When a deluge of coronavirus cases threatened to overwhelm the NHS in March, Covid-19 was a brand new and little-understood disease, causing panic as well as deaths. Hospitals under huge pressure did all they could.
Next time round, if, as everyone supposes, there is a next time, it will be different. In a second wave, or even localised spikes across the nation, the health service will know more about what it is dealing with – and will be better able to help people recover and send them home, say doctors.
First, two drugs have been shown to work to some extent, even though neither is a cure. Most exciting is the revelation that a 60-year-old steroid, dexamethasone, reduces deaths among those who are most sick – saving one in eight lives among those on ventilators and one in 25 of those on other oxygen support. Remdesivir is also useful, reducing the length of the illness.
Mervyn Singer, a professor of intensive care medicine at University College London, is delighted with the dexamethasone result. Covid-19 causes inflammation in the lungs and steroids are already used to reduce inflammation, but he said “medicine is conservative with a small ‘c’”, and some clinicians worried that they suppress the immune system, “so they have generally been used later rather than earlier”. However, the Recovery trial, a global trial into possible treatments, showed how well low-dose dexamethasone works in Covid-19 and it will now become standard of care.
He thinks medical staff will next time feel less anxious carrying out procedures such as intubation, which carries the risk of viral particles shooting into the air. They will also be happier about chest compression and humidification – ventilating patients in a way that allows water vapour to emerge when they breathe.
“We have become more confident in dealing with it. I think we’d be much less paranoid about the risk of infection. Obviously we wear PPE but the people looking after the patients in intensive care have had a low level of infection – no different from the man in the street – which I think is important because there was a lot of fear,” said Singer.
What helps now is the reduced numbers of patients in intensive care with breathing problems. Even in bad flu outbreaks, it was never like the peak numbers for Covid-19. “Normally we’d have two to three of these patients in an intensive care unit. We got up to 62 at one time,” Singer said.
“When you have got one nurse to one patient doing everything we normally do, it’s a very different kettle of fish from one nurse to four patients.”
Epidemics of infectious diseases behave in different ways but the 1918 influenza pandemic that killed more than 50 million people is regarded as a key example of a pandemic that occurred in multiple waves, with the latter more severe than the first. It has been replicated – albeit more mildly – in subsequent flu pandemics.
How and why multiple-wave outbreaks occur, and how subsequent waves of infection can be prevented, has become a staple of epidemiological modelling studies and pandemic preparation, which have looked at everything from social behaviour and health policy to vaccination and the buildup of community immunity, also known as herd immunity.
Is there evidence of coronavirus coming back in a second wave?
This is being watched very carefully. Without a vaccine, and with no widespread immunity to the new disease, one alarm is being sounded by the experience of Singapore, which has seen a sudden resurgence in infections despite being lauded for its early handling of the outbreak.
Although Singapore instituted a strong contact tracing system for its general population, the disease re-emerged in cramped dormitory accommodation used by thousands of foreign workers with inadequate hygiene facilities and shared canteens.
Singapore’s experience, although very specific, has demonstrated the ability of the disease to come back strongly in places where people are in close proximity and its ability to exploit any weakness in public health regimes set up to counter it.
In June 2020, Beijing suffered from a new cluster of coronavirus cases which caused authorities to re-implement restrictions that CHina had previously been able to lift.
What are experts worried about?
Conventional wisdom among scientists suggests second waves of resistant infections occur after the capacity for treatment and isolation becomes exhausted. In this case the concern is that the social and political consensus supporting lockdowns is being overtaken by public frustration and the urgent need to reopen economies.
The threat declines when susceptibility of the population to the disease falls below a certain threshold or when widespread vaccination becomes available.
In general terms the ratio of susceptible and immune individuals in a population at the end of one wave determines the potential magnitude of a subsequent wave. The worry right now is that with a vaccine still many months away, and the real rate of infection only being guessed at, populations worldwide remain highly vulnerable to both resurgence and subsequent waves.
Early on, he and colleagues at UCL realised fewer patients needed ventilation than had been forecast. The assumption that the UK would need 18,000 ventilators when it had 8,000 was one of the reasons it was thought the NHS would be unable to cope with the epidemic – and that led to the lockdown.
But only half of the sickest patients were intubated and put on a machine, while just as many have been given other help with their breathing, such as with the use of a Cpap (continuous positive airway pressure) mask. The long-term outcomes are better.
Clinicians also now have more idea of which patients are likely to become sickest. There was a lot of talk earlier on about the “cytokine storm” triggered by the patients’ immune system going into overdrive and attacking its own cells. “If you look at the data, it isn’t particularly high,” Singer said.
There is a hyper-inflammatory reaction from the body, but it manifests in a different way and can be measured by a standard inflammatory marker called C-reactive protein, or CRP. “It’s part of the body’s host response. It goes up hugely in Covid, whereas cytokine levels don’t go up very much,” he said.
It means a patient’s CRP level can be checked on arrival in hospital. It is the patients who are more hyper-inflamed who are more likely to die. “We can target those patients more or less as they come through the door,” said Singer.
One of the big and alarming surprises has been the damage Covid-19 does to the heart and circulatory system. “There is a really increased risk of clotting, probably due to damage to the blood vessels,” said Prof Sir Nilesh Samani, the medical director of the British Heart Foundation.
“The virus attacks the lining of the blood vessels and makes them more likely to clot.”
People who have had heart attacks or strokes are more vulnerable to the virus, which can also cause them in sick patients. “The heart attacks are peculiar,” said Samani. “It is the smaller arteries downstream that are affected, where the inflammation is more acute.”
One small study looking at the lungs of people who died, published in the New England Journal of Medicine, found they had nine times as many blood clots as people who died from swine flu (H1N1).
Knowing the danger, many hospitals are now giving those at risk anticoagulants and antiplatelet therapy soon after admission. These are drugs that thin the blood, making clotting less likely.
“The lesson we have learned is that we should treat these people before they have the clot,” said Samani. The risk can be measured by looking at the levels of D-dimers in the blood. These are proteins – the leftovers from the normal clotting of blood when people have a wound that heals, for instance. But high levels can indicate a clot is forming.
The British Heart Foundation, together with the government’s National Institute for Health Research, is supporting six major research programmes to discover more about the effects of the virus. These will combine data from hospitals, information about our health and lifestyle, genetic studies, and imaging and artificial intelligence techniques.
That research, and much more in other fields, will help find the optimal way to treat Covid-19 patients and reduce the death rate when – and if – it returns.