A medical blueprint for when the next coronavirus strikes

Professor Carl Kirkpatrick has helped edit a new collection of research papers largely focused on COVID-19 and what happens next. The start-point for society, and healthcare, he says, is that something similar will reoccur. He can even estimate when.

“In eight to 10 years, there will very likely be another novel [new] virus,” says the Monash University pharmaceutical scientist. “We've had SARS-COV1 [SARS, 2003], H1N1 [Swine Flu, 2009], MERS-COV [Camel Flu, 2012], and now COVID-19. This current virus will change again, or it may be a different coronavirus, or another novel respiratory virus.”

At the onset of the COVID pandemic, he says, there was no industry, regulatory or government guidance “to help researchers, drug developers, clinicians and policymakers determine the best pathways to either repurpose existing medicines or swiftly develop new medicines to treat people with COVID infections”.

The way forward

The research papers published in the prestigious British Journal of Clinical Pharmacology are, he says, a blueprint for the way forward in the development and repurposing of medicines for respiratory virus patients in the post-COVID era. Currently, there are vaccines but no useful therapies. In the future, these new or existing drugs (or a combination of both) look likely to be used for patients or when vaccines don’t work.

“They are the guidelines for the next coronavirus, next respiratory virus, or the next pandemic that comes out,” he says. “These are the guidance documents we desperately needed in early 2020 – a ‘cookbook’, if you will, of what we need to do, and in hindsight, what we could have done better.”

Tracking the life cycle of a virus

Professor Kirkpatrick leads the pharmacometrics research program at Monash’s Centre for Medicine Use and Safety. He's co-edited the journal’s special edition and contributed papers, as a co-author, examining COVID-19’s highly problematic life cycle. The study was funded by the Gates Foundation and completed in partnership with Certara, a global drug development company.

Professor Kirkpatrick’s specific area of expertise is viral kinetic modelling, where infections, the journey of a virus in the body, the inflammation caused, and the ability of the drug to stop or reduce viral replication by medicines are mathematically mapped.

His pharmacological and mathematical examination of COVID-19 and potential future pandemics began almost 10 years ago with the influenza drug oseltamivir, or Tamiflu. The modelling work undertaken was then used as a blueprint to map a fictional pandemic.

“The questions we were answering then were, what would we need to do to shut a pandemic down, and how many people would we need to treat, and at what dose of oseltamivir,” he says.

Then, still pre-COVID, he was involved in another project on early-phase development of lumictabine for the acute children’s virus RSV, or respiratory syncytial syndrome, which enabled greater insights into the time course of viral replication, and how to optimise drug therapy.

“Treatment needs to be something that can knock the viral load down as quickly as possible, along with other medications that can then mop up that inflammatory soup in the respiratory and other tissues.”

In January last year, COVID-19 hit – and much of this previous work on respiratory viral loads in people, and the life and death of respiratory viruses, was about to come in extremely handy.

Professor Kirkpatrick’s collaborator, Dr Craig Rayner (president of Integrated Drug Development at Certara in the United States), was immediately seconded to a World Health Organisation taskforce. The Bill and Melinda Gates Foundation funded the COVID-19 Pharmacology Resource Centre, which was supported and curated by Certara, with Dr Rayner leading this global program, and Professor Kirkpatrick contributing to the review of proposed COVID compounds for further examination.

The COVID compound claims

As the virus spread exponentially, creating the pandemic, claims were published reagarding certain compounds (drugs or therapies) and their alleged effectiveness against the new coronavirus. These included hepatitis drugs, HIV drugs, ivermectin (a lice or parasite drug), and hydroxychloroquine, a medicine for rheumatoid arthritis, lupus and malaria.

Professor Kirkpatrick’s paper in the journal has used the largest available COVID-19 viral load dataset (data on viral particles inside people) to show the key difference between COVID-19 and other respiratory viruses – which is the time between infection and symptoms.

With flus and other viruses (such as RSV, which accounts for a significant number of children in intensive care units), the time gap is one to three days. COVID-19 stretches between five and 24 days. This means it’s harder to treat the virus early, since symptoms only appear later, which means more people get sick.

As the vaccine rollout in Australia gears up through essential workers towards the public in the next few months, Professor Kirkpatrick knows the vaccines – while critically useful – are not a “silver bullet”.

The current vaccines are from Pfizer and AstraZeneca; Pfizer has 90-95% effectiveness, while AstraZeneca is 70-76% effective, although no direct comparison has been made, and the numbers are continually updated.

Also, viruses change into variants and mutations. Communities will therefore ideally need access to pharmaceutical drugs as well as vaccines to best counter new infections.

“Therapeutics will still be needed in severe infections, or when new strains emerge that are less susceptible to current vaccines,” he says.

“The early hope was that we pull something off the shelf that we already had, like oseltamivir – but we realised there was not one. The vaccine had to come. What we saw in Wuhan, the US and Europe has been dramatic. We also now know we’re going to have to treat people who are sick in hospital.”

Drug combinations may be the answer

The secret, he thinks, may be drug combinations – repurposed and pre-existing antiviral drugs.

“We may be able to effectively treat the virus later in the viral cycle with them. People that are vaccinated are still going to get sick, undeniably. Every year, people who get flu vaccinations still get sick and need ICU support in hospital.

Even if we got 100% of people vaccinated in Australia – which is ideal, but unlikely – or herd immunity (where enough people are vaccinated to halt spread), there are still people who will get sick and need treatment.

“Treatment needs to be something that can knock the viral load down as quickly as possible, along with other medications that can then mop up that inflammatory soup in the respiratory and other tissues.”

Aside from potential combination drugs, he says, Regeneron One – a monoclonal antibody – may become cheaper and more available. That was the experimental drug former US president Donald Trump was given; it binds to active viruses and makes them inactive.

“There is no magic bullet,” he says. “But I believe we’re heading in the right direction to be able to identify a combination product or monoclonal antibody approach that will work.”