Respiratory Virus Infections in Acutely Hospitalized Adult Patients With Pulmonary and Extrapulmonary Complications

Respiratory virus infections are one of the major causes of hospitalizations, and outbreaks of respiratory virus infection have led to severe economic loss. In addition to pulmonary complications, respiratory viruses can also lead to non-pulmonary complications.

However, many previous studies on the complications of respiratory viruses are retrospective in nature, and therefore many patients with respiratory virus infection may not be tested. Furthermore, these studies did not take into account that respiratory viruses can be found in some asymptomatic individuals. The aim of this study is to capture the burden of respiratory viruses in patients with acute pulmonary and extrapulmonary complications. We will recruit patients admitted to our hospital with acute coronary syndrome, stroke and exacerbation of underlying lung diseases. We will collect saliva from these patients and test for respiratory viruses. As controls, we will recruit asymptomatic patients at the out-patient clinic for follow up of chronic heart, lung or neurological diseases.

We anticipate that this study will greatly enhance our understanding of the epidemiology of respiratory viruses in acutely hospitalized patients. Our findings will be important for clinicians, public health practitioners and scientists.

Study Overview

• Status: Unknown
• Conditions: Stroke; Acute Coronary Syndrome; Lung Disease; Respiratory Virus Infection
• Intervention / Treatment: Diagnostic test: Respiratory virus testing

Detailed Description

Respiratory viruses cause severe infections, and contribute to a substantial number of hospitalizations, admission to intensive care units and deaths. Many hospitalizations due to respiratory virus infection are related to pneumonia or exacerbation of chronic lung disease. In addition, many hospitalizations are related to extrapulmonary complications, such as acute coronary syndrome or stroke.

Previous studies have reported the incidence of respiratory viruses among patients with pulmonary complications, or the association of respiratory viruses with acute coronary syndrome or stroke. However, there are several problems associated with these studies. First, many of these studies are retrospective in nature, and therefore testing was only performed in selected patients with respiratory symptoms. Hence, many patients without respiratory symptoms were not recruited. Second, respiratory virus can be detected in some asymptomatic individuals. Therefore, the presence of respiratory virus may be an incidental finding rather than the cause of the complication. Third, many studies only focus on a few respiratory viruses, especially on influenza virus.

This study aims to address these issues. The investigators propose to conduct a prospective cohort study. The investigators will recruit hospitalized adult patients with exacerbation of underlying lung disease, acute coronary syndrome or stroke. As controls, the investigators will recruit outpatients follow-up for chronic heart disease, chronic lung disease or neurological conditions. The investigators will collect saliva from study participants and perform respiratory virus testing using a multiplex PCR panel. Previous studies have shown that there is a high concordance between results from respiratory virus testing on saliva and nasopharyngeal specimens. The investigators will also use a standardized questionnaire to collect information regarding symptoms.

This study will provide accurate data on the epidemiology of respiratory viruses in pulmonary and extrapulmonary complications.These data are important for clinicians, public health practitioners and scientists.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Kelvin To, MD; Phone Number: (852)-22552413; Email: kelvinto@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital
    • Contact: Kelvin To, MD; Email: kelvinto@hku.hk
    • Principal Investigator: Kelvin To, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. Hospitalized patients with acute coronary syndrome, stroke or exacerbation of underlying lung disease
2. Outpatients follow-up for chronic conditions

Description

Inclusion Criteria: (For hospitalized patients)

1. Admitted to the acute medical ward of Queen Mary Hospital via the accident and emergency department
2. Aged 18 years or above
3. Hospitalized for less than 24 hours at the time of recruitment
4. Presented with exacerbation of underlying lung disease, acute coronary syndrome or stroke
5. Competent and agree to provide written informed consent

Exclusion Criteria: (For hospitalized patients)

1. Admitted to any hospitals in the past 14 days
2. Respiratory virus testing performed in the past 14 days
3. Antiviral against respiratory virus given within the past 14 days
4. Not sufficient saliva

Inclusion Criteria: (For out-patients)

1. Aged 18 years or above
2. Follow-up at out-patient clinic or at the physiotherapy department of Queen Mary Hospital
3. Competent and agree to provide written informed consent

Exclusion criteria: (For out-patients)

1. Admitted to any hospitals in the past 14 days
2. Respiratory virus testing performed in the past 14 days
3. Antiviral against respiratory virus given within the past 14 days
4. Onset of new respiratory or non-respiratory symptoms within the past 14 days
5. Not sufficient saliva

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hospitalized - ACS; Hospitalized patients with acute coronary syndrome	Diagnostic test: Respiratory virus testing; All patients will be tested for respiratory viruses
Hospitalized - stroke; Hospitalized patients with stroke	Diagnostic test: Respiratory virus testing; All patients will be tested for respiratory viruses
Hospitalized - chronic lung disease; Hospitalized patients with exacerbation of chronic lung disease	Diagnostic test: Respiratory virus testing; All patients will be tested for respiratory viruses
Outpatient; Outpatients	Diagnostic test: Respiratory virus testing; All patients will be tested for respiratory viruses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of respiratory viruses	Incidence of respiratory viruses	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Length of hospital stay	1 month
Length of stay in general medical ward	Length of stay in general medical ward	1 month
Length of stay in high dependency unit	Length of stay in high dependency unit	1 month
Length of stay in intensive care unit	Length of stay in intensive care unit	1 month
Proportion of patients requiring oxygen supplementation	Proportion of patients requiring oxygen supplementation	1 month
Proportion of patients requiring positive pressure ventilation	Proportion of patients requiring positive pressure ventilation	1 month
Proportion of patients requiring intubation	Proportion of patients requiring intubation	1 month
Proportion of patients admitted to intensive care unit	Proportion of patients admitted to intensive care unit	1 month
Proportion of patients admitted to coronary care unit	Proportion of patients admitted to coronary care unit	1 month
Proportion of patients admitted to high dependency unit	Proportion of patients admitted to high dependency unit	1 month
Proportion of patients who die during hospitalization	Proportion of patients who die during hospitalization	1 month
White blood cell on admission	White blood cell count in blood (x 10^9 cells/L)	1 day
Platelet count upon admission	Platelet count in blood (x 10^9 cells/L) upon admission	1 day
Alanine aminotransferase upon admission	The level of alanine aminotransferase in blood (U/L)	1 day
Creatinine on admission	The level of creatinine in blood (umol/L) upon	1 day
Blood culture result	The result of blood culture	3 days
Sputum culture result	The result of sputum culture	3 days
Proportion of patients with pneumonia	Proportion of patients with pneumonia	1 month

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Publications and helpful links

General Publications

• Sellers SA, Hagan RS, Hayden FG, Fischer WA 2nd. The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017 Sep;11(5):372-393. doi: 10.1111/irv.12470.
• To KK, Lau SK, Chan KH, Mok KY, Luk HK, Yip CC, Ma YK, Sinn LH, Lam SH, Ngai CW, Hung IF, Chan KH, Yuen KY. Pulmonary and extrapulmonary complications of human rhinovirus infection in critically ill patients. J Clin Virol. 2016 Apr;77:85-91. doi: 10.1016/j.jcv.2016.02.014. Epub 2016 Feb 20.
• Warren-Gash C, Blackburn R, Whitaker H, McMenamin J, Hayward AC. Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland. Eur Respir J. 2018 Mar 29;51(3):1701794. doi: 10.1183/13993003.01794-2017. Print 2018 Mar.
• To KK, Lu L, Yip CC, Poon RW, Fung AM, Cheng A, Lui DH, Ho DT, Hung IF, Chan KH, Yuen KY. Additional molecular testing of saliva specimens improves the detection of respiratory viruses. Emerg Microbes Infect. 2017 Jun 7;6(6):e49. doi: 10.1038/emi.2017.35.
• To KKW, Yip CCY, Lai CYW, Wong CKH, Ho DTY, Pang PKP, Ng ACK, Leung KH, Poon RWS, Chan KH, Cheng VCC, Hung IFN, Yuen KY. Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study. Clin Microbiol Infect. 2019 Mar;25(3):372-378. doi: 10.1016/j.cmi.2018.06.009. Epub 2018 Jun 12.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Actual): June 30, 2019
• Study Completion (Anticipated): April 20, 2020

Study Registration Dates

• First Submitted: January 15, 2019
• First Submitted That Met QC Criteria: January 20, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Asthma; Myocardial infarction; Chronic obstructive pulmonary disease; Cerebrovascular disease; Bronchiectasis; Respiratory virus infection; Extrapulmonary complications
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Disease Attributes; Lung Diseases; Infections; Communicable Diseases; Virus Diseases; Acute Coronary Syndrome
• Other Study ID Numbers: 20190104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No