COVID-19 - Quality of Life After Infection
Conditions: COVID-19, Quality of Life
Sponsor: Chinese University of Hong Kong

 
 
COVID-19 - quality of life after infection 
 
Research Protocol 
Version 1 
29 April 2020 
 
 
 
PI: Prof. Joseph Harold WALLINE 
Accident and Emergency Medicine Academic Unit, The Chinese University of Hong Kong 
 
Co-I: Prof. Colin Alexander GRAHAM  
Accident and Emergency Medicine Academic Unit, The Chinese University of Hong Kong 
 
Co-I: Prof. Grace Chung Yan LUI 
Department of Medicine and Therapeutics. The Chinese University of Hong Kong 
 
Co-I: Prof. Kevin Kei Ching HUNG 
Accident and Emergency Medicine Academic Unit, The Chinese University of Hong Kong 
 
Co-I: Dr. Ling Yan LEUNG 
Accident and Emergency Medicine Academic Unit, The Chinese University of Hong Kong 
 
Co-I: Mr. Dicken Tak Kan WONG 
Accident and Emergency Medicine Academic Unit, The Chinese University of Hong Kong 
 
 

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Statement of compliance 
The study will be undertaken in full compliance with the Declaration of Helsinki. 
 
 
Introduction  
Nearly two million cases have been documented, and thousands have died of the 2019 
coronavirus disease (COVID-19).1 Hong Kong has seen nearly 1,000 documented cases of 
COVID-19 as of April 11, 2020.2 Potentially many more cases have gone unreported.3 The virus 
that causes the COVID-19 disease, SARS-CoV2, is a coronavirus, from the same group of 
viruses as the SARS virus from 2003. Worldwide, COVID-19 has killed many more patients than 
SARS, yet the two viruses share a similar background. 
 
As the peak of viral infections begins to recede, however, the main priority will shift to the 
process of recovery. Over the past 17 years, Professor David SC HUI has published multiple 
follow-up examinations of SARS patients conducted at the Prince of Wales Hospital (PWH) 
outpatient clinics.4,5 He found that SARS patients suffered serious long-term effects after 
ostensibly recovering from their illnesses. Moreover, healthcare workers, who were 
disproportionately affected by SARS infections in 2003 were also disproportionately affected by 
long-term disability. Like SARS, many COVID-19 patients require intensive care, intubation, 
and aggressive medical therapy.6 One of the treatments tried for SARS patients was high-dose 
corticosteroids, which has been associated with avascular necrosis of major joints and long term 
disability.7 As the COVID-19 pandemic only started a few months ago, it is still unknown if 
COVID-19 patients will suffer the same fate as SARS survivors. 
 
Recent COVID-19 research has logically focused on the acute diagnosis and treatment of 
affected patients in order to avoid short-term morbidity and mortality.8–11 Past research looking at 
SARS outcomes showed that both the six month exercise capacity and health status of SARS 
survivors was lower than that of normal controls.12 Sepsis patients also experience serious 
disease caused by infection, and long-term reductions in quality of life have been described in 
survivors of sepsis.13 Patients who survive intensive care go on to show deficits in verbal 
learning and memory,14 resulting in limitations in returning to work or school.15 Many SARS 
survivors developed post-traumatic stress disorder and other debilitating psychological 
illnesses.16 Based on the Hong Kong experience with SARS, we are concerned that COVID-19 
survivors are at risk for similar challenges in quality of life after discharge from acute care.  

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The Accident and Emergency Medicine Academic Unit of the Chinese University of Hong Kong 
based at PWH has worked on multiple studies involving quality of life.12,17,18 In particular, we 
have previously collaborated with Professor Hui and the CUHK Department of Medicine and 
Therapeutics (M&T) on a quality of life follow-up study on SARS patients.12 As for studying 
health-related quality of life, we currently have an ongoing project examining the subject in 
trauma patients after discharge.18 
 
Several instruments have been widely used in quality of life research, including the 36-Item 
Short Form Health Survey (SF-36), the 12-Item Short Form Health Survey (SF-12), the World 
Health Organization Quality of Life Instruments (WHOQOL-BREF), EuroQoL-5D (EQ-5D-5L) 
and the Short-Form Six-Dimension (SF-6D). Our team has experience using the SF-36, SF-
12v2(HK) and the EQ-5D-5L survey instruments for monitoring quality of life in research 
subjects in Hong Kong. For example, we found that trauma patients in Hong Kong scored 
significantly worse on the SF-36 twelve months after injury.17 We also found the most dramatic 
improvements happened in the first one to six months post-injury,19 and that 45% of subjects had 
achieved an excellent outcome by four years post-injury.20 The SF-12v2(HK) with four week 
recall is a modified version of the SF-36 to be shorter and quicker to use, while also already 
translated and validated in Hong Kong.21 We aim to combine our experience with conducting 
quantitative quality of life studies with the CUHK Department of M&T’s expertise in 
coronavirus treatment and follow-up to explore the quality of life of COVID-19 patients in 
recovery. 
 
The reported mortality rates for COVID-19 has so far been lower than SARS, although the 
higher absolute numbers of COVID-19 patients mean worldwide deaths are overall much higher. 
Trauma, sepsis and SARS survivors have all experienced significant long-term morbidity and 
decreased quality of life as a result of their injuries or infections. A previous study of patients 
infected with SARS-CoV-1 in 2003 at PWH showed that significant numbers of recovering 
patients had impaired long-term health status.12 The question this study hopes to answer is to 
what degree do COVID-19 patients suffer a similar fate? Has the knowledge gained from the 
SARS experience led to improved quality of life outcomes compared to SARS survivors? Or do 
the similarities between the viruses that cause SARS and COVID-19 extend to a reduced quality 
of life after recovery as well? 
 
 
Aims 

COVID‐19 & Quality of Life After Infection Research Protocol   
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This study aims to determine the quality of life of COVID-19 survivors up to six-months after 
discharge from hospital or quarantine. We also aim to compare the quality of life of COVID-19 
survivors to baseline known Hong Kong quality of life norms.  
 
By identifying overall COVID-19 quality of life as well as specific associations or differences 
between COVID-19 and baseline local quality of life values, we hope to be able to provide 
evidence-based conclusions to medical practitioners trying to achieve the best quality of life for 
patients recovering from COVID-19. 
 
 
Hypotheses  
The null hypothesis is that recovered COVID-19 patients have no difference in quality of life 
compared to a normal control (baseline Hong Kong quality of life norms). 
 
The alternative hypothesis is that there is a difference in quality of life measures between 
recovered COVID-19 patients and a normal control. 
 
 
Plan of Investigation  
Subjects 
All adult patients aged ≥18 years who present to the infectious diseases specialist outpatient 
follow-up clinic at PWH will be screened for inclusion in this study. The inclusion criteria are 
age ≥18 years, laboratory-confirmed COVID-19 infection with SARS-CoV-2, and patients who 
agree to follow-up for up to six months following their first interview. 
 
Exclusion criteria:  
Patients aged below 18 years will be excluded.  
Patients will be excluded if they meet ANY of the following criteria: 
Patients or their next of kin are unable to communicate in Chinese or English, 
Unwilling or unable to provide written informed consent, 
or Patients who will not be available for telephone follow-up at the scheduled times. 
 
We will record all patients who are not enrolled and the reasons for exclusion. 
 
Sample size calculation 
As of April 10, 2020, in the NTEC Hospital Authority cluster there have been 89 patients 

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admitted to PWH (of which 17 patients have already been discharged) and 117 admitted to 
United Christian Hospital with 42 discharged so far.22 Both PWH and United Christian 
Hospital’s COVID-19 patients will follow-up at the PWH infectious diseases specialist 
outpatient follow-up clinic. Based on prior studies at PWH with SARS patients, approximately 
80% agreed to participate in follow-up studies, so we will likely enroll approximately 200 
COVID-19 patients.  
 
 
Methods  
This will be a prospective, observational, multicenter, cohort study. We plan to recruit 100 
patients with laboratory confirmed COVID-19 disease who have been discharged from inpatient 
care or quarantine. Quality of life will be assessed using the SF-12v2(HK) and EQ-5D-5L survey 
instruments, and their return to work status will be measured up to six months from the date of 
discharge.  
 
After written consent is obtained, the pre-COVID-19 and baseline information will be collected. 
Their COVID-19 information will be collected via face-to-face interview or telephone follow-up 
or by email. 1, 3 and 6-month data post-discharge will be collected via telephone follow-up 
interview with the patient or e-form completed by the patient. 
 
Quality of life assessment tools 
SF-12 
The 12-Item Short Form Health Survey is an abbreviated version of the 36-Item Short Form 
Health Survey. It is a widely used, international, validated survey for investigating health-related 
quality of life in a variety of both acute and chronic conditions. The survey instrument has eight 
domains: physical functioning, physical role, bodily pain, general health, vitality, social 
functioning, emotional role, and mental health. Each domain is measured on a 0-100 scale. A 
higher score correlates with a higher quality of life. The survey generates a Mental Component 
Summary (MCS) and a Physical Component Summary (PCS). A Chinese version of the survey, 
the 12-item Chinese (Hong Kong) Short Form Health Survey (version 2) (SF-12v2 (HK)) has 
been previously validated and used in Hong Kong.21 We will be using the four week recall 
(standard) version of the SF012v2(HK). 
 
EQ-5D-5L 
The EQ-5D-5L is a brief health status measure that comprises of five domains: mobility, self-
care, pain, usual activities, and psychological status. EQ-5D-5L has been validated in Hong 

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Kong, recently for use in patients with chronic obstructive pulmonary disease.23   
 
Return to work status 
Patients’ pre-COVID-19 infection work status will be compared to their post-infection status. 
The type of employment, salary and each patients’ subjective work experiences before and after 
infection will be queried. 
 
Definitions 
COVID-19 = Coronavirus Disease 2019, the new disease pandemic caused by the SARS-CoV-2 
virus.  
CUHK = The Chinese University of Hong Kong 
EQ-5D-5L = EuroQol Five Domain survey, one of the two main survey instruments we will use 
to quantitatively judge quality of life for enrolled study subjects. 
NTEC = New Territories East Cluster, a grouping of healthcare facilities in northeast Hong 
Kong. 
PWH = Prince of Wales Hospital, the largest acute care hospital in the Hong Kong Hospital 
Authority’s New Territories East Cluster as well as the major teaching hospital for the Chinese 
University of Hong Kong’s medical school. 
SARS = Severe Acute Respiratory Syndrome, the disease associated with the coronavirus 
epidemic of 2003 (not to be confused with SARS-CoV-2, which is the virus causing COVID-19 
disease).  
SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2, the virus identified as the 
causative organism of the COVID-19 disease. 
SF-12 = The 12-Item Short Form Health Survey, one of the two main survey instruments we will 
use to quantitatively judge quality of life for enrolled study subjects. We will use the SF-
12v2(HK) version of the SF-12, which has been specifically validated for use in Hong Kong. 
 
 
Study design       
Recruitment 
All adult COVID-19 patients aged ≥18 years who present to the infectious diseases specialist 
outpatient follow-up clinic at PWH will be screened for inclusion in this study by research 
assistants involved in this study. 
 
First interview 
After consent, the pre-COVID-19 assessments of SF-12v2(HK) and EQ-5D-5L will be obtained 

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by face-to-face interview or by phone interview by a research assistant or by e-form completed 
by the patient. The interview process should take no longer than 10 minutes. The questionnaire 
may be completed by a proxy if the patient is unable to respond to the interviewer. Work status 
one month prior to COVID-19 diagnosis will be determined at this time as well. 
 
Follow-up interviews 
The SF-12v2(HK) and EQ-5D-5L will be obtained by telephone interview from the patient or e-
form completed by the patient. The follow-up measures will be performed at 1, 3, and 6-months 
after date of recovery by a research assistant.  
 
Studies have found differences between quality of life assessments completed by the patient or 
by proxy. In previous studies, it has been shown that when using EQ-5D-5L as an assessment 
tool, there is good agreement on the domain of self-care, but only a “fair” agreement on domains 
such as mobility, pain and anxiety were observed between the patients and caregiver rating.24 
However, if all proxy responses were excluded, quality of life for survivors of sepsis with 
communication problems would not be included, which would be a significant methodological 
and ethical problem. Thus, in this proposed study, the questionnaire may be completed by a 
proxy if the patient is unable to respond to the interviewer (e.g. patients with dementia or stroke). 
A subgroup analysis will be performed accordingly.  
 
 
Data processing and analysis 
Outcomes 
Primary outcome 
The primary outcome measure will be the health summary scores from SF-12v2(HK) in COVID 
patients at six-months post-discharge from hospital. 
 
Secondary outcomes 
The secondary outcome measures will include the health status measures of the EQ-5D-5L and 
return to work status in COVID patients at six-months post discharge from hospital.  
 
Other measures 
The required clinical data for patient characteristics and data for investigating each patient’s 
relative illness severity will be collected at the earliest opportunity after subject enrollment. The 
final COVID-19 diagnosis and any other final diagnoses will be recorded from the patient’s 
existing clinical notes. The Hospital Authority’s computerized Clinical Management System (the 

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system used by all hospitals under Hospital Authority for storing and retrieving patients’ data) 
will be reviewed to identify hospital admissions, emergency department reattendance, lengths of 
stay (intensive care, step-down units or general wards) and mortality. 
 
Statistical analysis 
General 
Chi-square and Fisher’s exact tests will be used for categorical data while t-tests will be used to 
compare means of continuous variables. A p value <0.05 will be considered statistically 
significant and all tests will be two-tailed. 
 
Primary analysis 
A univariate and multivariate analysis of the data set will be conducted at six months. SF-12v2 
dimensions of survivors of COVID-19 will be compared with data from past survivors of SARS 
infection, sepsis or trauma. We will also compare this data to the general Hong Kong population 
summary score data. Data from the EQ-5D-5L survey instrument will be compared using the 
Chi-square or Fisher’s exact tests.  
 
Secondary analyses 
COVID-19 is still an incompletely understood disease. We will perform secondary analyses on 
the data to allow us to focus on specific groups and to adjust for variability. We will consider the 
severity of COVID-19 by examining each patient’s clinical record, number of hospital days 
admitted, number of days spent in the intensive care unit, number and severity of organ(s) 
dysfunction, co-infections, pathogen(s) identified, pre-COVID-19 health status and pre-existing 
conditions. It is anticipated that there will be marked changes and differences in health status and 
functional outcome depending on patient age. Comparisons of quality of life between four time 
points (pre-sepsis, hospital stay, 3-months and 6-months after discharge) will be assessed using 
paired t-test or Wilcoxon (W) tests as appropriate. 
 
Multivariate logistic regression analysis  
All parameters will be entered into a multiple logistic regression model and used to evaluate 
associations and account for variation. Multiple logistic regression adjusts for variable 
interactions and will be used to identify predictors of quality of life in COVID-19 patients during 
follow-up.  
 

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