It remains one of the biggest puzzles of the Covid-19 pandemic. The disease generally causes serious problems only in older people or those with underlying health problems. But occasionally it strikes down young, apparently fit individuals, including medical staff exposed to patients with the virus. In some cases, previously undiagnosed conditions are later revealed but in others no such explanations are available, leaving scientists struggling to find reasons for the behaviour of the coronavirus. Several theories have been proposed. Some researchers believe the amount of virus that infects an individual may have crucial outcomes. Get a huge dose and your outcome may be worse. Others argue that genetic susceptibility may be involved: in other words, that there are individuals whose genetic makeup leaves them more vulnerable to the virus as it spreads through their bodies. This latter idea is favoured by virologist Michael Skinner at Imperial College London. “It is very possible that some of us could have a particular genetic makeup that makes it more likely that we will respond badly to an infection with this coronavirus,” he said. An example of such susceptibility is provided by the herpes simplex virus, which causes cold sores. In some people, a mutation that affects cell receptors known as TLR3, in their central nervous system, leaves them unable to deal with the worst impact of the virus: they contract a disease called herpes simplex encephalitis, which can lead to seizures and convulsions in children. “It could be that we are seeing a similar sort of susceptibility in some individuals who get Covid-19, and that leads them to suffer more acutely from serious side-effects,” added Skinner. Others, however, suggest that the amount of virus that a person is infected with could be a crucial factor in determining their outcome. Such individuals are said to be affected by a high viral load. “A person with a high viral load has more virus particles than one with a low load,” said virologist Alison Sinclair at Sussex University. “We do not yet know what impact viral load has on the symptoms of a person infected with Covid-19. Whether there is a link between a high viral load and worse outcomes is going to be important to find out.” This point was backed by Edward Parker at the London School of Hygiene and Tropical Medicine. “For Covid-19, early reports from China suggest that the viral load is higher in patients with more severe disease, which is also the case for Sars and influenza. “So it is crucial for us to limit all possible exposures to Covid-19, and if we are feeling unwell we need to observe strict self-isolation measures to limit our chance of infecting others.”