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Scientists tried to reinfect people with Covid but found it impossible, even when they ramped up the dose 10,000-fold, according to the latest results from the Covid challenge trials.

When Paul Zimmer-Harwood volunteered to be intentionally infected with SARS-CoV-2, he wasn't sure what to expect. He was ready for a repeat of his first brush with COVID-19, through a naturally acquired infection that gave him influenza-like symptoms. But he hoped his immunity would help him feel well enough to use the indoor bicycle trainer that he had brought into quarantine.

It turned out that Zimmer-Harwood, a PhD student at University of Oxford, UK, had nothing to worry about. Neither he nor any of the 35 other people who participated in the 'challenge' trial actually got COVID-19.

The study's results, published on May 1st in Lancet Microbe, raise questions about the usefulness of COVID-19 challenge trials for testing vaccines, drugs and other therapeutics. "If you can't get people infected, then you can't test those things," says Tom Peacock, a virologist at Imperial College London. Viral strains used in challenge trials take many months to produce, making it impossible to match emerging circulating variants that can overcome high levels of existing immunity in populations.

Researchers use challenge trials to understand infections and quickly test vaccines and therapies. In March 2021, after months of ethical debate, UK researchers launched the world's first COVID-19 challenge trial. The study identified a minuscule dose of the SARS-CoV-2 strain that circulated in the early days of the pandemic that could infect about half of the participants, who had not previously been infected with the virus (at that time, vaccines weren't yet widely available). [Read the Daily Sceptic write-up of the study here.]

In parallel, a team led by Helen McShane, an infectious-disease researcher at Oxford, launched a second SARS-CoV-2 challenge study in people โ€” including Zimmer-Harwood โ€” who had recovered from naturally caught SARS-CoV-2 infections, caused by a range of variants. The trial later enrolled participants who had also been vaccinated.

The first participants got the same tiny dose of the 'ancestral' SARS-CoV-2 strain as did those in the first trial. When nobody developed a sustained infection, the researchers increased the dose by more and more in subsequent groups of participants, until they reached a level 10,000 times the initial dose. A few volunteers developed short-lived infections, but these quickly vanished. Worth reading in full.

Despite this immunity to the old strains, nearly 40% of the participants reported an Omicron infection after being released from quarantine by December 2022 (and one even reported getting it twice).

The upshot? Natural immunity is extremely robust - even more robust than has previously been suggested - but new variants can appear that evade it with relative ease. We'd kind of figured that out, but it's good to have it experimentally confirmed.