Chapter 1: Genetic Insights into Covid-19

In recent months, geneticists globally have been investigating whether variations in human genomes affect the likelihood or severity of Covid-19 infections. Initial findings suggest a correlation between a specific segment of chromosome 3 and increased Covid-19 risks. Hospitalized individuals in Italy and Spain exhibit a "risk" allele in the 3p21.31 region approximately 1.7 times more frequently than the general population.

A recent preprint study links this risk allele back to our Neanderthal ancestors. As a researcher in human evolution, such discoveries excite me, but they also come with the potential for misunderstanding. Many might assume that insights from genetic testing, like those from 23andMe, could indicate their Covid-19 risk, which is misleading.

Factors such as environment and behavior significantly outweigh the role of genetics in the virus's spread. Currently, the most effective strategies for curbing transmission include social distancing and mask-wearing, while vaccines present the best long-term solution. Although human genetics may offer valuable insights into the virus's biology and its impact, they do not provide definitive answers regarding infection susceptibility.

Understanding Neanderthal DNA provides a temporal context—Covid-19 is a novel pathogen interacting with a human biology that has evolved over the last half-million years.

Section 1.1: The Complexity of Genetic Traits

Most people associate genes with straightforward traits like blood types. However, the reality is much more intricate; the majority of human traits are influenced by numerous genes, each contributing a small effect, making them difficult to isolate.

To identify these subtle gene-trait relationships, researchers conduct genome-wide association studies (GWAS), which involve analyzing millions of genotypes across extensive participant groups. The larger the sample size, the more minute genetic influences can be detected.

For instance, the UK Biobank, with its 500,000 DNA samples and detailed health records, has allowed scientists to pinpoint thousands of genes linked to traits like height and weight. The sheer volume of data enables researchers to differentiate genetic effects from other influencing factors, such as age and socioeconomic status.

Emerging diseases pose unique challenges for GWAS due to the need for large samples. The Covid-19 Host Genetics Initiative is gathering genetic studies on Covid-19 cases worldwide. Currently, the UK Biobank has a modest number of confirmed Covid-19 cases (1,190), which limits the identification of significant genetic factors.

Subsection 1.1.1: Early Findings and Caution

Last month, the New England Journal of Medicine released a preliminary genetic study focused on around 1,500 severe Covid-19 patients from Italy and Spain, led by David Ellinghaus. This research identified two genomic regions associated with higher Covid-19 risk, particularly spotlighting the ABO gene locus responsible for blood types. Initial findings suggested that type A blood might correlate with a 50% increase in severe Covid-19 symptoms.

As newer data emerges, it appears that the ABO connection may not hold up across larger patient groups, casting doubt on earlier conclusions. The historical context of blood type research has seen many flawed associations with various traits, highlighting the necessity for caution in interpreting genetic correlations.

Chapter 2: Neanderthal Influence on Modern Genetics

The first video titled Ancient genetics are facing the coronavirus | COVID-19 Special delves into the connections between ancient genetic markers and contemporary Covid-19 dynamics. It provides a comprehensive examination of how ancient DNA informs our understanding of the virus.

The second video, Genetics and covid deaths, explores the implications of genetic factors in relation to Covid-19 mortality, contributing to the broader discourse surrounding genetics in the pandemic.

The Ellinghaus study found that the 3p21.31 region's link to severe Covid-19 is most pronounced for the polymorphism known as rs11385942, which involves an additional adenine in some individuals' genomes. Those carrying this variant were about 1.77 times more likely to fall into the severe Covid-19 category.

However, it is crucial to note that this finding represents only a small fraction of the variance in Covid-19 susceptibility. Among the European populations studied, the frequency of the additional "A" allele is roughly 8%, and while 15% of individuals have at least one copy, 76% of severe Covid-19 patients do not possess this risk allele.

Emerging studies must also consider socioeconomic status, age, and other factors that may influence the impact of host genetics on Covid-19 outcomes. Although the discovery of the 3p21.31 variant may not significantly predict Covid-19 risk, it serves as a stepping stone for further investigations into the disease's biology.

Scientists are now scrutinizing the 3p21.31 region more closely, as GWAS results alone do not determine which specific gene variant causes an effect. While the positive GWAS outcome indicates potential relevance, the extra "A" allele may merely be correlated with another genetic change affecting Covid-19 susceptibility.

This region encompasses several intriguing genes. The rs11385942 variant resides within an intron of the LZTFL1 gene, while nearby genes like CCR9 and CXCR6 are involved in immune signaling. Understanding these interactions may shed light on the immune response to Covid-19, similar to how the CCR5 gene variant confers resistance to HIV.

Without further research, the mechanisms behind increased Covid-19 risk—whether due to heightened susceptibility, symptomatic progression, or rapid respiratory failure—remain unclear. The last decade of human genomics teaches us that larger patient samples will likely reveal more genes influencing Covid-19, each contributing small effects. The aggregate impact of numerous genes may ultimately yield a more comprehensive understanding than isolated loci.

Neanderthal DNA adds an evolutionary perspective to this narrative. Researchers Hugo Zeberg and Svante Pääbo examined the 3p21.31 region for SNP alleles present in ancient Neanderthal genomes. They discovered that the Vindija 33.19 Neanderthal, among others, carried many of the linked SNP alleles associated with Covid-19 risk.

Despite the presence of this haplotype in some populations, its rarity in parts of Asia and sub-Saharan Africa raises questions about its relevance to contemporary Covid-19 susceptibility. While Neanderthal genes contribute to genetic diversity, their impact on Covid-19 remains a topic of ongoing inquiry.

In conclusion, understanding the role of Neanderthal genetics in modern humans highlights the complex interplay of evolutionary history and genetic variation. Although some Neanderthal-derived genes may provide advantageous traits, the predominant factors influencing Covid-19 transmission are behavioral and environmental, rather than purely genetic.

The ongoing research into host genetics may eventually elucidate some of the pandemic's mysteries, such as asymptomatic infections and superspreaders. Yet, it is essential to emphasize that no genetic test currently exists to predict individual Covid-19 risk. Insights from Neanderthal genetics are valuable for understanding human evolution, but they do not serve as a health guide in the face of the pandemic.