Type A Blood Linked to Higher COVID-19 Risk

The data are pretty clear. But the question is why?

One of the things that has really bothered me about COVID-19 is the dramatic variability in presentation. From asymptomatic, to sniffles, to complete respiratory failure requiring ECMO and of course death. I’ve seen all of these first hand at this point. And sure, we know that there are risk factors for bad outcomes — older age, comorbidities. But ask any of us who have cared for these patients and we’ll tell you that there is clearly other stuff going on. I’ve seen a 35 year old man with no comorbidities fighting for his life on ECMO.

It seems logical that genetics may play a role here, but those studies are just in the early phases. Nevertheless some tantalizing clues are emerging — and some from really unlikely places.

The Wilson blood typing lab in action

OK a couple of months ago, my family did tests to figure out our blood type.

We did this for no scientific or medical reason, but because we were bored stuck at home, wanted some fun sciency stuff to do with the kids, and found some cheap kits on Amazon.

I am type O. My wife, type A.

And that was that. Until I started seeing that blood type may be associated with the risk of coronavirus infection and death from COVID-19.

This supposition immediately raised red flags for me. Correlating blood type with various outcomes has long straddled the border between regular science and pseudoscience — and often had a racially-tinged flavor to them. I am pretty sure blood type does not correlate with various personality traits, for example.

So why would blood type dictate susceptibility to a respiratory virus?

But, since I am often wrong and love to find out when I’m wrong, I looked into it. And I honestly think there may be something here.

Caveats: data is really limited. Studies are sort of trickling out in pre-print form and in various esoteric journals. But I’ll point out a couple that hold water for me.

The first, a pre-print out of China, looked at just over 2000 COVID-positive individuals and reported that there was a higher infection rate in people with Type A blood.

Distribution of Blood Types, China Study

What you see here is that there was a higher than expected rate of individuals with blood group A diagnosed with COVID-19 than in the general population.

Conversely, fewer than expected individuals with blood group O appeared in the pool of those infected. Similar results were seen when the analysis was restricted to the 206 individuals who died from COVID-19, again blood group A was over-represented.

One study, especially in pre-print form, is never definitive, but we now have this study from New York City to add to the data.

This study looked at 1,559 patients who were tested for COVID-19–682 were positive. And check out the distribution of blood types in the positive versus negative groups.

Distribution of Blood Types, NYC Study

Again, blood group A is over-represented and blood-group O is under-represented among the infected.

23andme Data — Not Peer-Reviewed yet

The commercial DNA testing company 23andme has reported that their analysis of over 750,000 genomes shows a similar pattern by blood group. They haven’t published their data yet, but you can see here that the self-reported infection rate was lower in type O indviduals and higher in type A individuals — though overall rates are still low.

This data doesn’t come totally out of the blue. Back in the SARS era, a Hong Kong study reported that Type A individuals were at higher risk of infection from that coronavirus.

But what’s the biologic rationale here? Even if we believe the epidemiology — the question is “why”.

There are a few theories floating around out there, but most of them focus on antibodies.

Inhibition of SARS-COV-1 binding by anti-A Antibody

An in vitro study of the SARS coronavirus from 2008 found that Anti-A antibodies inhibited the ability of the viral spike protein to bind to its receptor — ACE2.

So a leading theory is that people with blood type O, like me, might be protected if they have some anti-A antibodies floating around.

Of course people with type B blood also have anti-A antibodies, and we haven’t seen protection in them so far.

The other possibility is that the antibodies generated against the virus are cross-reactive with the blood group A antigen — so when someone with blood group A is generating those antibodies, they might also be making antibodies that make their platelets a bit stickier — leading to some of the thrombotic events we’ve seen in COVID-19 patients. Of course, this doesn’t explain why the risk of infection would be higher, only the risk of bad outcome after infection.

I’m left a bit puzzled. Am I convinced there is something here? Yes — but I’m not sure what it is. Whether it’s a direct biologic effect of blood type, or whether blood type is a marker for something else — a nearby gene for instance — or maybe even socioeconomic status is ongoing work. As we get more answers, we’ll tell you about them here.

A version of this commentary first appeared on medscape.com

Writing about medicine, science, statistics, and the abuses thereof. Commentator at Medscape. Associate Professor of Medicine at Yale University.

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