Связь между уровнем глюкозы в крови, сопутствующими заболеваниями и исходами лечения пациентов с COVID-19 в больнице третичного звена

Резюме

Сопутствующие заболевания увеличивают риск тяжелого течения COVID-19 и повышают летальность. В Южной Индии проведено небольшое количество исследований, в которых оценивали сниженный уровень глюкозы в крови и наличие сопутствующих заболеваний в качестве прогностических показателей исходов у больных COVID-19.

Цель исследования - изучение связи между уровнем глюкозы в крови, наличием сопутствующих заболеваний и исходом в качестве прогностического показателя COVID-19.

Материал и методы. Проведен ретроспективный перекрестный анализ 593 подтвержденных случаев COVID-19. Проанализированы демографические данные, сведения о сопутствующих заболеваниях [сахарный диабет (СД), заболевания сердца, печени и почек], результаты лабораторных исследований [уровень глюкозы в крови натощак, случайный уровень сахара в крови (RBS), С-реактивный белок]. Сравнивали средние значения непрерывных переменных c использованием двустороннего независимого t-критерия. Для оценки категориальных переменных использованы критерий χ2 Пирсона и точный критерий Фишера. Для определения факторов риска, связанных с исходами, были рассчитаны отношения шансов (OR) и 95% доверительный интервал (ДИ). Различия считали статистически значимыми при р<0,05.

Результаты. В выборке мужчины составляли 66,78%, выздоровели 99,4% и не находились в отделении интенсивной терапии 91,6%. Средний возраст (±SD) выживших и умерших пациентов составил 50,93±14,36 и 63,92±14,99 года соответственно. Исходы COVID-19 были достоверно связаны с полом (р=0,036), сопутствующими заболеваниями (р=0,003), СД (р=0,014), RBS (р=0,042), артериальной гипертензией (р=0,02), заболеваниями сердца (р=0,001). OR составили 0,419 (95% ДИ 0,182-0,967) для пола, 2,403 (1,173-4,921) для сахарного диабета, 1,953 (1,014-3,759) для RBS, 2,146 (1,117-4,124) для артериальной гипертензии.

Заключение. В исследовании установлено значительное влияние СД и уровня глюкозы крови на исходы COVID-19, наряду с другими сопутствующими заболеваниями.

Ключевые слова:COVID-19; глюкоза крови; сахарный диабет; исходы; сопутствующая патология

Финансирование. Исследование не имело финансовой поддержки.

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов. Концепция, дизайн, отбор участников исследования и пациентов, получение информированного согласия, интерпретация лабораторных отчетов, сбор, мониторинг и интерпретация данных, составление окончательного отчета, подготовка к публикации - Пуран К.; дизайн, отбор участников исследования и пациентов, интерпретация лабораторных отчетов, интерпретация данных, статистический анализ, составление окончательного отчета, подготовка к публикации - Навин Шри Л.А.; статистический анализ и интерпретация - Сандхия В.; интерпретация лабораторных отчетов, интерпретация данных, статистический анализ и обработка, составление окончательного отчета - Дханашри Б.; ведение данных, сбор и мониторинг данных, составление окончательного отчета - Картикеян Р.; ведение данных, сбор и мониторинг данных, составление итогового отчета - Мурали А.; надзор, лабораторные исследования, ведение, сбор и мониторинг данных, рецензирование и окончательная подготовка рукописи - Рамалингам С.

Для цитирования: Пурани К., Навин Шри Л.А., Сандхия В., Дханашри Б., Картикеян Р., Мурали А., Рамалингам С. Связь между уровнем глюкозы в крови, сопутствующими заболеваниями и исходами лечения пациентов с COVID-19 в больнице третичного звена // Инфекционные болезни: новости, мнения, обучение. 2023. Т. 12, № 4. С. 33-38. DOI: https://doi.org/10.33029/2305-3496-2023-12-4-33-38 (англ.)

Coronavirus disease (COVID-19) emerged as a pandemic in December 2019. Till date COVID-19 has affected 594 million people worldwide, with a mortality of 6 million. India alone has witnessed over 44 million cases and half a million deaths [1]. Several risk factors have been identified that lead to disease progression to severe COVID-19 needing intensive care and can result in death. These risk factors include demographic factors such as age and sex, various laboratory test indicators including peripheral blood cell counts, C-reactive protein, alanine, and aspartate transaminases [serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT)], etc., and the presence of comorbidities like hypertension, diabetes, obesity, cerebrovascular disease, chronic obstructive pulmonary disease, chronic liver, and kidney diseases [2-4].

Arterial hypertension contributes to increased risk of severe illness due to COVID-19. Angiotensin converting enzyme-2 (ACE-2) receptor is said to enable the entry of severe acute respiratory syndrome (SARS) COVID-2 virus into the host cell, and drugs modulating ACE-2 is generally prescribed for hypertension, that increases susceptibility to COVID-19 and hence, poorer outcomes [5]. Similarly, increased severity of COVID-19 infection course with other pre-existing comorbidities like obesity, cerebrovascular diseases, etc., have been suggested in different studies [2-4].

Blood glucose levels are reported to be positively correlated with COVID-19, where patients with hyperglycemia have a higher mortality rate (7.3%) than those with normal blood glucose levels (0.9%) [6]. In addition, hyperglycemia, and a history of diabetes during admission was noted as a predictor of poor COVID-19 prognosis, with twice the risk of mortality and severe COVID in diabetes mellitus (DM) patients [7, 8]. In patients with DM, pre-DM, and obesity, impaired glucose metabolism is said to be the common factor that increased the risk of severe COVID-19 [9]. A study postulated that elevated glucose levels and aerobic glycolysis in monocytes can promote viral replication increasing susceptibility to COVID-19 infection [10]. Presence of pre-diabetes or newly diagnosed at the time of admission increases the incidence of admission to intensive care unit (ICU), when compared to absence of diabetes [11]. This highlights the need to evaluate blood glucose levels in COVID-19 patients, in addition to other comorbidities. The present study evaluated the association of blood glucose levels with outcome of COVID-19 patients at a tertiary care clinic and its role as a predictive indicator of outcome inCOVID-19 patients.

Material and methods

This was a cross-sectional study using retrospective data of COVID-19 confirmed patients admitted to a tertiary care hospital. The study was approved by Institutional Human ethics Committee (IHEC) (PSG/IHEC/2021/Appr/Exp/030). The medical records of 593 patients admitted between April 2020 to December 2020 were analyzed and their outcomes recorded.

Patients with confirmed and treated COVID-19 who were both ICU and non-ICU inpatient records were included for the study. Patient records of pregnant women and children below 18 years and patients with missing data were not included for the analyses. Demographic data, presence of comorbidities like diabetes mellitus, heart, liver, and renal diseases, laboratory tests conducted including fasting blood sugar (FBS), random blood sugar (RBS), HbA1c, C-reactive protein (CRP), red blood cell (RBC) and white blood cell (WBC) count, creatinine, urea levels, etc. were collected.

Statistical analysis

Data was analyzed using SPSS software version 25.0 and Microsoft Excel. Continuous data was represented as mean ± standard deviation (SD). Categorical data was represented as percentage and frequencies. Two-tailed independent t-test was used to compare means of continuous variables. Pearson’s chi square and Fisher’s exact tests were used to evaluate the association of categorical variables with outcomes (live and death). Odds ratio (OR), and 95% confidence interval (CI) were calculated to determine the risk factors associated with outcomes. Statistical significance was considered at P values less than 0.05.

Results

The medical records of 593 confirmed COVID-19 patients were included in this study, among which 396 were males (66.78%) and 197 were females (33.22%). Patients’ age ranged between 15-99 years with a mean (±SD) age of live patients being 50.93±14.36 years and of dead patients being 63.92±14.99 years, which was significantly different (p=0.000). Majority of the patients manifested comorbidities (n=370, 62.4%), and were not admitted to the ICU (n=543, 91.6%). Of total 593 patients, 554 were alive (93.4%) and 39 were dead (6.6%).

Mean values of laboratory tests conducted and frequencies of comorbidities manifested by the patients are summarized in tables 1 and 2. Table 3 lists the comparison of means of laboratory findings between live and dead patients. Highly significant difference was observed between the outcome groups with respect to mean pulse, RR interval (inter-beat interval), oxygen saturation (SpO2), CRP, WBC, urea, creatinine, total, direct and indirect bilirubin (TBIL, DBIL, IBIL), aspartate and alanine transaminases (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT)), alkaline phosphatase (ALP), albumin, and globulin (p<0.0001).Significant differences, however, were observed with respect to mean partial pressure of oxygen (PaO2) (p=0.002), partial pressure of carbon dioxide (PaCO2) (p=0.032), SGPT (p=0.019), gamma-glutamyl transferase (GGT) (p=0.012) values between the outcome groups.

Using Pearson’s Chi square test and Fisher’s exact test, significant association of outcomes, were observed with sex (p=0.036), comorbidities (p=0.003), diabetes mellitus (p=0.014), RBS (p=0.042), systemic hypertension (p=0.02), heart disease (p=0.001), liver (p=0.012), and renal abnormalities (p=0.008), see Table 4.

Univariate analysis of risk estimate in patients with COVID-19 revealed odds ratio of 0.419 (95% CI 0.182-0.967) for sex, 3.542 (95% CI 1.460-8.593) for comorbidities, 2.403 (95% CI 1.173-4.921) for diabetes mellitus, 1.953 (95% CI 1.014-3.759) for RBS, 2.146 (95% CI 1.117-4.124) for systemic hypertension (SHT), 4.553 (95% CI 2.069-10.023) for heart diseases, 29.892 (95% CI 95% CI, 2.649-333.311) for liver diseases and 11.458 (95% CI 2.470-53.153) for renal diseases, see Table 5.

Discussion

Several studies points at different risk factors and markers in patients with severe COVID-19 complications [2-4, 12]. Hematological markers such as lymphocyte count, neutrophil count, inflammatory markers like CRP, erythrocyte sedimentation rate, interleukin-6, creatine kinase, SGOT, and markers involved in coagulation, followed by acute respiratory distress syndrome (ADRS), which marks the critical stage of COVID-19, have been identified [12]. Other risk factors that has been found to increase the incidence of severe COVID-19 are hypertension, diabetes, cardiovascular and cerebrovascular diseases, etc. [4]. However, there is lacuna of research on risk factors involved in outcomes of COVID-19 patients in India.

Aging is known to cause changes in immune system, resulting in gradual decline in ability to fight infections and hence increasing susceptibility to coronavirus infections as well as determining progression and outcome of disease. Therefore, elderly population are most affected [13]. Among the cases included in this study, 93.4% were alive and 6.6% were dead. There was significant difference in mean age between the live and dead cases, where mean (SD) age of dead cases was 63.92 (14.99) years. A meta-analysis conducted by Starke et al., 2021, reported a 7.4% increase in risk of mortality with age, along with disease severity [14].

In the present study, sex (p=0.036), comorbidities like RBS (p=0.042), systemic hypertension (p=0.02), heart disease (p=0.001), liver (p=0.012), and renal abnormalities (p=0.008), were significantly associated with outcomes of COVID-19. A meta-analysis of studies conducted in India reported around 50.5% of COVID-19 cases who died had history of comorbidities, and diabetes was cited as the leading comorbidity, followed by chronic heart diseases and hypertension [15]. However, other studies reported variable prevalence of diabetes, hypertension, heart disease, chronic kidney diseases, etc. [2, 4, 7, 16].

History of diabetes and fasting plasma glucose were previously reported as independent predictors of poor outcomes [7]. Several other studies highlighted the importance of imbalance in fasting blood glucose levels and diabetes in predicting outcomes of COVID-19 [17-20]. In the present study, however, RBS level (OR 1.953; 95% CI 1.014-3.759) and diabetes (OR 2.403; 95% CI 1.173-4.921) influenced the outcomes of the patients, along with other comorbidities. Patients with high RBS at admission were reported to be susceptible to poor outcomes, but there is a lacuna of studies that could establish RBS as an independent predictor like that of FBS [19]. Nevertheless, monitoring glucose levels at admission is necessary, as even a small increase can substantially increase the risk of ICU admission or mortality [20].

The current study also found significant difference in mean values of different blood parameters like CRP, urea, creatinine, SGOT, SGPT, ALP, bilirubin, albumin, globulin, SpO2, PaO2, PaCO2, etc., between live and dead COVID-19 cases. Liu et al., reported higher WBC, CRP, creatine kinase, etc., in ICU patients [7], Gao et al., reported the role of high sensitivity CRP in monitoring progression of disease [2], and a meta-analysis showcased elevated levels of CRP, SGOT, and SGPT in patients with severe COVID [3]. These marker patterns are indicated in severe disease patients compared to mild COVID and thus, could help risk stratification [12].

Conclusion

The present study conducted in a tertiary care centre in South India highlights the significant influence of diabetes and blood sugar levels on COVID-19 disease outcomes, along with other comorbidities.

ЛИТЕРАТУРА/REFERENCES

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ГЛАВНЫЙ РЕДАКТОР
Горелов Александр Васильевич
Академик РАН, доктор медицинских наук, заведующий кафедрой инфекционных болезней и эпидемиологии НОИ «Высшая школа клинической медицины им. Н.А. Семашко» ФГБОУ ВО «Российский университет медицины» Минздрава России, профессор кафедры детских болезней Клинического института детского здоровья им. Н.Ф. Филатова ФГАОУ ВО Первый МГМУ им И.М. Сеченова Минздрава России (Сеченовский Университет), заместитель директора по научной работе ФБУН ЦНИИ Эпидемиологии Роспотребнадзора (Москва, Российская Федерация)

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