Covid-19 has spread across the world with fearsome speed. In just 100 days, the number of cases has risen from just a handful in Wuhan, China, to almost 1.5 million in more than 180 countries. Barely 20 nations have yet to report a case, including North Korea, Yemen to the tiny Pacific island of Nauru. It’s likely that some of those countries have also been infected, the lack of confirmed cases being due to a failure – or reluctance –to carry out tests or report the outcome. Of those confirmed cases, almost 85,000 have died, a fatality rate of more than 5 per cent. But these raw global figures are both more and less significant than they seem. Sceptics of the global response to the pandemic have made much of the fact that seasonal flu infects hundreds of millions each year, killing up to 500,000, and yet does not prompt global lockdowns and economic mayhem. The difference with Covid-19 is that it seems to be both more infectious and more lethal than seasonal flu. As a result, the number and severity of cases rise so quickly that hospitals struggle to cope, and the death-toll soars – as it did in Italy, Spain and now the United States. This depends of a number of factors ranging from age and health status to the quality of healthcare systems. Those over 60 are at considerably greater risk than the average person, as are those with high blood pressure and diabetes or those who smoke. Perhaps surprisingly, however, the true mortality rate is still unknown. That’s because the true mortality rate needs reliable figures for the total number of people infected – and confirmed cases are a poor guide to that. They typically include only those who show symptoms of infection, and therefore get tested. It’s thought that many people show no signs of being infected and as a result are never tested. The latest estimate, published in the Lancet by UK researchers last week, puts the fatality figure at around 0.7 per cent of cases, rising to 3.3 per cent for those aged 60-plus. Even that lower figure is around 15 times higher than for seasonal flu. No matter how deadly Covid-19 really is, the final toll can be reduced by minimising the number of people infected. And different countries have adopted different ways of doing that. Many – including the UAE – have imposed lockdowns of varying severity. A few – notably Sweden – have chosen a more laissez faire policy, banning only large gatherings and leaving schools and cafes open. But trying to fathom “what works” from the headline figures for each country is perilous. That’s because different countries have adopted different policies on testing. Some – like the locked-down UK – only test people with serious symptoms. Yet such people are only a minority of all those infected, and are also more likely to die. And that makes the raw death rate based on confirmed UK cases – currently around 10 per cent - misleadingly pessimistic. Meanwhile, other countries – including the UAE – carry out more comprehensive testing, leading to more reliable death rate statistics. The figure for the UAE is currently 11 deaths and 2,076 cases, or 0.5 per cent, lower than the Lancet figure. So has the UAE blundered by imposing a UK-style lockdown policy? Not at all. The UK’s far worse figures simply reflect its less comprehensive policy on testing. The single biggest risk factor for dying from Covid-19 is age. With their increasing frailty and risk from other health conditions, the over-60s are over 20 times more likely to succumb than the under-60s. Covid-19 typically poses very little threat to the young: the chances of those in their 20s dying from infection are estimated to be less than 1 in 1,000. And yet tragic cases still occur, even among the fit and healthy. The reasons are still hotly debated. One theory is that perhaps these young adults were simply unlucky, being somehow exposed to levels of the virus too high even for their vigorous disease-fighting immune systems to handle. But another possibility is that they have a genetic quirk that leads to a tragic irony, in which they are killed by their own immune system. Once infected by a virus, the body’s immune system fights back using molecular troops co-ordinated by messengers known as cytokines. But in some people the fight continues long after the virus has been defeated. The resulting “cytokine storm” can damage the lungs and other organs with potentially fatal results. Researchers are now investigating ways of spotting when a cytokine storm breaks out, and finding drugs that can calm the trigger-happy immune system. A vaccine is widely seen to be the ultimate defence against Covid-19. By making enough people immune to the Sars-CoV-2 virus responsible, mass vaccination promises to end the threat from Covid-19 forever. The idea is simple – in theory at least. The immune system is “trained” to recognise the virus by being exposed to some part of it, like soldiers being shown an enemy uniform. That allows the immune system to attack before the virus can make any headway. The challenge is making sure the “uniform” is a reliable guide to the enemy, and that it doesn’t pose a danger itself. Many promising vaccines have proved to be useless or spark nasty side-effects – or both. More than 30 companies and research groups are now working on the problem, some using new approaches they hope will minimise the risks. But there are no short cuts to showing a vaccine is safe and effective. Large-scale human trials are essential. The challenge is especially severe with Covid-19. Its infectivity is so high that most people on Earth will have to be vaccinated to reach “herd immunity”, where the virus can no longer spark epidemics. Given such numbers, even a tiny probability of serious side-effects could thus become a health threat affecting millions of people. Human trials are about to start, but a vaccine for Covid-19 is at least a year away – and further still from global deployment. In the absence of a vaccine, the focus has been on slowing the rate of infection – “flattening the curve” - so that healthcare systems are not overwhelmed. The now-familiar measures of lockdowns, social distancing and regular handwashing are buying time for the development of drugs for treating Covid-19 patients. The World Health Organisation has identified four candidates: the anti-viral drug remdesivir, a mix of two HIV drugs lopinavir and ritonavir, a combination of those plus a cytokine called interferon-beta and the anti-malarial compounds chloroquine and hydroxychloroquine. Human trials are under way, amid concern about whether they will be safe and effective. The antimalarials and remdesivir have been linked to potentially serious side-effects, while a small study of the effectiveness of the HIV drugs proved disappointing. There is mounting interest in a treatment that uses the only known cure for Covid-19: the immune system. First tried during the Spanish Flu pandemic, it involves extracting virus-killing <a href="http://www.thenational.ae/uae/health/coronavirus-us-experts-call-for-introduction-of-serum-treatment-1.993056">antibodies from the blood of people who have recovered</a> from the disease and giving them to patients. A US Government-backed blood donation and <a href="https://www.uscovidplasma.org/">distribution programme is now under way</a>, organised by the Mayo Clinic in Minnesota. The same approach is also being seen as a way of protecting front-line healthcare workers. Everyone agrees that no matter how effective lockdowns and social distancing might be, their economic, social and psychological impact makes them unsustainable. With Austria and Denmark already joining China in easing restrictions and death rates declining in several European countries – including Italy and Spain – just 6 to 8 weeks after their first cases, it is tempting to think the pandemic might end by the autumn. But epidemiologists warn against rushing to restore normality too quickly. Simply ending the lockdowns and letting people return to their former lives risks the possibility of a second pandemic as the virus infects vast numbers of fresh victims. The Spanish Flu roared back just a matter of months after it first struck in 1918, claiming even more victims than before. Instead, epidemiologists are calling for staged lifting of lockdowns, backed by extensive testing and “contact tracing”, where those who comes into contact with an infected person are traced and monitored. Some countries – including the UK – are also considering “immunity passports”, where those who recover from Covid-19 are given certificates showing they cannot pass on the virus and return to normal life. Many experts are deeply sceptical about such schemes, however. They point out there are still doubts about the reliability of the tests required, and also about how long immunity lasts. They also fear it could encourage people to deliberately become infected, simply to return to work. There is no doubt that one day the pandemic will end. What no-one can say is just what state the economy and society will be in when that day finally comes. <em>Robert Matthews is Visiting Professor of Science at Aston University, Birmingham, UK</em>