Correlation between ABO blood group and neutralizing anti-SARS-CoV-2 antibody titers in convalescent plasma donations.

Many efforts have been made during the last 18 months to identify factors associated with SARS-CoV-2 antibody response in COVID-19 convalescent plasma (CCP) donors, with older age, male sex and disease severity having been identified as the main predictors [1], [2]. Although the association between ABO blood type and susceptibility to COVID-19 is well known and studied [3], with individuals having O blood type being less prone to infection, there is more uncertainty regarding ABO blood group-driven SARS-CoV-2 antibody response. Hayes and colleagues [4] recently observed that blood group O CCP donors have significantly lower levels of SARS-CoV-2 IgG antibodies than do donors with other blood groups. Antibody levels were measured using a semi-quantitative chemiluminescent immunoassay as a surrogate for the traditional plaque reduction neutralization test (PRNT). To assess their findings, we studied the correlation between 496 consecutive CCP donations, given at the Transfusion Center of Mantova city hospital, and the SARS-CoV-2 neutralizing antibody titer, measured using the gold-standard PRNT (performed at the Molecular Virology Unit of the University Hospital of Pavia and based on the determination of the in vivo cytopathic effect, as previously described) [5].

The ABO blood group distribution among the study population (394 CCP donors) was the following: O = 165 (41.9%), A = 173 (43.9%), B = 36 (9.1%) and AB = 20 (5.1%). There were 319 (81.0%) male and 75 (19.0%) female CCP donors. Their mean age was 45.8 (±11.4) years. Of the 394 donors, 292 (74%) gave one CCP donation, while the remaining 102 donors made repeat CCP donations (37 gave 2 donations, 8 gave 3 donations and 1 gave 4 donations). The average time interval between recovery from symptoms and CCP donation was 39.6 (±21.1) days. No statistically significant differences in the distribution of donors’ sex, donors’ age and interval between symptom resolution to donation by ABO blood group was observed. At one-way analysis of variance, the ABO system did not appear to exert any significant effect on neutralizing antibody levels (P  = 0.78). However, as reported in Table 1a , the marginal effects (i.e., the mean values of the neutralizing antibody level) appeared somewhat different, the mean titer being highest in the AB group and lowest in the O group, although the 95% confidence interval (CI) was too high to support this being of any statistical significance. Similarly, the pairwise comparisons of the marginal linear predictions were all not significant (Table 1b ). Again, however, the greatest difference was between O and AB blood groups (−52.98). Interestingly, the proportion of donations reaching a high neutralizing titer (defined as ≥ 80) was lower in O blood type donors than in non-O blood type donors, among whom we observed a progressive increase from A to B and AB blood groups, with CCP AB donations comprising the highest proportion of those with a neutralizing titer ≥ 80 (Table 2 ).

Table 1a

Correlation between anti-SARS-CoV-2 neutralizing antibody titer and ABO blood group, marginal linear predictions (1a) and pairwise comparisons of marginal linear predictions (1b).

			Unadjusted
	Margin	Std. Err.	95% Conf. Interval
ABO
A	194.10	16.72	161.26	226.94
AB	238.08	48.29	143.19	332.96
B	192.22	36.71	120.10	264.34
O	185.10	17.07	151.55	218.64

Table 1b

					Unadjusted
	Contrast	Std. err.	t	P > t	95% Conf. Interval
ABO blood group
AB vs A	43.98	51.10	0.86	0.390	−56.43	144.38
B vs A	−1.88	40.33	−0.05	0.963	−81.13	77.37
O vs A	−9.01	23.89	−0.38	0.706	−55.95	37.94
B vs AB	−45.85	60.66	−0.76	0.450	−165.04	73.33
O vs AB	−52.98	51.22	−1.03	0.301	−153.62	47.66
O vs B	−7.13	40.48	−0.18	0.860	−86.67	72.42

Table 2

Proportion of donations reaching the neutralizing titer ≥ 80 according to ABO blood type.

ABO	< 80	≥ 80	Total	%
A	68	149	217	68.7
AB	6	20	26	76.9
B	12	33	45	73.3
O	70	138	208	66.3
Total	156	340	496	68.5

In conclusion, although the ABO system-related effect was weaker, the results of our study are consistent with those of Hayes and colleagues [4] and support the preferential collection of CCP from non-O blood type donors, with the aim of producing CCP units with the highest anti-SARS-CoV-2 neutralizing antibody titer. High levels of anti-SARS-CoV-2 neutralizing antibodies have been clearly related to a favorable clinical effect of CCP as early treatment for COVID-19 [2]. It is probable that statistical significance could have been achieved by increasing the number of observations in our study. Further, adequately powered studies are therefore needed to definitely determine the role of ABO blood group in driving the SARS-CoV-2 antibody response in CCP donors.

Funding

None.

Disclosure of interest

The authors declare that they have no competing interest.