key: cord-0833646-e7q33rqb
authors: Taha, Safa Abdallah H.; Osman, Makarim Elfadil M.; Abdoelkarim, Esameldeen Ahmed A.; Ibrahim Holie, Mohamed A.; Elbasheir, Mohamed M.; Abuzeid, Nadir Musa K.; Al-Thobaiti, Saed A.; Fadul, Sharief B.; Konozy, Emadeldin Hassan E.
title: Individuals with “A” Rh-positive but not Rh-negative blood group are more vulnerable to SARS-COV-2 infection: Demographics and trend study on COVID-19 cases in Sudan
date: 2020-09-22
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2020.100763
sha: 3d3f61910e63a22e24c1d61f8fe63c90d1c9cb09
doc_id: 833646
cord_uid: e7q33rqb

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Sudan, several hematological studies were conducted to study the ABO blood group distribution among the population, in which the "O" blood group was dominating followed by the "A" blood group. However, there is no systematic study that has been done to correlate between COVID-19 infection and the population’s blood group types, therefore we have intended to study the possible effect of blood group on the acquisition of COVID-19 infection. A questionnaire-based case-control study was carried out on 557 COVID-19 patients in Sudan, factors such as age, blood group, previous malaria infection, back history ailments such as diabetes, hypertension, and symptoms suffered were also considered and analyzed. The number of infected females was more than males, whereas the age between 25 to 35 years was the most affected age group. O Rh-positive (O+) blood group was the least affected by the disease while “A” Rh-negative (A-) individuals were the most venerable. Symptoms like fatigue, fever, and loss of smelling sensation were the major ones among the patients. Whereas 13% of SARS-COV-2 positive individuals remained asymptomatic. Since the Sudan population is largely constituted of “O” Rh-positive inhabitants (approx. 50%) these results might explain the relatively lower COVID-19 incidence in the country.

CoV-2), which was first detected and identified in December 2019 in Wuhan, China [1] from where it spread and shattered the economy and growth of many countries in the developed and underdeveloped world and causing a toll death of more than 500 000 lives [2] . The disease was first called by World Health Organization (WHO) as 2019-nCoV, which was later renamed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) by the coronavirus study group of the International Committee on Taxonomy of Viruses [3] . The rapid spread and rise of the disease in all continents of the world sent an alert to scientists to screen for the characteristics that might let some individuals more susceptible to the virus, as well as risk factors that would increase the severity and progression of the disease. High SARS-COV-2 contraction is associated with those with old age, diabetes, hypertension, chronic respiratory disease, cardiovascular ailment, etc. [4] . Association of human ABO blood group types with many diseases is known from as early as 1950 th [5] and was recently reviewed by Liumbruno and Franchini [6] . For instance, individuals with non-O blood groups were more prone to develop coronary heart diseases and venous thromboembolism as compare to O blood type [7] . Another Malaysian group conducted a study to correlate between ABO blood group types with probabilities to develop diabetes mellitus, the study concluded that people with "A" and "O" group were with least chances of having diabetes [8] . ABO blood groups' susceptibilities to the different types of cancers were also studied. Individuals with B blood groups were found to have the least risk of gastrointestinal, colorectal, stomach, and bladder cancer [9] . Several studies have also reported close associations between ABO blood types and susceptibility to malaria contraction. Individuals with blood group "A" are highly susceptible to P. falciparum infection whereas blood group "O" is providing protection against severe malaria, the mechanism of this protection is based on the rosette formation phenomenon [10] . The same noticeable selectivity of J o u r n a l P r e -p r o o f the malaria parasite with the ABO blood group system is proved to apply to SARS-COV-2. In which "O" blood people were with the least susceptibility to the virus infection whereas "A" blood type is with the highest risk [11, 12] . In Sudan several hematological studies were conducted at different states, to find the blood group dissemination pattern among populations, in which the "O" blood type was the dominant, followed by "A", then "B", and finally "AB" with slight differences among these studies [13, 14] . So far, there is no systematic study that has been done in the country to correlate between COVID-19 infection and the population's blood group types, therefore, in this study, we have investigated the possible correlation between blood groups and the acquisition of COVID-19. In addition, factors such as the previous infection with malaria, sex, age, diseases such as diabetes and hypertension as well as the number of symptoms suffered were also studied. To the best of our knowledge, this is the first study in Sudan in specific and Africa in general, to correlate between ABO blood system and COVID-19 J o u r n a l P r e -p r o o f Statistical analysis: data were statistically analyzed using Statistical Packaged for Social Science (SPSS) Version-20. The significance of the results was investigated using one-tailed z-test at significance level P= 0.001, two-tailed binary logistic regression. One Way ANOVA test was used for the analysis of variance.

Ethical consideration: All patients who participated in this questionnaire were informed about the aim and objectives of the study and they were agreed to participate. The ethical approval for the individuals who participated as control was obtained from the ethical committee of Omdurman Maternity Hospital.

Among the 557 COVID-19 participants 234 (42%) were males whereas 323 (58%) were females; with female more likely to get COVID- 19 The dissemination of the blood group types among the participants' patients is shown in Table 1 ; 241 patients (43%) of the total study population were of "O" blood group (O+ve 39%, O-ve 4.5%). 180 patients (32%) were of A blood group (A+ve 30.9%, A-ve 1.4%). 102 patients (18.3%) had "B" blood group (B+ve 16.5%, B-ve 1.8%), and finally 34 patients (6.1%) of AB blood group (AB+ve 5.6%, AB-ve 0.5%). The susceptibility to SARS-CoV-2 infection is correlated to A +ve blood group (OR = 1.316, 95% CI 0.782 -2.215, P 0.05 = 0.008). questionnaire copies were filled online and submitted, of which 8 were improperly filled and therefore, excluded from the study.

The gender ratio in the Sudan population is disaggregated into almost 1:1 males to females, however, based on the current study the susceptibility to SARS-CoV-2 infection appears to be more towards the females than the males, (1.4: 1). In surveyed 125 countries, areas, and territories, UNWOMEN reported that 54% of men were more vulnerable to COVID-19 infection than women [15] . The current results are also contradictory to the study performed in India in which male patients (76%) were significantly higher than the females (24%) [16] , whereas in China, the prevalence of the disease among both genders was of equal proportion, however, the mortality rate was more in men than women [17, 18] . Since this study was meant to explore the prevalence, no data about the mortality rate among genders were collected. Analysis of the demographic data of the 557 COVID-19 patients reported in this article revealed that around 86% of patients were between the ages of 19 -45 years, which indicates that most of those who got COVID-19 infection were in the working age. Of the 557 patients who filled the questionnaire only 22 (4%) were above 56 years. These results are similar to the one conducted in India [16] . Another study conducted in Italy revealed that the older ages are more susceptible to SARS-COV-2 infection [19] . Since the only available continuous variable within the dataset is the age, we have performed One Way ANOVA test to correlate between the age and the patients' blood groups which has resulted in an insignificant correlation between these two factors (mean sample age= 32.7 years, α=0.05).

It's worth mentioning that since this study was conducted online, older ages in a country like Sudan, are least exposed to the smartphone technologies, hence these results might not truly reflect a correct estimate for those seniors who contracted the disease.

The region falls in the malaria-endemic zones (MEAs) is known with the lowest COVID-19 cases as compared to the countries that fall outside this zone [20] [21] [22] . MEAs remain a matter of scientific debate in justification of this limited spread [20] . In Sudan, the 1 st case of coronavirus was reported in the mid of February 2019, although the population doesn't follow strict social distancing instructed by medical regulations [23] , only around 12.5 thousands cases of COVID-19 were officially recorded after 6 months of the onset of the disease in Sudan. Reports that correlate the low incidences of COVID-19 cases in this zone with malaria infection are accumulating. Some hypotheses were already put forward to explain the reduced rate of COVID-19 rates in the MEAs. Thoughts like weather, environmental factors, and previous exposure to malaria drugs like hydroxychloroquine were discussed [20, 21, 24] . This relation was further supported by several in-common characters between the two diseases. Firstly both malaria and COVID-19 are observed to be interlinked with ABO blood group system, in which the "O" blood group is protected against the severe progression of the diseases, whereas blood group "A" is highly susceptible to infections. Secondly the use of anti-malaria drugs like chloroquine, hydroxychloroquine, mefloquine, and recently artemisinin as potential choices for COVID-19 treatment [25] . Thirdly the finding that besides the use of the ACE2 receptor SARS-COV-2 could also invade cells through the interaction of spike protein with the CD147 receptor, a J o u r n a l P r e -p r o o f receptor that is used by the Plasmodium falciparum to cause malaria. Moreover, the nano-lipid

Metadichol which inhibits SARS-COV-2 could equally suppress the Plasmodium falciparum from entering the erythrocytes [26, 27] . It was previously observed that the interaction between the virus glycoprotein (spike) and the host receptor is mediated by the virus' spike protein segment S1A of the domain S1 is a sialic acid-binding lectin that recognizes the sialic acid receptor on the host cell surface [28] . While Silva-Filho et al have hypothesized that the sialic acid-containing host receptors ACE2 and CD147 as the target for the spike agglutinin [29] . SARS-COV-2 through spike protein-basigin/CD147 interaction [30] . Blood groups have routinely been related to many ailments such as coronary heart diseases, cancer, and diabetes [8, 31] . A few articles have already been published testing for the relation between COVID-19 and the ABO blood group system [32, 33] . Studies have observed the susceptibility of "A" blood group individuals to SARS-COV-2 infection, whereas individuals with "O" blood group are protected against the severe progression of the disease. The current study didn't deviate from this concept, however, interestingly our study indicates that "A" blood group with the positive rhesus J o u r n a l P r e -p r o o f factor but not the negative one is more prone to contract the disease as compared to the control (P= 0.0008 ), the same applies to the individuals with AB+ve but not AB-ve. On the other hand, "O" positive but not "O" negative is shown statistically significant reduced number infections'

tendency as compared to control (P=0.0006 ). Whereas no blood group effect was noticed with B blood group individuals. Testing the possible relation between the blood type and the asymptomatic patients gave insignificant results (not shown) which indicates that the susceptibility to COVID-19 infection is only associated with the blood group rather than the symptoms [12] . Furthermore, the study corroborated that individuals with "A" Rh-positive but not Rh-negative are more vulnerable to contract the disease, whereas "O" Rh-positive rather than "O" Rhnegative is least exposed to severe symptoms of the pandemic. Though some of the data presented in this article replicate the Chinese findings, it remains unique with respect to the Rh factor, the variability of symptoms, and the gender infection profile. Moreover, since the Sudanese population is dominated by the "O" Rh-positive group this study might justify the low COVID-19 spreading rate in the country. Individuals with the blood group, "A" should observe maximum precaution to protect themselves against acquiring the infection, while this study shouldn't be considered by "O" blood carriers are a guarantee that would shield them from the disease, they must still be cautious to avoid increasing risk of infection [12] .

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Taha: Investigation; Formal analysis; Writing -Original Draft

Writing -Original Draft; Formal analysis

Formal analysis

Thobaiti: Resources; Writing -Original Draft

Fadul: Formal analysis

Konozy: Conceptualization; Methodology; Resources

Writing -Original Draft; Writing -Review & Editing

Authors would like to thank Dr. Sushma Sabharwal, Department of Chemistry, Division of Biochemistry, University of Pune, India for revising the manuscript.