Universal health care access for all residents reduce mortality in COVID-19 patients in Abu Dhabi , UAE : A retrospective multicenter cohort study

1 Infection control chair and Chief Medical Officer, Sheikh Khalifa Medical City, Abu Dhabi Health Services (SEHA) 2 Corporate Academics and research Affairs, Abu Dhabi Health Services (SEHA) 2 Corporate Academics and research Affairs, Abu Dhabi Health Services (SEHA) 3 Infectious Disease Department, Al Rahba hospital, Abu Dhabi Health Services (SEHA) 4 Infectious Disease Department, Sheikh Khalifa Medical City, Abu Dhabi Health Services (SEHA) 5 Infectious Disease Department, Al Ain hospital, Abu Dhabi Health Services (SEHA) 6 Infectious Disease Department, Tawam hospital, Abu Dhabi Health Services (SEHA) 7 Department of Pediatrics, Al Ain hospital, Abu Dhabi Health Services (SEHA) 8 Department of Laboratory and Pathology, Sheikh Khalifa Medical City, Abu Dhabi Health Services (SEHA)


Introduction
Coronavirus disease , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. The severity of COVID-19 infection ranges from being asymptomatic to severe infection leading to death (1). On March 11 th , 2020, The World Health Organization (WHO) announced the emergence of a new MERS-CoV2 virus pandemic (2) and on January 29 th , 2020, the United Arab Emirates (UAE) had officially reported the first case of COVID-19 (3). As of August 14 th , 2020, the estimated total number of cases in UAE is 63,819 cases and the mortality cases reported is 359 with wide spread testing reaching 5,851,453 tests done covering almost 60% of UAE population (4). Globally, the world total number of cases are estimated to be more than 18 million cases and mortality cases exceeding 800,000 deaths (2). The outcomes of patients treated for COVID-19 from UAE have not been reported in the literature. Anecdotally, the patients are faring better compared to the west. We have younger patients of wide range of nationalities with less comorbidities and these factors may have contributed to our relatively better outcomes. Surprisingly, children are noted to have less severe symptoms and much better outcomes compared to adult cases. However, children have a rare presentation of a serious condition called multisystem inflammatory syndrome, which constitutes of multi-organ failure (5). Significant differences have been noted in the clinical and demographic features of COVID-19 patients in different regions of the world (6). We wish to analyze patients' characteristics, the impact of our current therapeutic options and patient clinical outcomes.
We report hospitalizations and intensive care admissions from Abu Dhabi Health services (SEHA), the largest government health care provider in the Emirate of Abu Dhabi, UAE. It serves three regions; western, eastern and middle region of Abu Dhabi, with an estimated per annum encounters of 5 million for both in-patient and out-patient services (7). We gathered the electronic data from 5 major hospitals. The UAE is considered one of the countries having the highest testing rate for COVID-19 averaging more than 50,000 test per day across all regions. The country leadership took a very early initiative to assure full accessibility of all individuals to testing and needed medical care regardless of their insurance coverage plan. All SEHA facilities were following the National Guidelines for Clinical Management and Treatment of COVID-19 unified by all health regulatory bodies issued by UAE ministry of health and prevention (8) (9).

Study design
This is a retrospective observational cross-sectional study of adults hospitalized at any of SEHA's healthcare facilities, who tested positive for nasal swabs for SARS-CoV-2 by polymerase chain reaction (PCR) between March 1 st , 2020 and May 31 st , 2020. We characterized patients by baseline demographics, comorbidities, severity of illness, laboratory parameters, respiratory support and therapies used. Outcomes like survival, length of hospital stay and viral clearance were evaluated accordingly. UAE National guidelines for treatment of pneumonia and acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 were followed (8) and for the intensive care management, the national guidelines for critical care were followed (9).

Inclusion and exclusion criteria
All in-patients diagnosed with COVID-19 in SEHA hospitals between the period of March 1 st till May 31 st , 2020 in Abu Dhabi. The age group included were all hospitalized adult patients aged 18 years and above. We excluded pediatric patients.
Admitted patients with an ongoing COVID-19 prior to study dates were excluded from analysis.The groups were divided into severe and non-severe based on the need for admission to intensive care unit (ICU) or high dependency unit (HDU) across all

Data collection and variables
The data were sourced from hospital information system and relevant data for all COVID-19 patients who were admitted to SEHA hospitals within the study period was extracted.
The data extraction process was based on the documentation and handled through Cerner team located in the UAE in addition to SEHA corporate Health Information System application analysts. The variables that were considered for the study included age, gender, comorbidities, lifestyle habits, signs and symptoms, assessment at admission and laboratory values collected on within the first 24 hours of admission.
Outcome measures includes, status of the patient (recovered or died), duration of admission, viral clearance and type of medications used. Sample of the study was further divided based on level of care provided and the need for ICU or HDU admission and mechanical ventilation to two groups; severe or non-severe infection.
Due to the large amount of data included in the study and the nature of descriptive studies, we have not performed any imputation for missing data, and describe the data as they stand.

Statistical analysis
Baseline characteristics are summarized using descriptive statistics including mean, median, interquartile range (IQR) and standard deviation (SD) for continuous measures, and frequencies tables for categorical variables. Categorical variables will be compared using the chi square or Fisher's exact test and continuous variables using the unpaired t-test or its non-parametric equivalent. Statistical significance was set at p value ≤ 0.05 (two-sided). The data analysis was performed using STATA statistical software version 12.0 The data is further analyzed using Time to Event analysis (Survival Analysis). The survival time is the duration of time, from the date of admission, until the date of any event of interest, which is death in this case. In this situation, patients lost-to-follow up or withdrawn from the study will be considered as right censored. Discharge from the hospital will be considered as a competing event. Survival curves of different comorbidities will be compared using the equivalent of log-rank test in the case of competing events.

SARS-CoV 2 detection
SARS-CoV-2 Virus was diagnosed by real-time reverse-transcriptase PCR with detection of the N and ORF1ab gene using the U-Top COVID-19 Detection Kit (Seasun Biomaterials, Daejeon, Korea) or the E and the S gene using the RealStar PCR (Altona Diagnostics, Hamburg, Germany). Interpretation of the result was performed according to the manufacturer's recommendation.

Demographics
The UAE is considered one the highest countries to have COVID-19 testing across its population in all the seven Emirates, with an average test number reaching more than 50,000 tests per day across the country. The Total number of patients admitted to SEHA hospitals in the Emirate of Abu Dhabi over our study period was 9390 patients.
We further divided the patients according to their level of medical care and found 721 (7.68%) patients required ICU or HDU admissions, while the remaining majority (92.32 %) with mild-moderate symptoms were admitted to either regular wards at designated SEHA hospitals or quarantine hotels depending on their clinical symptoms. The mean age of our patients was 41.8 years (SD (±11.89 and 95 % CI 41.61, 42.09). Figure 1 shows the mean overall age in our study and the mean age between the severe and non-severe groups (P<0.001). The male to female ratio was obvious with a male predominance of 4.9:1.
The baseline demographics and nationality of the patients as described in table 1 and figure 2 demonstrated a higher percentage of Indian patients at 39.12 % followed by Pakistani 13.57% and Bangladeshi 10% patients then Filipino at 8% while the Emirati patients were only 7.3% and the others (14%) were from different 21 nationalities across the globe.

Comorbidities and lifestyle
The comorbidities listed in the records are illustrated in table 2 and figure 3. It was found that 75% of the severe cases had at least one comorbidity, and the 3 major ones in the severe group were hypertension (HTN) (32.8%) followed by diabetes mellitus

Admission assessment
Admission assessment within the first 24 hours of hospital stay was analyzed for all patients. The overall signs and symptoms and vital signs as illustrated in table 3 were within normal limits as an average measurement for the majority but looking at the range it does reflect the spectrum of the severe cases at presentation. Table 4 demonstrates the need for oxygen therapy and mechanical ventilation in addition to the difference in clinical scores between the two groups. We used Sequential Organ

Laboratory values
The laboratory values for all admitted patients are summarized in table 5 with the mean values and SD during the first 24 hours of admission. Looking into specific laboratory values and comparing the severe and non-severe groups differences (table   6), it is noted that there is a statistically significant difference in both lymphocyte and neutrophil count but not in the total white blood cell count. Certain inflammatory markers like ferritin, C reactive protein (CRP) and lactate dehydrogenase (LDH) were also significantly different in mild and severe groups (P<0.0001). Additionally, Interleukin-6 (IL6), which is a pro-inflammatory marker anticipated to have a major role in predicting progression and severity of COVID-19 was showing significant difference between both groups (p<0.0001).      (10)  Some hospitals were using Doxycycline as a presumptive treatment for COVID-19.  In the mortality assessment, the total number of deaths in this cohort is 158 patients.
We have a mortality rate of 19.56 % in the sever group admitted to HDU or ICU which is relatively lower than published data (14) (15). If we stratify the mortality by age group, the majority of deceased patients were below the age of 60 years; 152 cases (89.9%) and only 6 cases were 60 years or above (0.9%). It is observed that the younger age group of less than 30 years had a higher mortality rate compared to the elderly. The exact reason for this observation cannot be explained using retrospective observation data and will require further analysis in this age group.
Currently there are no available framed laboratory abnormalities directly related to COVID19 (16). From the review of the variables in laboratory findings electronically, we can see a clear difference in a certain set of labs as illustrated in table 5 and 6. This suggests that certain laboratory sets can be significantly different between mild to severe cases. Those labs were the neutrophil count rather than low lymphocyte count, CRP level, LDH, Ferritin, IL6 and creatinine level suggesting the predisposition of renal diseases and as well the risk of acute renal failure. There is emerging evidence suggesting that the neutrophil-lymphocyte count ratio is a possible predictor of severity in COVID19 patients (17). These set of labs can serve as a predictive tool for severity but will require further correlation assessment.

Conclusions
This retrospective descriptive analysis suggests that Abu Dhabi had a relatively low morbidity and mortality rate and a high recovery rate compared to published rates in China, Italy and United States. The demographic of the population is younger and has an international representation of a multinational population assessment of COVID risk factors and outcome, which is characteristic of UAE. The risk of diabetes, hypertension and chronic renal failure did not affect the outcome at ICU level. The country had the highest testing rate in relation to the population volume. The wide spread screening for COVID 19 has led to early identification of cases and relatively better outcome with a lower mortality rate. Both early identification and younger demographic had affected the favourable comparative outcome in general with early identification of cases leading to a lower mortality rate. There is a lower average age of mortality in Abu Dhabi but more awareness is needed, as the mortality in young adults in our population is higher than the elderly.
Certain set of labs do predict severity of the disease, we identified LDH, IL6, Ferritin, neutrophil count and creatinine level. The major two antiviral combinations used jointly in Abu Dhabi were Hydroxychloroquine and favipiravir, however through retrospective studies we cannot conclude efficacy through this observation.

Declarations
Ethics approval and consent to participate Institutional Review Board (IRB) approval was obtained through the National COVID-19 IRB committee on June 6 th , 2020 with reference number (CVDC-10-06/2020-10-1). Informed Consent was waived for this research because of the nature of the study which is retrospective chart review of unidentified data.

Consent for publication: Not applicable
Availability of data and material: The data that support the findings of this study are available from Health information System department at Abu Dhabi Health services, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Abu Dhabi health services and Abu Dhabi Department of health.
Competing interests: authors declare that they have no competing interests Funding: None