Is being of direct African ancestry a risk factor for severe COVID-19 disease?

Question

In the initial outbreak of COVID-19 in Asia, the populations affected were fairly homogenous though ethnicity data isn't available from the studies published from China. However, Chinese are ethnically 92% Han, and even non-Han have tended to label themselves Han eventually (assimilation).

However, in the UK and USA there are alarming reports that the disease is worse in people of African descent.

According to the CDC, even though the racial breakdown from the population in the report was 59% white, 14% Latino and 18% black, 45% of hospitalized coronavirus patients were white and 8% were Latino, while 33% were black, "suggesting that black populations might be disproportionately affected by COVID-19."

and

Louisiana released data showing that while African-Americans only make up roughly 32% of the population they account for 70% of the deaths in the state

Traditionally this is being attributed to the poorer health of African Americans who have jobs in the service industry and are unable to work from home, higher incidence of co-morbid conditions, and less access to health care amongst many other reasons.

But could there be a biological reason for this? We know blacks are more susceptible to autoimmune disease such as lupus so there may be good reasons to suspect that this is the case.

https://abcnews.go.com/Politics/coronavirus-disproportionately-killing-black-community-experts/story?id=70011986

Answer 1

As pointed out in the question, there are immune differences between those of African ancestry, and those from out of Africa.

We know from genetic studies that there is a major difference between African and out of African genetics

Ancient DNA has enabled us to answer long-standing questions about the relationship between archaic and modern humans. Admixture among archaic groups and between them and modern humans seems to have occurred whenever they came into geographic proximity. In that way, they were no different from groups of modern humans. Although most present-day human ancestry can be traced to African populations that dispersed into Eurasia ∼100,000 y ago, aDNA has allowed us to also determine which parts of our genomes are from archaic hominins that occupied Eurasia before modern humans (68): all non-African genomes carry small amounts of Neanderthal ancestry, and some carry an additional component of Denisovan ancestry.

So, the question is whether Neanderthal/Denisovan genes help protect against viral diseases such as SARS-CoV-2.

There are some hints that this might be the case in European populations:

Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli—ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus—and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.

and

Genetic variation transmitted through admixture with Neandertals can also represent a source of functional, potentially advantageous variants (Vattathil and Akey, 2015). Relative to genome-wide expectations, we show that genetic segments introgressed from Neandertals have preferentially introduced regulatory variants into European genomes, affecting steady-state expression and responses to TLR7/8 stimulation and IAV. Furthermore, we report several loci presenting strong evidence of archaic ancestry that exert a regulatory effect in cis. Among these, we find the IAV-induced reQTL of PNMA1, which encodes a protein that physically interacts with the IAV protein PB2 and stimulates interferon production (Shapira et al., 2009). That the PNMA1 haplotype presents a frequency in Europeans that is not compatible with neutral evolution, together with its strong levels of population differentiation between modern Europeans and East Asians, supports its contribution to European adaptation and provides a case of adaptive introgression. The functional roles of the introgressed regulatory variants require further investigation, but our results clearly establish that archaic admixture, whether adaptive or not, has increased the diversity of the immune repertoire of contemporary Europeans.

So, it appears that the introduction of Neaderthal genes that influence immune responses has lead to an increased range of possible responses to viral infection than was possible from pure African genomes.

Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations https://www.cell.com/cell/fulltext/S0092-8674%2816%2931306-X

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988579/