A two-gene marker for the two-tiered innate immune response in COVID-19 patients.

For coronavirus disease 2019 (COVID-19), a pandemic disease characterized by strong immune dysregulation in severe patients, convenient and efficient monitoring of the host immune response is critical. Human hosts respond to viral and bacterial infections in different ways, the former is characterized by the activation of interferon stimulated genes (ISGs) such as IFI27, while the latter is characterized by the activation of anti-bacterial associated genes (ABGs) such as S100A12. This two-tiered innate immune response has not been examined in COVID-19. In this study, the activation patterns of this two-tiered innate immune response represented by IFI27 and S100A12 were explored based on 1421 samples from 17 transcriptome datasets derived from the blood of COVID-19 patients and relevant controls. It was found that IFI27 activation occurred in most of the symptomatic patients and displayed no correlation with disease severity, while S100A12 activation was more restricted to patients under severe and critical conditions with a stepwise activation pattern. In addition, most of the S100A12 activation was accompanied by IFI27 activation. Furthermore, the activation of IFI27 was most pronounced within the first week of symptom onset, but generally waned after 2-3 weeks. On the other hand, the activation of S100A12 displayed no apparent correlation with disease duration and could last for several months in certain patients. These features of the two-tiered innate immune response can further our understanding on the disease mechanism of COVID-19 and may have implications to the clinical triage. Development of a convenient two-gene protocol for the routine serial monitoring of this two-tiered immune response will be a valuable addition to the existing laboratory tests.

A single transcript for the prognosis of disease severity in COVID-19 patients.

With many countries strapped for medical resources due to the COVID-19 pandemic, it is highly desirable to allocate the precious resources to those who need them the most. Several markers have been found to be associated with the disease severity in COVID-19 patients. However, the established markers only display modest prognostic power individually and better markers are urgently needed. The aim of this study is to investigate the potential of S100A12, a prominent marker gene for bacterial infection, in the prognosis of disease severity in COVID-19 patients. To ensure the robustness of the association, a total of 1695 samples from 14 independent transcriptome datasets on sepsis, influenza infection and COVID-19 infection were examined. First, it was demonstrated that S100A12 was a marker for sepsis and severity of sepsis. Then, S100A12 was found to be a marker for severe influenza infection, and there was an upward trend of S100A12 expression as the severity level of influenza infection increased. As for COVID-19 infection, it was found that S100A12 expression was elevated in patients with severe and critical COVID-19 infection. More importantly, S100A12 expression at hospital admission was robustly correlated with future quantitative indexes of disease severity and outcome in COVID-19 patients, superior to established prognostic markers including CRP, PCT, d-dimer, ferritin, LDH and fibrinogen. Thus, S100A12 is a valuable novel prognostic marker for COVID-19 severity and deserves more attention.