key: cord-0702480-exdkyf9k
authors: Wang, Jian; Zhu, Li; Liu, Longgen; Yan, Xuebing; Xue, Leyang; Huang, Songping; Zhang, Biao; Xu, Tianmin; Ji, Fang; Li, Chunyang; Ming, Fang; Zhao, Yun; Cheng, Juan; Chen, Kang; Zhao, Xiang-an; Sang, Dawen; Guan, Xinying; Chen, Xiaobing; Yan, Xiaomin; Zhang, Zhaoping; Liu, Jiacheng; Huang, Rui; Zhu, Chuanwu; Wu, Chao
title: Características clínicas y pronóstico de los pacientes de COVID-19 con síndrome metabólico: un estudio multicéntrico y retrospective
date: 2021-06-17
journal: Med Clin (Barc)
DOI: 10.1016/j.medcli.2021.05.014
sha: d90f96e35ff3efada32822de5c3a16db44f2d800
doc_id: 702480
cord_uid: exdkyf9k

Background Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P=0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P<0.001) and critical illness (4.4% vs. 0.5%, P=0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P<0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P=0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS. Antecedentes Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta. Métodos Se incluyeron retrospectivamente 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu, China. Se describieron las características clínicas de los pacientes con COVID-19 y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística. Resultados Cuarenta y cinco (19,3%) de los 233 pacientes de COVID-19 tenían EM. La mediana de edad de los pacientes de COVID-19 con EM fue significativamente mayor que la de los pacientes sin EM (53,0 años frente a 46,0 años, P=0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los dos grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%, P<0,001) y críticas (4,4% frente a 0,5%, P=0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome de dificultad respiratoria aguda en los pacientes con EM también fueron mayores que en los pacientes sin EM durante la hospitalización. El análisis multivariante mostró que la EM concurrente (odds ratio [OR] 7,668, intervalo de confianza [IC] del 95%: 3,062-19,201, P<0,001) y la linfopenia (OR 3,315, IC del 95%: 1,306-8,411, P=0,012) eran factores de riesgo independientes de enfermedad grave de COVID-19. En una mediana de seguimiento de 28 días tras el alta, se encontró neumonía bilateral en el 95,2% de los pacientes con EM, mientras que sólo el 54,7% de los pacientes sin EM presentaron neumonía bilateral. Conclusiones El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes de COVID-19 con EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes de COVID-19 con EM.

Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 . Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta.

Se incluyeron retrospectivamente 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu, China. Se describieron las características clínicas de los pacientes con COVID-19 y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística.

Cuarenta y cinco (19,3%) de los 233 pacientes de COVID-19 tenían EM. La mediana de edad de los pacientes de COVID-19 con EM fue significativamente mayor que la de los pacientes sin EM (53,0 años frente a 46,0 años, P=0,004).

No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los dos grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%, P<0,001) y críticas (4,4% frente a 0,5%, P=0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome 

El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes de COVID-19 con EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes de COVID-19 con EM.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading all over the world [1] . As of February 24, 2021, there were 111,762,965 confirmed cases of COVID-19 resulting in 2,479,678 deaths globally [1] . However, the severity and prognosis of COVID-19 differ across countries and regions according to previous reports [2] [3] [4] .

A growing body of evidence suggested that elderly patients and patients with comorbidities presented poor outcomes [2] [3] . More patients with hypertension (23.7% vs. 13.3%, P<0.001) and type 2 diabetes (16.2% vs. 5.7%, P<0.001) developed severe illness than non-hypertension and non-diabetes patients in a large retrospective study from China [2] . A retrospective study by matching age and gender found that COVID-19 patients with diabetes had worse outcomes compared to patients without diabetes [5] . Wang et al. reported that patients admitted to intensive care units (ICU) presented higher proportions of hypertension and type 2 diabetes compared to non-ICU patients [4] . Another study also reported that the proportion of hypertension in deceased patients was significantly higher than recovered patients [3] . These results suggested that metabolic factors may be associated with prognosis of COVID-19 patients.

Metabolic syndrome (MS) consists of five determining factors, including obesity, elevated blood pressure, increased triglycerides and cholesterol, and impaired glucose tolerance [6, 7] . MS is generally regarded as a risk factor for progression of cardiovascular disease and type 2 diabetes [7] . However, the impacts of MS on COVID-19 remain unclear. This study aimed to describe the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge in a multicenter cohort of COVID-19 patients in Jiangsu province, China.

The clinical data of 342 confirmed COVID-19 patients form 10 hospitals in 10 cites in Jiangsu, China between January 18, 2020 and February 26, 2020 were retrospectively collected and reviewed. Confirmed patients were diagnosed based on the criterion of World Health Organization (WHO) interim guidance [8] . The diagnostic criteria of acute respiratory distress syndrome (ARDS) was based on previous study [9] . To reduce the impact of potential factors, patients under 12 years and pregnant women were excluded [10] . In addition, patients with unavailable data of body mass index (BMI), blood pressure, triglycerides (TG), total cholesterol (TC), and fasting blood glucose (FBG) were also excluded. The study was approved by the Ethics Committee of these hospitals and the written informed consent was waived.

The medical records of patients were reviewed by health care workers in each medical center. The characteristics of epidemiology, laboratory, radiology, treatment, and prognosis were collected from medical records. Routine physical examination, including height, Page 9 of 35 J o u r n a l P r e -p r o o f 9 weight, systolic pressure and diastolic pressure, were measured on admission. The computational formula of BMI was weight (kg) divided by the square of height (m) [7] . All data was entered in a computerized database and checked by different researchers for further analysis.

Central obesity (waist circumference ≥90 cm in male or ≥80 cm in female) is one of the diagnostic criteria of MS [7] . However, waist circumference data were not available in our study. The diagnosis of obesity was based on BMI index [11] [12] [13] . The diagnostic criterions of metabolic syndrome were as follows according previous studies: (1) Obesity, BMI ≥ 28 kg/m 2 ; (2) TG, > 150 mg/dL or use of triglyceride lowering medication; (3) TC, > 200 mg/dL or use of cholesterol lowering medication; (4) Blood pressure, systolic pressure > 130 mmHg and/or diastolic pressure > 85 mmHg or use of blood pressure lowering medication; (5) FBG, > 5.6 mmol/L or use of diabetes medication [6, 7, 11, 14] . The presence of any three of the above five criterions was considered as metabolic syndrome.

In addition, previous study reported that a determinant effect of age > 50 years on prognosis of COVID-19 patients [15] . Therefore, the age of 50 years was used as a threshold to analyze the association between age and severe illness in our study. Severe illness of COVID-19 was defined according to the current guideline as follows: (1) respiratory frequency ≥ 30/min, (2) pulse oximeter oxygen saturation ≤ 93% at rest, (3) oxygenation index ≤ 300 mmHg [16] . Critical illness of COVID-19 was defined as follows: (1) respiratory failure and requiring mechanical ventilation, (2) shock, (3) with other organ failure that requires ICU care [16] . The poor prognosis was defined as developed respiratory failure, ARDS, severe illness, critical illness, or admission to ICU during hospitalization in this study.

COVID-19 patients were followed up for 3 to 6 weeks after discharge. SARS-CoV-2 nucleic acid in throat swab samples, blood routine examination, biochemical examination, and chest CT were tested during follow-up. Additionally, symptoms of patients were also recorded.

Continuous variables were described as means (standard deviations) or medians (interquartile range (IQR)). Categorical variables were showed as the counts and percentages. Two-sample t tests or Mann-Whitney U were used for continuous variables, and Chisquare tests or Fisher's exact tests were used to compare the categorical variables. Binary logistic regression was used to analyze the risk factors of severe illness. Variables with P values <0.05 in the univariate analysis were further entered into a multivariate logistic regression analysis. P<0.05 was considered as statistically significant. Age, gender, smoking, lymphopenia and leukopenia were reported to be associated with the severity of COVID-19 [17] . Therefore, these variables were also adjusted in the multivariate logistic regression. SPSS version 22.0 software (SPSS Inc., Chicago, IL, United States) was used for the data analysis.

Page 11 diabetes (20.0% vs. 4.8%, P=0.001) in patients with MS were significantly higher than non-MS patients. Other comorbidities were not significantly different between two groups. In addition, symptoms at onset of illness were also comparable between MS patients and non-MS patients (Table 1) .

The most common symptoms were fever (72.1%) and cough (61.4%), followed by fatigue (18.9%), sore throat (11.6%), muscle ache Table 2 ).

The proportions of onset symptoms such as fever and cough were similar between patients with MS and without MS. The proportions of leukopenia and lymphopenia were also comparable between two groups. Patients with MS showed higher levels of FBG (median, 6.3 mmol/L vs. 5.6 mmol/L, P<0.001), TG (median, 177 mg/dL vs. 98.2 mg/dL, P<0.001), and TC (median, 162 mg/dL vs. 144 mg/dL, P<0.001) than non-MS patients. There was no significant difference in the proportion of abnormal chest CT images between two groups ( Table 2) .

The proportions of patients treated with atomized inhalation of interferon α-2b, lopinavir/ritonavir, or arbidol were 45.9%, 72.5%, and 46.8%, respectively. During hospitalization, 22 (9.4%) patients developed respiratory failure and 3 (1.3%) patients progressed to We further analyzed the clinical characteristics and prognosis of patients with different numbers of MS components (Table S1) Table   4 ).

Among these COVID-19 patients, 107 patients (86 non-MS patients and 21 MS patients) with available follow-up data after discharge were analyzed. The median follow-up days of non-MS patients and MS patients were 28 (IQR 28-33) days and 28 (IQR 28-31.5) days, respectively. The laboratory and chest CT examinations during follow-up were shown in Table 5 . The median WBC and lymphocyte counts were 6.6 (IQR 5.8-7.6) ×10 9 /L and 2.1 (IQR 1.8-2.6) ×10 9 /L in MS patients, which were significantly higher than that of non-MS patients. However, the proportions of leukopenia and lymphopenia were comparable between non-MS patients and 

Several impact factors of severity and prognosis of COVID-19 have been reported which included age, gender, comorbidities, etc [2] [3] [4] . Nevertheless, few studies reported the impacts of MS on COVID-19. MS is a global epidemic and the complications of MS are diverse [7] . The common consequences including cardiovascular disease and type 2 diabetes [7] . In our study, 19.3% of COVID-19 patients had MS. The global prevalence of MS was ranged 20%-35% in general population [18, 19] . The prevalence of MS was consistent with general population in our study, which suggested that MS may not a susceptible factor of COVID-19.

Consistent with previous studies, the most common symptoms were fever and cough in our study [20, 21] . There were no significant differences in clinical features between with MS patients and non-MS patients. About one third of patients presented leukopenia and lymphopenia on admission, while the proportions of leukopenia and lymphopenia were comparable between two groups. Also, the abnormal images of chest CT were not significantly different between two groups. These results indicated that concurrent MS may not associate with clinical manifestation of COVID-19.

Although no patient died in our study, 27 (11.6%) patients had severe illness and 18 (7.7%) patients were admitted to the ICU.

Compared with non-MS patients, more MS patients developed severe illness and were admitted to the ICU. In addition, the proportions of respiratory failure and ARDS patients in MS patients were also significantly higher than non-MS patients. Despite the laboratory examinations were comparable between non-MS patients and MS patients, chest CT findings were more severe in MS patients during follow-up. These results implied that MS may be a risk factor of adverse outcomes of COVID-19. Further logistic regression analysis also demonstrated that concurrent MS increased the risk of severe illness in our study. Although previous studies found elderly patients had a worse prognosis [3, 20] , age was not associated with severe illness in our study. The possible interpretation may be that the age of patients was younger in our study than other studies [3, 20] . The treatment drugs, including atomized inhalation of interferon α-2b, lopinavir/ritonavir, or arbidol were comparable between MS patients and non-MS patients.

Currently, the mechanisms of the impact of MS on COVID- 19 are not yet clear. Bijani et al. reported that MS was an independent risk factor of hypoxaemia in influenza A (H1N1) [10] , which was associated with the severity of diseases. Similar results were observed in our study which found that more MS patients had respiratory failure and ARDS than non-MS patients during hospitalization. As an important determinant of MS, obesity could affect the progress of the many diseases [22, 23] . Excessive adipose accumulation may affect energy metabolism, neuroendocrine function, and immune function [24] . Previous studies found that obesity could result in functional disorder of the body defense mechanisms. The mechanism may be interpreted as adipose accumulation induce the chronic aggravation of the pro-inflammatory responses of Th-1 type [25, 26] . Animal experiment also demonstrated that obesity could decreased the expression of pro-inflammatory cytokines and the cytotoxicity of natural killer cells [27] . Several studies of influenza Page 17 of 35 J o u r n a l P r e -p r o o f 17 also found obesity was a risk factor for incidence of severe complications and mortality [28] [29] [30] . Blood glucose level was another determinant of MS. Previous study reported that high blood glucose level was an independent risk factor of mortality and morbidity in patients with severe acute respiratory syndrome (SARS) [31] . Elevated blood glucose might reflect the severity of viral infection with multisystem involvement, which may increase the risk of hypoxia and mortality in patients with SARS [31] . Our study also analyzed impacts of the numbers of MS components on COVID-19 patients which showed the severity of COVID-19 increased with the numbers of MS components.

Although some studies have reported the impacts of metabolic factors on COVID-19 and other virus infection-related respiratory diseases [3, 4, 10] , association of concurrent MS with the prognosis of COVID-19 needs to be explored. COVID-19 patients with MS are more likely to develop severe complications. However, no patient was deceased in our study. Thus, the impacts of MS on the mortality of COVID-19 deserve further investigation. Furthermore, more than 90% patients remained had bilateral pneumonia in MS patients, which is significantly higher than non-MS patients during follow-up. Thus, long-term follow-up is necessary for these patients.

Our study has some limitations. First, our findings might be limited by the small sample size. However, by including consecutive COVID-19 patients in 10 designated hospitals from 10 cities, we consider our study population is much representative of cases diagnosed and treated in Jiangsu, China. Second, the association of MS and fatal outcome could not be analyzed in our study. Third, we only included hospitalized COVID-19, while those who were asymptomatic or had mild cases and treated at home were not included in our study. Thus, our study may represent the more severe COVID-19 patients. Fourth, this study used BMI and total cholesterol as alternative criteria of waist circumference and high-density lipoprotein cholesterol since these indexes were not routine 

Novel Coronavirus (COVID-19) Situation

Clinical Characteristics of Coronavirus Disease 2019 in China

Clinical Characteristics of 113 Deceased Patients With Coronavirus Disease 2019: Retrospective Study

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan

Clinical Characteristics and Risk Factors for Mortality

Harmonizing the Metabolic Syndrome: A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute

Diagnosis and Management of the Metabolic Page

American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance

Acute respiratory distress syndrome: the Berlin Definition

Metabolic Syndrome as an Independent Risk Factor of Hypoxaemia in Influenza A (H1N1) 2009 Pandemic

Metabolic Syndrome and Liver Steatosis Occur at Lower Body Mass Index in US Asian Patients With Chronic Hepatitis B

Use of BMI as the Marker of Adiposity in a Metabolic Syndrome Severity Score: Derivation and Validation in Predicting Long-Term Disease Outcomes

A New Look at the Genetic and Page

Environmental Coherence of Metabolic Syndrome Components

Hepatitis B Virus Infection and Risk of Non-Alcoholic Fatty Liver Disease: A Population-Based Cohort Study

The Effect of Age on Mortality in Patients With COVID-19: A Meta-Analysis With 611,583 Subjects

National Health Commission. Guidelines for the Diagnosis and Treatment of coronavirus disease 2019 (COVID-19) by the National Health Commission

Potential Effects of Coronaviruses on the Cardiovascular System: A Review

Dairy Consumption and Risk of Metabolic Syndrome: A Meta-Analysis

Nutritional Challenges in Metabolic Syndrome

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Cardiorespiratory Fitness Attenuates the Effects of the Metabolic Syndrome on All-Cause and Cardiovascular Disease Mortality in Men

Metabolic Syndrome in a sub-Saharan African Setting: Central Obesity May Be the Key Determinant

Adipose Tissue as an Endocrine Organ

Nutrition and the Immune System: An Introduction

Increased T-helper Interferon-Gamma-Secreting Cells in Obese Children

Diet-induced Obese Mice Have Increased Mortality and Altered Immune Responses When Infected With Influenza Virus

Clinical Aspects of 2009 Pandemic Influenza A (H1N1) Virus Infection in Austria

Prognostic Factors for Fatal Adult Influenza Pneumonia

Barboza P; epidemic intelligence team at InVS. Epidemiology of Fatal Cases Associated With Pandemic H1N1 Influenza

Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS

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