4.Discussion
With COVID-19-specific antiviral therapy advancing in clinical development, the question of differentiating SARS-CoV-2 infection from that of influenza and assessing their clinical impact in adult populations will likely become highly relevant to care decisions worldwide26. We reported here the clinical characteristics and severity of 505 patients hospitalized with illness caused by H1N1, SAR-COV-2 or mixed-infection of both viruses. H1N1-infected patients more frequently showed clinical symptoms than patients with SARS-CoV-2 infected alone, especially for fever. During hospitalization, COVID-19 patients were more likely to develop pneumonia than H1N1 patients. Compared with infected by single virus, mixed-infection affected a predominantly older age group and was associated with poorer clinical outcome.
For the comparison between patients with H1N1 or SARS-CoV-2 infected alone, the symptoms commonly observed in both study groups included fever, dry cough, expectoration, and chill. We found that fever and dry cough were the dominant symptoms in two groups. Except for dry cough and diarrhea, symptoms were more frequent in H1N1 group. The absence of fever in COVID-19 was more common than in H1N1 influenza, moreover, higher body temperature was collected in H1N1 patients at admission, thus specified surveillance case definition on fever may facilitate identification of viral types of infection at admission. Compared with the H1N1 group, patients with SARS-CoV-2 infection had fewer prominent upper respiratory tract signs and symptoms (eg, expectoration or sore throat), indicating that the target cells might be located in the lower airway27. Correspondingly, SARS-CoV-2 group had a higher probability of pneumonia (OR:3.22, 95%CI: 2.16-4.80) compared to H1N1 group, which further confirmed a difference in viral tropism between two viruses28,29. Consequently, SARS-CoV-2-caused pneumonia may account for the prolonged duration of hospitalization. The pathogenic mechanism underlying these differences between the two viruses are not clear yet and warrants further virological research. Of note, 10 (4.02%) patients in SARS-CoV-2 group had diarrhea as an initial symptom which was more common than the H1N1 group (0.91%); these findings echo a previous report13, and collectively suggesting this possibly a distinguishing clinical symptom of COVID-19. In the current study, laboratory test findings of H1N1 group at admission tended to be more abnormal, especially concerning measurements of inflammatory markers (eg. C-reactive protein level and Procalcitonin level). These findings were in line with the study conducted by Li Y et al.12; and can be attributable to the more common acute upper respiratory tract infection in hospitalized H1N1 patients30. This could explain the reason we have observed more symptoms of acute infection in H1N1 patients at admission. The diverse characteristics of infection provides the rationale for advancing antiviral interventions in efforts to improve outcomes of these two types of patients.
Of the 285 COVID-19 patients analyzed, 36 (12.6%) patients were detected mix-infected by A(H1N1)pdm09. Co-infections more frequently occurred in patients with older age and more comorbidities, which may due to the relative lack of immunity to respirovirus in this population31. CRP and PCT, which was the severity index of pneumonia32, were lower in those with COVID-19 than the co-infection patients, suggesting co-infection is more severe than SARS-CoV-2 infected alone. Furthermore, after adjusting age, sex, comorbidities and smoking history, co-infection was associated with higher odds of several adverse clinical outcomes. This finding was in accordance with a previous report on other respiratory disease18. Thence, it’s recommended that COVID-19 patients be detected for H1N1 infection at admission, and treat the detected mix-infected patients with rigorous clinical surveillance.
Secondary bacterial infection is a common and serious complication of influenza33,34. In this study, a higher rate of secondary bacterial infections was recorded among mix-infected patients. Therefore, similar to the recommendation for community-acquired pneumonia, it’s reasonable for adults with COVID-19 who test positive for influenza to take initial antibacterial treatment, because it is difficult to exclude the presence of bacterial co-infection in these patients35.
There are limitations in this study. It was a single-center analysis, the features of the setting may not be representative of Chinese patients as a whole. As a retrospective study, the further clinical progression could not be collected. We also failed to explore the relationships regarding 30-days mortality due to the limited number of death cases (n = 2).
In conclusion, H1N1 patients more frequently showed clinical symptoms than COVID-19 patients, especially for fever, which may provide recommendations for initial differential diagnosis. In contrast, COVID-19 patients have a higher incidence of pneumonia than H1N1 patients during hospitalization. Mixed-infection affected a predominantly older age group and was associated with poorer clinical outcomes. So far, we do not yet have a COVID-19 vaccine, but safe and moderately effective influenza vaccines are available. Thus, a widespread use of influenza vaccines is important now than ever to reduce the risk of co-infection. Additionally, molecular diagnostic testing for both viruses is recommended for all patients with acute respiratory illness which would enable patients with co-infection to be recognized and given appropriate treatments in time in efforts to improve outcomes.