Respiratory viruses in adults with acute respiratory tract infections

Background: Respiratory viruses are the main pathogens of acute respiratory infections. Viral respiratory pathogens in children are well studied, but the study on adults are limited. So we design this subject to determine viral respiratory pathogens in patients with acute respiratory tract infections of adults. Methods: We conducted a retrospective study for the patients with acute respiratory infections from June, 2017 through July, 2018 at Fever Clinic in Peking University Third Hospital. We collected throat swab from the patients diagnosed with acute upper respiratory tract infections and sputum or throat swab diagnosed with community-acquired pneumonia. RT-PCRs were performed to detect infection with the following virus: human rhinovirus, inuenza A virus, inuenza B virus, human coronavirus 229E/HKU1(cid:0) Coronavirus OC43/NL63 (cid:0) ADV, RSV, PIV1-4, hMPV and EV. Results(cid:0)185 throat swabs and sputum were collected from outpatients. Overall, 23.8% (44/185) were found to be positive for at least one respiratory virus. The virus detection rate for AURTIs and CAP was 23.3% (14/60) and 24.0 % (30/125), respectively. The most prevalent viruses detected were IFVs (13.5%, 25/185), PIVs (3.24%, 6/185) and HRVs (2.70%, 5/185). In the Inuenza Virus, the highest positive detection rate is 21.4%(cid:0)6/28(cid:0)in the group >60 years old, while 11.0%( 14/127) in the group <40 years old and 13.3% (4/30) (P<0.05). Conclusion: In one-year study, IFVs were the dominant pathogens both in acute upper respiratory tract infections and community-acquired pneumonia, followed by PIVs and HRVs. The patients in the group >60 years old had a higher rate of inuenza infection

The most prevalent viruses detected were IFVs (13.5%, 25/185), PIVs (3.24%, 6/185) and HRVs (2.70%, 5/185). In the In uenza Virus, the highest positive detection rate is 21.4% 6/28 in the group >60 years old, while 11.0%( 14/127) in the group <40 years old and 13.3% (4/30) (P<0.05). Conclusion: In one-year study, IFVs were the dominant pathogens both in acute upper respiratory tract infections and communityacquired pneumonia, followed by PIVs and HRVs. The patients in the group >60 years old had a higher rate of in uenza infection Background Acute respiratory infections (ARIs) are a major global public health problem, and lead to frequent morbidity, and sometimes cause severe outcomes including death. Respiratory viruses (RVs) are the main pathogens of ARIs. The most common viral causes of ARIs respiratory are respiratory syncytial virus (RSV), parain uenza viruses (PIVs), in uenza viruses (IFVs), adenoviruses (ADVs), human rhinoviruses (HRVs), enteroviruses (EVs), human metapneumovirus (hMPV), human coronaviruses, and human bocavirus. RVs are implicated in 50% of community-acquired pneumonia (CAP) in young children, and over 90% of bronchiolitis cases in infants and young children [1,2]. In adults 15-56% of CAP are associated with RVIs. About 200 million cases of viral community-acquired pneumonia occur every year [3,4] .Viral respiratory pathogens in children are well studied, but the study on adults are limited. So we design this subject to determine viral respiratory pathogens in patients with acute respiratory tract infections of adults in Beijing, China.

Study Patients
Respiratory etiological surveillance monitoring system of Centers for Disease Control (CDC) of Beijing is designed to monitor respiratory pathogens in Beijing. Peking University Third hospital is a sentinel hospital and responsible for routine surveillance of respiratory tract infection. We conduct a retrospective study for the patients in routine surveillance with acute respiratory infections from June 2017 through July 2018 at Fever clinic. The patients were enrolled according to the following criteria.
1. CAP are diagnosed according to the diagnostic criteria of Chinese adult community acquired pneumonia (2016 edition) developed by Chinese society of respiratory medicine: (1) fever (a body temperature > 38.0 °C) or hypothermia (a body temperature < 35.5 °C), (2) leukocytosis (a white blood cell count > 10,000/ml) or leukopenia (a white blood cell count < 4000/ml); (3) had signs/symptoms of cough, sputum ,respiratory symptom aggravation, With or without purulent sputum, chest pain, dyspnea and hemoptysis. (4) chest radiological imaging features are patchy in ltration leaf segment consolidation shadow, leaf segment consolidation shadow, interstitial in ammation change, with or without pleural effusion (5) Signs of lung consolidation or rales of lung auscultation. CAP can be established when tuberculosis, pulmonary tumor, non-infectious pulmonary interstitial disease, pulmonary edema, pulmonary atelectasis, pulmonary embolism, pulmonary eosinophil in ltration and pulmonary vasculitis are excluded. presented as a percentage (P), or mean ±SD. Differences in categorical variables between groups were compared by the χ2 test. A single-tailed P value of <0.05 was considered to be statistically signi cant.
Experimental methods 1. Nucleic Acid Extraction: Total nucleic acids including DNA and RNA were extracted from 200 L of each specimen using magnetic bead nucleic acid Extraction Kit (Thermo Fisher, American, NO.KFR-805496) by ABI Mag MAX express 96 according to the manufacturer's instructions.

Characteristic of patients with acute respiratory infection
Of all the enrolled patients, 93 (50.3%) were male and 92 (49.7%) were female, the age of the patients ranged from18.5 to 84.2 years, with a median of 37.9 years. The patients enrolled are all with fever and body temperature ranged from37.5 to 41 degree centigrade, with a median of 38.8 degree centigrade. In the 185 patients, 135 patients (73.0%) are with cough, 75 (40.5%) with expectoration, 12 (6.5%) are with nasal congestion, 24 (13.0%) are with nasal discharge, and 98 (53.0%) are with sore throat (Table 1).  (Table 2).

Seasonality of respiratory virus infection distribution
In one-year study, the top three months of viral isolation are January, February and July (53.3%, 33.3%, and 33.3%). In uenza virus was highest in January and February which were in u season. In July, PIVs were the main virus. IFV A was detected at the highest frequency and throughout the year. There were three peak of IFV A in December, January and February. IFV B was almost in winter. PIVs and HRVs were not detected in winter. EVs were existed in summer and autumn. RSV, ADVs and hMPV were only existed in winter, autumn and spring respectively (Table 3, Figure 1 and 2).

Age distribution of respiratory virus pro les
The positive detection rates of viruses that corresponded to different age groups. Overall, virus infection rate is 39.3% in the patients >60 years old 18.9% in the patients of the group <40 and 23.3% in the patients of the group 40-60 years old (23.3%) group (P>0.05). In the In uenza Virus, the highest positive detection rate is 21.4% 6/28 in the group >60 years old, while 11.0%( 14/127) in the group <40 years old and 13.3% (4/30) in the group 40-60 years old (P<0.05). The major infectious virus in the older patients in the group 40-60 and >60 years old is In uenza Virus B and the positive rates are 10% (3/30) and 14.3% (4/28). In uenza A Virus is the most common virus in the group of <40 years old (7.9%, 10/127). (Table 4  and Figure3) 5. Distribution of respiratory virus pro les in AURTI group and CAP group.

Discussion
Respiratory viruses are the main pathogens of ARIs, and in our study, we analysis the respiratory viruses in the AURTI and CAP. In one-year-study, we found that 23.8% of the outpatients with AURTI and CAP were found to be positive for at least one respiratory virus. The virus detection rate for AURTIs and CAP was 23.3% and 24.0 %, which was similar with other studies [5]. The most prevalent viruses were IFVs (13.5%), PIVs (3.24%), and HRVs (2.70%). In uenza viruses are signi cant human respiratory pathogens that cause both seasonal and endemic infections. In uenza viral infections were common in our study and were found almost throughout the year.
We collected the patients with acute respiratory tract infections including the AURTIs and CAP for virological analysis. In the AURTI group and CAP group, IFVs are the main virus, 15.0% (9/60) in AUTRI and 12.8% (16/125) in CAP group. IFV-B was dominant in the in uenza season, because of the epidemic strain of seasonal in uenza virus was B type in 2018. The risk of IFV infection was higher (21.4%) in the group >60 years, and 11.0% in the group <40 years old, 13.3% in the group 40-60(P<0.05).
In another study of the Chinese, IFVs was also the most common agent in hospitalized patient≥65 years [6]. In the IFA infection, patients <40 years old took the highest rates of infections (7.8%), while in the IFB infection, patients in the group >60 years old took the highest peak rates of infections (14.3%). In the previous study, patients with age ≥65 years take highest case fatality rate but lowest rate of infection [7].
In the seasonal distribution analysis, in uenza A was throughout the year and founded in four seasons, while IFV B was almost in winter. In another two-year-study on the Chinese people, in uenza A was also the leading virus of ARIs, but there was some difference in IFV B from our study. In the two-year study, in uenza B is active in spring in Beijing and rates of in uenza B infection were low throughout the study period. The IFV B peaks occurred following IFV A peaks. In our study, in uenza B is active in winter and the peaks occurred with the in uenza A because of the epidemic strain of the seasonal in uenza virus was B type in 2018 [8].In our daily clinical work, we should take emphasis on IFV, especially IFV A for its high incidence and serious consequence.
In the CAP group of our study, IFVs were the most common (12.8%), especially in uenza A (7.2%). In a study on the incidence and characteristics of viral community-acquired pneumonia in adults of New Zealand, rhinoviruses (10%) and in uenza A (8%) being the most common. Another respiratory Viruses in adults with community-acquired pneumonia of Israel, the results are quite different for the most common virus are coronaviruses(13.1%), RSV(7.1%), rhinovirus (4.9%) and in uenza virus(4.4%) [9].So the distribution of respiratory virus pro les differs between different regions for the unique climatic characteristic and geographical location In summary, In uenza is a global burden which is associated with signi cant morbidity and mortality, and it was the main virus of ARIs and founded throughout the year in our study, so it deserves our more attention in the clinical work. It is a vaccine-preventable disease, so our government should pay full attention on the disease prevention to reduce the economic burden and medical burden.

Conclusions
In the analysis of respiratory viruses in adults with acute respiratory tract infections, the positive rate of viral isolation was 23.8%, and in the group of AURTIs and CAP was 23.3% and 24.0%. IFVs were the dominant pathogens both in acute upper respiratory tract infections and community-acquired pneumonia, followed by PIVs and HRVs. The patients in the group >60 years old had a higher rate of in uenza infection

Study limitations
There are several limitations that should be stated. First, we chose the data of one year and the sample size is not large enough, so the conclusion may has limitations. Second, the viral respiratory pathogens differ year by year, and especially in 2018, IFV B is active so the conclusion deserves further studied.

Availability of data and material
The datasets used in the current study are available from the corresponding author.

Consent for publication
All the authors read and approved the publication.

Funding details
This study was supported by Centers for Disease Control (CDC) of Beijing and the Respiratory etiological surveillance monitoring system for their integrated planning and nucleic acid tests of the samples collected.

Competing interests
The authors declare that they have no competing interests.