Blood Group Antigen Combinations and COVID-19: Complexity, Associations and Possible Clinical Relevance

Area of Science:

• Immunogenetics
• Transfusion Medicine
• Infectious Disease Epidemiology

Background:

• Red blood cell (RBC) antigens are crucial for blood transfusion compatibility.
• The potential influence of RBC antigens on susceptibility to infectious diseases, including COVID-19, remains an area of investigation.

Purpose of the Study:

• To explore associations between specific red blood cell antigens and systems with COVID-19 susceptibility.
• To investigate if combinations of RBC antigens offer more insight into COVID-19 risk than single antigens.

Main Methods:

• An exploratory case-control study involving 263 Polish blood donors (121 convalescents, 142 healthy controls).
• Microplate method used to analyze 21 RBC antigens from eight clinically relevant blood group systems.
• Statistical analysis included single antigen assessment and multi-antigen combinations (3-, 4-, and 5-element).

Main Results:

• No statistically significant correlation was found between individual RBC antigens and COVID-19 susceptibility.
• Exploratory analysis of multi-antigen combinations revealed nominal associations, but none persisted after multiple testing adjustments.
• Strongest nominal associations for three-antigen combinations included cc, Ee, and kk (OR=4.49); for four-antigen combinations, RhD(+), kk, Fy(b), and P1(-) (OR=4.49).

Conclusions:

• Single red blood cell antigens appear to have limited predictive value for COVID-19 susceptibility.
• Combinations of RBC antigens may offer more significant correlations, though requiring cautious interpretation.
• Further validation in larger, diverse populations is essential to confirm these exploratory findings.