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.