Characteristics of the COVID-19 patients treated at Gulu Regional Referral Hospital, Northern Uganda: A cross-sectional study

Coronavirus Disease 2019 (COVID-19) is a severe respiratory disease that results from infection with a new coronavirus (SARS-CoV-2). One of the most critical issues related to the COVID-19 is the high rate of spread, millions of people have been infected around the world, and hundreds of thousands of people have died till now. However, reports from Africa paint a different picture of the SARS-CoV-2 and its effects on the population. The objective of this study was to describe the characteristics of the COVID-19 patients treated at the Gulu Regional Referral Hospital and determine factors associated with COVID-19 manifestations, socio-demographic characteristics, and treatment outcomes from March 2020 to October 2021. distress (ARDS) and septic shock The Adjusted Odds on factors associated with recovery were treated with steroids AOR=138.835 at 95% CI:12.258-1572.50; p<0.000 and Vitamin D AOR=0.016 at 95% CI:1.902-520.98; p=0.016. This study shows successful management of COVID-19 patients in low resource settings in Gulu Regional Referral Hospital with a recovery rate of 95.2%. The pattern of admission to the Hospital suggests Uganda has experienced three waves of COVID-19, contrary to the ocial government position of two waves. Treatment of COVID-19 patients with steroids and Vitamin D is associated with recovery of COVID 19 patients. However, there is a need for Randomized Controlled Clinical Trials to determine the actual effects of these drugs in the Treatment of COVID-19 infections.


Introduction
Coronavirus Disease 2019 (COVID-19) is a severe respiratory disease that results from infection with a new coronavirus (SARS-COV-2) [1]. One of the most critical issues related to the COVID-19 is the high rate of spread, millions of people have been infected around the world, and hundreds of thousands of deaths till now have been recorded [1]. Patients suffering from different symptoms like fever, dry cough, and fatigue which is usually mild in about 80% of cases, but the more severe cases may progress to develop respiratory distress or respiratory failure, and hence the increased need for intensive care unit (ICU) services [1].
The severity of the disease is related to the age and comorbidities of the infected person; elderly persons are affected more severely with a need for ICU services [2]. The severity of symptoms is also related to its duration, where for mild cases, symptoms may last for two weeks, while for severe cases, it ranges from 3 to 6 weeks [3]. Direct contacts to con rmed cases are the disease's primary way of spreading because the SARS-COV-2 is transmitted through exhaled air and aerosols [4]. Diagnosis of COVID-19 is conducted using Reverse Transcriptase Polymer Chain Reaction (RT-PCR), Computed Tomography (CT) scan, and blood tests [5]. Supportive treatment is the primary choice for mild cases, including antibiotics, vitamins, trace elements, and antipyretics. At the same time, oxygen therapy with or without mechanical ventilation is introduced and individualized according to each case [6]. Many drugs have been included in clinical trials to act as antiviral agents to the coronavirus disease. Still, no precise results indicate the con rmed effect for any investigated drugs [7][8][9]. In addition to symptomatic therapy, corticosteroids as an antiin ammatory agent have been found to play a vital role in the management of severe cases [10].
Thousands of infected patients have recovered from the disease, and this recovery is con rmed by another RT-PCR test or by the absence of the symptoms of the disease for several days. However, no documented study in Uganda provides information on the clinical characterization of COVID-19 cases, treatment outcomes, and factors associated with the clinical presentations and treatment outcomes.
The objective of this study was to describe the characteristics of the COVID-19 patients treated at the Gulu Regional Referral Hospital and determine factors associated with the COVID-19 manifestations, socio-demographic characteristics, and treatment outcomes.

Study site
This study was conducted at Gulu Regional Referral Hospital in Northern Uganda, covering admissions of COVID-19 patients from March 2020 to October 2021. Gulu Hospital is a regional referral center for patients from northern Uganda. However, it receives patients from neighboring countries, for example, South Sudan and the Democratic Republic of Congo (DR Congo). It is also a teaching hospital for Gulu University Medical school and many other health training institutions in the region. It is a 394-bed capacity hospital with outpatient and inpatients services estimated at 120,000 patients every year. The Hospital has specialized units such as internal medicine, surgery, pediatrics, reproductive health, TB, HIV, cardiac, chest, dental, dermatology, sickle cell disease, diabetes, hypertension, Ear, Nose and throat, nutrition, accident and emergency, laboratory, ophthalmology, mental health, and orthopedic clinics that consultants manage from Gulu Hospital and Gulu University.
Gulu Regional Referral Hospital was designated by the Ugandan Ministry of Health as a treatment center for COVID-19 patients in March 2020 when COVID-19 was declared a pandemic. As a result, a particular treatment unit for the management of COVID-19 (Gulu CTU) was established with a fully-edged high dependency unit (HDU), with Oxygen supply and staff to manage the department. The team leader for the Gulu CTU is a consultant physician who cares for all the COVID-19 patients admitted to the unit. In addition, the Ugandan Ministry of Health and WHO health experts provided additional support for managing the COVID-19 patients at the center using standard protocols developed and practiced in Uganda.

Study design
A retrospective data review and abstraction of all COVID-19 hospital admissions registered in the Gulu Health Management Information System (HMIS) database and other tools were conducted. The period of the review was March 2020 to October 2021. Established by the Ugandan Ministry of Health, HMIS has been the primary source of information on COVID-19 hospital admissions and deaths. COVID-19 noti cation is compulsory in Uganda, and the emergency operation center at the Uganda National Public Health Institute receives reports on patients admitted to both public and private hospitals with COVID-19.

Sources of data
For the period of this study, COVID-19 patients admitted to Gulu Regional Referral Hospital with COVID-19 were estimated at 900. We included each patient registered in the HMIS database, information on individual's sociodemographic characteristics, self-reported symptoms, signs, comorbidities, COVID-19 Treatment Unit (CTU) admissions, ICU admissions, and ventilatory support, dates of symptom onset, date of hospital admission, date of discharge, duration of the hospital stay, reported circumstances when the disease was contracted, vaccination status and in-hospital outcome (deaths, referrals, and releases/discharges).
HMIS data were accessed, which were already de-identi ed and publicly available documents. Following ethically agreed principles on open data access, this analysis did not require stringent ethical approval in Uganda as we mainly worked on records with no identi ers included. However, we obtained ethical and administrative licenses from the Gulu Regional Referral Hospital Institution and Ethical Review Committee to access the archived Gulu hospital data on COVID-19 patients.

Selection criteria
Inclusion criteria: The following were the inclusion criteria for the participants (i) Con rmed cases of COVID-19 with RT-PCR results as positive (ii) records of patients 12 years and above (iii) completed information on the chart and other medical tools (iv) admission records Exclusion criteria: We excluded (i) incomplete records, (ii) records with no RT-PCR results (iii) participants below 12 years.
Selection of records: The medical records for the COVID-19 patients in Gulu Regional Referral Hospital archives were accessed. The choice of the COVID-19 patients' les was conducted consecutively and reviewed by the research team.
The selection criteria were applied to each admission le, and a total of 664 les were included in the participating medical records for this research.
Sample size: We determined the sample size for the study population using the selection criteria on the medical records. Six hundred and sixty-four (664) records were included as the sampled population.
Training of research assistants: To obtain excellent and clean information from these COVID-19 patients' medical les, the research team trained the research assistants who were four in number (two medical o cers, one clinical o cer, and one nurse) on how to use the selection criteria, accurately record data from the admission forms and exclude forms that were considered incomplete. The research teams were trained on infection, prevention, and control of COVID-19 and were required to use facemasks, eye shields, and sanitizers during and after reviewing documents.
The corresponding author supervised the data collection exercise from the beginning to the end, ensuring that he checked every le to con rm the completeness of the data collected.
Procedures for data collection: Consecutively registered COVID-19 patients treated at Gulu Regional Referral Hospital with a positive quantitative RT-PCR test result for SARS-CoV-2 admitted to Gulu Hospital were used. SARS-CoV-2 diagnostic tests followed national and international standards. They were done in certi ed laboratories of Gulu Regional Referral Hospital and Uganda Virus Research Institute (UVRI) as the Ugandan Ministry of Health protocols required.
Variables for the study: The dependent variables for this study were treatment outcomes (alive or dead). The independent variables were the socio-demographics of the COVID-19 patients (age, sex, occupation, religion, tribe, districts, and level of education), comorbidities and treatments used, oxygen saturation at admission, date of discharge from the hospital, duration of hospital stay, disease severity, and others), clinical presentations (signs and symptoms), vaccination status, place of residence and circumstance under which the patient contracted the virus.
Data analysis: The analysis period was from the epidemiological week (starting month and date of March 2020) to the epidemiological week (until month and date of October 2021). The analysis was pre-speci ed and de ned before any reading of the medical data in the records of Gulu Regional Hospital. The sample size was all patients (aged ≥12 years) with COVID-19 diagnosis admitted to the Gulu Regional Referral Hospital and registered in the database between epidemiological weeks of March 2020 and October 2021.
Means, standard deviations, bar graphs, histograms, frequencies, and percentages were used to summarize continuous variables, while frequencies and proportions were calculated for categorical variables. Age-adjusted and sex-adjusted rates for each district by the direct method using the estimated Ugandan population for 2020 as a reference were calculated.
We used the Chi-Square tests at bivariate analysis to observe associations between independent and dependent variables at 95% con dence Intervals. Factors with p-values less or equal to 0.2 were entered into a multivariable regression analysis to determine factors associated with COVID-19 patients treated at Gulu Regional Referral Hospital. However, the Gulu Hospital HMIS data contained much-missing information for some variables, such as reported symptoms, medicines used, and comorbidities. Therefore, we used additional Gulu Regional Referral Hospital records to ll in the missing data. Also, in the post hoc analysis, we evaluated the missing data pattern and conducted a sensitivity analysis via multiple imputations by chained equations, generating 30 imputed datasets. SPSS version 25.0 was used for data analysis, and various imputations were performed utilizing the STROBE guideline recommendations. In addition, Adjusted Odds Ratios (AOR) for independent variables were calculated for the COVID-19 patients treated at the Gulu Regional Referral Hospital from March 2020 to October 2021.
Ethical considerations: This retrospective data review of COVID-19 patients' medical les at the Gulu Regional Referral Hospital was approved by the Gulu Regional Hospital Institutional, Ethics, and Review Committee.

Results
This study abstracted six hundred and sixty-four (664) medical records of COVID-19 patients treated at the Gulu Regional Referral Hospital from March 2020 to October 2021. Only medical records of COVID-19 patients who met the inclusion criteria for the study were included. Most COVID-19 patients treated at the Gulu Regional Referral Hospital recovered from the disease with a recovery rate of 632(95.2%) and a mortality of 32(4.8%). In addition, most COVID-19 patients treated at Gulu Regional Referral Hospital were unvaccinated 661(99.5%) for COVID-19.
In gure 1, there were three waves of COVID-19 in Gulu, Northern Uganda, and these were May and September in 2020. In addition, there was a small observable wave in July 2021.
In gure 2, COVID-19 discharges from the CTU of Gulu Regional Referral Hospital mirrored the admission pattern where June, October, and July registered the most releases from the CTU. Figure 3 shows the peak duration of Hospital stays (days) among COVID-19 patients treated at GRRH as 16 days.

Discussions
The most signi cant ndings were the three waves of COVID-19 in Gulu in Northern Uganda, and these were in May and September of 2020 and July of 2021 ( Figure 1, Figure 2, and Figure 3). The third wave of COVID-19 in 2021 was less pronounced (Figure 1, Figure 2, Figure 3). This nding contrasts with the o cial Ugandan Ministry of Health position on the number of COVID-19 waves Uganda has gone through since the pandemic began in March 2020. The Ugandan Ministry of Health speci ed two waves of the COVID-19: one in 2020 and another in June 2021. This Ugandan Ministry of Health report is not surprising as regional waves of COVID-19 have been reported in many studies [11,12,13,14]. This nding has implications on how Uganda could respond to the COVID-19 waves as the regional approach to managing and controlling the pandemic has become eminent. The regional occurrence of the COVID-19 wave has advantages in that the Ugandan Ministry of Health could use this information to harness support and allocate resources to effectively manage and control the pandemic at the regional level in different parts of the Country. This may include mass mobilization and sensitization of the population at a regional level to embrace mass vaccination with COVID-19 vaccines now that they are available in the Country. It is expected that this approach could limit the spreading of COVID-19 country-wide and reduce the morbidity and mortality of the coronavirus in Uganda.

Socio-demographic characteristics of the COVID-19 patients
Findings from this study show that most COVID-19 patients treated at the Gulu Regional Referral Hospital were males, 30-39-years-old, Acholi, Catholics with certi cates as the highest level of education, civil servants, and from Gulu District (Table 1). These socio-demographic characteristics are comparable to previous studies conducted in Northern Uganda, where the most affected people were males and certi cates at their highest level of education (Table 1).
What is different in this study population is that the most affected age group is a decade older (Table 1) compared to previous studies in Northern Uganda, where most participants were 20-29-years-old [15,16].
The age factor could be explained by the susceptibility pattern of the COVID-19 among the older population of Northern Uganda and elsewhere. The aging population appears more vulnerable and susceptible. The overall reasons for the susceptibility in the older people in Northern Uganda may not be known for now but perhaps attributable to lifestyles, exposure to multiple risk factors, comorbidities, and immunity problems of the more aging population. As shown in Table 1, the younger age groups were least affected as per the GRRH COVID-19 treatment center's admission details. However, it could also mean that many of the younger age groups got affected but remained asymptomatic, did not test for COVID-19, did not develop severe disease, and did not get hospitalized with the coronavirus.
Findings from this current study show that nearly one-fourth of the COVID-19 patients treated were asymptomatic, and less than 10% of the patients were below 20 years of age (Table 3). These authors argue that this information was not wholly new. Similar ndings in many studies conducted elsewhere in the world show that younger persons were least susceptible to severe COVID-19 and hospitalization [13,14,17].
Factors associated with the COVID-19 patients treated at the Gulu Regional Referral Hospital This report shows that most COVID-19 patients treated for severe COVID-19 and died at the GRRH had comorbidities, for example, Diabetes mellitus, cardiovascular diseases (CVDs) including (Stroke, valvular heart diseases, dysrhythmias, heart failure, and cardiac septal defects), hypertension, and symptomatic cases ( Table 2 and Table 3). Many studies have observed similar ndings, particularly those with comorbidities [2,17,18]. This nding implies that the Ugandan Ministry of Health could adopt the "Enhanced shielding" approach, where persons with comorbidities and the elderly are shielded from the general population to protect them from contracting the COVID-19 virus [12,19]. These suggestions have implications on the approach the Ugandan health systems could adopt to control the spreading of COVID-19 among the elderly and those with comorbid conditions. The rural structure and relationship between the elderly and younger generation need thorough analysis as the elderly in the rural community live with and together with the young people who provide support and protection to the elderly. The practicality of this approach needs thorough thinking as this new approach may disrupt traditional ways of how people in the African rural communities live. These authors argue that with the lockdown, the economy, and health systems collapsing in many African countries, it is high time government planners came with solutions that allow the economy to be opened but ensure a reduced incidence and prevalence of COVID-19 in communities. One of the recommended approaches was to practice the enhanced shielding approach, which is more favorable to a country's social and economic systems. In addition, there is a need to sensitize and mobilize the population to embrace mass COVID-19 vaccination as vaccines are now available in the country to reduce the incidence of severe diseases which require hospitalization.

Treatment and complications observed among COVID-19 patients in Gulu Regional Referral Hospital
Findings from this study show that most COVID-19 patients were treated with antibiotics, vitamin C, steroids, Ivermectin, and vitamin D (Table 3, Table 4, Table 5, Table 6, and Table 7) and the outcomes of the treatment have been encouraging as shown by a very high recovery rate at 95.2% and a statistically signi cant association with steroid and Vitamin D treatment (Table 8).
In the same study, the most typical complications observed among the COVID-19 patients were pneumonia, acute respiratory distress syndrome (ARDS), systemic infections, septic shock, chronic fatigue, depression, and nightmares (Table 4). These authors argue that there were justi ed reasons for using antibiotics in treating COVID-19 patients at Gulu Regional Referral Hospital, as many cases developed complications treated with antibiotics.
In addition, the role played by the other drugs in the management of COVID-19 was suggested by scholars and academicians across the world and particularly their use as immune system modulators [17]. To come up with a conclusive decision on the bene cial effects of the two drugs for managing COVID-19 patients at GRRH, formal Randomized controlled Trials will be required.
On the mental health complications observed among the COVID-19 patients treated at the Gulu Regional Referral Hospital, the authors recommend comprehensive mental health support for COVID-19 patients and the follow-up after recovery. Effective management of mental health conditions such as depression relieves the ever-increasing sense of depression and isolation experienced by the COVID-19 patients. If the numbers of mental health cases become widespread, a grassroots approach using trained village health teams (VHTs) would be the recommended approach for handling the problem. Notably, the VHTs should be trained and capable of dealing with COVID-19 related Psychosocial symptoms in the community. This idea is supported by studies conducted elsewhere in Africa, which suggest a grass-root approach to mental health problems after the lockdown in African [12,19].
The independent determinants of COVID-19 cases treated at Gulu Regional Referral Hospital: This study showed that the recovery rate from the COVID-19 treated at the Gulu Regional Referral Hospital was 95.2%, yet 99.5% of the COVID-19 patients were unvaccinated (Table 3). Furthermore, this study found the Adjusted Odds Ratios (AOR) for factors associated with COVID-19 patients' recovery at GRRH were treatment with steroids AOR=138.835 at 95% CI:12.258-1572.50; p<0.000 and Vitamin D AOR=0.016 at 95% CI:1.902-520.98; p=0.016 (Table 8). Statistically signi cant associations of Vitamin D and steroids with a positive outcome in the treatment and management of COVID 19 patients in our study have also been observed in previous studies [20,21]. Could these successes be for this center only, or could this apply to diverse settings worldwide? A formal review study in different locations would be required in the long term to determine the effectiveness of the drugs in managing mild and severe cases of COVID-19. Authors recommend global studies on the two drugs to assess their actual effects on the treatment outcomes of COVID-19 patients.

Circumstances under which the coronavirus infected participants
Findings show that most of the circumstances were unknown 581(87.5%), others were congregated situations such overcrowding at Elegu border and interacting with international truck drivers 50(7.5%), Aswa Dam construction workers 12(1.8%) who lived in dormitories, health facility 2(0.3%), persons who nursed a relative with COVID-19 2(0.3%), bars 1(0.2%) and others 16(2.4%). This nding implies that the known source of the COVID-19 infection in Northern Uganda was from international truck drivers and mainly at the Elegu border point. Other sources such as bars, churches, and markets were fewer. Authors argue that regional controls of COVID-19 would be ideal for the East African region, where there is brisk trade among the countries. Therefore, the management and surveillance of international truck drivers as a regional approach would be suitable for controlling the coronavirus, ensuring that COVID-19 testing and management were conducted as per the international protocols across all the East African countries [11].

Strengths and limitations of the study
This study was a retrospective review of datasets from the COVID-19 medical records of Gulu Regional Referral Hospital. The period of the evaluation was from March 2020 to October 2021. The study has limitations on how Gulu Hospital handled records and record keeping. In addition, vital information, for example, weight, height, and BMI of COVID-19 patients, was not recorded due to the emergency handling of the cases at the beginning of the pandemic in March 2020. The missing variables in the Gulu Hospital HMIS records excluded some les from participating in this study. In this, authors have suggested a need for a prospective or longitudinal assessment of the COVID-19 cases in the future, ensuring that all data were measured and recorded accordingly.
This data is vital as it is one of the well-documented completed data for over 664 cases of COVID-19 treated in a Regional Referral Hospital in Uganda. Findings from this study show tremendous and good clinical practices at Gulu Regional Referral Hospital despite the challenges faced during the pandemic.
Generalization of the data from this study These ndings should be cautiously interpreted and generalized only to Regional Referral Hospitals in Uganda. However, they could be similarly observed in many hospitals in African countries with low-resource settings.

Figure 1
The pattern of COVID-19 admissions to the Gulu Treatment Unit (CTU). In gure 1, there were three waves of COVID-19 in Gulu, Northern Uganda, and these were May and September in 2020. In addition, there was a small observable wave in July 2021.