Clinical presentation and persistent symptoms in patients at a post-COVID-19 clinic in Ghana

Introduction on March 11th, 2020, the World Health Organization recognized COVID-19 as a pandemic. By March 31st, 2021, the Ghana Health Service had recorded a cumulative 90,782 positive cases and 748 deaths in the country. Despite the significant resources and efforts being put into containing and treating individuals with COVID-19, there is a lack of information within sub-Saharan Africa on clinical presentations and factors associated with experiencing persistent symptoms of COVID-19. Methods in this retrospective study, we collected data obtained from patients with COVID-19 who were discharged from the post-COVID-19 clinic at the Ga East Municipal Hospital, Ghana, between April 1st, 2020, and March 31st, 2021, to assess clinical presentations and identify predictors of COVID-19 symptoms that persist beyond 14 days from the onset of the symptom. Results of the 253 patients who experienced symptoms of COVID-19, 81 (32.0%) experienced symptoms that persisted beyond 14 days. Cough (64.0%), headache (38.7%), and chest pain (28.1%) were the most common symptoms. After adjusting for covariates, the odds of patients presenting with COVID-19 symptoms that persist beyond 14 days are 98% higher among patients who experienced chest pain compared to those who did not and 2% increased for each additional year of their age. Conclusion patient´s age and experiencing chest pain were significant predictors of symptoms that persist beyond 14 days. The findings of our study highlight the need to continue to monitor and care for individuals with identified predictors of experiencing persistent symptoms of COVID-19.


Introduction
In December 2019, a series of unusual pneumonia cases were reported in Wuhan, China. The cause of the outbreak was determined to be a novel coronavirus, referred to as COVID-19 [1]. On March 11 th , 2020, the World Health Organization (WHO) declared COVID-19 a pandemic with significantly higher infection and mortality rates compared to its predecessors, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [2]. At the end of March 2021, the WHO had recorded a cumulative of 128,197,827 confirmed cases, 3,092,693 of which were recorded in Africa [3]. By March 31 st , 2021, the Ghana Health Service had recorded a cumulative 90,782 positive cases and 748 deaths in the country [4].
COVID-19 has an unprecedented effect on the immune system and triggers a sudden upregulation of different pro-inflammatory cytokines [5]. The clinical characteristics of COVID-19 are well established. However, studies conducted on different continents reported variations in the most common symptoms [6][7][8].
Although most patients with COVID-19 recover within weeks of illness, studies have highlighted cases in which patients report symptoms of COVID-19 persisting for several weeks after being infected with the virus [9,10]. Symptoms that include shortness of breath, fatigue, and sleep disorders are symptoms of COVID-19 reported to persist in patients who have recovered from the disease [9,10]. Other similar follow-up studies have identified anosmia and diarrhea [11], age, and sex [12], as well as the severity of COVID-19 [13] as risk factors associated with persistent symptoms of COVID-19. The findings of these studies suggest that there may be additional demographic and clinical factors that may predict individuals who are at risk of experiencing persistent symptoms.
As new cases and recoveries from COVID-19 continue to emerge, identifying the proportion of recovered individuals suffering from and those who are at greater risk of experiencing persistent symptoms will become critical for the development of effective treatment and management strategies. In this study, we evaluated the clinical presentation and persistent symptoms in patients who attended a post-COVID-19 clinic in Ghana. Specifically, we carried out this study to identify the proportion of individuals experiencing persistent symptoms of COVID-19 and assess the associations between the demographic characteristics of the patient, the clinical characteristics, and the persistent symptoms of COVID-19.

Methods
Study design: this is a one-year retrospective cohort study.
Setting: this study involved analyzing archived data of COVID-19 patients who were discharged from the post-COVID-19 clinic at the Ga East Municipal Hospital, Ghana, between April 2020 and March 2021. This facility was designated as the national COVID-19 treatment center in Ghana, receiving COVID-19 positive patients from both the Kotoka International Airport and the local community from March 2020 until April 2021. The 100-bed facility is also equipped with a 4-bed high dependency unit/intensive care unit and has a unit for post-COVID-19 review.
Participants: our study population consisted of all patients admitted to the facility who were confirmed by polymerase chain reaction (PCR) for COVID-19. Patients were followed up daily until they were declared fully recovered by the medical staffs and discharged from the facility.
Variables: we used the term "persistent symptoms" to describe patients with self-reported COVID-19-like symptoms that persisted beyond 14 days after symptom onset. Furthermore, we used the term "experienced" for all self-reported symptoms from the onset of the symptom until the last report from the patient. The presence or absence of persistent symptoms was the dependent variable. Independent variables were demographic and clinical characteristics, including patient age, sex, nationality, underlying health conditions, as well as clinical information including admission period, worst COVID-19 severity recorded during admission, and symptoms.
Data sources: self-reported age, sex, nationality, underlying health conditions, and symptoms were collected from the hospital records. Clinical information on the patient´s admission period, worst COVID-19 severity during admission documented by the medical staffs were also collected from the medical records. Disease severity was categorized as mild, moderate, or severe based on the standard WHO classification of COVID-19 severity.
Bias: potential recall bias was kept to a minimum since patients, while on admission, reported their symptoms to the doctors daily.
Study size: to focus our assessment on patients brought in from the local community, we excluded COVID-19 positive travelers who were brought in from Kotoka International Airport. We also excluded patients who were asymptomatic from diagnosis until they were declared fully recovered, and those discharged from the facility to continue home-based treatment.
Quantitative variables: in our study, patient age was grouped as those ≤19, 20-39, 40-64, and ≥65 years. These categories were used to present age distribution and compare differences in the patient´s characteristics with the presence or absence of persistent symptoms. Self-reported age (continuous variable) was used in the logistic regression analysis.
Statistical methods: we collected the archived medical records of patients using a structured data collection form and exported the data to Stata 16.1 (StataCorp, College Station, Texas, USA) for analysis. We had no missing data from those included in the study. The continuous variables are presented as medians and interquartile range (IQR), while categorical variables are presented as frequency and percentages. We used Chi-square test or Fisher´s exact test to analyze differences between dependent and independent variables as well as a logistic regression to assess factors associated with developing symptoms of COVID-19 that persisted beyond 14 days. The results of the logistic regression analysis are reported as crude odds ratio (COR) and adjusted odds ratio (AOR). Backward elimination was used for sequential removal of non-significant variables (p ≥ 0.05) from the adjusted model. We set the confidence interval (CI) at 95% and two-tailed p-values <0.05 were considered significant.

Results
Main results: after adjusting for variables with p-value <0.05 from the crude odds ratio analysis, the results revealed that the patient´s age and experiencing chest pain were significant predictors of symptoms that persist beyond 14 days ( Table 4). The odds of patients experiencing COVID-19 symptoms that persist beyond 14 days are 98% higher among patients who reported chest pain compared to those who did not (adjusted odds ratio (AOR) = 1.98, 95% CI 1.10-3.55, p = 0.02). Furthermore, the odds of experiencing COVID-19 symptoms that persist beyond 14 days are increased by 2% for each additional year of their age (AOR = 1.02, 95% CI 1.00-1.04, p = 0.02).

Discussion
Our study assessed the clinical presentation of COVID-19 and factors associated with the experience of persistent symptoms. Our findings on the most common symptoms of COVID-19 were consistent with the results of an earlier published study in Accra, Ghana, which also identified cough in over half (57.5%) of their symptomatic patients [14]. However, the low reporting (20.6%) of fever among patients in this study suggests that noncontact infrared thermometers are not suitable as a stand-alone screening tool for COVID-19 positive patients.
We identified age as a significant predictor of symptoms that persist beyond 14 days. This finding is consistent with a previous study that analyzed 4,182 cases of COVID-19 and reported that age is significantly associated with symptoms that persist beyond 28 days [12]. Experiencing chest pain was also identified as a significant predictor of persistent disease symptoms. The chest pain reported in recovered patients may be attributed to inflammation of the pleura [1].
One limitation of our study was the dependence on self-reported symptoms. However, the potential recall bias was kept to a minimum since patients, while on admission, reported their symptoms to the doctors daily. Another limitation was the inability to distinguish between possible variants of COVID-19 within the study population, which may have influenced the study findings.
In contrast to a previous retrospective study of 274 COVID-19 survivors from the Lagos State COVID-19 Outpatient Clinic, we did not identify the severity of COVID-19 as a predictor of experiencing persistent symptoms [13]. The findings of our study highlight the need to continue to monitor and care for individuals with identified predictors of experiencing persistent symptoms of COVID-19.

Conclusion
Cough (64.0%), headache (38.7%), and chest pain (28.1%) were the most common symptoms. More than a quarter (32.0%) of the patients experienced symptoms of COVID-19 that persisted beyond 14 days after the onset of the symptoms. After adjusting for covariates, the odds of patients presenting with COVID-19 symptoms that persist beyond 14 days are 98% higher among patients who experienced chest pain compared to those who did not and 2% increased for each additional year of their age.  Table 1: demographic characteristics of patients with symptoms Table 2: clinical presentation of patients by symptoms Table 3:

Tables
relationship between patient characteristics and persistent symptoms Table 4: characteristics associated with symptoms persisting beyond 14 days