Clinical Profile of COVID-19 Patients Admitted at a Private Hospital During Three Surges in Mandalay, Myanmar

Introduction During the coronavirus disease 2019 (COVID-19) pandemic, private hospitals in Mandalay started to manage COVID-19 infections according to national treatment guidelines since February 2021. Variations of clinical characteristics and their outcomes in different surges could be evaluated in the private hospital. This study aimed to assess the clinical profile and outcomes of COVID-19 patients admitted at a private hospital during three surges in Mandalay. Methods This study is a retrospective record review of the case series of COVID-19 patients admitted at City Hospital, Mandalay. The study was conducted from January to December 2022. All of the hospital records of COVID-19 patients admitted during the second wave from February 2020 to 26 May 2021, the third wave from 27 May 2021 to 27 January 2022, and the fourth wave from 28 January to April 2022 were included in the study. Results A total of 1606 admitted cases were included in the study. The mean with standard deviation (SD) of age was 55.7±18.5, and males were 778 (48.4%). The mean duration of hospital stay in days was 10.8±5.94, 10.6±6.11, and 7.3±2.88 in second, third, and fourth waves, respectively. The mean duration of hospital stay was shortened in the fourth wave. Comorbid conditions with hypertension and/or diabetes diseases were mostly observed in three waves of COVID-19 infection. Fever was the most presented symptom in three waves. Cough, sore throat, and rhinorrhea were observed more in the fourth wave compared with previous waves. Complication with pneumonia (71.3%), liver dysfunction (21.0%), acute respiratory distress syndrome (10.0%), thrombocytopenia (6.2%), acute kidney injury (5.5%), bleeding (3.9%), and pulmonary embolism (2.9%) were investigated. Antiviral treatment such as remdesivir or molnupiravir was used more in the patients of third and fourth waves than those of the second wave. Oxygen therapy (59.9%), prone position (35.5%), non-invasive ventilation (9.5%), invasive ventilation (0.5%), inotropes (4.6%), and renal replacement therapy (1.1%) were recorded in serious cases. Only 7.9% and 9.4% died in the hospital in second and third waves. No mortality was observed in the fourth wave. Conclusions The study recommended that COVID-19 patients with comorbid conditions of hypertension or diabetes and ages 65 and older should be taken with intensive care support at the hospital. This study also concluded that a private hospital in Mandalay could tackle with COVID-19 severe cases in line with national treatment guidelines since the second wave and could provide better management in the fourth wave. Antiviral treatment should be used in severe COVID-19 cases for further emergency management. In conclusion, private hospital involvement in the COVID-19 pandemic is supportive of the healthcare provision in Myanmar in an emergency situation.


Introduction
The coronavirus disease 2019 (COVID- 19) pandemic transmission started at Wuhan, China, in late 2019. It is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients may present with many symptoms such as fever, cough, anorexia, fatigue, shortness of breath, and myalgia. Moreover, flu-like symptoms are also presented. Clinical presentations may vary in accordance with regional variation, pandemic waves, and pathogen alteration. COVID-19 pandemic waves occur due to the rising of infection transmission with new variant appearances in countries [1]. Regarding the diagnosis, clinical presentation is highly supportive. Nucleic acid amplifying test of respiratory specimens such as reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 infection is used as laboratory confirmatory diagnosis. However, rapid antigen testing is useful if RT-PCR is not available in some conditions with limited resources [2]. In the World Health Organization's (WHO) living guidance paper, other differential diagnoses such as influenza, dengue, malaria, typhoid, and respiratory tract infections are not negligible in hospital management [3].
Critical COVID-19 cases such as acute respiratory distress syndrome (ARDS) and septic shock are cared aligned with standard management guideline [4]. Treatment with antimicrobial therapy for co-infections and secondary infections coinciding with COVID-19 has to be started as soon as possible according to laboratory investigations, clinical judgment, local epidemiology, and patient host factor [5]. COVID-19 patients are manifested with neurological, neuropsychiatric, and mental problems. Those should be treated appropriately at the hospital [6]. If the disease becomes very severe, intubation with mechanical ventilation is a lifesaving management in advanced hospitals. Antiviral as a specific treatment for severe disease is also practicable. Remdesivir, a ribonucleic acid (RNA)-dependent polymerase inhibitor, is the most promising broad-spectrum antiviral agent that resulted from clinical studies [7,8].
Severe COVID-19 patients may be cured and die. The mortality of severe and critically ill patients may be different substantially in different case series all over the world. The World Health Organization (WHO) recommended collecting clinical data of admitted COVID-19 patients from countries all over the world and contributing clinical characterization data at the WHO Global COVID-19 Clinical Data Platform [1]. transmission. In 2020, clinical treatment for hospitalized patients was focused by public hospitals such as secondary-level (township/district) hospitals and tertiary-level (state/regional/general) hospitals. However, because of increasing transmission and human resource shortage that resulted from an unstable country situation, the support from private sector involvement was needed to manage the surge of infection. Therefore, in early 2021, some specialized private hospitals were allowed to treat COVID-19 patients in line with national treatment guidelines [9].
During the COVID-19 pandemic in Myanmar, there were four surges called as waves: the first wave was from 23 March to 15 August 2020, the second wave from 16 August 2020 to 26 May 2021, the third wave from 27 May 2021 to 27 January 2022, and the fourth wave from 28 January 2022 up to the present. These waves were determined by the Central Epidemiological Unit of the Department of Public Health and approved by the Ministry of Health, Myanmar. Therefore, variations of clinical characteristics in different waves have been practiced in the private hospitals. These clinical characteristics and their outcomes among the patients are evaluated by waves. Therefore, this study aimed to assess the clinical profile and outcomes of COVID-19 patients admitted at a private hospital in Mandalay.

Materials And Methods
This study is a retrospective record review of the case series of COVID-19 patients admitted at a private, city hospital at Mandalay. It is 300-bedded specialist hospital equipped with high-technology medical care units, intensive care units, high-standard medical laboratories, and operation theaters. This study was conducted from January to December 2022. All of the hospital records of COVID-19 patients admitted at City Hospital from February 2021 to April 2022 were included in this study. During the COVID-19 pandemic in Myanmar, there were four waves: the first wave was from 23 March to 15 August 2020, the second wave from 16 August 2020 to 26 May 2021, the third wave from 27 May 2021 to 27 January 2022, and the fourth wave from 28 January 2022 up to the present. According to wave distribution, the studied cases were distributed in three waves: second, third, and fourth waves. The patients who presented to the hospital with no symptoms but needed investigation, the patients with clinical signs of pneumonia, and the suspected patients with comorbid conditions and severely ill cases were confirmed with either rapid diagnostic testing or PCR testing.
All of the COVID-19-confirmed cases were admitted to the hospital except the mild cases without risk or comorbid conditions. Those mild cases were transferred to the regional-level clinical management committee. Then, the admitted cases were categorized and treated according to national management guidelines for COVID-19 of Myanmar. The symptomatic patients without evidence of viral pneumonia or hypoxia were defined as mild disease; adolescents or adults with clinical signs of pneumonia (fever, cough, dyspnea, and fast breathing) as moderate disease (pneumonia); adolescents or adults with clinical signs of pneumonia (fever, cough, dyspnea, and fast breathing) plus either respiratory rate of >30 breaths/minute, severe respiratory distress, or saturation of peripheral oxygen (SpO 2 ) of <93% on room air as severe disease (severe pneumonia); and complications such as ARDS, organ failure, sepsis, and shock as critically ill. This study included all COVID-19-confirmed cases. Hospital records of patients who had a history of COVID-19 infection and were admitted for the second time for another disease were not enrolled in this study. The patients who were vaccinated and re-admitted for COVID-19 infections were included in the study. Both the hospital patient chart and the electronic medical record (EMR) system of the hospital were used as a source of data document. The clinical data were collected in case record form (CRF) modified from the standard case record form (CRF) developed by the WHO Guideline Development Group for the WHO Global COVID-19 Clinical Data Platform [1].

Data analysis
The data on clinical characteristics, laboratory investigations, treatment, and final outcome status were reviewed using the electronic medical record (EMR). Individual clinical data were abstracted after discharge from hospital. The data on the clinical profile of COVID-19 patients were collected with CRF developed using the WHO Global COVID-19 Clinical Data Platform. Data entry and analysis were done using the Statistical Package for Social Sciences (SPSS) software (version 18.0, PASW Statistics, Chicago, IL). Descriptive analysis was carried out presenting with mean, medium, standard deviation (SD), and interquartile range (IQR) for continuous numerical data and frequency and percentage for categorical data.
The variables among the waves were analyzed using chi-square (χ 2 ) test for comparing categorical data, analysis of variance (ANOVA) for comparing means, and nonparametric test (median test) for comparing medians. Statistical significance was set at p-value of <0.05.

Ethical approval
The study was conducted after obtaining the ethical approval from Research Ethics Committee of University of Medicine, Mandalay (approval number: 1535/UMM/Research, dated 14 June 2022). The waiver of informed consent taking in conduct of this retrospective record review was approved by the Research Ethics Committee. This research was registered at Myanmar Health Research Registry (http://www.mhrrmohs.com) (PLRID-00192_V14).

Results
Between 8 February 2021 and 14 April 2022, a total of 1606 cases were admitted at City Hospital, Mandalay, for COVID-19 infections. Among them, 67 (4.2%) were re-admitted as post-COVID-19 complications, and 306 (19.1%) were vaccinated. The patients were distributed in the second, third, and fourth waves. A total of 139 cases in the second wave, 1330 cases in the third wave, and 137 cases in the fourth wave were reviewed. The following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram shows the distribution of cases by waves and their outcomes ( Figure 1).

STROBE: Strengthening the Reporting of Observational Studies in Epidemiology
In this study, the mean (±SD) age of a total of 1606 cases was 55.7±18.5. The mean age by wave distribution showed 58.2±16.8, 54.35±18.34, and 65.6±18.1 in the second, third, and fourth waves, respectively. More than half of them were within 51 and 75 years old age group. Males were 778 (48.4%), and females were 828 (51.6%). Among them, healthcare workers were 128 (8.0%), and laboratory workers were six (0.4%). Pregnant mothers were 24 (1.5%) ( Table 1).     Skin rash 0 (0) 6 (0.5) The distribution of the complications of COVID-19 patients in three waves are shown in Figure 2. Among all patients, as a cumulative incidence during three waves, complication with pneumonia (71.3%), liver dysfunction (21.0%), ARDS (10.0%), thrombocytopenia (6.2%), acute kidney injury (5.5%), bleeding (3.9%), and pulmonary embolism (2.9%) were investigated. Respiratory complications such as ARDS and pneumonia were observed more in the second and third waves compared to the fourth wave. Liver dysfunction was also recorded less in the fourth wave compared to previous waves.  Table 4 shows the laboratory findings on admission, mid-time, and discharge in three waves of the COVID-19 patients. The reduction of mean lymphocyte count was observed among the patients during three waves especially in the second wave. Similarly, the increased median value of procalcitonin, hyper-sensitive Creactive protein (hsCRP), and D-dimer were also recorded throughout three waves especially in second and third waves. High levels of the mean of ferritin were also reviewed among the patients in three waves especially in third and fourth.    Treatment with intravenous fluids, oral fluids, corticosteroid, antiviral such as remdesivir, antibiotics such as fluoroquinolone, cephalosporin, and carbapenem was mostly used for the COVID-19 patients admitted at the hospital in three waves of the study period. Antiviral treatment had been used since the second wave, and antiviral drug such as remdesivir or molnupiravir was used more in the patients of the third and fourth waves than those of the second wave. Most of the patients were supplied with pipeline oxygen therapy. Noninvasive ventilation, invasive ventilation, and inotropes were observed in serious cases. Renal replacement therapy was also done in 1.1% of the cases during three waves. Disease severity during three waves was cumulatively showed as mild, moderate, severe, and critical cases with 56 (3.5%), 344( 21.4%), 871 (54.2%), and 335 (20.9%), respectively. Critical cases were observed mostly in the second wave compared to later waves ( Table 5).  Treatment outcomes of the COVID-19 patients admitted at the hospital were described in Table 6. The mean duration of hospital stay in days was 10.8±5.94, 10.6±6.11, and 7.3±2.88 in the second, third, and fourth waves, respectively. About 90% of the hospitalized COVID-19 patients were discharged alive, and only 7.9% and 9.4% died in the hospital in the second and third waves. No mortality was observed in the fourth wave. There were 67 cases re-admitted as post-COVID-19 complications. Among them, only 13 (19.4%) had been vaccinated, and four (6%) died with post-COVID-19 complications.

Discussion
At the beginning of the COVID-19 pandemic in 2020, transmission was controlled by the Department of Public Health, and serious cases were treated at public hospitals of the Department of Medical Services under national treatment guidelines developed by the Ministry of Health. Later, a shortage of human resources resulted because of both the pandemic severity and the unstable country situation. Moreover, a surge in infection also led to the need for support by private sector involvement. Therefore, private hospitals started to manage COVID-19 infections in early 2021. This study evaluated the management of hospitalized patients by a private hospital in three different waves, the second, third, and fourth waves, in Myanmar. This study describes the clinical profile and outcomes of COVID-19 patients admitted at a private hospital in Mandalay, Myanmar. According to the findings, the private hospital in Mandalay could tackle COVID-19 severe cases in line with national treatment guidelines since the second wave and could provide better management in the fourth wave.
The mean age of the patients in the third wave was younger than those admitted in the second wave. COVID-19 immunization in Myanmar started in January 2021 with old-age people and healthcare workers as the first priority. Because of the immunization schedule mentioned earlier, older people were prioritized, and younger people who were going out for work were infected more than older people. This is similar to the studies of other countries in Asia [10][11][12]. However, the mean age of the patients in the fourth wave was older than those admitted in the second and third waves. In the later wave, people became familiar with mild-to-moderate infection and took self-care at home, and old people with severe infection took hospital care at a private hospital. Another reason may be because old people suffered more severe effects of the omicron variant than young people. Therefore, old age with severe cases should be closely monitored at the hospital. This finding is consistent with other studies [13][14][15][16]. Infection among healthcare workers was involved at 8.0%. The proportion was higher in the second and third waves with 8.6% each. However, it was lower in the fourth wave with 1.2%. It might be due to the vaccination effect among healthcare workers in the fourth wave, and the finding is similar to a retrospective study in India [17].
Comorbid conditions with hypertension or diabetes diseases were most commonly observed in three waves of COVID-19 infection in City Hospital, Mandalay. These were recorded with 48.2%, 39.8%, and 54.0% for hypertension and 41.0%, 34.3%, and 39.4% for diabetes in the second, third, and fourth waves, respectively. Therefore, patients with comorbid conditions of hypertension or diabetes and who are old should be taken with close care at the hospital. Although fever, cough, and headache were the most presenting symptoms in all waves, influenza-like symptoms such as sore throat and rhinorrhea were observed in high proportion in the fourth wave compared to previous waves. These findings were in contrast with the findings of the studies in Qatar and Iran [10,18].
Complications such as pneumonia, liver dysfunction, anemia, ARDS, cardiac injury, coagulopathy, acute kidney injury, and shock were observed in three waves. Respiratory complications such as ARDS and pneumonia were observed more in the second and third waves compared to fourth wave. Those are similar with a study in Wuhan and Qatar [14,18]. This led to higher proportion of oxygen therapy and higher proportion of ICU admission in the second and third waves compared to the fourth wave. This finding is also similar with the study done in 41 hospitals in India [19].
In this study, increased level of procalcitonin, C-reactive protein, and D-dimer were recorded among the patients throughout three waves especially in the second and third waves. Therefore, oxygen requirement with assisted ventilation was high among the patients who had high CRP and D-dimer in the second and third waves like other studies [10,20].
The hospital could manage the severe cases according to national treatment guidelines in all waves. Antiviral treatment was observed more in patients of the third and fourth wave than those of the second wave because of the less proportion of severe cases needed for antiviral treatment in the second wave, or locally recommended antiviral treatment were not available in the area or hospital in that period. Nevertheless, antiviral treatment might lead to better outcomes in the fourth wave. Similarly, treatment with non-invasive ventilation and invasive ventilation was used in more patients of the third wave compared to those of other waves. These findings are similar to those found in Africa [21].
The mean duration of hospital stay was shortened in the fourth wave compared to previous waves. This finding is also consistent with other studies [18,21]. No mortality was observed in the fourth wave. This successful result may be reflected from experienced practices of the hospital achieved in previous waves. Therefore, it showed that hospital management became better in the fourth wave compared to previous waves [22,23].

Limitations of the study
This study is a retrospective record review, so it is not a prospective study. This study describes the clinical profile of COVID-19 patients by assessment with CRF developed using the WHO Global COVID-19 Clinical Data Platform. The CRF contains three modules: module 1, to be completed on the first day of admission to the health center; module 2, to be completed daily during hospital stay for as many days as resources allow and to continue to follow-up patients who transfer between wards; and module 3, to be completed at discharge or death. However, the current study reviewed the patients' records using WHO module that was modified. It could not be completed during hospital stay and continued to follow-up. The record review was done after the patients were discharged. Therefore, the assessment might not be complete enough. Another limitation is that although there were four waves in Myanmar, the clinical profile of the patients of the first wave was not studied in this research. In this connection, the emergency response and control activities were sufficient with available and efficient workforce in 2020. Therefore, private hospital involvement was not needed in 2020, resulting in no studies relating private hospital management in the first wave of 2020. In addition, laboratory results were reviewed on available findings in EMR. Many laboratory investigations of the patients were not available, and those were not included in the analysis. Moreover, clinical outcomes of the admitted patients were determined by reviewing the EMR, and those who were discharged or referred to other facilities were not followed. This study was conducted in one private hospital only; it was not done as a multicenter study.

Conclusions
At the beginning of the COVID-19 pandemic in 2020, cases were contained and treated at public hospitals in Myanmar. However, because of an unstable country situation, the private hospitals supported the management of the COVID-19 crisis in the subsequent waves: Delta in 2021 and Omicron in 2022. This study recommended that COVID-19 patients with comorbid conditions of hypertension or diabetes and who are 65 years and older should be taken with intensive care support at the hospital and should be encouraged for vaccination. This study also concluded that a private hospital in Mandalay could tackle COVID-19 severe cases in line with national treatment guidelines since the second wave and could provide better management in the fourth wave. Antiviral treatment should be used in severe COVID-19 cases for further emergency management. In conclusion, private hospital involvement in the COVID-19 pandemic is supportive of the healthcare provision in Myanmar in an emergency situation.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. The Research Ethics Committee of University of Medicine, Mandalay, issued approval 1535/UMM/Research. The study involves minimal to no risk to subjects because it is just reviewing the records. The waiver of informed consent does not adversely affect the rights and welfare of human subjects. The waiver does not adversely affect the rights and welfare of subjects because the study did not collect the personal identity and clinical data were kept confidentially. This study is non-interventional and does not affect the subject's rights for patient care and does not interfere in their welfare. The study would not be practically arrived without the waiver of informed consent. The research could not practicably be carried out without the waiver because secondary data of the subjects were reviewed and analyzed in the study. The waiver is needed because it would be impractical to obtain consent for taking personal and clinical data as these subjects are not seen by research staff on a regular basis or much time has elapsed since these subjects were last seen locally or the hours needed to contact these subjects for consent would exceed the ability of our research staff. This study is noninterventional, and thus, providing information to patients is not likely. Furthermore, there was no information that needed to be provided to the subjects. The authors reviewed the medical records but are not recording identifiers. The authors would not be able to link subjects back to the study and therefore would not be able to provide additional information. 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.