Elevated Level of C Reactive Protein May Predict Risk for Worsening COVID-19

Higher levels of C reactive protein (CRP) may be a predictive marker in determining which patients with mild coronavirus disease 2019 (COVID-19) will progress to a severe case.

Higher levels of C reactive protein (CRP) may be a predictive marker in determining which patients with mild coronavirus disease 2019 (COVID-19) will progress to a severe case, according to study results published in Open Forum Infectious Diseases.

In this case series, researchers used data from patients admitted to a public health treatment center in Changsha, China from January 17, 2020 to February 20, 2020. All patients were diagnosed with laboratory-confirmed COVID-19 and were deemed as nonsevere case on admission. Knowing that a subset of mild cases will develop into severe COVID-19, researchers described the clinical characteristics of the patients, analyzed related factors, and explored any predictable marker of disease aggravation.

Progression from a mild to severe case of COVID-19 was defined using 1 of the following criteria: respiratory rate ≥ 30/min; oxygen saturation ≤ 93%; PaO2/FiO2 ≤ 300 mmHg; progression of lung lesions > 50% within 24 to 48 hours; implementation of mechanical ventilation; shock; or, admission to intensive care unit.

Of the 209 adults patients included in the study, 16 patients (62.5% men) progressed to severe cases after admission by February 20, 2020, including 2 patients who became critically ill. The median duration from the onset of symptoms to disease progression was 9.5 days (range, 3-12 days). The most common comorbidities were hypertension (n=5), cerebrovascular disease (n=2), and cardiovascular disease (n=1). The most common symptoms were fever (87.5%), cough (56.3%), anorexia (56.3%), and fatigue (56.3%).

All 16 patients showed pulmonary exudative lesion on chest computed tomographic scans, 10 of whom showed ground glass opacity in the lungs. Noninvasive ventilation, high-flow oxygen therapy, and invasive mechanical ventilation were adopted in 6.3%, 18.8% and 6.3% of patients, respectively.

Compared with patients with a mild case of COVID-19, the patients with worsening condition were significantly older (median age, 54 vs 42 years; P =.021). Patients with a severe case of COVID-19 also showed higher ratios of symptoms than those with mild cases including fatigue, chills, anorexia, dyspnea, and headache. In addition, patients with severe COVID-19 had lower lymphocyte proportion (median, 23.9% vs 27.7%; P =.021), as well as higher levels of CRP (median, 43.8 vs 12.1 mg/L; P <.001) and aspartate aminotransferase (median, 29.2 vs 23.2 U/L; P =.010).

In the univariate analysis, the association between the progression of mild to severe case of COVID-19 and clinical characteristics were as follows:

  • Hypertension (odds ratio [OR], 3.533; 95% CI, 1.123-11.120; P =.031).
  • Creatine kinase (OR, 1.006; 95% CI, 1.000-1.012; P =.047).
  • Lymphocyte proportion (OR, 0.932; 95% CI, 0.876-0.991; P =.025).
  • Aspartate aminotransferase (OR, 1.044; 95% CI, 1.001-1.088; P =.044).
  • CRP (OR, 1.049; 95% CI, 1.028-1.070; P <.001).

In the multivariate analysis, only CRP was significantly associated with the progression to a severe case of COVID-19 (OR, 1.056; 95% CI, 1.025-1.089; P <.001).

The receiver operating characteristic curve analysis indicated a moderate accuracy, with an area under the curve of 0.844 (95% CI, 0.761–0.926; P <.001) for CRP to predict the possibility of patients developing a severe case of COVID-19. The optimal threshold value was 26.9 mg/L and was associated with a sensitivity of 81.3% and specificity of 79.3%.

Related Articles

Although more studies are needed with larger sample size, researchers concluded that because the elevated CRP occurred before the disease progressed, CRP “could be a valuable marker to predict the possibility of aggravation of non-severe COVID-19 [in] patients, which can help health care workers identify those patients at an early stage for early treatment.”


Wang G, Wu C, Zhang Q, et al. C reactive protein level may predict the risk of COVID-19 aggravation [published online April 29, 2020]. Open Forum Infect Dis. doi:10.1093/ofid/ofaa153