We read with the interest the recent paper by Chen et al. who described the clinical progression of 249 patients with coronavirus disease 2019 (COVID-19). 1 As the author mentioned, some factors, such as age and CD4 T cell counts, would be associated with intensive care units (ICU) admission. In addition, the application of host-directed therapy and early control of viral replication might be crucial for improving the prognosis of COVID-19. We are interested in investigating the potential risk factors associated with the progression and prognosis of COVID-19.
To date, cases of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and influenza A co-infection have been reported in COVID-19 patients. [2] [3] [4] We suspected that the recent infection with influenza among COVID-19 patients might affect disease prognosis and progression to some extent. The high specificity and the sensitivity of Immunoglobulin M (IgM) assays suggest that IgM is a reliable biomarker for the surveillance of recent influenza infection. 5, 6 Here, we reported that recent infection of influenza A/B and produce specific IgM in COVID-19 might be a common phenomenon, and influenza IgM status could be the significant factor associated with clinical outcomes and prognosis of COVID-19. 4.8%, 67/1386). The A IgM + / B IgM + group was not included as we identified no such cases. In Figure 1 , in terms of the clinical outcome, the mortality rates of the A IgM + / B IgMgroup and A IgM -/ B IgM + group were lower than that of the A IgM -/ B IgMgroup. Figure 1 also indicates that the A IgM -/B IgMgroup had the highest rate of severe cases among the three groups. Statistically significant differences existed across the different groups when considering mortality (P = 0.0008) and severe illness rates (P < 0.0001).
To further explore the relationship between the influenza A/B IgM status and clinical outcome and illness severity among the COVID-19 patients, we established univariate analysis and multivariate analysis models (Table 1) . For the univariate analysis, we found that sex, age, and comorbidities were significant cofactors among mortality and severe illness. The A IgM + / B IgMgroup has showed lower risk of mortality (OR =0.514, 95%CI: 0.360-0.732) and severe illness (OR =0.511, 95% CI:0.408-0.640).
For multivariate analysis, after adjustment for cofactors, patients in the A IgM + / B IgMgroup were less likely to die than patients in the A IgM -/ B IgMgroup (OR = 0.671, 95% CI: 0.463-0.973). However, the mortality rate of the A IgM -/ B IgM + group was not statistically different from that of the A IgM -/ B IgMgroup according to the adjusted model (OR = 0.903, 95% CI: 0.359-2.272). Furthermore, our analysis also indicated that a similar trend was also observed in severe/non-severe analysis.
The A IgM + /B IgMgroup had a lower rate of severe illness than the A IgM -/B IgM -group (OR = 0.601, 95% CI: 0.476-0.760), whereas no such difference was found for the A IgM -/B IgM + group (OR = 0.968, 95% CI: 0.563-1.665).
In the analysis, older age, male gender, and comorbidities were more prone to poor outcomes and progression, which were consistent with previous studies. 1, 9 Therefore, in the multivariate analysis, we adjusted these cofactors. We found that COVID-19 patients positive for influenza A IgM had a lower risk of mortality and severe illness compared with those showing negative A/B IgM status. However, these trends were not significant differences between A IgM -/ B IgM + group and A IgM -/ B IgMgroup.
The reason for better prognosis and clinical outcome in influenza A IgM + COVID-19 patients is likely complicated, but could be due to potential interactions between influenza A and SARS-Cov-2, or because IgM + is a marker of patient functional immune status. However, the second hypothesis cannot fully explain why these protective effects were not observed among influenza B IgM + COVID-19 patients.
Due to the suddenness of the COVID-19 pandemic outbreak, more studies are needed to confirm these findings. 