Study of Post-COVID-19 Syndrome in Saudi Arabia

Background Post-COVID-19 syndrome may be predisposed by organ damage as a complication of COVID-19. Patients may experience persistent symptoms after recovering from their initial illness. Objectives To identify manifestations and predisposing factors for post-COVID-19 syndrome in Saudi Arabia. Methods A cross-sectional study was conducted from May 2021 through June 2021 using an online structured pre-coded closed-ended, pilot-tested questionnaire in Arabic. It included male and female inhabitants of Saudi Arabia aged 18 years and above with a past history of COVID-19 infection. Descriptive statistics were carried out for all variables. A univariate analysis Chi-square test and independent t-test were used. A p-value of less than 0.05 was considered significant. Results A total of 85.3% of post-COVID-19 cases had general manifestations: 77.3% had musculoskeletal and joint complaints, 61.3% had mental and psychological problems, 58.7% had gastrointestinal manifestations, 44% had renal complaints, 41.3% had respiratory complaints, and 36.0% had cardiovascular symptoms. Gender, age, smoking, BMI, associated morbid condition, number of previous COVID-19 attacks, the severity of illness, place of treatment, and complications of COVID-19 due to treatment or hospitalization were significantly correlated with the occurrence of post-COVID-19 syndrome. Conclusion Post-COVID-19 syndrome could be manifested by fatigue, malaise, myalgia, joint pain, depression, anxiety, sleep, memory and concentration disturbances, cough, dyspnea, palpations, arrhythmias, and chest pain. It may be influenced by male gender, smoking, old age, high BMI, comorbidities, and past COVID-19 attacks with regard to the number, place of treatment, and occurrence of complications.


Introduction
COVID-19 is a zoonotic respiratory disease that started in Wuhan city in China and turned into a pandemic stated by World Health Organization (WHO) [1].
People who are in close contact with infected persons and those with impaired immunity and chronic medical conditions are more susceptible to the disease and its complications [1]. Mortality is higher among males in all age groups [7]. Complications of COVID-19 include acute respiratory failure, pneumonia, acute respiratory distress syndrome, acute liver injury, acute cardiac injury, secondary infection, acute kidney injury, septic shock as well as post-COVID-19 syndrome and death [8].
The post-COVID-19 syndrome is a syndrome of persistent symptoms or development of sequelae beyond 3 or 4 weeks from the onset of acute symptoms of COVID 19 attack regardless of the severity of this attack. It could be also defined as persistent symptoms and/or delayed or long-term complications of SARS-CoV-2 infection beyond 4 weeks from the onset of symptoms [9 -13]. Based on recent literature, it could be divided into two types: (1) subacute or ongoing symptomatic COVID-19, which includes symptoms and abnormalities present from 4-12 weeks beyond acute COVID-19; and (2) chronic or post-COVID-19 syndrome, which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID- 19 and not attributable to alternative diagnoses [12]. The main presentations are fatigue, shortness of breath or difficulty breathing, cough, joint, muscle, and chest pain, memory disturbances, concentration or sleep problems, headache, tachycardia, loss of smell or taste, depression or anxiety, fever, dizziness [9].
Post-COVID-19 syndrome may result in organ damage that resulted as sequelae of COVID-19, multisystem inflammatory syndrome following COVID 19 illness, blood clots, and leaking blood vessels that complicate COVID-19 may be another predisposing factor [9].
Little is known about the manifestations and predisposing factors for post-COVID-19 syndrome throughout the world and in Saudi Arabia. So this study was carried out to answer the following questions: What are the manifestations and predisposing factors of the post-COVID-19 syndrome in Saudi Arabia?

Study context and design
A cross-sectional study using an online questionnaire conducted by researchers from Ibn Sina National College for Medical Studies (ISNC) starting from May 2021 through June 2021.

Sampling
A voluntary response convenient sample of male and female participants aged above 18 years old with a past history of COVID-19 infection were included. The sample size was arrived at using the margin of error approach as seen in the equation below: where n is the sample size, Z is the statistic corresponding to the level of confidence, P is expected prevalence (that can be obtained from the same studies or a pilot study conducted by the researchers), and d is precision (corresponding to effect size) [14].
The sample size was set at 150 participants divided into two groups according to whether they suffered from the post-COVID-19 syndrome or not.
Where, Z2 = Z raised to power 2 d2 = d raised to power 2 n = minimum sample size Z2 = Standard score corresponding to a given confidence level. Example, at 95% confidence level or 5% level of significance (a = 0.05), Z = 1.96. P = Prevalence of disease is 1% q = (1 -p) or percentage of failure which is 100 -1 = 99% d = Precision limit or proportion of sampling error, which is usually 5% confidence limit.
The actual prevalence of COVID-19 in the Kingdom of Saudi Arabia was nearly 1.7 (about 600,000 cases with a total population of 35 million).
Here, in the equation, the prevalence used was .01 (as expected among the studied group, for response rate and duration and feasibility of the study)

Data collection methods
A structured pre-coded closed-ended, pilot-tested questionnaire in Arabic was developed. It included the following data: demographic data (age, sex, marital status, education, occupation, smoking history, and BMI), medical history, COVID-19 vaccination state, history of last COVID-19 attack, and clinical manifestation of post-COVID-19. The reliability of the questionnaire (content validity) was tested by SPSS Statistics (IBM Corp, Armonk, USA) using Cronbach's alpha test (r = 0.89).

Statistical analysis
Data were collected and processed using SPSS version 22. Descriptive statistics were carried out for all variables. The participants were divided into two groups: Group I without post-COVID-19 syndrome and Group II with post-COVID-19 syndrome (according to the following: persistent symptoms of COVID-19 or development of sequelae beyond 4 weeks from the onset of acute symptoms of COVID-19 attack). A univariate analysis Chi-square test and independent t-test were used. A p-value < 0.05 was considered statistically significant. Spearman's correlation was used to study the predisposing factors for developing the post-COVID-19 syndrome.

Ethical considerations
Ethical approval for the study was obtained from Ibn Sina National College (ISNC) Research and Ethics Committee (IEC Ref No: H-04-03062021) in accordance with the Declaration of Helsinki for Human Studies [14]. Participation in the study was voluntary and during the online questionnaire, the participants were all informed about the purpose of the study and their right to refuse participation. Ethical conduct was maintained during data collection and throughout the research process.

Results
The total number of participants that were included in the study was 150, divided into two groups. The first group was without post-COVID-19 syndrome and the second group suffered from post-COVID-19 syndrome.

COVID-19)
GIT: gastrointestinal tract Gender, age, smoking, BMI, associated co-morbid condition, number of previous COVID-19 attacks, the severity of illness, place of treatment, and complications of COVID-19 due to treatment or hospitalization were significantly correlated with the occurrence of the post-COVID-19 syndrome (   The post-COVID-19 syndrome is a syndrome of persistent symptoms or development of sequelae beyond 3 or 4 weeks from the onset of acute symptoms of COVID-19 attack regardless of the severity of this attack [9][10][11][12]. The exact mechanism for the syndrome, in general, is still unknown. Yet, one recent study [9] Which investigated the mechanism of severe post-COVID-19 syndrome form of the multisystem inflammatory syndrome in children determined that viral particles remaining in the gut long after initial COVID-19 infection and could pass into the bloodstream [9]. Another research [15] claimed that the mechanism of its development may be direct viral toxicity; endothelial damage and microvascular injury; immune system impaired regulation and stimulation of a hyperinflammatory state; hypercoagulability with resultant in situ thrombosis and macrothrombosis; and maladaptation of the angiotensin-converting enzyme 2 (ACE2) pathway [15].
The current work concomitant with other researches demonstrated that fever, dyspnea, anosmia/ cacosmia, and loss of taste were the most frequently encountered clinical manifestations of COVID-19. [9,[16][17][18][19] The severity of these symptoms varies according to the presence of underlying morbid conditions [16,20]. The present work revealed that respiratory, hepatic, renal, and cardiovascular comorbidities were encountered among the great proportion of the studied participants; especially those having post-COVID-19 syndrome. Moreover, these co-morbid conditions may predispose to the development of post-COVID-19 syndrome [15,21].
The present work revealed that the main manifestations encountered among those with the post-COVID-19 syndrome were general manifestations (as fatigue, and malaise), musculoskeletal (muscle and joint pain), mental health (depression, anxiety, sleep, memory and concentration disturbances), respiratory (cough and dyspnea) and cardiovascular (palpations, arrhythmias, and chest pain). The same findings were reported by a comprehensive review of current literature on post-COVID-19 syndrome done by Nalbandian A et al on April 2021 [22].
Mental stress, in general, has been reported to impair immunity, therefore, increasing susceptibility for diseases [23]. Moreover, infection with COVID-19 will negatively affect a patient's life, sleep pattern, and mood. That will predispose him again to a vicious circle of depression, stress and anxiety, and impaired immunity [24][25][26]. These findings were in coherence with our study results which revealed that a great portion of the study participants with post-COVID-19 syndrome experienced headaches, mental complaints in form of anxiety, depression, and sleep disturbances during their last COVID-19 attack. Those symptoms would precipitate stressful conditions that lower immunity and therefore predisposed them to post-COVID-19 syndrome .
Until now, there is no promising treatment option for COVID-19, and the drugs used have many toxic side effects [27]. This may explain our result of a high percentage of reported complications among post-COVID-19 syndrome patients treated from their last COVID-19 attack at hospitals. Another explanation is that those cases were severe enough to develop complications on their own so that they need hospitalization or intensive care admission.
The present study demonstrates that almost all study participants without post-COVID-19 syndrome had more vaccination coverage whether partially (with only one dose) or fully vaccinated (with two doses). Effective vaccines are important to prevent and control epidemics of emerging viruses as SARS-CoV-2 [28,29]. Vaccination prevents severe forms and hospitalization due to COVID-19 infection including post-COVID-19 syndrome.
The present study proved that male gender, smoking, increase in age, high BMI, associated comorbidities, number, place of treatment, severity, and associated complications of COVID-19 attacks; all were correlated with the development of the post-COVID-19 syndrome. Nalbandian A et al discussed all those parameters and considered them also as predisposing factors for the development of post-COVID-19 syndrome [22].
collection and throughout the research process. . Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.