Health-Related Quality of Life Assessment in Post-Covid Patients: A Cross-Sectional Online Survey

This work was carried out in collaboration among all authors. All authors have mutually read, discussed and approved the final manuscript with equal contributions.  To compare the impact of covid-19 infection and its associated factors among various domains of quality of life (general health (GH), physical health (PH), mental health, and pain).  To determine the variation and it’s contributing factors to the quality of life (QoL).  For non-normal data, the Kruskal Wallis test (KWT) and Mann Whitney U (MWU) test were used to compare the effect of covid-19 and its associated factors among various domains of HRQoL. KWT and MWT showed that the ability to perform physical activity was highly impaired in most post-covid patients. Cough, myalgia, arthralgia, and headache were the significant persisting symptoms of covid-19, reported by our participants. IBM SPSS software version 28.0 was used for statistical analysis. Conclusion: We conclude that health care intervention is needed to manage persisting symptoms and to improve HRQoL.


INTRODUCTION
The coronavirus disease 19 (COVID-19) is an infectious disease caused by the worldwide transmission of the severe acute respiratory coronavirus 2 (SARS-CoV-2) [1]. Coronavirus Disease 2019, which was originally found in Wuhan, China, in December 2019, has sparked a global public health crisis. Covid-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. More than 200 countries have been hit by the pandemic, which has had a significant impact on world health [2]. The clinical manifestations of covid-19 are fever, cough, shortness of breath, loss of taste or smell, diarrhea, nausea, vomiting, and fatigue [3]. Some of these symptoms can last even after a patient has recovered from the condition [4].
Post-acute covid-19 syndrome (PACS, or long COVID) is defined by persistent and debilitating symptoms that persist at least four weeks after infection [5]. Extreme fatigue, muscle, joint pain, shortness of breath, heart palpitations, loss or alteration of taste and smell, gastrointestinal distress, and problems with attention, memory, and cognition are the symptoms of post-covid-19 [6]. The patient's quality of life (QOL) has suffered as a result of the persistence of these symptoms. QoL is a commonly used parameter for assessing and evaluating one's health and well-being [4].
WHO defines Quality of Life as an individual's perception of their position in life in the context of the culture and value systems in which they live and about, expectations, standards, and concerns [7]. It is a broad concept that is influenced by a person's physical health, psychological state, personal beliefs, social relationships, and relationship to salient features of their environment in a complex way [8].
Health-related quality of life (HRQoL) is an individual's or a group's perceived physical and mental health over time [9]. There are at least 150 different instruments available to assess a person's quality of life. The SF-36, SF-12, EQ-5D-5L, and EQ-5D-3L are the most widely used in various settings around the world [4].

Background
Understanding the impact of covid-19 on the quality of life (QoL) of infected patients is emerging as a global challenge. Studies have reported post-covid patients have persistent symptoms and impaired QoL [10,11]. So, it is important to ascertain persisting impact of covid-19 on the QoL of infected individuals to aid the healthcare workers to support them.
Despite the need for information, there Is only limited data available. Considering this, we aim to perform this online survey to explore the consequences and its, associated factors of covid-19 on QoL of post-covid patients.

Study Design and Participants
Our study is a cross-sectional, community-based online survey done for a period of 6 months (March 21-September 21). The participants included in the study where those who recovered from covid-19 infection, since the day 1 of recovery up to 6 months. Our study was conducted in South-India (Tamil Nadu). We shared the google form link via online means to our known contacts. Respondents who met our inclusion criteria were selected among them. Only patients over the age of 18 and those who had recovered from covid-19 were included in our study. Our exclusion criteria include patients under the age of 18, pregnant women and lactating mothers, patients with psychiatric illnesses, and patients with chronic complex comorbidities.

Sampling Method
Our sampling method is convenience sampling which comes under non -probability / nonrandom sampling.
Convenience sampling is a type of nonprobability sampling that involves the sample being drawn from the population that is close to hand. Our literature survey also forms the basis for this.

Questionnaire Validation
As our questionnaire is self-made, we followed the validation technique. This technique includes the following steps:

Data Collection
The questionnaire was circulated using Google form through web and mobile-based social networks like WhatsApp & E-mail. Informed consent was also attached with the google form to know the will of the patient to participate or not.

RESULTS
A total of 120 participants responded to our survey. In our self-made and validated questionnaire, 11

Gender
The majority of our respondents were male.

Age
The respondents were categorized into 4 age groups such as 18-35 years, 36-55 years, 56-75 years, and above 75 years. The majority of our respondents were within the category of 18-35 years of age. Mean age = 34.41; SD = 14.66; Median age = 28.00

Risk Factors: (RF)
A risk factor is a variable that increases the risk or susceptibility of an outcome usually unpleasant i.e., disease, disorder, or syndrome. Based on the response we received, we have categorized risk factors as abnormal BMI (including those who are underweight, overweight, and obese), medical history (HTN and T2DM mainly), social history (smoking and alcoholism), and abnormal BMI with medical history (  Table 2 showed that age significantly affects the HRQoL of post-covid patients. A decrease in HRQoL with an increase in age was found in PH and PAIN. As HRQoL decreases with an increase in age, patients in the age group of 56-75 years have less HRQoL compared to post-covid patients in the age group of 18-35 years and they would have higher HRQoL.

Educational Qualification
The majority of the respondents were undergraduates.

Occupation
The majority of our respondents were employed.
A Kruskal Wallis test showed that occupation significantly affects the HRQoL of post-covid patients. A decrease in HRQoL was reported in physical health. Homemakers have lesser HRQoL compared to students.

Marital Status: (MS)
The majority of our respondents were married.
A Kruskal Wallis test showed that marital status significantly affects the HRQoL of post-covid patients. A decrease in HRQoL was reported in Physical health and Pain. For the domain, PH married post-covid patients had lower HRQoL. For the domain of Pain, the widow post-covid patient had lower HRQoL.

Vaccination
It is observed that the majority of our respondents were not vaccinated.

Severity
Risk factors associated with the patients tend to pave way for severe infection. The majority of respondents had a mild infection.

Hospitalization
The majority of the respondents were not hospitalized. A Mann-Whitney U test indicated that this difference was statistically significant (Table 3). A decrease in the HRQoL Domain -PAIN was observed in post-covid patients, hospitalized during covid-19 infection. HRQoL was affected more in post-covid patients, who were hospitalized during covid-19 infection.

Length of Hospital Stay (LOHS)
It generally depends upon the severity of infection in the patient. The majority of our respondents were not hospitalized. Mean LOHS = 4.00; SD = 4.996; Median LOHS = 0.00.
A Kruskal Wallis test showed that length of hospital stay significantly affects the HRQoL of post-covid patients. A decrease in HRQoL was reported with an increase in length of hospital stay. Patients hospitalized for more than 14 days showed a decrease in HRQoL to a higher extent comparatively.A decrease in HRQoL was reported with an increase in length of hospital stay in PH, Mental health, and pain.

Length of Hospital Stay (LOHS)
It generally depends upon the severity of infection in the patient.

Kruskal Wallis Pairwise comparison
The Post Hoc Dunn's test using a Bonferroniadjusted alpha level was done to identify the difference in QoL among patients in each domain. It showed that there was a significant difference in each domain between the patients according to their independent variable.
The difference in QoL between the groups that have statistical significance is given in Table 4. There was no significant difference between the other groups.

Multiple Linear Regression
Multiple linear regression revealed that several factors were predictors of TQoL. The test showed that Age, RF, MS, Severity of covid-19, hospitalization due to covid-19, and LOHS have a significant correlation with TQoL. Gender, Educational Qualification, occupation, and vaccination were not significant.
To summarize the MLR results from

Post Covid Manifestations
The sample consists of 120 respondents shown in Fig. 1. The prominent 3 post-covid manifestations reported by the study participants in terms of descending frequency are:  Cough -50%  Myalgia -39.17%  Arthralgia and Headache -37.50%.

DISCUSSION
Our study reflects the impact of covid-19 infection after recovery. We observed that ability to perform physical activity was highly impaired in post-covid patients. The severity of covid-19 infection, risk factors (Medical history, social history & abnormal BMI), and length of hospital stay due to covid-19 are found to be the factors that contribute to the impairment of health-related quality of life in patients.

Physical Health
The mechanisms leading to impaired physical functioning are multifactorial and arise as a consequence of the infection, prolonged hospitalization, and/or immobility [12]. The patients demonstrate decreased VO2max independent of pulmonary and ventilatory function; leading to decreased cardiorespiratory fitness, which accounts for the reduction in physical functioning. Patients also experience significant muscle weakness, especially in the lower limb muscles which are involved in functional mobility. This acquired weakness may attribute to a decrease in muscle cross-sectional area and muscle fiber size or a reduction in type II muscle fibers. Lower levels of aerobic capacity and changes in muscle function are associated with decreased physical functioning in patients.
A physical impairment may also be explained by a higher burden of premorbid disease, frailty, and severity of covid-19 infection. In their study, a similar interpretation like this was concluded by Ke-Yang Chen et al. [1].
Our study also reported that there has been a significant decrease in the QoL of post covid patients who were hospitalized. A similar interpretation was given by Jennifer K. Logue et al., [13] in their study.

Fig. 1. Distribution of post-covid manifestations in 120 respondents
Promoting recovery of physical function in people with SARS-CoV should be a key target of postcovid management since long-term physical function and quality of life was shown to be positively correlated in infected people.

Mental Health
Psychiatric ill-health was associated with severity of infection, attributable risk factors, and persistent physical symptoms such as myalgia, arthralgia, and headache.
This could be bidirectional: persistent physical symptoms may lead to psychiatric illness, and disturbed mental health could manifest as physical impairment. Additionally, the coronavirus may directly cause psychiatric complications through cerebral infection or hyperinflammation. [1,12] Breakdown of social networks and physical isolation due to the alarming pandemic throughout the globe and fear of mortality increases the potential for the development of PTSD, anxiety, and depression.
Pain is believed to have a bidirectional relationship with such psychological factors. In the acute phase, it may be an inducer of the development of mental illness. This matches with the study done by Luca Carenzo, et al. [14].

Pain
Immobilization from hospitalization and bed rest and physical inactivity due to prolonged quarantine can reduce the organ system's ability to resist viral infection and raise the risk of musculoskeletal damage. The study conducted by Manuel Taboada, et al., also concluded the same [15].
Due to the breakdown of protein in muscle fibres, direct tissue infection and the inflammatory response of cytokines produced to resist the viral invasion most likely induce muscle soreness and bone fragility. Some individuals continue to have musculoskeletal problems like joint pain, backaches, sore muscles, fatigue, and joint stiffness even after they have recovered from covid-19. Multi-morbidity and advancing age are baseline patient characteristics associated with the development of severe COVID-19 that are similar to those associated with chronic pain following severe illness. In our study too,pain has been an influential domain in determining the HRQoL. The research study of Guangbo Qu, et al., also indicated a similar idea [3].

General Health
Our study coincides with the study done by Matan Elkan et al., and Iqbal A, Iqbal K, Arshad Ali S, et al. in the aspect that patients affected with severe infection, exhibited impairment in their general health as a whole [10,16].
Besides cough, myalgia and arthralgia and headache were the most prominent post-covid manifestations reported by our study participants. This seems to be corresponding to the interpretations given by Kamal, M, et al. [17].

CONCLUSION
The purpose of our study is to evaluate the impact of covid-19 on HRQoL. Our study illustrates that covid-19 has a significant impact on the HRQoL of affected individuals. We found that poor HRQoL was associated with advanced age, severe covid-19 infection, and comorbidities. Although the factors that contribute to the impact of covid-19 on HRQoL have been established, it lacked a clear explanation of how these factors are linked to covid-19. This knowledge gap emphasizes the need for additional research to better understand the long-term consequences of covid-19. Furthermore, we propose proper therapeutic care should be given to assist the post-covid-19 patients' recovery.

CONSENT
All authors declare that electronic informed consent was obtained from the patients involved in this study.

ETHICAL APPROVAL
It is not applicable.

ACKNOWLEDGEMENT
We are greatly indebted to our respected and beloved Principal, and all staff members, of C.L.Baid Metha College of Pharmacy for their valuable guidance and suggestion with the help needed to carry out the work with great attention.
Our deepest gratitude goes to our dear parents who inspired and guided us on the right path and are also the backbone of our successful endeavors in life.

Validation Scheme:
We followed this five-step validation method which include: (1) Step One: Check the Questionnaire by Face validation: This is a two-step process involving two groups of experts. The first group checked and determined whether the questions are relevant to capture the intended research topic of the survey. The second group of experts checked for common errors, including leading, confusing, and repeated questions. The following are few changes we made as per their suggestions.
 The options in severity assessment question were defined (please refer our questionnaire).  Some questions were removed as they found it similar to already existing questions. (2) Step Two: Pilot Test of the Questionnaire: pilot test of the survey was conducted using the developed questionnaire for a small group of 20 respondents. Based on their response, we removed few words (e.g., Stooping) as most of them couldn't understand it. Also, we removed few unimportant questions as they felt our questionnaire is lengthy. (3) Step Three: Clean Collected Data: we transformed the data collected from the pilot study on a spreadsheet. Then we compared the scores of individuals on positive phrased questions and negative phrased questions for checking consistency. The scores of positively phrased questions were consistent with negatively phrased question. (4) Step Four: Use Principal Component Analysis (PCA): We did Principal component analysis using SPSS. The range of factor loading scale is usually between -1.0 to +1.0 and commonly accepted value is above ±0.6. Our result is given below