COVID-19 has been prevalent in many countries in the world, and the number of deaths is rising daily. Identification of early warning signs for severe COVID-19 and timely intervention may become the urgent issues.
The results of the present study showed that there were significant differences in age, cancer incidence, NLR, CRA between the severe COVID-19 patients and mild COVID-19 patients, and there was a positive correlation between age, cancer, NLR, CAR and severe COVID-19 (P < 0.05). In the multivariate analysis logistic regression model, high CAR (CAR > 0.296) was a significantly independent predictor for severe COVID-19 (OR = 17.652, P = 0.001), as well as NLR and age, which was in accordance with previous studies [14, 15]. An ambispective cohort study by Li et al. indicated that older age, underlying hypertension and high cytokine levels were significantly associated with severe COVID-19 on admission. Compared with non-severe cases, inflammation-related marker levels such as CRP and erythrocyte sedimentation rate were significantly higher in severe cases. Low ALB was observed in critically ill cases compared with severely ill cases. Huang et al. reported that ICU patients had higher plasma levels of inflammatory cytokines such as IL-2, IL-7, IL-10, GCSF, IP10, MCP1, MIP1A and TNF-α than non-ICU patients, which reflected the obvious inflammatory reaction in severe and critical patients and was consistent with our results .
CRP, an acute-phase protein, is a sensitive systemic marker of inflammation and tissue damage. It was speculated that CRP may have significant proinflammatory effects by binding to ligands exposed on cells or other autologous structures as a result of infection, inflammation, and other pathologies, and then triggering complement activation, eventually it may exacerbate tissue damage and lead to more severe disease. Previous studies reported that CRP was a poor independent prognostic factor for patients with cardiovascular disease, non-small cell lung cancer and gastric cancer [17–19]. A retrospective study by Li et al. lately reported that the rising of CRP can be used as indicators of disease progression in patients with COVID-19.
ALB concentration is negatively associated with the systemic inflammatory response due to increased catabolism and the down-regulation of hepatic synthesis by cytokines TNF-α. ALB, associated with inflammation and nutritional status, was revealed to be significantly related to poor survival in previous studies [22, 23]. Miura et al. concluded that preoperative ALB could predict overall survival in patients with non-small cell lung cancer . A retrospective multicenters study by Gong et al. indicated that lower albumin was associated with severe COVID-19.
As expected, we observed a strong positive association between CAR and severe COVID-19. The CAR, the ratio of CRP to ALB, is considered an important marker of the systemic inflammatory response and more accurately reflects the balanced relationship between the severity of inflammatory reactions and the immune state. The CAR was a widely used marker for the assessment of the prognosis of patients with cancers. The increased CAR indicated poor clinical prognosis. Recent studies revealed that the CAR was predictive of disease progression and mortality in patients with cancerss [12, 24, 25]. The result of Miyamoto et al. concluded that CAR was an independent factor to predict short-term survival of within two weeks, in particular, CAR is a useful tool for predicting survival times in end-stage patients with or without cancer .
To the best of our knowledge, our study is the first to observe a significantly positive association between CAR and the severity of patients with COVID-19. However, there were limitations to the current study. Firstly, our study was an observational study, further prospective studies are needed to confirm our findings. Secondly, missing data on some pretreatment variables may cause bias in the estimation and reduce the representativeness of the samples. Finally, the statistical limitations of the study due to the small sample size, especially in mild and critically ill patients.