How far away are researchers from an effective treatment?

SCIENTISTS are in a race against time to better understand the novel coronavirus that is wreaking havoc the world over.

Their findings will help shape the trajectory of the pandemic – and determine how quickly it can be brought to a close.

“When this began, the word I’d use to describe how we were working is desperation,” Nick Cammack, therapeutics accelerator lead at the Wellcome Trust, told The Sunday

Telegraph. “But increasingly there is this spirit of collaboration … science is the exit strategy.”

So what have researchers found out about the disease so far? And how far are we from an effective treatment?

Symptoms

In early January the World Health Organization issued an alert warning that a “pneumonia of unknown cause” had been identified in Wuhan, China. It said the clinical signs of the mystery illness were mainly fever, with a few patients struggling to breathe.

Since then, the global case count has surpassed one million, though experts estimate that millions more people have been infected but not tested, and the symptom list has grown.

We know, from the WHO’s mission report from China at the end of February, that 80 per cent of patients will have mild symptoms, while roughly five per cent will require critical care.

The study of 55,000 patients also suggested that 88 per cent had a fever, 68 per cent a dry cough and 38 per cent experienced fatigue. Fewer than 20 per cent of people had difficulty breathing, a sore throat or headache.

But more and more evidence has emerged suggesting that taste and smell deprivation is another common symptom, often in otherwise asymptomatic carriers.

Almost 60 per cent of people report these symptoms, according to a team at King’s College London, who have developed an app to track symptoms.

Of 1.9million app users, 3,000 have gone on to be tested, allowing researchers to use machine learning to develop a model which identifies the symptoms that are most predictive of returning a positive result.

“Loss of smell stood out as the strongest predictor of a test being positive – it was stronger than cough and fever, though these were also important,” said Professor Tim Spector, the lead researcher. “I suspect it wasn’t mentioned earlier because people weren’t asked about it.”

Treatment

Identifying effective treatment options is essential to reduce both the death toll – which is nearing 60,000 – and the average time spent in hospital.

But developing new drugs from scratch and proving their safety and efficacy is a long and complicated process. It can take years, time the world does not have. Experts say that the most promising option right now is to repurpose existing drugs.

In mid-March the WHO launched a “megatrial” called Solidarity in 10 countries to test four already approved treatments. The French firm Inserm has started a trial called Discovery and in the UK, talmost 1,000 patients from 132 different hospitals have been recruited to join the Recovery trial of three potential therapies led by the University of Oxford.

Remdesivir

This broad-spectrum antiviral was originally developed by Gilead Sciences to combat Ebola, but it showed no effect during a trial in the Democratic Republic of Congo.

However in 2017, researchers in the US showed remdesivir inhibited the coronaviruses that cause SARS and Mers in test tube and animal studies, and it has been tipped as one of the most promising options.

The drug works by disrupting the virus’s ability to replicate and it attacks a key viral enzyme, not the human cell, so has a targeted effect.

“The big challenge with remdesivir is it’s intravenous, so you’ve got to be in hospital – you can’t be handing this out over the counter,” said Dr Cammack. Experts hope that within the next month it will become apparent whether the drug works.

Chloroquine and hydroxychloroquine

These malaria treatments were originally tested during the Second World War and, unlike remdesivir, would be used for patients in the very early stages of a coronavirus infection.

The treatment was used to treat patients during the SARS outbreak in 2002 to 2003. It is also cheap and easy to manufacture so could be widely distributed, even in weaker health systems.

The drugs are included in all three large-scale trials.

Wellcome is also working with the Bill and Melinda Gates Foundation to identify whether they could be given to healthy people at risk of exposure, for instance health workers or contacts of confirmed cases, to offer some protection ahead of picking up an infection – a bit like a vaccine.

Dr Cammack said it would be roughly six months before we see conclusive results.

Ritonavir and lopinavir

This is a combination drug used to treat HIV patients. It works by inhibiting the enzymes required for the virus to replicate, and experts hope it might have a similar effect on SARS-CoV-2.

“The best place for this is when someone is already sick, either at home or in the hospital,” said Dr Cammack. “There are some side effects, for instance diarrhoea, so you wouldn’t want to give it to otherwise healthy people as a preventive drug.”

Early in the outbreak, doctors in Thailand reported success in treating patients using a combination of HIV drugs alongside oseltamivir, a drug sold as Tamiflu to treat influenza. But a study in China found “no benefit was observed with lopinavir – ritonavir treatment beyond standard care”. It is included in the Solidary, Discovery and Recovery trials.

Anti-inflammatories

In the late stages of a coronavirus infection patients can experience massive inflammation, known as a cytokine storm, as their body goes into overdrive to fight the infection.

Included in the large studies are therapies, including dexamethasone and interferon-beta, which may help reduce inflammation in severely ill patients and could be used in combination with other drugs to treat the coronavirus.