Couples who share beds but not Covid may hold clue to ‘invincibility’

The writer is a science commentator

Evangelos Andreakos is wary of answering his phone. The immunologist, at the Biomedical Research Foundation of the Academy of Athens, launched a study last month to find people who are genetically immune to Covid-19 — and was besieged: “I got hundreds of emails and phone calls — from Greece, of course, but also the US, Brazil, Mexico, Russia and even India.”

Andreakos and co-author Andras Spaan, from Rockefeller University in New York, are members of the Covid Human Genetic Effort, an international consortium hunting down variants of single genes that influence immune response to the disease.

Most of its work is geared to finding genes that make people more susceptible. Earlier this month, Oxford university scientists identified a gene, LZTFL1, that doubles the risk of death from Covid-related respiratory failure. The variant is found in about 60 per cent of people of South Asian descent, 15 per cent of white people, and 2 per cent of black people, which might help to explain the disproportionate impact Covid has had on some communities and countries.

Andreakos is exploring the other end of the susceptibility spectrum: “Our hypothesis is that, because the human genome is so heterogenous, there must be individuals who have variants that make them resistant to infection, even if they are exposed again and again.”

Their theory is that these particular variants stop the virus from either entering human cells or replicating once inside. While the “spike” protein of the virus is the main crowbar into human cells, via the ACE2 receptor, other proteins latch on using ‘co-receptors’. A gene that causes one or more of these accomplice receptors to be absent or dysfunctional, might plausibly hamper the cellular break-in.

Once inside the cell, the virus commandeers cellular machinery to make copies of itself. There are proteins inside the cell, however, that recognise and interfere with foreign viral material; so any gene variant allowing such proteins to be pumped out in high amounts would confer protection.

Studies have identified families in which everyone, including children, has had PCR-confirmed infections — except for one spouse or partner consistently testing negative. Andreakos is especially interested in these “discordant couples” who share a bed but not Covid. He wants to enrol “immune” partners who have dodged Covid on at least two PCR-confirmed occasions, which must predate vaccination.

Those meeting these criteria will have their genomes analysed. Genes that crop up repeatedly will then be checked against those of Covid patients: any true invincibility genes must be unique to the immune and absent in the infected. Andreakos anticipates preliminary results next year but does not expect to find many genuine invincibles. Some apparently resistant individuals, he explains, might have been coincidentally infected with other viruses or bacteria, producing antibodies that, while not Covid-specific, were effective. “Vaccination is still the best protection,” he says.

Identifying genes of resilience could point the way to other antiviral treatments, an approach that has precedence. In the 1990s, scientists noticed that some Kenyan sex workers repeatedly exposed to HIV escaped disease; an uncommon mutation meant they lacked a key receptor that enabled certain forms of the virus to enter cells. It led to the development of maraviroc, a HIV treatment approved by the US Food and Drug Administration in 2016.

Uncovering genes associated with pandemic vulnerability will raise fresh issues. Should the Covid-immune be exempt from vaccine mandates? Should high-risk countries be fast-tracked for jabs? Twenty months into the pandemic, the curveballs keep coming.