In this observational study, we have focused on the infection markers in severe and very severe patients with COVID-19. The serum levels of LDH, CRP, PCT and ferritin are markedly increased in very severe patients compared with severe COVID-19, suggesting that increased LDH, CRP, PCT and ferritin level might stand for more severe secondary bacterial infection and exacerbated COVID-19. Moreover, lymphocyte count is decreased in very severe patients compared with severe COVID-19, indicating that lower lymphocyte count correlate to poor prognosis in COVID-19.
In the present analysis, we firstly evaluated serum ferritin levels in COVID-19, which are significantly elevated during critical infection. The function of ferritin including iron binding and storage is associated with the immune and inflammatory response16. The reasons of increased ferritin include bacterial and/or viral infection, hemochromatosis and long-term transfusion17. When bacterial and/or viral infection takes place, the increase of serum ferritin is related to the release of iron in the reticuloendothelial system, the decrease of the ability of transporting ferritin in liver and spleen, and increased synthesis and release of intracellular ferritin18, 19. Some studies showed that patients with bacterial infection had higher ferritin level compared to viral infection20, 21. Previous review has also proposed a model that the inflammatory response to viral (IL-18/ferritin) presents as specific plasma patterns of immune biomarkers17. Moreover, elevation of serum ferritin levels predicts a poor outcome in hospitalized patients with influenza infection16. In the present study, the patients in severe and very severe COVID-19 both exhibits increase serum ferritin level, but the serum ferritin in very severe COVID-19 group is significantly higher than that of severe COVID-19 group. The increased ferritin might indicate severe secondary bacterial infection in COVID-19, and might be utilized as a marker of poor prognosis.
As we known, when inflammation or tissue damage happens, CRP can be significantly increased in serum, which is usually used as a unique inflammatory marker in the current clinical practice22. On the other hand, PCT, as the precursor of calcitonin, is a kind of glycoprotein without hormone activity, which is significantly higher in bacterial infection, but remain normal or slightly increased in viral infection22, 23. Consistently, our study shows that CRP and PCT are markedly increased in severe and very severe COVID-19, and significantly higher in very severe COVID-19. This further correlates to the implication of the serum ferritin alteration, that most of severe patients in COVID-19 have viral infection and secondary bacterial infection.
One important limitation of the present study is that we have only observed infection biomarkers in limited COVID-19 patients; the small sample size have prevented us from reaching diagnostic value of infection markers in very severe COVID-19. Secondly, the present study hasn’t evaluated the relationship between infection matkers and prognosis of all the patients enrolled. With more clinical information acquired from COVID-19 patients, further large population-based prospective studies coulf provide further evidence how infection biomarkers are altered and what it indicate in COVID-19.