MANDATORY reporting and isolation following a positive COVID-19 case are now things of the past, however GPs are being urged to make sure vulnerable patients in their practices understand how important early COVID-19 treatment can be.

Associate Professor James Branley told InSight+ that ongoing waves are expected and there are still challenges ahead.

“There is still an ongoing challenge to COVID management and keeping our recommendations based on scientific information is important,” he said.

Associate Professor Branley is co-author of one such piece of scientific information – a narrative review of early treatment medications, published in the MJA.

The review outlines the current modes of action that are approved in Australia, including nirmatrelvir plus ritonavir, remdesivir, molnupiravir, inhaled corticosteroids and monoclonal antibodies with specificity for COVID-19.

Study finds molnupiravir doesn’t reduce hospitalisations and deaths

The evolution of mRNA viruses is rapid and treatments come and go after more extensive scientific reviews.

Just last week, a preprint preliminary analysis from the United Kingdom found molnupiravir did not reduce already low hospitalisations/deaths among higher risk, vaccinated adults with COVID-19 in the community. However, it did result in faster time to recovery and reduced viral detection and load.

“We don’t yet know whether molnupiravir had activity and then lost it or whether its activity was never as good as we thought,” Associate Professor Branley told InSight+.

“Real-world data is what we have been lacking. It’s good to get real-world data that confirms or refutes whether drugs and treatments are effective or not.”

According to the lead of the ASCOT ADAPT COVID-19 trial, Professor Steven Tong, this real-world data are particularly important when considering the cost effectiveness of some of these treatments.

“If a drug costs … about $1100 for molnupiravir and it’s not reducing hospitalisations but might reduce the symptom duration a little bit, you want to ask the question whether we should be using treatments which are that expensive but which are not making that much difference to at least the hospitalised patient rate?” he said.

Choosing a treatment for vulnerable or ineligible patients

One challenge for clinicians is how to choose the right COVID-19 treatment for each individual patient.

There are several clinical guidelines and flowcharts available from the National COVID-19 Clinical Evidence Taskforce.

“Nevertheless, questions remain regarding which drugs to choose when there are often several correct treatment options available. For example, under current guidelines, some patients can simultaneously qualify for nirmatrelvir plus ritonavir (with medication modification), molnupiravir, and an appropriate [monoclonal antibody] (the latter depending on the variants circulating in the population),” the authors wrote in the MJA review.

The authors provide a simple algorithm based on guidance from the NSW Government Agency for Clinical Innovation to further guide clinicians.

But they highlight that there are still many clinical gaps where there aren’t enough data, including treatment for pregnant and breastfeeding women and for those with liver or renal disease.

“These are the more difficult groups to get clear guidelines for as to how to treat these patients. They’re important groups because many of those same groups are significantly at risk of COVID-19,” Associate Professor Branley explained.

Of particular concern are immunocompromised patients who don’t respond well to the vaccine.

“We’re also seeing … particularly those with haematological malignancies and significant immunosuppression, who are remaining positive for many, many weeks and the virus can still be grown from their specimens,” said Associate Professor Branley.

“That is concerning because that group of patients act as a reservoir in the society for new outbreaks of disease and we have limited ability to clear it.”

According to Professor Tong, the best way to know what treatments work is to include more of these risk groups in trials.

“They can be tricky to do, but it’s still the best form of evidence that we have. So ideally, you’ll get 20 hospitals contributing. And when they have a patient who presents with immunocompromise and with COVID-19, you flip the coin, and you either get 5 days Paxlovid or you get 10 days, as an example,” he explained.

The MJA authors also highlighted that, for those who aren’t eligible for antivirals, inhaled corticosteroids can be effective.

“As a treating clinician rather than in terms of the literature – because the literature is not strong on this – I find that patients respond [to inhaled corticosteroids] if they are getting respiratory symptoms in the early phases of the disease,” said Associate Professor Branley.

Future of antiviral treatments

In the MJA narrative review, the authors highlighted COVID-19 infection consists of two parts – “an initial phase in which patients have an asymptomatic infection or symptoms consistent with a mild to moderate viral upper respiratory disease and, potentially, a later phase of severe respiratory illness in which patients may develop hypoxaemia that can progress to hypoxic respiratory failure,” they wrote.

However, there is now an increasing focus on morbidity, particularly with evidence that suggests organ dysfunction beyond the 2 weeks of the illness as well as long COVID.

Associate Professor Branley said there isn’t yet evidence to suggest antivirals could reduce the chance of developing long COVID.

“But it’s very logical to assume that if you eliminate the virus early in the disease, the impacts of the disease are going to be less,” he speculated.

Part of the problem is not having sensitive tests to determine what causes long COVID.

“As a broad epidemiology, we do know that younger women, for example, are more at risk of long COVID. That’s a population that wouldn’t normally be selected for early treatment with antivirals. So I think we need studies in this area to determine not only the clinical effects of early treatment on prolonged symptoms but also the cost effectiveness of that as a strategy,” he explained.

Treatments are rapidly developing and will grow in the coming months. However, at the moment, early treatment is most effective.

“If the presentation is later, and the treatment is later, then it’s less effective at preventing both mortality and probably morbidity,” Associate Professor Branley concluded.

Caitlin Wright is a Sydney-based freelance journalist and 2022 Copywriter of the Year who writes for communities and organisations that care for others.


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