Therapy for patients with asymptomatic and mild cases of COVID-19 in Indonesia [version 1; peer review: 1 approved with reservations]

Background: Though coronavirus disease (COVID-19) has been designated as a global pandemic, its nature as a viral infection means that it is essentially a self-limiting disease. We studied the application of symptomatic, isolation, relaxation, nutrition and observation (SIRNO) therapy in patients with asymptomatic and mild symptoms of COVID-19 at a rescue hospital in Indonesia. Methods: This is a retrospective cohort study involving 2122 patients who were admitted to Indrapura Field Hospital in Surabaya from 28 May 2020 to 20 September 2020. We analyzed demographic data, clinical signs and symptoms, laboratory data, therapy and clinical outcomes. Result: The total sample of 2122 patients consisted of 1403 male patients (66.12%), and 719 female patients (33.88 %). The most Open Peer Review


Conclusion:
The SIRNO method provides excellent results in the management of COVID-19 at a rescue hospital for patients with asymptomatic and mild symptoms. Economic pharmacological research can initiate a follow-up study in order to objectively measure the effectiveness and efficiency of SIRNO treatment methods in patients with asymptomatic, mild symptoms of COVID-19, and the small number of 24 patients (0,.1%) with moderate symptoms.

Keywords
Symptomatic, Isolation, Relaxation, Nutrition, Observation,  This article is included in the Emerging Diseases and Outbreaks gateway.
This article is included in the Coronavirus collection.

Introduction
Coronavirus disease (COVID-19) is a global public health issue that was confirmed as a pandemic in March 2020. Defined by the World Health Organization (WHO), COVID-19 is caused by a new coronavirus called the 2019-novel coronavirus (2019-nCoV) 1 . However, the International Committee on Taxonomy of Viruses named the novel coronavirus as "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) 2 .
On September 21, 2020, a total of 30,675,675 confirmed COVID-19 cases were reported in more than 216 countries, including 954,417 deaths, resulting in a mortality rate of 3.1%. In Indonesia, the total number of cases was 248,852 with a death rate of 9,677, while in East Java the total number of cases was 40,708 (16.35%) with a mortality rate of 7.28 %, or 2,695 patients 3 . As the number of COVID-19 sufferers in some countries continues to increase, as well as the deaths resulting from it, epidemiological studies are very important in order to determine the source of transmission and devise effective and efficient therapeutic methods 4 . Although the understanding of COVID-19 epidemiology continues to develop, it is assumed that SARS-CoV-2 is primarily transmitted through droplets and close contact with a person that is carrying the virus 4 and the likelihood of death strongly depends on the methods of therapy and comorbidities found in patients.
COVID-19 has a very wide clinical output, from asymptomatic to severe and critical symptoms; more than 75% cases are asymptomatic cases 5 . Among those symptomatic patients, clinical presentations of this include fever, non-productive cough, dyspnea, myalgia, fatigue, normal or decreased leukocytes count, and radiography evidence of pneumonia 6 . Severe complications can include organ dysfunction, including shock, acute respiratory distress syndrome (ARDS), acute heart injury and acute kidney injury. These manifestations may continue and lead to death 7 . The WHO recommended therapies for asymptomatic and mild symptomatic COVID-19 cases are symptomatic, isolation, and observation, related to complaints as well as the monitoring of vital signs and the progress of the disease. In addition, highly nutritional therapy 8 and relaxation are also needed in the form of light exercise, communication with fellow patients, a psychological approach and calming of the patient with spiritual lectures and studies into religion, as well as a relaxed atmosphere in the hospital 9 . This approach was based on the nature of viral infection which is a self-limiting disease. Viruses that enter the body will be countered by our body's defense system, either naturally via non-specific defences, or specific antibodies.
If the body's non-specific defenses are unable to prevent the virus, then the virus will enter the cell, damage the cell and replicate itself. Antiviral drugs specifically for SARS-COV-2 are still in clinical trials, the administration of antiviral side effects damages the body's cells, so the type, time and dosage of its administration must be precise. In addition the effectiveness of virusidal against the virus that causes COVID- 19 has not yet been empirically proven. A review of the economic pharmacology also needs to be considered, the efficiency and effectiveness of therapy is key to the success of the therapy method 10 .
Kogabwilhan II Indrapuara Field Hospital is a specialized hospital that treats COVID-19 patients, which is confirmed by swab results with positive PCR (polymerase chain reaction) examination infected with SARS-COV-2. The hospital was established for the treatment and isolation of COVID-19 patients without symptoms and with mild symptoms, in an effort to support COVID-19 services in existing referral hospitals. The initiator of the establishment of Indrapuara Field Hospital was the COVID-19 Control Task Force of East Java Province, with financing from the National Disaster centre and fully supported by the Provincial Government of East Java, military regional command V Brawijaya, East Java regional police, the Ministry of Health and the Commander of Joint Command Region II.
The purpose of this study is to describe application of symptomatic, isolation, relaxation, nutrition, and observation (SIRNO) therapy for asymptomatic and mild symptomatic patients at rescue field hospital.

Study design
This study is a retrospective cohort study of COVID-19 patients who were admitted at Kogabwilhan II Indrapura Field Hospital from 28 May 2020 to 20 September 2020 in Surabaya, East Java Indonesia. This date range was chosen as the opening date of service of the Indrapura Field Hospital for COVID-19 patients. The obtained data was downloaded from the hospital electronic medical records, including demographic data, clinical signs and symptoms, laboratory data, therapy and clinical outcomes (24).

Patient criteria
All patients with COVID-19 enrolled in this study diagnosed according to the guidelines for diagnostic criteria from Clinical management of COVID-19: interim guidance (World Health Organization, 27 May 2020). All patients suffered from the infection of SARS-CoV-2, ascertained in the laboratory (the results of RT-PCR [reverse-transcription polymerase chain reaction] specific for SARS-CoV-2 was positive). Diagnosis of mild case patients is made based on the criteria of symptomatic patients and meets the definition of COVID-19 cases without evidence of viral pneumonia or hypoxia, and moderate cases of patients with clinical symptoms of pneumonia (fever, cough, dyspnea, rapid breathing) but no sign of severe pneumonia, including SpO2 ≥ 90% in the air of the room. All patients treated in Indrapura field hospital according to the criteria constitute the sample of the study.

Data characteristics
Data demographic characteristics of patients were obtained with form collection from the electronic medical record. The collected information included age, gender, occupation, and domicile.
The patients' clinical data were data related to current and past patient medical history. Current signs and symptoms were fever, cough, shortness of breath, fatigue, anorexia, muscle pain, headache, chills, nausea and vomiting, diarrhea, and confusion. Patients' past history included hypertension, heart disease, diabetes, obesity, chronic obstructive pulmonary disease, liver disease. Serial vital signs included blood pressure, pulse, respiratory rate, body temperature, oxygen saturation, and body mass index. The date of onset of the disease is defined as the day when symptoms are first known. Determination of COVID-19 positivity was based on RT-PCR SARS-CoV-2 from naso/ oropharyngeal swabs which were collected on the day of admission and evaluated when patients were discharged. Clinical outcome data, including recovery rates, length of treatment, referred cases and death cases, were also analyzed in this study.

SIRNO therapy
Symptomatic by providing therapy according to the complaints felt by the patient, such as the administration of antipyretics, anti diarrhea, decongestan, antitussive and so on.
Isolation by dividing into red zones for patients, which are not mixed between patients and service providers. The room includes a bed space, space for rest and a field for outdoor activities, as well as a garden.
Relaxation by doing gymnastics activities on the field, as well as deep breathing exercises. In addition, there are karaoke activities while still using masks and keeping distance, and regular spiritual and religious lectures and stress management.
Nutrition provided is adjusted to the patient's caloric needs and comorbidity. The type of food provided should also meet the balance of macro nutritional needs such as carbohydrates, proteins, fats, vitamins, and minerals.
Observations are divided into three shifts, each shift will enter the isolation zone for 3 hours to observe the patient's vital signs, complaints and progress. During observation, patients can also consult both physical and mental complaints such as sleep difficulty and restlessness. Patients can also contact the care team at any time online.
All patients are not given antiviral therapy or antibiotics.

Statistical analysis
Statistical analysis was performed using SPSS Version 24. All continuous data is presented as a mean ± standard deviation (SD) or median ± interquartile range (IQR). Categorical data is presented as numbers and percentages.

Ethics approval and consent to participate
The study protocol was approved by the Ethics Committee of Dr. Soetomo Teaching Hospital (Surabaya, Indonesia), and Universitas Airlangga Faculty of Medicine (Surabaya, Indonesia). All participants have provided written consent for the usage of their data for research purposes.

Swab RT-PCR SARS-CoV-2 results
All RT-PCR SARS-CoV-2 swab results were positive for patients treated at Indrapura field hospital. Recovered patients are patients with missing or mildly tolerated clinical symptoms after treatment without symptomatic drugs, and for whom swabs have been negative as much as two times. After leaving the hospital, 181 patients (8.5%) gave feedback related to posttreatment re-swab examination. Of these 181 patients, there were 52 patients (28.7%) who re-examined after exiting the Indrapura field hospital, while 129 patients (71.3%) did not do the re-swab. A total of 19 patients (37.3%) did the re-examination after more than 15 days of returning home, followed by eight patients (15.3%) on the 14th day, and the rest did the examination on the 6th day. Of the 52 patients who did the re-swab, we found 43 patients (82.8%) with negative results, and 9 patients (17.2%) with positive results (Table 2).

Discussion
COVID-19 has been reported to have caused the deaths of more than one million people, and the nature of viral infection remains a concern of many medical doctors worldwide. As for the asymptomatic and mild symptom cases, isolation and supportive therapy is the recommended approach 11 . The clinical outcome was mainly affected by patient comorbidities, including old age, chronic metabolic diseases, obesity and long term viral exposure 12 . Our data showed various medical comorbidities, with the most common being hypertension and diabetes mellitus. In addition, occupation-based analysis showed most patients were private employees, followed by military and police and civil servants. These occupations were occupations with high risk for contact with other people and high risk for COVID-19 infection 3 .
The latest guidelines for the treatment of COVID-19 patients indicate that suspected and confirmed cases should be treated in isolated hospitals with effective isolation and protection conditions 17 . As for asymptomatic and mild COVID-19 cases, the WHO recommends that COVID-19 patients are given symptomatic treatments such as antipyretics for fever and pain, adequate nutrition and appropriate rehydration 7 . In this study, it was found that all patients treated at Indrapura field hospital did not receive antiviral therapy. The procedures were provided There were several limitations to this study. Firstly, the included subjects in this study were asymptomatic and mild symptom patients without any comparison between the treated and untreated groups, hence we could not generate a good conclusion. Secondly, this study only covers one location with mostly Javanese patients. Since Indonesia does not only consist of Javanese people, a multi-center study involving more patients will give a more comprehensive understanding of the management of COVID-19 patients in Indonesia.

Conclusion
The conclusion of this study is that SIRNO method provides excellent output in the management of COVID-19 at Indrapura field hospital. Economic pharmacological research can perform a follow-up study in order to objectively measure the effectiveness and efficiency of SIRNO treatment methods in asymptomatic and mild symptomatic infections of COVID-19. The full data are not publicly available due to restrictions for ethical reasons, as the information could compromise the privacy of research participants. The datasets used and/or analysed during the current study are available from the corresponding author (Erwin Astha Triyono, erwintriyono@yahoo.com) on reasonable request.

Data availability
be explored individually for its effectiveness for COVID-19.