The Association of Initial Viral Load among COVID- 19 Patients with Sociodemographic Characteristics and Travel History in Jeddah, Kingdom of Saudi Arabia, 2020

Background: Since declaration of COVID-19 as a pandemic; researchers are trying to find out the clues for determining spread and transmission of the disease. Although viral load had been used for assessing severity, progress and transmissibility of the disease, yet, little is known about all factors associated with its changes. This study aims to explore the association of initial viral load among COVID-19 patients with sociodemographic characteristics and travel history. Subjects and Methods: Through a record based retrospective study, laboratory confirmed cases in the period from 7th March to 31st May 2020 were included in the study (n=381); The dependent variable was the recorded viral load measured in Ct count; while the dependent variables included socio-demographic characteristics of the patients and travel history. Data were analyzed using Statistical Package for Social sciences (SPSS) version 21. Student t test and ANOVA test were used and P value less <0.05 was considered as a level of significance. Original Research Article Kareem and Ghamdi; JPRI, 33(45B): 49-56, 2021; Article no.JPRI.75033 50 Results: Out of all respondents (n=381), there was dominance of male cases (74.0%) over females (26.0%). The great majority (83.5%) were primarily classified as being cases, while the rest were contacts (16.5%). Most of them were symptomatic (82.9%); mainly cough (44.4%), fever (41.2%), sore throat (22.0%) and runny nose (13.1%). Fifteen percent of the respondents reported that they had travelled abroad before coming back to the Kingdom of Saudi Arabia and discovered as positive for COVID-19.The mean vial load was higher in males (26.2±5.55), older cases (26.5±5.39), Saudis (26.4±5.58) and health care workers (26.9±6.32), nevertheless, these differences are not statistically significant p>0.05.There was no statistically significant difference in the viral load between symptomatic and asymptomatic cases (26.0±5.48 vs 26.6±5.63) p>0.5. Nevertheless, viral load was significantly lower among those who had fever (25.2±5.70) and dyspnea (26.4±5.46) and those who reported that they did not travel abroad (29.1±4.97) p<0.05. Conclusion and Recommendations: The current findings add more evidence to the assumption that it is likely that asymptomatic pre-symptomatic and symptomatic transmission is occurring and there is no difference between them in viral load whether they present as cases or contacts; therefore, the repeated assessment of viral load could be more valuable and informative for assessing progress of the COVID-19 on individual level rather than comparison between positive cases. Therefore, it is highly recommended to conduct further researches based on the changes of viral load along the course of the disease and find out the role of the demographic and clinical determinants on these changes.


INTRODUCTION
In December 2019 the outbreak of corona virus disease  began in China, to turn shortly into a pandemic affecting the whole world. The symptoms of the novel corona include fever, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting and diarrhea [1]. In February, 2021, more than 106 million cases were diagnosed worldwide, over 2 million deaths reported, with a death rate around 2% [2]. Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay has routinely been used for the detection of causative viruses from respiratory secretions and final pathogenic diagnostics of COVID-19 according to the cycle threshold (Ct). Ct values were inversely related to viral RNA copy numbers with a Ct value <40 being considered positive [3]. Studying viral dynamics and their variation among population subgroups may help in understanding the role of epidemiological characteristics in the disease development and outcome. Uncertainty still exist regarding the relationship between viral load and severity, infectivity and duration of COVID-19's viral dynamics and how they relate to factors in the population [4,5]. Moreover, evidence on the association between viral load and other factors, including age and sex, nationality has not been conclusive. Some studies found that higher viral load in the respiratory system was associated with higher in-hospital mortality and morbidity [6,7]. and a higher risk of transmission; [8] while other studies found no such relationship [4]. Understanding viral load dynamics and covariates is critical for identifying protective measures for individuals and the general public. Therefore, this study investigates the association of viral load with certain sociodemographic and the outcome of COVID-19 patients.

MATERIALS AND METHODS
Through a record based retrospective study, all laboratory confirmed COVID-19 cases who were diagnosed at health care facilities in Jeddah governorate in the period from 7th March to 31st May 2020 were included in the study (inclusion criteria); the exclusion criteria were the cases recorded out of the study designated duration and cases confirmed outside Jeddah. The data were extracted from the database of the Health Electronic Surveillance Network (HESN) which is originally designated for registering and reporting communicable diseases in the Kingdom of Saudi Arabia.
The data include demographic characteristics of each patient together with clinical and laboratory findings along progress of the case, and it is accessible for treating physicians, lab personnel and authorized personnel in charge in the health directorates over the whole country. After getting the approval for conducting the research, the researchers accessed the relevant data and retrieved it in an excel sheet. The dependent variable was the recorded viral load measured in Ct count; while the independent variables included sociodemographic characteristics of the patients (age, gender, nationality and job), clinical findings and travel history. Data were coded and analyzed using Statistical Package for Social sciences (SPSS) version 21. Qualitative variables are summarized and presented as frequency distribution, while quantitative normally distributed variables are presented in mean and standard deviation. Student t test was used for comparing continuous outcome (viral load) in two subgroups, while ANOVA test was used to compare it within three or more groups. A confidence level of 95% (CI 95%) was adopted throughout the study, P value less than 0.05 was considered as a level of significance.

DISCUSSION
In March 2020, the world health organization (WHO) considered the rapid and aggressive spread of COVID-19 as a pandemic [9]. By the end of June 2020, the number of cases exceeded seven million cases worldwide with about 400,000 deaths [10]. Since its early beginning and along its progress, the researchers as well as the general community were concerned with the transmissibility of the virus, as it is the cornerstone for prevention and control of the pandemic [11][12][13]. Basically, the transmission of COVID-19, as is the case of most of the viral respiratory infectious diseases, depends on many factors, mainly the shedding of the virus which is the expelled viral particles from the infected individuals while they talk, exhale, eat, and perform other normal daily activities [13][14][15]. The intimate relation between viral shedding and viral load had been discussed in numerous researches; that mostly pointed to direct correlation between viral load (number of viral particles in a given unit of body fluids) and the viral shedding (infectivity) [16][17][18]. In this respect Jeroen and his colleagues (2020) identified that viral loads above 7 log10 RNA copies/mL increases likelihood of isolating infectious SARS-CoV-2 from the respiratory tract by almost fourteen times (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001). [16] The crucial problem in transmission of COVID-19 is that the viral load from upper respiratory tract reaches its highest level at or even before appearance of clinical symptoms and for a few days after (generally within one week), with levels slowly decreasing over the next one to three weeks [19]. The long incubation and high pre-symptomatic infectivity makes transmission between family members a potential risk, since modelling of viral shedding

*Based on Independent sample t test ** Statistically significant
suggests that the highest viral load is at or just before symptom onset, with 44% of transmission occurring before symptoms. [15]. That could explain the non-significant difference in viral load observed in the current study between symptomatic and asymptomatic positive COVID-19 cases (26.0±5.48 vs 26.6±5.63); and those who were initially categorized as being cases and those categorized as contacts (26.0±5.59 vs 26.6±5.07) p>0.05. In this regards, Jing et al (2020) claimed that assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation," the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8-15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3-21·8) when household contacts were defined on the basis of residential address" [10]. These notions could also explain the relatively high viral load among those who got domestic infection than those who got infected abroad, as the first are more in close contact with relatives who could be asymptomatic or pre-symptomatic.
Elderly households are more susceptible to exhibit relatively high viral load as shown in the current study and supported by what had been reported by To, Kelvin Kai-Wang et al (2020) that older age was significantly correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074-0·75; p=0·020). [20]. Also, Wang and his colleagues suggested that the easy transmission even when symptoms are mild; could explain the efficient person-to-person transmission noted in healthcare settings; [21] that had been shown in the current study. The significant low viral load demonstrated in our cases who had fever or dyspnea, this difference is not conclusive per symptom, as it could partly be attributed to the fact that all symptomatic cases in Saudi Arabia receive imminent treatment per protocol as soon they are discovered to be positive for COVID-19; this explanation is supported by what had been asserted by several researches that the combined treatment of COVID-19 was associated with a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials [20,[22][23][24]. The non-significant relation between sociodemographic characteristics and viral load could be verified if further researches are conducted based on the successive changes in viral load rather than one point estimate [25].

CONCLUSION AND RECOMMENDA-TIONS
There is no difference in viral load between symptomatic and asymptomatic COVID-19 cases, only significant differences were realized with the symptomatic cases particularly those who fever and dyspnea, that could explain the rapid progressive dissemination of the virus in the community; and lead to the conclusion that the repeated assessment of viral load could be more valuable and informative for assessing progress of the COVID-19 on individual level rather than comparison between positive cases. Therefore, it is highly recommended to include spaces for recording successive readings of viral load in HESN application to facilitate monitoring for its progress. Also, there is a need to conduct further researches based on the changes of viral load along the course of the disease and find out the role of the demographic and clinical determinants on these changes

LIMITATION OF THE STUDY
The main limitation of the current study comes in line with what is known about the inherited limitations in the record-based study design where the researchers are confined to the available data which are not essentially the optimal data needed for the research, this fact showed itself in the current study that only one reading of the viral load was recorded in the database, it would be more beneficial if several readings were recorded to assess the changes of the viral load along the course of each case.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

CONSENT
It is not applicable.

ETHICAL APPROVAL
Ethical approval was obtained from the regional Institutional Research Board (IRB) in Jeddah (Number: A01155).