key: cord-0731920-5nonxvzi
authors: Farajallah, Halah Mohammed; AlSuwaidi, Sara Khamis; AlSuwaidi, Shatha Mohammad; Ali, Ghada AlAhmdani Al; AlZubaidi, Amani Salem; Carrick, Frederick Robert; Abdulrahman, Mahera
title: Large Variations in Disease Severity, Death and ICU Admission of 2993 Patients Infected with SARS-CoV-2: The Potential Impact of Genetic Vulnerability
date: 2021-04-22
journal: J Infect Public Health
DOI: 10.1016/j.jiph.2021.04.008
sha: 50b8f7929e7f69c4afa356d093d29d21ff014514
doc_id: 731920
cord_uid: 5nonxvzi

Background The COVID-19 pandemic has had an immeasurable impact, affecting healthcare systems, the global economy, and society. Exploration of trends within the existing COVID-19 data may guide directions for further study and novel treatment development. As the world faces COVID-19 disease, it is essential to study its epidemiological and clinical characteristics further to better understand and aid in its detection and containment. Methods We aimed to study the clinical characteristics of patients infected with COVID-19 in Dubai, a multi-national Society. Results Our findings demonstrate that during the first wave of the COVID-19 epidemic, age, gender, and country of origin were associated with more severe cases of COVID-19, higher risk for hospitalization and death. Male individuals between 41-60 years of age from India had the most significant hospitalization and death predictor (p =.0001). The predictors for COVID-19 related deaths were slightly less than UAE Nationals by individuals from GCC (p =.02) that were followed closely behind by Pilipino (p =.02) and Arabs (p =.001). Conclusion The vulnerability of individuals to infection and in the spectrum of COVID-19 symptoms remains to be understood. There are large variations in disease severity, one component of which may be genetic variability in responding to the virus. Genomics of susceptibility to COVID-19 infection and the wide variation in clinical response to COVID-19 in patients should become active investigation areas.

Humanity faces extreme public health challenges in contemporary history when dealing with the disease caused by a new type of coronavirus, called coronavirus disease 2019 -COVID- 19 . In early 2020, a novel coronavirus was isolated and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] . The World Health Organization named the disease coronavirus disease 2019 (COVID- 19) and subsequently declared it a pandemic due to the widespread infectivity and high contagion rate. The COVID-19 outbreak has become a pandemic threatening global health, undermining the global economy, and destabilizing societies across the world [2] . It has been well established that at the onset of the disease, the main manifestations of COVID-19 are fatigue, fever, dry cough, myalgia, and dyspnea, with less typical symptoms being nasal congestion, headache, runny nose, sore throat, vomiting, and diarrhea [3] . Severe patients often have dyspnea or hypoxemia one week after onset, after which septic shock, acute respiratory distress syndrome (ARDS), difficult-to-correct metabolic acidosis, and coagulation dysfunction develop rapidly. Of note, severe and critical patients can also present with a J o u r n a l P r e -p r o o f low fever, or even no apparent fever, while mild patients show only low fever, mild fatigue, and no pneumonia [4] . These asymptomatic or mild cases are challenging, as they can spread COVID-19 between individuals.

Although severe lung injury has been described at all ages, in some high-risk individuals, such as the elderly or those affected by multi-morbidities, the virus is more likely to cause severe interstitial pneumonia, ARDS, and subsequent multi-organ failure, which are responsible for severe acute respiratory failure and high death rates [6] . It is now evident that not all infected patients develop a severe respiratory illness; the reason for this is currently not apparent. Moreover, very little is understood about inter-individual genetic differences in the immune response to this virus.

Like global patterns, the number of confirmed cases in the United Arab Emirates (UAE) has also increased. The UAE was the first country in the Middle East to report a confirmed case, announced on January 29, 2020, and linked to a family of Chinese tourists traveling from Wuhan, China, the virus epicenter [7] . As of November 9, 2020, the total number of confirmed cases has reached 142,143, according to the Ministry of Health and Prevention, with a daily average increase of around 514 cases countrywide https://www.mohap.gov.ae/en/AwarenessCenter/Pages/COVID19 -Information-Center . aspx . UAE, and particularly Dubai, is a society with a multi-ethnicity component. People from different genetic backgrounds are living in the same geographic place. As the world faces this new infectious disease, it is essential to study its epidemiological and clinical characteristics further to understand better why COVID-19 has different susceptibility and severity on different individuals with dissimilar genetic backgrounds. An enormous rush of research and studies is being published around the globe. The Middle East and J o u r n a l P r e -p r o o f specifically the Gulf region were found to be short with this regard and still require more efforts in that area as the burden of this disease continues to increase, which is why this study was found to be of particular necessity and importance. In this study, we summarize and present the epidemiological and clinical characteristics of COVID-19 positive patients in the Emirate of Dubai, aiming to gain more information to understand the prevalence, clinical manifestations better, and risk factors for COVID-19 severity and mortality in the UAE compared to the published global patterns.

This descriptive retrospective study was conducted on all patients who attended primary healthcare centers in Dubai Health Authority (DHA) from Feb 2020 to April 2020 and were diagnosed with COVID-19 (tested positive through Coronavirus PCR pharyngeal or nasopharyngeal swabs).

Data was recruited from DHA's Electronic medical records (Salama).

Demographic information, clinical characteristics, exposure information, lab results, and Chest x-ray of each patient were collected, reviewed, and analyzed by different independent researchers. Both UAE citizens (UAE nationals) and expatriates were included in this study. The related data were double-checked and insert into the study tool independently. Data that were missing were omitted. The severity of COVID-19 was   considered  as  per  Dubai  health  authority  guideline  for  COVID-19 https://www.dha.gov.ae/en/HealthRegulation/Documents/National_Guidelines_of_COVI D_19_1st_June_2020.pdf .

All collected data were entered into STATA version 15 Males were predicted to die from COVID-19 infection (p=.001) more than females ( Figure   2 ). When analyzing the nationality correlations, individuals from India that contracted COVID-19 were predicted to have the highest death rate (p<.001); out of 6 death cases, three were from India.

The predictors for COVID-19 related deaths were slightly less than UAE Nationals by individuals from GCC (p=.025) that were followed closely behind by Pilipino (p=.02) and

J o u r n a l P r e -p r o o f Arabs (p=.001) (Figure 3) . Individuals between 41-60 years of age (p=.001), males (p=.001), and People with an Arab Country of origin had a more significant predictive margin of having symptoms than all other countries of origin (p=.001) had the most significant predictability of having symptoms after COVID-19 infection (Figure 4 ).

The global health and economic consequences of the COVID-19 pandemic are severe.

It has been reported that progression into critical cases could happen within 3-10 days in 10%-20% of cases [8] . Studies show that all age groups are susceptible to being infected with COVID-19;

however, most patients currently affected are between 35 and 55 years [9] . The male gender has been shown to hold a bigger share of COVID-19 infection, at 60% compared to women [10] . Also, adult male patients with established comorbidities are more likely to be affected by the virus. Those most significant were cardiovascular and cerebrovascular J o u r n a l P r e -p r o o f diseases, in addition to diabetes. This phenomenon was attributed to the weaker immune functions of these patients [7] . However, low overall comorbidities in infected patients in this study may be due to under-reporting and missing data. Our data showed that critical cases consisted of around 0.3% of the COVID-19 patient population, with a 30-day mortality of 0.2% ( [11, 12] .

Management is based mainly on supportive therapy and treating the symptoms, and trying to prevent respiratory failure. Several clinical trials of possible treatments for COVID-19 are underway, based on antiviral, anti-inflammatory, and immunomodulatory drugs, cell therapy, antioxidants, and other therapies [13] .

Large differences in outcomes for invasively ventilated patients with COVID-19 have been reported for different countries-e.g., mortality rates for these patients in China [14] were reported to be two times higher than those in Italy [15] and the USA [16] and even within a single country, such as the UK [17] . Several studies suggest that genetics plays an essential role in making some people more vulnerable than others to SARS-CoV-2, influencing infection efficiency, the immune response to infection, or the severity of COVID-19 symptoms [18] [19] [20] [21] [22] [23] . Differences in outcomes motivate urgent comparative research to characterize between-country differences to inform best practice in the context of a surge of cases. Since treatments and vaccines for COVID- 19 have not yet been developed, strategies to contain the virus's spread have been implemented, such as encouraging social distancing and, in the most affected regions, mandatory population confinement [24] . The main objective of adopting such measures is limiting the number of infected people to a threshold at which the healthcare system and services can meet J o u r n a l P r e -p r o o f the demand, distributing the total number of cases over time, a phenomenon that has been popularly called flattening the curve [25] .

The COVID-19 pandemic has had an immeasurable impact, affecting healthcare systems, the global economy, and society as a whole. Exploration of trends within the existing COVID-19 data may guide directions for further study and novel treatment development. Our study demonstrates that men in almost every age group have higher test positivity, hospitalization, and death rates. This finding mirrors data from over 50 countries across six continents in which death rates were more significant in men versus women, with an estimated 60% increased risk of severe illness or death [26] . The differences in mortalities among the countries may be explained by genomic variations of susceptibility to SARS-CoV-2 infection and the differences in the prevalence of the comorbid conditions of the patients and overwhelmed healthcare systems.

Our findings demonstrate that during the first wave of the COVID-19 epidemic, age, gender, and country of origin were associated with more severe cases of COVID-19, higher risk for hospitalization and death. It is known that advanced age and preexisting comorbidities render a person more vulnerable to the more severe health consequences Some data was missing in our dataset, as the study was conducted during a large-scale infectious disease outbreak setting when the healthcare system was overwhelmed by a large number of patients seeking medical care. Nevertheless, given our study size, including population-level adjustments, we can assume our findings are sufficiently powered, generalizable, and externally valid. Although this study is a retrospective cohort study in nature, the results could indicate the context measured. Nevertheless, a more extensive national study with data from all emirates in the UAE is needed for better representative sampling.

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