Abstract

FIELD: psychiatry.SUBSTANCE: used to predict the probability of developing cognitive impairment in patients with COVID-19. The socio-demographic data and a history of concomitant diseases are collected, namely: the age in years is recorded, and the presence or absence of comorbid endocrine pathology is clarified: diabetes mellitus, thyroid disease, adrenal disease, obesity. In case of presence of one of the indicated diseases, the indicator is estimated at 1 point. In the absence of diseases – 0 points. The level of education is specified. If the person has secondary or secondary vocational education, the indicator is assessed as 1 point; if the person has a different level of education, it is assessed as 0 points. The respiratory rate is determined and the value is set to 1 for a respiratory rate of 22 per minute or less, and 0 for a respiratory rate of more than 22 per minute. Then the probability of developing cognitive impairment is predicted using the stated mathematical formula.EFFECT: prediction of the risk of an unfavorable course of COVID-19 in the form of neuropsychiatric complications with cognitive impairment.1 cl, 1 tbl, 2 ex

Description

[0001] In the novel coronavirus infection COVID-19 (U 07.1, U07.2), in addition to respiratory dysfunction with the development of respiratory failure and acute respiratory distress syndrome due to autoimmune inflammation, the generalized course of the infection is associated with viral damage to the gastrointestinal tract, brain, heart, and blood vessels. With varying degrees of COVID-19 severity, one of the diagnostic criteria for which is a respiratory rate of more than 22 breaths per minute for moderate severity, cognitive impairment, including decreased memory, attention, and executive functions, develops in 5% or more cases. Among the more severe neuropsychiatric disorders accompanying the infectious process, disturbances of consciousness in the form of delirium and delusion may also develop [Dimensional approach to assessing delirium in COVID-19 in the elderly / V. E. Pashkovsky, N. N. Petrova, M. S. Sivashova [et al.] / / Review of Psychiatry and Medical Psychology named after V.M. Bekhterev. - 2023. - Vol. 57, No. 3. - Pp. 59-69. - DOI 10.31363 / 2313-7053-2023-738. - EDN VADGXX.]. Hospitalization in the intensive care unit (ICU) is recommended for cases of extremely severe COVID-19, the diagnosis of which is based on measuring oxygen saturation, respiratory rate and recording disturbances of consciousness. In half of the cases, concomitant SARS-CoV-2 infections, neuropsychiatric and, in particular, cognitive impairment, develop in elderly patients [Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19): Temporary guidelines / S. N. Avdeev, L. V. Adamyan, E. I. Alekseeva [et al.]. Moscow: Ministry of Health of the Russian Federation, 2022. - 249 p. - EDN AUQCCK.].Due to the decreased overall reactivity of the body, even in elderly patients, individual symptoms of COVID-19 may be mild or not correspond to the severity of the disease, thus complicating the prognosis of the course of the disease and planning the necessary amount of medical care.

[0002] Routine prognostic indicators include invasive and expensive laboratory tests for D-dimer, ferritin, lactate dehydrogenase, C-reactive protein, platelet and white blood cell counts, and aminotransferases [Prevention, diagnosis, and treatment of novel coronavirus infection (COVID-19): Temporary guidelines / S. N. Avdeev, L. V. Adamyan, E. I. Alekseeva [et al.]. Moscow: Ministry of Health of the Russian Federation, 2022. 249 p. EDN AUQCCK.]. Analysis of concomitant organ dysfunctions against the background of chronic diseases is an additional source for prognosticating the course of the novel coronavirus infection COVID-19. When assessing risks, unfavorable outcomes of the infectious disease as a whole are usually predicted, rather than the development of individual concomitant symptoms and syndromes.Moreover, in case of complications with the development of cognitive impairment, ensuring the recommended high-quality monitoring of the condition of a COVID-19 patient is difficult and falls on caregivers or medical personnel. Impairments in attention, memory, and executive functions lead to a decrease in the patient's ability to critically assess their condition, which reduces the value of independent (subjective) assessments of health in general. In turn, developing mental disorders concomitant with a viral disease reflect the generalization of the infection and the likelihood of its more severe course [The Impact of Mental Disorders on the Outcome of COVID-19 / N. N. Petrova, V. E. Pashkovsky, M. S. Sivashova [et al.] / / Neurology, Neuropsychiatry, Psychosomatics. 2021. Vol. 13, No. 5. pp. 40-47. DOI 10.14412 / 2074-2711-20215-40-47. EDN NEUPYK.]. In this case, predicting the development of initial manifestations of cognitive impairment plays an important role in improving the effectiveness of medical care for COVID-19 patients.

[0003] Quantitative assessment of individual cognitive areas, such as attention and concentration, executive functions, memory, language, visuoconstructive skills, abstract thinking, counting and orientation, is possible using standardized scales applicable to cases of COVID-19 [Association of Anxiety and Depression with Objective and Subjective Cognitive Decline in Outpatient Healthcare Consumers with COVID-19: A Cross-Sectional Study / NA Gomzyakova, EI Palchikova, MA Tumova [et al.] / / Consortium Psychiatricum. 2022. Vol. 3, No. 3. P. 46-57. DOI 10.17816 / CP189. - EDN LAFOBQ.]. One such screening tool for assessing the state of cognitive functions is the Montreal Cognitive Assessment Scale, where total scores of 26 or less reflect a clinically significant impairment.In this case, patients may demonstrate fussiness, acceleration or deceleration of speech, unproductive activity, irritability and conflict, decreased readiness and ability to cooperatively behave with medical personnel [Features of cognitive functioning in elderly people with COVID-19 / V. E. Pashkovsky, N. N. Petrova, M. S. Sivashova, G. A. Prokopovich / / Review of Psychiatry and Medical Psychology named after V. M. Bekhterev. 2023. Vol. 57, No. 1. Pp. 61-70. DOI 10.31363 / 2313-7053-2023-698. - EDN PDPXNO.].

[0004] A method for predicting the outcomes of patients with COVID-19 based on quality of life assessment is known [Predicting the outcomes of patients with COVID-19 based on quality of life assessment / I. I. Ayupova, I. N. Tyurin, D. S. Tyufilin [et al.] / / Healthcare Manager. 2022. No. 8. pp. 46-53. DOI 10.21045 / 1811-0185-2022-8-46-53. - EDN NGEASV.]. With this method, the criteria for predicting the unfavorable course of COVID-19 in the form of a fatal outcome are an assessment of functional impairment according to the EQ index - a calculated indicator of health-related quality of life according to the EQ-5D-5L questionnaire, completed independently by the patient; patient age; patient gender; comorbidity according to the calculated Charleston index; the fact of treatment in the intensive care unit (ICU) - which is the closest in technical essence and the achieved result.Male gender, older age, the Charleston Comorbidity Index, ICU stay, and a lower EQ score are independent predictors of disease outcomes and increase the likelihood of death in COVID-19 patients. For every 1 point increase in the EQ score, the odds ratio for death decreases by 1.453 logarithms. This method has been selected as a prototype.

[0005] The objective of the proposed invention is the ability to predict the development of an unfavorable course of COVID-19 in the form of clinically significant cognitive impairment in patients.

[0006] The problem is solved by recording the age A in years of a COVID-19 patient, establishing the X1 indicator characterizing the presence or absence of comorbid endocrine pathology, where X1 is equal to 0 in the presence of at least one of the following diseases: diabetes mellitus, thyroid disease, adrenal disease, obesity, and is equal to 1 in the absence of these diseases; establishing the X3 indicator equal to 1 in the presence of secondary or secondary vocational education and equal to 0 for a different level of education; determining the respiratory rate and establishing the X2 indicator equal to 1 for a respiratory rate of 22 per minute or less and equal to 0 for a respiratory rate of more than 22 per minute; then calculating the Z value using the formula

[0007] Z = −3.202 − 1.91⋅X1 − 2.488⋅X2 + 2.671⋅X3 + 0.051⋅A,

[0008] after which the probability of developing cognitive impairment is predicted using the formula

[0009] P = 1 / (1 + e^(−Z)),

[0010] where e is Euler's number.

[0011] The proposed method is new in that it predicts the risk of developing an unfavorable course of COVID-19, as reflected in a complex of symptoms of cognitive impairment, and also derives this prognosis based on objective assessment methods. This allows for the prediction of earlier and more reversible adverse outcomes of the infectious disease, compared to the prototype's prognosis of an unfavorable course, such as death. The proposed method, compared to the prototype, in addition to the patient's age, takes into account a different criterion for functional impairment, assessing it not by a subjective parameter from a self-administered questionnaire, which requires the patient to maintain a critical attitude toward their condition, but by an objective indicator of respiratory rate.does not require expensive instrumental examination or maintaining consciousness and critical awareness of the patient's condition. Comorbidity assessment is carried out based on the presence of four comorbidities important for the course of the new coronavirus infection (diabetes mellitus, or thyroid disease, or adrenal disease, or obesity), instead of analyzing twenty-one comorbidities of the Charleston comorbidity index when using the prototype (myocardial infarction, heart failure, peripheral vascular disease, transient ischemic attack, acute cerebrovascular accident with minimal residual effects, dementia, bronchial asthma, chronic non-specific lung diseases, collagenoses, gastric ulcer and / or duodenal ulcer, liver cirrhosis without portal hypertension, diabetes mellitus without end-organ damage, acute cerebrovascular accident with hemiplegia or paraplegia,Chronic renal failure with a creatinine level greater than 3 mg%, diabetes mellitus with end-organ damage, malignant tumors without metastases, acute and chronic lymphocytic or myeloid leukemia, lymphomas, liver cirrhosis with portal hypertension, malignant tumors with metastases, acquired immunodeficiency syndrome), making the proposed method less labor-intensive. Also new is the inclusion of previously acquired education indicators, which makes the prognosis more comprehensive, based not only on objective clinical but also socio-demographic indicators.

[0012] The proposed risk criteria for developing an unfavorable course of COVID-19 (comorbidity with endocrine diseases, respiratory dysfunction, low level of education, patient age) in the form of a complex of symptoms of cognitive impairment were obtained by examining 66 individuals who sought outpatient medical care in clinics in the Northwestern region of Russia due to COVID-19 from December 2020 to May 2021. The diagnostic assessment was carried out based on the temporary guidelines for the prevention, diagnosis, and treatment of novel coronavirus infection (COVID-19) approved by the Russian Ministry of Health. The average age of patients was 45 years (minimum - 20, maximum - 87). 33 people had no comorbidities, 40 patients had higher or incomplete higher education. The average respiratory rate of the examined patients was 17 respiratory movements per minute, minimum - 15, maximum - 24.In 9 patients, the total score on the Montreal Cognitive Assessment Scale was 26 or less, thus revealing the presence of a neuropsychiatric complication of COVID-19 in the form of cognitive impairment, since none of this group of patients had previously had mental and / or cognitive impairment [Association of Anxiety and Depression with Objective and Subjective Cognitive Decline in Outpatient Healthcare Consumers with COVID-19: A Cross-Sectional Study / NA Gomzyakova, EI Palchikova, MA Tumova [et al.] / / Consortium Psychiatricum. - 2022. - Vol. 3, No. 3. - P. 46-57. - DOI 10.17816 / CP189. - EDN LAFOBQ.] [Lila Adana Díaz, Andrea Arango, César Parra, Alberto Rodríguez-Lorenzana, Tarquino Yacelga-Ponce; Impact of Educational Level on Versions (Basic and Complete) of the Montreal Cognitive Assessment. Dement Geriatr Cogn Disord 22 November 2021; 50 (4): 341-348. https: / / doi.org / 10.1159 / 000518747; Oz M, Demirel A, Ozel Asliyuce Y, Ulger O.Education level is a strong determinant of cognitive function as measured by MoCA in people with chronic low back pain. Musculoskeletal Sci Pract. 2022;58:102503. doi:10.1016 / j.msksp.2022.102503].

[0013] To quantitatively assess the predictive indicators, a logistic binomial regression was constructed with the corresponding outcomes of the presence or absence of cognitive impairment according to the Montreal Cognitive Assessment Scale. According to the resulting statistically significant (p≤0.05) model, the risk of developing cognitive impairment was determined by five significant predictors (table).

[0014] Table. Significant predictors of the risk of developing cognitive impairment in patients with COVID-19

[0015] Predictor Coefficient Significance level, p Grade Age 0,051 0,026 1,053 Secondary or secondary vocational education 2,671 0,011 14,454 Respiratory rate less than or equal to 22 breaths per minute -2,488 0,07 0,083 Absence of comorbid endocrinological pathology -1,91 0,046 0,148 Constant -3,202 - -

[0016] The choice of educational level as a predictor of cognitive impairment is related to the data on the significant role of the number of years of education received for the development of mild cognitive impairment [Lila Adana Díaz, Andrea Arango, César Parra, Alberto Rodríguez-Lorenzana, Tarquino Yacelga-Ponce; Impact of Educational Level on Versions (Basic and Complete) of the Montreal Cognitive Assessment. Dement Geriatr Cogn Disord 22 November 2021; 50 (4): 341-348. https: / / doi.org / 10.1159 / 000518747; Oz M, Demirel A, Ozel Asliyuce Y, Ulger O. Education level is a strong determinant of cognitive function as measured by MoCA in people with chronic low back pain. Musculoskelet Sci Pract. 2022;58:102503. doi:10.1016 / j.msksp.2022.102503].Comorbidity assessed only for endocrine diseases instead of a comprehensive assessment of all possible variants of comorbidities in the prototype was chosen for the proposed method as a more specific predictor of an unfavorable course of COVID-19 with the development of a complication in the form of cognitive impairment. This specificity of comorbidities of the endocrine system is associated with the expression of the ACE2 protein and an imbalance of stress hormones in patients with diabetes mellitus, which play an important role in the pathogenesis of COVID-19, and is also mediated by endothelial dysfunction and disorders of the renin-angiotensin system in patients with endocrinological pathology, which are a link in the pathogenesis of cardiovascular diseases, which are also important for the prognosis of the course of COVID-19 [Chatterjee S, Nalla LV, Sharma M, Sharma N, Singh AA, Malim FM, Ghatage M, Mukarram M, Pawar A, Parihar N, Arya N, Khairnar A. Association of COVID-19 with Comorbidities: An Update. ACS Pharmacol Transl Sci.2023 Feb 27;6(3):334-354. doi: 10.1021 / acsptsci.2c00181.]. Respiratory rate was chosen as a probable predictor of an unfavorable course of COVID-19 with the development of complications in the form of cognitive impairment as an indicator of a functional impairment that has an objective change and is recommended for analysis when assessing the severity of the infectious process in moderate and severe stages of the course [Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19): Temporary methodological recommendations / S. N. Avdeev, L. V. Adamyan, E. I. Alekseeva [et al.]. - Moscow: Ministry of Health of the Russian Federation, 2022. - 249 p. - EDN AUQCCK.].

[0017] Thus, the clinical and sociodemographic characteristics of patients at risk for an unfavorable course of COVID-19 and the development of complications such as cognitive impairment include a low level of education (secondary and vocational), comorbid endocrine diseases (thyroid, adrenal, obesity, and diabetes), functional impairments such as respiratory pathology (manifested by an increased respiratory rate of more than 22 breaths per minute), and advanced age. This combination of features allows for a new, more comprehensive, and objective assessment of the combination of risk factors for an unfavorable course of COVID-19, which is not immediately apparent to specialists, and the prediction of earlier and more reversible forms of the infectious disease's adverse course, manifested by cognitive impairment, than previously available from the state of the art.

[0018] An identical set of distinctive features was not found during the analysis of patent and scientific-medical literature.

[0019] The method proposed as an invention can be widely used in medicine and, in particular, psychiatry, to predict the risk of an unfavorable course of COVID-19 in the form of neuropsychiatric complications with cognitive impairment, and can also be used to improve the effectiveness of medical care.

[0020] The method is implemented as follows: information on the age, level of education, and comorbid endocrine diseases is collected from patients diagnosed with coronavirus infection COVID-19. The respiratory function is assessed based on the respiratory rate, and the risk of an unfavorable course of COVID-19 with the development of cognitive impairment is predicted. The method is implemented as follows. Information on the age, level of education, and comorbid endocrine diseases is collected from patients diagnosed with COVID-19, and the respiratory rate is determined. The age A in years is then recorded. The X1 indicator characterizing the presence or absence of comorbid endocrine pathology is determined, where X1 is equal to 0 in the presence of at least one of the following diseases: diabetes mellitus, thyroid disease, adrenal disease, obesity, and is equal to 1 in the absence of these diseases.The X3 indicator is set to 1 for secondary or vocational education and 0 for any other level of education. The X2 indicator is set to 1 for a respiratory rate of 22 breaths per minute or less and 0 for a respiratory rate greater than 22 breaths per minute. The Z value is then calculated using the formula.

[0021] Z = −3.202 − 1.91⋅X1 − 2.488⋅X2 + 2.671⋅X3 + 0.051⋅A,

[0022] after which the probability of developing cognitive impairment is predicted using the formula

[0023] P = 1 / (1 + e^(−Z)),

[0024] where e is Euler's number.

[0025] We provide clinical examples as illustrations.

[0026] Clinical Example N1

[0027] Patient M., born in 1986 (first half of the year). Male nurse. He visited the clinic due to fever, malaise, and weakness in July 2022. A PCR test confirmed the diagnosis of "COVID-19 coronavirus infection, virus identified" (U 07.1).

[0028] Amnesis: the patient's early growth and development are normal. He has a secondary specialized medical education. Of the chronic diseases, ankylosing spondylitis is noted, in remission. Excess body weight is noted, with a body mass index of 31, corresponding to grade 1 obesity. The patient became ill acutely; during a shift at work, he noted absent-mindedness, severe weakness, chills, and a temperature increase to 37.9°C. No catarrhal symptoms were noted, but shortness of breath increased to 25 breaths per minute at rest. In terms of mental status, the patient is correctly oriented, states the date, location, and biographical information. Memory for current and past events is not impaired. Speech rate is normal, thinking is unchanged in content and form. The emotional background is stable. Delusional or hallucinatory symptoms are not detected. Sleep is disturbed, with a long period of falling asleep.

[0029] Thus, in patient M. the X1 value is 0, since stage 1 obesity is detected; the X2 value is 0, since the respiratory rate is 25 per minute, that is, more than 22 per minute; the X3 value is 1, since the patient has secondary vocational education; A's age is 36 years. The Z value is

[0030] Z = −3.202 − 1.91⋅0 − 2.488⋅0 + 2.671⋅1 + 0.051⋅36 = 1.305.

[0031] The probability of developing cognitive impairment is

[0032] P = 1 / (1 + e^(−1.305)) = 0.787, or 78.7%.

[0033] Therefore, patient M., as someone at risk for developing cognitive impairment, should be advised to limit the use of medications that negatively impact cognitive function, particularly hypnotics used to treat insomnia. Neurorehabilitation planning is indicated in the post-infection period.

[0034] Clinical example N2.

[0035] Patient O., born in 1962 (first half of the year). Engineer. She visited the clinic in August 2022 due to cough, fever, and anxiety, escalating to fear of death, accompanied by shortness of breath and moderate emotional depression. A PCR test confirmed the diagnosis of "COVID-19 coronavirus infection, virus identified" (U 07.1).

[0036] Anamnesis: the patient's early growth and development are normal. She has a higher technical education and a PhD in physics and mathematics. Among chronic diseases, she notes hypertension, stabilized against the background of antihypertensive therapy. Her body mass index is normal. She developed a subacute illness; for a week at work, she experienced malaise and decreased tolerance to psycho-emotional stress. In the evenings, she recorded an increase in body temperature to a subfebrile 37.1-37.2 °C. She did not seek medical attention. On the 6th day, in the morning, she noted severe weakness, chills alternating with sweating, a dry cough, and an increase in temperature to 38.2 °C. She did not observe catarrhal phenomena. Objectively, the respiratory rate is 19 per minute at rest. In terms of mental status, the patient is correctly oriented, states the date, location, and biographical information. She is anxious, actively inquires about her condition, and fears death. Her memory for current and past events is intact.Speech rate is moderately accelerated, thinking is not altered in form, but she expresses feelings of guilt and inferiority. She blames herself for possibly infecting colleagues at work and considers herself useless in her profession. Her emotional state is labile, with depression predominating. No delusional or hallucinatory symptoms are detected. Sleep is disturbed, with delays in falling asleep and early awakenings.

[0037] Thus, for patient O., the X1 value is 1 because there is no comorbid endocrine pathology; the X2 value is 1 because the respiratory rate is 19 per minute, that is, 22 per minute or less; the X3 value is 0 because the patient has higher education; A's age is 70 years. The Z value is

[0038] Z = −3.202 − 1.91⋅1 − 2.488⋅1 + 2.671⋅0 + 0.051⋅70 = −4.030.

[0039] The probability of developing cognitive impairment is

[0040] P = 1 / (1 + e^(−(−4.030))) = 0.0175, or 1.75%.

[0041] Based on this, patient O., who is at moderate risk for developing cognitive impairment, should be advised to avoid medications that negatively impact cognitive function when choosing sedatives for anxiety management. Antidepressants with a procognitive effect may be recommended if depressive symptoms worsen. Neurorehabilitation planning is indicated in the post-infection period.

Claims

A method for predicting the likelihood of developing cognitive impairment in patients with COVID-19, including collecting socio-demographic data, a history of concomitant diseases and determining the respiratory rate, characterized in that the age of the patient with COVID-19 is recorded A in years, the indicator X1 is established, characterizing the presence or absence of comorbid endocrine pathology, wherein X1 is equal to 0 in the presence of at least one of the following diseases: diabetes mellitus, thyroid disease, adrenal disease, obesity, and is equal to 1 in the absence of these diseases; the indicator X3 is established equal to 1 in the presence of secondary or secondary vocational education and equal to 0 for a different level of education; the respiratory rate is determined and the indicator X2 is established equal to 1 for a respiratory rate of 22 per minute or less and equal to 0 for a respiratory rate of more than 22 per minute; then the value Z is calculated using the formula Z = −3.202 − 1.91⋅X1 − 2.488⋅X2 + 2.671⋅X3 + 0.051⋅A, after which the probability of developing cognitive impairment is predicted using the formula P = 1 / (1 + e^(−Z)).