Department of Health Sciences, University of Genoa, Genoa, Italy.
Department of Health Sciences, University of Genoa, Genoa, Italy.
Mult Scler Relat Disord. 2022 Jul;63:103909. doi: 10.1016/j.msard.2022.103909. Epub 2022 May 25.
Many risk factors for the development of severe forms of Covid-19 have been identified, some applying to the general population and others specific to Multiple Sclerosis (MS) patients. However, a score for quantifying the individual risk of severe Covid-19 in patients with MS is not available. The aim of this study was to construct such score and to evaluate its performance.
Data on patients with MS infected with Covid-19 in Italy, Turkey and South America were extracted from the Musc-19 platform. After imputation of missing values, data were separated into training data set (70%) and validation data set (30%). Univariable logistic regression models were performed in the training dataset to identify the main risk factors to be included in the multivariable logistic regression analyses. To select the most relevant variables we applied three different approaches: (1) multivariable stepwise, (2) Lasso regression, (3) Bayesian model averaging. Three scores were defined as the linear combination of the coefficients estimated in the models multiplied by the corresponding value of the variables and higher scores were associated to higher risk of severe Covid-19 course. The performances of the three scores were compared in the validation dataset based on the area under the ROC curve (AUC) and an optimal cut-off was calculated in the training dataset for the score with the best performance. The probability of showing a severe Covid-19 course was calculated based on the score with the best performance.
3852 patients were included in the study (2696 in the training dataset and 1156 in the validation data set). 17% of the patients required hospitalization and risk factors for severe Covid-19 course were older age, male sex, living in Turkey or South America instead of living in Italy, presence of comorbidities, progressive MS, longer disease duration, higher Expanded Disability Status Scale, Methylprednisolone use and anti-CD20 treatment. The score with the best performance was the one derived using the Lasso selection approach (AUC= 0.72) and it was built with the following variables: age, sex, country, BMI, presence of comorbidities, EDSS, methylprednisolone use, treatment. An excel spreadsheet to calculate the score and the probability of severe Covid-19 is available at the following link: https://osf.io/ac47u/?view_only=691814d57b564a34b3596e4fcdcf8580.
The originality of this study consists in building a useful tool to quantify the individual risk for Covid-19 severity based on patient's characteristics. Due to the modest predictive ability and to the need of external validation, this tool is not ready for being fully used in clinical practice to make important decisions or interventions. However, it can be used as an additional instrument to identify high-risk patients and persuade them to take important measures to prevent Covid-19 infection (i.e. getting vaccinated against Covid-19, adhering to social distancing, and using of personal protection equipment).
已经确定了许多导致 COVID-19 严重形式的风险因素,其中一些适用于普通人群,另一些则特定于多发性硬化症 (MS) 患者。然而,目前尚无针对 MS 患者 COVID-19 严重程度个体风险的评分。本研究旨在构建这样的评分,并评估其性能。
从 Musc-19 平台提取了意大利、土耳其和南美洲感染 COVID-19 的 MS 患者的数据。在缺失值插补后,数据分为训练数据集(70%)和验证数据集(30%)。在训练数据集中进行单变量逻辑回归模型,以确定纳入多变量逻辑回归分析的主要风险因素。为了选择最相关的变量,我们应用了三种不同的方法:(1)多变量逐步法,(2)套索回归,(3)贝叶斯平均模型。将三个评分定义为模型中估计的系数乘以变量相应值的线性组合,评分越高,COVID-19 严重程度的风险越高。在验证数据集中基于 ROC 曲线下面积(AUC)比较了三种评分的性能,并在训练数据集中计算了性能最佳评分的最佳截断值。基于性能最佳的评分计算出现 COVID-19 严重程度的概率。
共有 3852 名患者纳入研究(2696 名在训练数据集中,1156 名在验证数据集中)。17%的患者需要住院治疗,COVID-19 严重程度的危险因素包括年龄较大、男性、居住在土耳其或南美洲而非意大利、合并症、进展性 MS、疾病持续时间较长、更高的扩展残疾状态量表、使用甲基强的松龙和抗 CD20 治疗。性能最佳的评分是使用套索选择方法得出的(AUC=0.72),并使用以下变量构建:年龄、性别、国家、BMI、合并症、EDSS、甲基强的松龙使用、治疗。计算评分和 COVID-19 严重程度概率的 Excel 电子表格可在以下链接获得:https://osf.io/ac47u/?view_only=691814d57b564a34b3596e4fcdcf8580。
本研究的新颖之处在于构建了一种有用的工具,可根据患者特征量化 COVID-19 严重程度的个体风险。由于预测能力有限,且需要外部验证,因此该工具尚未准备好在临床实践中全面用于做出重要决策或干预。然而,它可以作为识别高危患者的附加工具,并说服他们采取重要措施预防 COVID-19 感染(即接种 COVID-19 疫苗、遵守社交距离和使用个人防护设备)。