Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 in Ulin Regional Hospital Banjarmasin

Article history: Background: Corona Virus Disease (COVID-19) has become a global pandemic and Received 13 December 2020 has spread to more than 200 countries including Indonesia. South Kalimantan is one of Received in revised form 06 January the provinces in Indonesia that has a high COVID-19 mortality rate (case fatality rate 2021 4.1%). Information about characteristic of mortality patients with SARS-CoV-2 Accepted 16 January 2021 Available online 30 January 2021 infection in Indonesia was limited. The objective of this study to describe clinical


INTRODUCTION
World Health Organization (WHO) has determined that Corona Virus Disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-Cov)-2 has become a global pandemic. 1,2Currently, COVID-19 has spread to more than 200 countries including Indonesia. 3Clinical manifestations of COVID-19 patients have a broad spectrum, ranging from symptomless (asymptomatic), mild symptoms, pneumonia, severe pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, sepsis, to shock sepsis.According to the data of countries affected by COVID-19 pandemic, 40% of the cases experienced mild illness, 40% experienced moderate diseases including pneumonia, 15% experienced severe diseases (clinically or >50% lung involvement in imaging), and 5% experienced critical conditions. 4,5til September 24, 2020, Indonesia recorded 257,388 confirmed cases of COVID-19 and 9,997 of which died with a case fatality rate (CFR) of 3.9%. 6arly a third of COVID-19 infections were in the 31-45 years old age group (29.3%).However, the highest mortality rate occurs in elderly and is dominated by male. 7uth Kalimantan is one of the provinces in Indonesia that has a high COVID-19 mortality rate (CFR 4.1%). 8Some studies abroad mention that age and comorbidity (hypertension, diabetes, heart disease, and so foth) are the most important risk factors associated with death from COVID-19. 9,10The most common organ damage caused by COVID-19 is the lungs, followed by the heart, kidneys, liver, and hematology. 7,9,11,12Patients who died at the age of ≥ 65 years old had a higher number of comorbidities than the age of <65 years old.However, non-respiratory complications such as acute renal failure, cardiac injury, and superinfection are actually higher in young adult patients. 10Some laboratory variables such as lymphocytes, neutrophils, platelets, amyloid serum A (SAA), procalcitonin (PCT), cardiac thromboxine I (cTnI), D-dimer, lactate dehydrogenase (LDH), and lactate serum can be used as indicators of disease progressiveness. 9,11

METHODS
This research was a retrospective study using

RESULTS
Based on 108 confirmed cases of COVID-19 who died at Ulin Regional Hospital Banjarmasin in the period of March until August 2020, it obtained clinical characteristics data presented in Table 1.Laboratory results showed the majority of the cases had haemoglobin, leukocyte, platelet, and neutrophil values within the normal range, while lymphocytes and eosinophils tended to decrease by <20% and <1% (80.6% and 72.2%).Elevated CRP (≥6.00 mg/dl) in 92.6% of the cases and LDH (>220 U/L) in 91.7% of the cases.There were an increase in NLR results (≥3.13) in 86.1% of the cases and a decreased ALC (≤1500) in 72.2% of the cases.Liver function tests showed an increase in serum glutamic oxaloacetic transaminases (SGOT) in 82.4% of the cases, while serum glutamic pyruvic transaminases (SGPT) at 61.1% of the cases was within normal limits.
Renal function tests showed normal ureum levels in 53.7% of the cases, but there was an increase in creatinine levels (>1.25 mg/dl) in 57.4% of the cases.
Electrolyte test results showed the absence of hyponatremia (<136 Meq/L) in 55.6% of the cases, while potassium and chloride levels of most patients were within normal limits.

DISCUSSION
A number of cases of COVID-19 deaths at Ulin Hospital Banjarmasin are dominated by male, aged <65 years old with one or more comorbidities and severity of critical illness (ARDS).The number of deaths in men is greater than women at 2.7:1.This study is comparable to some studies which also mention that mortality in men is higher than in women. 4,7,11,13It is estimated due to the association of male with the prevalence of active smokers, the absence of comorbidity (hypertension and diabetes mellitus) resulting in increased expression of angiotensin converting enzyme (ACE)-2 receptors is higher in men than in women. 7,13,14In addition, women are thought to be able to fight the virus better due to the protection of the X chromosome and sex hormone (estrogen) which plays an important role in innate and adaptive immunity. 7,15e and comorbidity are the most influential risk factors in COVID-19 mortality. 13,15,166][17] This is associated with several things including decreased physiological immunity and the absence of comorbidities that contribute to a decrease in the body's functional reserves, thus reducing the capacity and the ability to fight infections. 10,16,17Nevertheless, in this study, the most mortality occurred at <65 years old (55-64 years old) with most cases having only one comorbidity (32.4%).This is expected because the distribution of COVID-19 patients treated at Ulin Hospital Banjarmasin is dominated by patients <65 years old.Palmeri L., et al.
mentioned that COVID-19 patients with young adulthood have less comorbidity than the elderly.However, they are more likely to die with complications that develop during treatment.In addition to the onset of symptoms up to hospital admission in patients <65 years old longer than the elderly, this suggests that delayed hospital referrals lead to less optimal care and increase the risk of disease progression and complications. 10rtain comorbidities are associated with strong ACE-2 receptor expression and higher release of proprotein convertase which increases the entry of the virus into the host cell.Comorbidity causes COVID-19 patients to be substantially associated with morbidity and significant mortality. 18The most common comorbidities found in COVID-19 cases are hypertension, diabetes mellitus, and cardiovascular disease, in which all three diseases are associated with high mortality rates in COVID-19 patients. 4,11,16,17In this study, obesity was ranked as the 3 rd most common comorbidity in addition to hypertension and diabetes mellitus.It had been previously known that the age group with the highest mortality rate in this study was <65 years old (85.2%).According to the research by Steinberg E., et al., it mentioned that obesity is an independent risk factor for severity and poor outcome in young adult patients with COVID-19. 19Hajifathalian K., et al. in his study also mentioned that obesity in the case of COVID-19 is strongly related to intensive care (ICU) and death. 20n general, the incubation period of COVID-19 is 3-14 days (median 5 days) with frequent symptoms being fever, cough, and fatigue. 7,14In this study, the initial symptoms of COVID-19 patients who died were fever/history of fever, cough, and shortness of breath with the majority of patients (54.4%) had experienced these symptoms within <7 days before finally being hospitalized.According to its pathophysiology, symptoms of shortness of breath in COVID-19 generally appear in the second attack which is about 4-7 days after the virus spreads through the bloodstream to the tissue expressing ACE-2 such as the lungs, heart, and gastrointestinal tract. 7,14Shortness of breath can also be a marker that pulmonary function has begun to be impaired until pneumonia and ARDS emerge.In addition, the absence of symptoms of shorthness of breath is also associated with a poor prognosis. 21,22ral infections can cause inflammation of the human body.Various inflammatory mediators produced during cytokine storms can cause systemic immune damage and even multi-organ failure. 9,14 In this study, there was an increase in the levels of SGOT, creatinine, LDH, and CRP similar to some other studies. 9,10,16Increased levels of SGOT and creatinine indicate the presence of renal and liver dysfunction.This phenomenon can occur in part because of the direct effects of SARS CoV-2 infection that causes cytokine storms.Aside from lungs and blood vessels, ACE-2 expression is also obtained in the kidneys, heart, liver, and other organs, thus SARS-CoV-2 can attack and damage those organs which then gives rise to immune cells to produce pro-inflammatory cytokines, cytokine storms that ultimately lead to tissue injury and failure of target organs. 18Bloom, et al. in his study mentioned that COVID-19 patients with increased SGOT require more intubation action.In addition, increased SGOT was also associated with hepatitis and myositis/heart damage infections. 27Research conducted by Cheng, et al. showed that patients who experienced an increase in serum creatinine at the beginning of hospitalization had a greater likelihood of being treated in an intensive care unit (ICU) and required mechanical ventilation, thus it can be said that kidney abnormalities at the beginning of hospitalization represent a higher risk of worsening. 28 addition to kidney and liver damage, the increase in LDH and CRP in COVID-19 patients also represents an overview of lung damage and respiratory distress due to inflammatory processes, thus it can be used to predict respiratory failure (ARDS). 291][32] A study showed significantly higher LDH levels in ICU patients compared to non-ICU patients. 32ome studies have shown that the majority of COVID-19 cases have electrolyte abnormalities correlated with a high risk of intensive care needs, mechanical ventilation and encephalopathy events with high mortality rates and longer treatment days. 33,34omparable to some other studies, most cases found that most cases had hyponatremia (55.6%).Tezcan, et al. mentions that hyponatremia is the most common electrolyte abnormality compared to other electrolyte abnormalities.In addition, hyponatremia can also be used as an independent predictor of poor prognosis in COVID-19 patients. 34ne of the clinical picture in COVID-19 is the development of lung injuries that have the potential to cause ARDS.Pneumonia and ARDS usually develop late in the course of infection between 5-10 days from the onset of clinical symptoms. 35ARDS is one of the leading causes of death in COVID-19 patients.The cause of ARDS in COVID-19 cases is cytokine storms, which are uncontrolled systemic inflammatory responses due to the release of large amounts of proinflammatory cytokines. 13,26In this study, 88% of COVID-19 patients who died were in critical condition and were dominated by severe ARDS conditions.
In this study, the sample used was quite a lot with complete data but had limitations because it did not exclude some cases of COVID-19 that had previously undergone treatment in other health facilities, thus there was a possibility of treatment of patients that could affect the results of the initial examination when the patient was hospitalized at Ulin Regional Hospital Banjarmasin.

CONCLUSION
COVID-19 deaths at Ulin Regional Hospital Banjarmasin from March to August 2020 were dominated by severe-critical degree cases consisting mostly of male, aged <65 years old with one or more comorbidities.Hypertension, diabetes mellitus, and obesity were the most commonly found comorbidities with early symptoms of fever, cough, and shortness of breath.Laboratory results in most cases showed haemoglobin, platelets, leukocytes, and neutrophils tended to be normal with increased NLR, as well as decreased lymphocytes, eosinophils, and ALC.Natrium levels tended to decrease and there was an increase in SGOT, creatinine, CRP, and LDH.

Table 1 .
Clinical characteristics of patients dying with COVID-19