Shoukat Maria, Khan Haseeb, Nazish Moona, Rehman Abdur, Raashid Sheharyar, Ahmed Saad, Munir Wajid, Alrefaei Abdulwahed Fahad, Umair Massab, Bin Abid Muhammad Osama, Akhtar Nasim, Zaman Wajid, Badshah Malik
Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
National Institute of Health, Islamabad, Pakistan.
BMC Infect Dis. 2025 Jan 14;25(1):59. doi: 10.1186/s12879-024-10314-2.
C-reactive protein (CRP) is one of the most commonly monitored inflammatory markers in patients with COVID-19 to gain insight into the inflammation level in the body and to adopt effective disease management and therapeutic strategies. COVID-19 is now less prevalent, and the study of CRP as a biomarker of inflammation still needs deeper understanding, particularly in understanding its role among patients with comorbidities, which are known to influence inflammatory responses and increase the risk of severe outcomes during acute and chronic infectious diseases. The objective of this study was to evaluate the association of major comorbidities such as ischemic heart diseases, diabetes, chronic kidney disease, hypertension, and lung infections e.g. tuberculosis with serum CRP levels in hospitalized COVID-19 patients.
This study involves a retrospective observational framework to monitor CRP levels among hospitalized COVID-19 patients after getting ethical approval and patient consent. The information on underlying health conditions or comorbidities and age was collected from the patient data files. The requirement of ventilation, ICU admission, mortality & survival, and CRP levels were monitored based on their daily updates in the data file. Furthermore, the association of CRP levels was evaluated with disease severity and mortality.
In this study 618 out of 750 hospitalized COVID-19 patients, of which 62.6% were male and 37.4% were female, the levels of serum CRP were significantly influenced by age and comorbidities. No case of hospitalization was observed in children (≤ 14 years) during the study period, while 38.3% of patients belonged to the old age group (≥ 65 years). Comorbidity status varied, with 36.1% of patients without having any comorbidities, 27.8% with one, 23.6% with two, and 12.5% with three or more comorbidities. Descriptive statistics revealed that the CRP levels in the study population averaged 88.92 mg/L (SD = 63.95), ranging from < 1 mg/L to 900 mg/L, with significant variations observed across different comorbidities and age groups. CRP levels, analyzed by the Kruskal-Wallis test, showed significant variations in different age groups of COVID-19 patients (χ² = 66.741, df = 3, p < 0.001). Moreover, pairwise comparisons showed considerable differences between young and middle-aged groups (Z = -2.724, p < 0.01) and young and old age groups of COVID-19 patients (Z = -3.970, p < 0.001). The most prevalent comorbidities observed in COVID-19 patients in this study were hypertension (42.1%), diabetes (33.8%), ischemic heart disease (16.5%), asthma (11.2%), chronic kidney disease (7.9%) and Tuberculosis (1.9%). The CRP levels fluctuate and also significantly differ among different comorbidities. COVID-19 patients with diabetes were observed to have higher CRP levels than non-diabetics (mean CRP: 126.96 mg/L vs. 88.92 mg/L, Z = -5.724, p < 0.001), and those with hypertension also encountered elevated CRP (mean CRP: 355.37 vs. 276.19 mg/L, Z = -5.447, p < 0.001). Similar tendencies were detected in COVID-19 patients with ischemic heart disease (mean CRP: 385.43 mg/L, Z = -4.704, p < 0.001), chronic kidney disease (mean CRP: 412.37 mg/L, Z = -4.206, p < 0.001) as well as with tuberculosis (mean CRP: 458.08 mg/L, Z = -2.914, p < 0.01). CRP levels on days 1 and 3 of hospitalization showed a decline (88.92 mg/L to 67.89 mg/L), representative of a response to treatment to reduce the inflammation in the body. Furthermore, high levels of CRP were significantly associated with a high requirement of non-invasive ventilation (mean CRP: 110.80 mg/L vs. 76.82 mg/L, p < 0.05), mechanical ventilation (mean CRP: 134.46 mg/L vs. 77.25 mg/L, p < 0.05) and ICU admission (mean CRP: 126.96 mg/L vs. 72.79 mg/L, p < 0.05). The Cox regression analysis showed that there is a considerable association of CRP level with the expected length of hospitalization, each 1-unit increase in CRP levels was associated with a 0.6% increase in extended stay risk (hazard ratio = 1.006, 95% CI: 1.004-1.008, p < 0.001). Furthermore, the logistic regression analysis performed on CRP levels that was monitored on the first day of hospitalization, revealed that there was a 2.7% increase in mortality odds with each unit increase in CRP (odds ratio = 1.027, 95% CI: 1.022-1.033, p < 0.001), which suggest CRP as a potential mortality predictor.
Elevated CRP levels in COVID-19 patients with comorbidities like diabetes, hypertension, ischemic heart disease, and chronic kidney disease were strongly associated with increased disease severity, including higher ventilation requirements and mortality. Patients with these comorbidities showed significantly higher CRP levels, which correlated with worse outcomes, including ICU admissions and prolonged hospital stays, emphasizing the importance of CRP as a predictor for severe complications in patients with infectious diseases along with one or more comorbidities.
C反应蛋白（CRP）是新型冠状病毒肺炎（COVID-19）患者中最常监测的炎症标志物之一，用于深入了解体内炎症水平，并采取有效的疾病管理和治疗策略。目前COVID-19的流行程度有所降低，对CRP作为炎症生物标志物的研究仍需更深入了解，尤其是在了解其在合并症患者中的作用方面，已知合并症会影响炎症反应，并增加急性和慢性传染病期间出现严重后果的风险。本研究的目的是评估缺血性心脏病、糖尿病、慢性肾脏病、高血压等主要合并症以及肺部感染（如结核病）与住院COVID-19患者血清CRP水平之间的关联。
本研究采用回顾性观察框架，在获得伦理批准和患者同意后，监测住院COVID-19患者的CRP水平。从患者数据文件中收集基础健康状况或合并症以及年龄的信息。根据数据文件中的每日更新情况，监测通气需求、入住重症监护病房（ICU）情况、死亡率和生存率以及CRP水平。此外，评估CRP水平与疾病严重程度和死亡率的关联。
本研究纳入了750例住院COVID-19患者中的618例，其中男性占62.6%，女性占37.4%，血清CRP水平受年龄和合并症的显著影响。研究期间未观察到儿童（≤14岁）住院病例，而38.3%的患者属于老年组（≥65岁）。合并症情况各不相同，36.1%的患者无任何合并症，27.8%的患者有一种合并症，23.6%的患者有两种合并症，12.5%的患者有三种或更多合并症。描述性统计显示，研究人群中的CRP水平平均为88.92mg/L（标准差=63.95），范围从<1mg/L到900mg/L，不同合并症和年龄组之间存在显著差异。通过Kruskal-Wallis检验分析的CRP水平显示，COVID-19患者的不同年龄组存在显著差异（χ²=66.741，自由度=3，p<0.001）。此外，成对比较显示COVID-19患者的青年组和中年组之间（Z=-2.724，p<0.01）以及青年组和老年组之间（Z=-3.970）存在显著差异，p<0.001）。本研究中COVID-19患者中最常见的合并症为高血压（42.1%）、糖尿病（33.8%）、缺血性心脏病（16.5%）、哮喘（11.2%）、慢性肾脏病（7.9%）和结核病（1.9%）。CRP水平在不同合并症之间波动且也存在显著差异。观察到患有糖尿病的COVID-19患者的CRP水平高于非糖尿病患者（平均CRP：126.96mg/L对88.92mg/L，Z=-5.724，p<0.001），患有高血压的患者CRP水平也升高（平均CRP：355.37对276.19mg/L，Z=-5.447，p<0.001）。在患有缺血性心脏病（平均CRP：385.43mg/L，Z=-4.704，p<0.001）、慢性肾脏病（平均CRP：412.37mg/L，Z=-4.206，p<0.001）以及结核病（平均CRP：458.08mg/L，Z=-2.914，p<0.01）的COVID-19患者中也检测到类似趋势。住院第1天和第3天的CRP水平呈下降趋势（8.....92mg/L至67.89mg/L），代表了对治疗的反应，以减轻体内炎症。此外，高水平的CRP与高无创通气需求（平均CRP：110.80mg/L对76.82mg/L，p<0.05）、机械通气（平均CRP：134.46mg/L对77.25mg/L，p<0.05）和入住ICU（平均CRP：126.96mg/L对72.79mg/L，p<0.05）显著相关。Cox回归分析显示，CRP水平与预期住院时间存在显著关联，CRP水平每增加1个单位，延长住院风险增加0.6%（风险比=1.0......，95%置信区间：1.004-1.008，p<0.001）。此外，对住院第一天监测的CRP水平进行的逻辑回归分析显示，CRP每增加1个单位，死亡几率增加2.7%（优势比=1.027，95%置信区间：1.022-1.033，p<0.001），这表明CRP是一种潜在的死亡预测指标。
患有糖尿病、高血压、缺血性心脏病和慢性肾脏病等合并症的COVID-19患者CRP水平升高与疾病严重程度增加密切相关，包括更高的通气需求和死亡率。患有这些合并症的患者CRP水平显著更高，这与更差的预后相关，包括入住ICU和延长住院时间，强调了CRP作为患有一种或多种合并症的传染病患者严重并发症预测指标的重要性。
