The Lancet Infectious Diseases July 17th,2020

Potential factors linked to high COVID-19 death rates in British minority ethnic groups

The Institute for Fiscal Studies (IFS), in their investigation into the vulnerability of the UK’s minority ethnic groups to COVID-19,1 found hospital deaths in England of Black and south Asian ethnic groups to be inexplicably higher than those of the white British majority after taking into consideration demographic and geographical profiles. However, they did not consider as possible factors the prevalence of sickle cell anaemia or ?-thalassaemia.

Sickle cell anaemia is inherited in an autosomal recessive pattern, with homozygotes having sickle cell disease and heterozygous carriers having sickle cell trait.
Sickle cell trait is asymptomatic. However, it is occasionally associated with sudden death induced by severe hypoxia. Hypoxaemia is a complication of COVID-19.2

Another complication of COVID-19 is pulmonary embolism: in one study,3 23% of patients with severe clinical features of COVID-19 had acute pulmonary embolism.
People who have sickle cell trait have twice the risk of pulmonary embolism compared with the general population.

The relative frequency of sickle cell trait is higher in Black ethnic groups than in the white ethnic majority in the UK (appendix).
Of interest, the Black African ethnic group has twice the number of fatalities and frequency of sickle cell trait as does the Black Caribbean group (appendix).

Similar to sickle cell anaemia, ?-thalassaemia is inherited in an autosomal recessive manner, with heterozygous carriers having ?-thalassaemia trait.
The relative frequency of ?-thalassaemia is higher in the south Asian ethnic groups than in the white ethnic majority (appendix).
The only known symptom of ?-thalassaemia trait is a tendency for mild anaemia, which could aggravate hypoxaemia due to COVID-19.

The IFS found the white Irish minority to have half the number of fatalities as the white British majority.
Haemochromatosis type 1, whose prevalence is higher in the white Irish ethnic group than in the white British ethnic group (appendix), could be having an effect here.
The mutation C282Y is inherited in an autosomal recessive pattern. People with the C282Y allele are less likely than those without to be anaemic, homozygotes sometimes having to be regularly bled to reduce their iron overload.

Iron-deficiency anaemia could aggravate hypoxaemia due to COVID-19. The prevalence of iron-deficiency anaemia has been reported to be lower in white Irish than in white British men (appendix).
These data highlight the potential hypoxic effect of anaemia in COVID-19 fatalities for sickle cell anaemia carriers and for ?-thalassaemia carriers. They also indicate that haemochromatosis type 1 might confer some protection.