Type O blood linked to lower respiratory failure in study

Genetic analysis involving Covid-19 patients in Italy and Spain who developed respiratory failure adds to the evidence linking blood type to disease prevalence and severity.

Patients with type A blood in the study cohort had a higher risk for disease involving acute respiratory syndrome, while type O blood appeared to be protective against severe disease.

A very early study of patients with Covid-19 in Wuhan and Shenzhen, China was among the first to suggest an association between blood type and SARS-CoV-2 susceptibility and disease severity. In that study, published ahead of peer review, the type A blood group appeared to be associated with a greater risk for acquiring Covid-19 and the type O blood group was linked to lower risk.

Another early study involving cases in New York City, also published ahead of peer review, found a higher prevalence of group A blood type in patients who were SARS-CoV-2 positive and a lower prevalence of infection with group O blood type.

And, preliminary data recently reported by the commercial genetic testing site 23andMe also suggested a protective role for type O blood type against the novel coronavirus when compared to other blood types.

Blood specialist Parameswaran Hari, MD, of the Medical College of Wisconsin, said while the research suggesting a role for blood type in Covid-19 remains preliminary, the findings appear to be consistent. Hari was not involved with the newly published study, but he talked to BreakingMED about the findings.

“The studies are all pointing in the same direction, and that is really intriguing,” he said.

He noted that glycoproteins are present on the surface of the red blood cells in people with A, B, and AB blood types, but not in those with type O blood types.

“Coronavirus surface proteins are also glycoproteins, and the hypothesis within the scientific community is that if you are in the type O blood group you are predisposed to forming antibodies against glycoproteins,” he said.

He added that if this is the case, people with type O blood may prove to be more responsive to a Covid-19 vaccine when a vaccine becomes available. The vaccine may also need to integrate A and B glycoprotein to boost responses in people with A, B, or AB blood types.

But before that happens, more rigorous studies are needed to confirm the association between blood type and novel coronavirus, Hari said.

“These findings really need to be validated in larger studies,” he said.

In the newly reported trial, published June 17 in New England Journal of Medicine, researchers detected a novel susceptibility locus at a chromosome 3p21.31 gene cluster and confirmed the potential involvement of the ABO blood-group in Covid-19 patients with respiratory failure.

Researchers performed a genome-wide association study (GWAS) involving Covid-19 and severe disease, characterized by respiratory failure, at 7 hospitals in Italy and Spain that treated large numbers of patients during major outbreaks of the novel coronavirus.

The meta-analysis included two case-control panels: 835 patients and 1,255 controls from hospitals in Italy and 775 patients and 950 controls from Spanish hospitals, with analysis of close to 8.6 million single-nucleotide polymorphisms.

The meta-analysis of the two case-control panels revealed cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genome wide level (P<5 x 10-8) (odds ratio, 1.77; 95% CI, 1.48-2.11; P=1.15 x 10-10 and odds ratio, 1.32; 95%, 1.20-1.47; P=4.95 x 10-8, respectively).

“At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1,” wrote researcher Andre Franke of Christian-Albrecht-University, Kiel, Germany, and colleagues with the Severe Covid-198 GWAS Group.

“The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20-1.75; P=1.48 x 10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53-0.79; P= 1.06 x 10-5).”

The researchers noted that the preliminary findings did not identify a causative gene.

“One candidate is SLC6A20, which encodes the sodium-imino acid (proline) transporter 1 (SIT1) and which functionally interacts with angiotensin-converting enzyme 2, the SARS-CoV-2 cell-surface receptor,” the researchers wrote.

“However, the locus also contains genes encoding chemokine receptors, including the CC motif chemokine receptor 9 (CCR9) and the C-X-C motif chemokine receptor 6 (CXCR6, the latter of which regulates the specific location of lung-resident memory CD8 T cells throughout the sustained immune response to airway pathogens, including influenza viruses.”

They further noted that flanking genes, including CCR1 and CCR2, may also play a role.

  1. In a genome wide association study of severe Covid-19 cases from Italy and Spain, patients with type A blood had a higher risk for severe disease with acute respiratory syndrome than other blood types and type O blood appeared to be protective against severe disease.
  2. Researchers detected a novel susceptibility locus at a chromosome 3p21.31 gene cluster, and confirmed the potential involvement of the ABO blood-group in Covid-19 patients with respiratory failure.

Salynn Boyles, Contributing Writer, BreakingMED™

Funding for this research was provided by Stein Eric Hagen and Canica, the Deutsche Forschungsgemeinschaft Cluster of Excellence, the Italian Ministry of Health, and others.


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