
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

MD-D-24-07749
00028
10.1097/MD.0000000000039673
3
4900
Research Article
Observational Study
Lack of association of ABO and RhD blood groups with COVID-19 mortality: A 2-center cross-sectional study in Saudi Arabia
https://orcid.org/0000-0003-1121-6256
Halawani Amr J. PhD a*
Alhamoud Abdullah H. MD abuhamoud123@hotmail.com
bc
Kabrah Saeed M. PhD smkabrah@uqu.edu.sa
a
Al Eissa Mariam M. PhD mariam_al_eissa@hotmail.com
defg
Daowd Rateb A. MD radawood@moh.gov.sa
h
Algarni Ateeg M. MD aal-garni@moh.gov.sa
h
Alqarni Abdulaziz H. BSc abdulazizalqarni30@gmail.com
ij
Alshahrani Musaed M. PhD shalan900@hotmail.com
k
Khan Anmar A. PhD aaakhan@uqu.edu.sa
a
Jalal Naif A. PhD najalal@uqu.edu.sa
l
Mujalli Abdulrahman PhD ammujalli@uqu.edu.sa
a
Malak Hesham A. PhD hamalak@uqu.edu.sa
m
Bantun Farkad PhD fmbantun@uqu.edu.sa
l
a Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
b Department of Paediatric, King Fahad Central Hospital, Ministry of Health, Jazan, Saudi Arabia
c Department of Laboratory, Imam Abdulrahman Alfaisal Hospital, First Health Cluster, Ministry of Health, Riyadh, Saudi Arabia
d Public health Laboratory, Public Health Authority, Riyadh, Saudi Arabia
e College of Medicine, AlFaisal University, Riyadh, Saudi Arabia
f King Khaled Eye Specialist Hospital (KKESH) Research Centre, Riyadh, Saudi Arabia
g Computational Sciences Department at the Centre for Genomic Medicine (CGM), King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
h Department of Urology, Imam Abdulrahman Alfaisal Hospital, First Health Cluster, Ministry of Health, Riyadh, Saudi Arabia
i Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
j Department of Laboratory, King Saud Medical City, First Health Cluster, Ministry of Health, Riyadh, Saudi Arabia
k Blood Bank Laboratory, Prince Sultan Military Medical City, Saudi Arabia
l Department of Microbiology and Parasitology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
m Department of Biology, Faculty of Science, Umm Al-Qura University, Makkah, Saudi.
* Correspondence: Amr J. Halawani, Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia (e-mail: ajjhalawani@uqu.edu.sa).
13 9 2024
13 9 2024
103 37 e3967309 7 2024
19 8 2024
23 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Several diseases, including both noninfectious diseases and bacterial and viral diseases, are associated with the ABO and RH blood group systems. Previous studies have shown a link between blood type and the probability of coronavirus disease 2019 (COVID-19) infection. In this study, we aimed to explore the correlation between deaths caused by COVID-19 and ABO and RhD blood types in Saudi Arabia. In this cross-sectional observational study, data from COVID-19 patients were collected from 2 major hospitals treating COVID-19 in Riyadh City, Saudi Arabia, between March 2020 and November 2021. The association between ABO and RhD blood types and COVID-19 outcomes was investigated. A total of 2302 real-time polymerase chain reaction-confirmed COVID-19 patients were enrolled in this study; a chi-square test was used to determine the statistical significance of the data. Of the 2302 enrolled patients, 1008 (43.8%) had blood type O, 677 (29.41%) had blood type A, 502 (21.8%) had blood type B, and 115 (5%) had blood type AB. Of the patients, 2143 (93.1%) were RhD-positive. The O-positive blood type had the highest mortality rate among COVID-19-infected patients, whereas the AB-negative type had the lowest. However, statistical analysis revealed no significant correlation between blood type (ABO or RhD) and COVID-19-based susceptibility or mortality. In conclusion, we found no association between ABO and RhD blood types and either susceptibility to or mortality due to COVID-19 in Saudi Arabia.

ABO blood group
COVID-19
RhD
SARS-CoV-2
Saudi Arabia
OPEN-ACCESSTRUE
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pmc1. Introduction

Coronaviruses are known to cause infections in many species of animals, and the emergence of such viruses in humans has resulted in diseases ranging from the common cold to severe acute respiratory syndrome (SARS). The current outbreak of coronavirus disease 2019 (COVID-19) is the latest of the 3 coronavirus outbreaks that have affected humanity in the last 2 decades. The number of recorded cases of COVID-19 worldwide has exceeded 700 million, and there have been over 7 million deaths.[1] In Saudi Arabia, there have been more than 841,469 documented cases of COVID-19 with a total of 9646 COVID-19-related deaths.[1]

Although the primary mode of transmission for COVID-19 is exposure to either respiratory droplets of an infected person or virus-contaminated surfaces, the noted variation in presentation and outcome of the disease between infected individuals suggests a strong association with some underlying condition or risk factor.[2] Since the outbreak of the COVID-19 pandemic, multiple risk factors have been associated with the severity and death rates of the disease, including age, gender, diabetes, smoking, and other chronic respiratory and cardiovascular diseases.[3]

Interestingly, epidemiological studies have reported that certain blood types are associated with an increased risk of COVID-19 infection.[4–7] A similar association has been proposed between human blood type and other viral infections, such as dengue fever, Hepatitis B, and Norwalk virus; certain blood types have demonstrated greater susceptibility to these infections.[8–10] In fact, the reaction of ABO antibodies, as part of the innate immune response, to the previous SARS outbreak, caused by SARS coronavirus (SARS-CoV), has been highlighted as a factor that might have led to its diminishing.[11] However, such a hypothesis is still debatable, as other studies have reported contradictory findings.[12–14]

Findings from Saudi Arabia have explored the association between ABO and Rh blood groups and COVID-19 infection, which have revealed contradictory outcomes. Several reports found a significant association, indicating that specific blood groups may influence the risk, susceptibility, severity, and even mortality rates associated with COVID-19.[15–18] For instance, Nasif et al[15] reported that the A and O blood types were more susceptible, whereas those with RhD-negative individuals tended to be protected against COVID-19. Al Bshabshe et al (2023) stated that patients with blood type B-positive observed a 100% mortality rate, though their numbers were very small. However, those with blood type O-negative had a mortality rate of 92.9%, while A-positive and A-negative groups had rates of 62.5% and 58.5%, respectively.[16] Jawdat et al[17] found that blood group B may increase COVID-19 risk, whereas blood group O could confer some protection. Finally, Jan et al[18] observed that individuals with blood groups B and AB were less susceptible to COVID-19 than those with O and A groups, with Rh-positive individuals in O-positive and A-positive groups showing increased infection rates. This could be a reflection of the normal distributions of ABO and RhD in Saudi Arabia and reject the hypothesis of the association of ABO and RhD with the COVID-19 infection.

Despite the above findings, other studies have reported no clear significant association between these blood groups and COVID-19 outcomes.[19–23] This variability highlights the necessity of additional research to address these associations.

Accordingly, this study aimed to investigate the correlation between ABO and RhD blood types, and COVID-19 infection and mortality. In this project, the health records of patients who were confirmed to have COVID-19 at 2 major hospitals in Riyadh City, Saudi Arabia, were collected to investigate any possible association between ABO and RhD blood types and COVID-19 mortality.

2. Methods

2.1. Ethical considerations

This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board at King Saud Medical City with a reference number (H1RE-16-Jul20-03) of Riyadh, Saudi Arabia. Informed consent was waived by the IRB because of the retrospective nature of the study, which focused on reviewing the patients’ medical records. The details of the patients were provided in a secure computerized database.

Data were received with medical record numbers only and were maintained with confidentiality. Therefore, the patients could not be identified, and there were no implications for their health and welfare. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines followed observational studies in this study.

2.2. Study design and procedure

A cross-sectional observational study was conducted to analyze 2302 medical records from 2 major hospitals that treat COVID-19 in Riyadh City in Saudi Arabia, King Saud Medical City and Imam Abdulrahman Alfaisal Hospital. The data were used to determine any association between ABO and RhD blood types in the patients and COVID-19 mortality.

2.3. Data collection

All patients who had been admitted to the 2 hospitals and tested positive for COVID-19 between March 2020 and November 2021, with recorded blood types, were included in our study. COVID-19 diagnosis was confirmed by a real-time polymerase chain reaction test using a nasopharyngeal swab. All patients were assessed according to the clinical outcomes of the infection: either recovered or died. The ABO and RhD blood types were determined using standard serological phenotyping techniques.

2.4. Statistical analysis

The sample size of 664 was required for suitable statistical power, and it was calculated using Raosoft Sample Size Calculator. The estimation was based on a confidence level of 99% a and 5% allowable margin of error.

Data were retrieved from the hospital data management systems and transferred to Excel spreadsheets (Microsoft Corp., Redmond, United States). The data were subsequently analyzed using SPSS version 28 (Statistical Package for Social Sciences, IBM, United States). A chi-square test was used to determine the statistical significance of the data; P ≤ .05 was considered statistically significant.

3. Results

A total of 2302 COVID-19 patients were enrolled in this study. Table 1 shows the characteristics of the study population. The mean age was 43 ± 20 years; 52.5% of the participants were female and (51.7%) were Saudis. The most common blood type was O (n = 1008, 43.8%), while the least common was AB (n = 115, 5%). In terms of RhD, 93.09% of the patients were RhD-positive, whereas RhD-negative patients accounted for 6.91%. Additionally, 16.3% of the participants died in the intensive care units.

Table 1 Characteristics of the COVID-19 patients.

Characteristics	Mean	Standard deviation	n	%	
Age (mean)	43 (0–98)	20			
 Newborn			146	6.34	
 1–17 yrs			51	2.22	
 18–30			380	16.51	
 31–45			755	32.80	
 46–60			513	22.28	
 >60			457	19.85	
Gender	
 Female			1209	52.52	
 Male			1093	47.48	
Nationality	
 Non-Saudi			1111	48.26	
 Saudi			1191	51.74	
ABO	
 A			677	29.41	
 AB			115	5.00	
 B			502	21.81	
 O			1008	43.79	
RhD	
 Negative			159	6.91	
 Positive			2143	93.09	
Death	
 No			1927	83.71	
 Yes			375	16.29	
COVID-19 = coronavirus disease 2019.

The relationships between ABO and RhD blood types and COVID-19 mortality are shown in Table 2. The distribution of ABO blood types was O > A > B > AB among the patients. Additionally, the ranking of ABO blood types among the percentage of study participants who died from COVID-19 was O > A > B > AB (43.73%, 30.67%, 21.60%, and 4%, respectively). There was no significant association between ABO blood type and COVID-19 mortality (P = .768; Table 2). Among the deceased population, 92.53% were RhD-positive and 7.47% were RhD-negative. However, the results showed no significant association between RhD blood type and death from COVID-19 (P = .640).

Table 2 Correlation between blood groups and COVID-19 mortality.

Blood groups	Death	Chi-square	P-value	
No	Yes	Total	
n	%	n	%	n	%	
ABO	A	562	29.16	115	30.67	677	29.41	1.139	0.768	
AB	100	5.19	15	4	115	5.00	
B	421	21.85	81	21.60	502	21.81	
O	844	43.80	164	43.73	1008	43.79	
RhD	Negative	131	6.80	28	7.47	159	6.91	0.218	0.640	
Positive	1796	93.20	347	92.53	2143	93.09	
COVID-19 = coronavirus disease 2019.

The correlation between the combination of ABO and RhD blood types and death due to COVID-19 is shown in Table 3. The results indicated that the most prevalent blood type among the patients who did not die was O-positive (n = 778, 33.8%), and the least prevalent type was AB-negative (n = 1, 0.4%). In the group that died, the most common blood type was O-positive (n = 151, 6.56%), while the least common was AB-negative (n = 1, 0.4%). The results showed no statistical association between blood type (ABO or RhD) and death caused by COVID-19 (P > .05).

Table 3 Correlation between ABO and RhD blood groups and COVID-19 mortality.

Blood groups	Death	Chi-square	P-value	
No	Yes	Total	
n	%	n	%	n	%	
A	RhD	Negative	38	1.65	8	0.35	46	2.00	0.006	0.940	
Positive	524	22.76	107	4.65	631	27.41	
AB	RhD	Negative	1	0.04	1	0.04	2	0.09	2.45	0.12	
Positive	99	4.30	14	0.61	113	4.91	
B	RhD	Negative	26	1.13	6	0.26	32	1.39	0.173	0.678	
Positive	395	17.16	75	3.26	470	20.42	
O	RhD	Negative	66	2.87	13	0.56	79	3.43	0.002	0.963	
Positive	778	33.80	151	6.56	929	40.36	
COVID-19 = coronavirus disease 2019.

4. Discussion

The COVID-19 pandemic has greatly influenced many aspects worldwide, including transfusion medicine.[24,25] In general, blood types have been known to be associated with several human diseases, including infectious ones.[26] Since the beginning of the COVID-19 pandemic, several studies have reported on the association between ABO blood types and COVID-19.

It has been reported that non-O blood types (A, B, and AB) can be a prognostic factor for respiratory diseases and infections.[27] It has been reported that the A blood type was associated with a higher risk of COVID-19 infection compared to non-A blood types.[4,28–30] In addition, a study by Copur et al[31] investigated a total of 2828 healthcare workers and found that the nongroup-O was prevalent in the risk of developing COVID-19 infection compared to the O blood group. However, there were only 510 infected individuals in the study population.

In the present study, we found that the O blood type was the most prevalent type of COVID-19 infection (1008, 43.79%) compared to the other blood groups. The ranking of ABO blood types among the entire study population who had developed COVID-19 infection was O > A > B > AB. The results showed no statistically significant difference between the ABO blood types in terms of either COVID-19 infection or mortality; the results were relatively similar to the normal distribution in Saudi Arabia, as reviewed by Elsayid et al.[32]

In this study, RhD type was found to have no association with either COVID-19 infection or COVID-19-related death. This is consistent with what has been reported by other scholars who also found no association between RhD blood type and COVID-19 infection.[33] These results indicated that the majority of the participants were RhD-positive (93.09%), and 16.1% of them died from COVID-19. However, there was no statistically significant correlation between RhD blood type and COVID-19 infection, and mortality.

Our observation was consistent with another study that demonstrated protective associations between RhD-negative blood types and COVID-19 infection and death.[7,15,33] However, it is known that RhD antigen is not commonly distributed across races,[34] and its presence was more common among Saudis.[32] Combining the ABO type with the RhD type indicated that the most common blood group was O-positive while the least common was AB-negative.

Other studies have contradicted the notion of an association between ABO blood types and COVID-19 infection and mortality.[12,19–23,35–37] Indeed, it has been reported that COVID-19 morbidity and mortality can instead be attributed to patients’ preexisting chronic conditions.[38–40]

After the COVID-19 outbreak, many published articles assessed the correlation between ABO blood group and susceptibility to either COVID-19 infection or its mortality.[29] The current study examined the correlation between ABO and RhD blood types and COVID-19 mortality in 2 hospitals in the capital of Saudi Arabia, Riyadh City. This city is cosmopolitan; therefore, the outcome of the present study includes an excellent normal distribution of the data between both gender (52.52% females and 47.48% males) and nationalities (48.26% non-Saudi and 51.74% Saudi), as shown in Table 1.

A systematic review and meta-analysis by Liu et al[41] indicated that the O blood type seems to be protective, while the A and B blood types may increase COVID-19-related risk and extremely serious outcomes may be linked to blood type. Conversely, this study indicated that the most frequent ABO blood type among mortality cases of COVID-19 was type O (43.73%), while AB (4%) was the least frequent type. Furthermore, statistical analysis showed no significant correlation between the ABO (P = .768) and RhD (P = .640) blood groups of the participants and COVID-19 mortality. These findings are in line with a recent UK study of 2200 COVID-19 patients, which demonstrated that ABO blood type may not influence COVID-19 infection and mortality.[42]

Although our study aimed to evaluate the association between ABO and RhD blood groups and COVID-19 mortality, our results are still observational. However, there are some limitations to our study, including the lack of information regarding COVID-19 patients, such as the origin of non-Saudi patients, severity level of disease, duration of hospitalization and patient follow-up, and cause of death and comorbidities. Moreover, the association of ABO and RhD blood groups with susceptibility to COVID-19 infection was not evaluated in the present study due to the absence of relevant data, which could be addressed in future work. Despite these drawbacks, the current study presented a large sample size, as well as consistency between our findings and those of previous reports.

In summary, the outcomes of the present study demonstrated that the most frequent blood group associated with mortality in COVID-19 patients was the O-positive blood group. However, the least frequent blood group was AB-negative. Our results showed no significant correlation between COVID-19 mortality and ABO and RhD blood groups. Nevertheless, the ABO and/or RhD blood groups may not be accountable for this association, as these may indicate unexplored underlying factors, such as comorbidity.

Acknowledgments

We thank the King Saud Medical City Riyadh, Saudi Arabia for facilitating the conduction of this study.

Author contributions

Investigation: Amr J. Halawani, Abdullah H. Alhamoud.

Methodology: Amr J. Halawani, Abdulaziz H. Alqarni, Abdulrahman Mujalli.

Project administration: Amr J. Halawani, Abdullah H. Alhamoud.

Supervision: Amr J. Halawani.

Writing – original draft: Amr J. Halawani, Mariam M. Al Eissa, Anmar A Khan, Naif A Jalal, Farkad Bantun.

Writing – review and editing: Amr J. Halawani, Saeed M Kabrah, Mariam M. Al Eissa, Musaed M. Alshahrani, Anmar A Khan, Naif A Jalal, Abdulrahman Mujalli, Hesham A. Malak, Farkad Bantun.

Data curation: Abdullah H. Alhamoud, Rateb A Daowd, Ateeg M. Algarni, Abdulaziz H. Alqarni.

Formal analysis: Abdullah H. Alhamoud, Saeed M. Kabrah.

Validation: Abdulrahman Mujalli.

Conceptualization: Farkad Bantun.

Abbreviations:

COVID-19 coronavirus disease 2019

SARS severe acute respiratory syndrome

STROBE Observational Studies in Epidemiology.

The authors of this work have nothing to disclose.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

How to cite this article: Halawani AJ, Alhamoud AH, Kabrah SM, Al Eissa MM, Daowd RA, Algarni AM, Alqarni AH, Alshahrani MM, Khan AA, Jalal NA, Mujalli A, Malak HA, Bantun F. Lack of association of ABO and RhD blood groups with COVID-19 mortality: A 2-center cross-sectional study in Saudi Arabia. Medicine 2024;103:37(e39673).
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