Treatment of acute COVID-19 in the community

[Music] Welcome to the Australian Prescriber Podcast, an independent no-nonsense podcast for busy health professionals.

I'm Dhineli Perera, your host for this episode. And joining me today for a 2026 update and refresh on the treatment of acute COVID-19 in the community is Prof Josh Davis. Josh is an infectious diseases (ID) physician at Newcastle's John Hunter Hospital and a clinical trialist and professor of infectious diseases at the University of Newcastle. In amongst his extensive ID experience, Josh was also a past panel chair of the National COVID-19 Evidence Task Force. Prof Davis and author Dr Eliza Milliken aim to hit reset on our community approach to managing this viral infection 7 years on from when it first emerged. A warm welcome to you, Josh.

Hi, Dhineli. Thanks for having me.

So Josh, most people don't need a detailed introduction to COVID-19. However, to refresh our community clinicians, I thought it would be useful to ask you to help us delineate between cases that can be managed in the community versus those that really do need a referral to hospital.

Yeah, and this has changed quite a bit over time as the scope of COVID-19 disease has evolved, but basically the majority, or I'd even say the vast majority of people with COVID-19 don't need hospital admission. COVID-19 can be classified as mild, moderate, or severe based primarily on oxygen saturations, which obviously is not available to people at home, but if they're unwell enough to seek medical care, that can get measured. And mild to moderate illness generally does not need hospital admission. Severe illness where people are hypoxic or have bad respiratory distress often does need hospital admission.

And the other thing that are not in the kind of published definitions of disease severity that often need hospital admission are comorbidities or just general functional decline. So often I see in my role as a clinician, people admitted to hospital with COVID who aren't all that sick from a respiratory point of view, but they may be vomiting, they're elderly and they're off their legs and have a fall and things like that. So it may just be a little, a small thing that tips people over.

Right. So that last part that you mentioned would be taking in the risk factors. Would that be right? So you've got disease severity combined with the risk factors?

Yeah, kind of. What I was trying to get at with the last thing is sometimes people need hospital admission for COVID-19 or indeed influenza or even rhinovirus, not because they're really unwell from a respiratory point of view, but because they're very comorbid and frail, anything can kind of tip them over. That does relate to what you're talking about with the risk factors for severe COVID disease, but that's generally severe pneumonitis that we worry about.

Right. And in your article, Box 1 has some really nice clear definitions of the disease severity. So if readers want to know more about that, they can definitely read up on it. But how did the radiological features fit into this?

Well, again, similar to oxygen saturation, most people don't have a chest X-ray done and most people don't need one. But if people have had a chest X-ray or even a chest CT, the results of those can be taken into account in defining illness severity. So basically, if there's any pulmonary infiltrate visible on imaging, that makes it at least moderate illness. And if there's significant more than 50% of lung involved, that makes it severe illness. But in real life, that is rarely one of the criteria we use because people haven't had an X-ray.

Until they get to hospital, right?

Yeah, exactly.

Let's talk about the risk factors for severe COVID. What, in your experience, have you found to be the most prominent or the most important ones for clinicians to remember?

By far the most important one in terms of the most powerful predictor of poor outcomes is age. And that really swamps out all the others, which we'll talk about in a moment, their comorbidities and immunosuppression. Age turns out to be in lots of publications and large observational studies, a thing that is most likely to predict mortality or need for hospital admission. And that's generally age over 65 to 70 years just because of accumulated comorbidities with age and also immunosenescence. So your immune system not being so good at fighting off pathogens as you get older.

Right. And then beyond age, what other risk factors would you be highlighting here?

I guess the second most important is immunocompromise. And the most common cause for immunocompromise is immunosuppression, as in therapy being given on purpose to suppress the immune system. And that's often in the setting of either an organ transplant or an autoimmune disease that needs immunosuppression such as rheumatoid arthritis or lupus, or finally a malignancy, a haematological or other malignancy that's getting chemotherapy. So immunosuppression or immunocompromise is the second most common important risk factors for severe disease with COVID.

And then the third category is just other comorbidities which in themselves increase the risk. And those are common comorbidities such as congestive heart failure, type 1 or 2 diabetes, chronic renal or liver impairment, obesity, and chronic neurological conditions such as having had previous strokes. It's really all the common comorbidities that we see all the time and that are quite common in the population. But I would rank those as I just have in terms of importance as age number one, immunosuppression 2, and other comorbidities 3.

Lovely. And so the PBS [Pharmaceutical Benefits Scheme] criteria for the therapies actually does utilise these sort of risk factors. And so that in your article, you've got Box 2, which actually nicely lists that out for readers to explore a bit further. Are there any complexities with prescribing using the PBS criteria that you would flag for clinicians to be aware of or is it fairly self-explanatory?

I mean, the criteria are pretty self-explanatory, but the thing I would flag is that these criteria were originally written when COVID was a totally different animal. And they were updated recently, but they still really reflect the state of knowledge about antiviral drugs and their efficacy from a few years ago. When COVID tended to be a much more severe disease, people were less likely to be vaccinated and have had previous COVID. So what I'm getting at here is, these are the criteria that the PBS will reimburse for antiviral drugs, but that doesn't necessarily mean everyone who meets these criteria should get an antiviral drug or are likely to benefit.

That makes sense. So that's where the risk factors and severity that we discussed earlier is more important to be assessing.

Yeah.

So back now in 2026, how do we monitor for COVID? And do we have reliable data on the incidence?

Yeah, look, we have pretty good data. It's not as intensive as it was during 2020 and 2021 with daily press conferences and people telling us the numbers of cases and so on, but there are pretty good data based on a range of surveillance systems. Most of them are based on laboratory diagnosis. So it undercalls the true number of cases because there's a lot of people who get COVID and never get a test done or they get COVID and they might do a RAT [rapid antigen test] test at home and that doesn't enter these numbers generally.

The new Australian CDC [Centre for Disease Control] publishes every fortnight a respiratory surveillance report, and that contains a lot of interesting data about COVID, but also flu and RSV [respiratory syncytial virus] cases. So one thing I was just having a look at the report earlier today that's pretty interesting this year is, it's a pretty good year for respiratory viruses, as in lower incidence than both the 5-year average and 2024 and 2025. So we've had about half the number of COVID cases this year than we did last year and the year before at this stage, and about a quarter of the number of flu cases.

Wow, that's good. I'm happy to hear that. And I feel like my own kids and their illness reflect that too. So I won't get too ahead of myself though. There's still a little bit of winter to go.

That's right. We still could get a late peak.

Yep, that's right. So are the public health units which were quite active during the peak of the pandemic, are they still contactable for guidance in the event of possible outbreaks, for example, in an aged care facility?

Yeah, in certain circumstances, and really specifically that one, aged care facilities, public health units in general are still able to help and interested in helping to control outbreaks. Outside that context, not so much. So in a hospital setting, for example, that's not their jurisdiction, it's the hospital infection prevention control team. And in just kind of community non-institutional, public health now are no longer doing any contact tracing or directly contacting people.

Right. So yeah, very specific to that age and coming back again to the risk factors you talked about earlier. So then, isolation and infection control, these were really points of constant contention and confusion during the pandemic. What is the advice now in the community?

Yeah. Well, I guess the first thing to point out is there are no longer any regulations or rules or laws. That was one of the big problems with – during 2020, '21, et cetera – is that there were these rules that we were obliged to follow and they changed all the time and they were different across different jurisdictions. Now there aren't any rules or laws. There are just guidelines and recommendations, and you're not obliged to follow them.

But they are basically, if you're unwell and you know you have COVID-19, you should stay home until your symptoms are resolved. If you're unwell with a flu-like illness or a respiratory tract infection and you haven't tested, I mean the same thing applies, right? Because it's not only COVID-19 that's contagious to other people. A couple of extra issues, if you know you have COVID-19, you're supposed to avoid going to high-risk areas for 7 days. And that means hospitals and aged care facilities primarily.

Right.

But again, that's not mandated. And then finally, if you have COVID or you have another acute respiratory infection and you need to go out to go to the shops or that sort of thing, you should wear a mask.

Right. Okay. So pretty simple and nothing that's too intrusive and far easier and simpler than what we had to follow. Do you foresee, Josh, the need for us to have an annual COVID vaccine for everybody? So not just those that are considered at risk. Similar to, I guess, to what we see now with the flu vax. And why or why not is that the case?

Yeah, so at the moment, that's not recommended. The Australian Immunisation Handbook recommends that everyone get at least an initial dose of COVID vaccine. But in terms of ongoing annual doses, that's only recommended at the moment for those who are at risk of severe disease. So that's basically people over age 65 or adults who have comorbidities.

Why is it not recommended for young, healthy adults or others? Because the risk of getting severe disease when you catch COVID for those people is vanishingly low, the inconvenience and cost of having to have an annual vaccine is not really justified in those who are at very low risk of severe disease, basically.

There was a lot of talk about developing combined flu/COVID vaccines so that when you get your annual vaccine, you're getting both. None of them have made it to market in Australia. I'm not quite sure why things went cold on that. Perhaps if that comes in, we'll be getting an annual vaccine for COVID. But currently, unless you have specific risk factors or age over 65, it's not recommended to get regular boosters.

Lovely. And I guess that speaks to the fact that things like influenza are a lot more dangerous for the younger cohort of the population.

Yeah.

Hence that continued advice. So when it comes to antivirals, who should have those and when?

Yeah, so I guess I alluded before to the fact that the PBS criteria tell you who can have antivirals. But in my view, most people who are eligible on the PBS criteria probably don't need to take antivirals because their risk of hospitalisation and severe disease, even with all these risk factors, is still really, really low, like less than 1%. However, the people that I think should have antivirals are those who have a combination of risk factors that make them at a very high risk.

So that would mean, for example, they're elderly and they're immunosuppressed and they have 2 or 3 comorbidities, the very pointy end. But the people that just scrape into those criteria, so let's say they're 30 years old and they've got type 2 diabetes that's well-controlled and no other comorbidities, technically that person meets the PBS criteria, but personally I wouldn't be recommending they take antiviral therapy.

That makes a lot of sense. Thank you for explaining that a bit better for us. But how effective are antiviral therapies in treating the new variants of COVID? I guess this is where you touched on the fact that a lot of the criteria and guidelines are based on information from 7 years ago. These new variants, will they work with them?

The short version is they're not very effective. And it's not because of the new variants so much. In terms of the actual antiviral activity in a test tube or in the lab, they still work. So nirmatrelvir–ritonavir (which is Paxlovid), molnupiravir, remdesivir. So they're the 3 antivirals that are available. All of them still work just as well against the current variants of COVID that are circulating (the Omicron variants) as they did against the previous Delta ones.

What's different though is that the chance of getting really sick from these newer variants is much, much lower. And that's due to a combination of population level immunity from vaccination and past infection. And also that these Omicron strains are just less pathogenic. They're much less likely to go down into your lungs and they're more an upper respiratory infection. So yeah, the short answer to that is, these antiviral drugs work just as well against current viruses in the lab, but because people are much less likely to get sick, their potential benefit is much less.

Right. So that kind of leads me onto my next question then, which is really, for example, if we start with Paxlovid and that's the nirmatrelvir with ritonavir, does it actually work? And if so, in whom?

Well, to be honest, it's kind of a controversial question. So the best data we have from this was probably what was published recently, the PANORAMIC trial, which is a big community-based trial from the UK. And that was combined with a Canadian trial called CanTreatCOVID. So they recruited people from the community who had COVID and had risk factors for severe disease. So they were over 50 or they had 2 comorbidities. And basically in both of those trials, Paxlovid was no better than standard care in terms of preventing hospitalisation or death, which was the primary outcome.

Right.

And that primary outcome only happened in 1 to 2% of people. So from that point of view, Paxlovid is not effective. However, we can't comment on its efficacy in those at much higher risk. So these were kind of moderate risk patients. The very high risk patients like the sorts I was talking about before were not included in this trial.

Right.

The other aspect, and it's probably not controversial to say that Paxlovid, and we'll talk about molnupiravir in a minute, but it has similar data. It's pretty clear these days it doesn't really reduce your risk of hospital admission or death if you're at moderate risk. What is a bit more controversial is, does it have any benefits at all? And the PANORAMIC trial showed that people got better a bit faster basically. So their duration of symptoms was less if they took Paxlovid. The problem with that is, it was an open-label trial. So people knew that they were taking Paxlovid or that they weren't taking any antiviral.

Right.

So it's certainly quite feasible that the difference in subjective outcomes were due to placebo effect.

Interesting. And I've also noted that there is an expansion now for Paxlovid to be used in more renally impaired patients, which is available in your article as well in Table 1, and I've noticed in the product info, but I will say not readily available in a lot of the tertiary references just yet.

Yeah, that's been a bit slow for that to percolate through. But yeah, with the initial prescribing information was to not use when the glomerular filtration rate was less than 30 or even less than 50 [mL/min/1.73 m²] initially, I think. But now, there's pretty good data that it's safe to use really at any level of renal function. It just requires dose adjustment.

Excellent. So yes, I would definitely flag that for readers to check out the table, which does guide through that information. So then the other tricky part with Paxlovid, well, that's also controversial now, right? It's not really as tricky as we thought it was at first, but the drug interactions. In your experience, have you seen clinically significant interactions manifest when using Paxlovid?

Yeah, I have a couple of times. Mostly we avoid them because we check the drug interactions before prescribing them, A. B, a lot of the drug interactions – maybe this is what you're implying with your question – are not really clinically significant. Like your statin might be a bit higher in your blood, but that usually doesn't cause anything. However, I've definitely seen some of the one that pops into mind is a patient who has started in primary care on Paxlovid, and they were also taking lercanidipine for hypertension. And they were admitted to hospital because they kept fainting, basically.

Oh, right.

And it turns out, there's a drug interaction and they were just getting hypotensive because of the drug interaction. Yeah.

Yeah. Okay. Interesting.

And there's a bunch of others, but look, most of the time they're sort of not that clinically significant, but there are some drugs where the potential risk is pretty substantial, such as antiepileptics and antiarrhythmic drugs, for example. So definitely important to check before you prescribe.

Excellent. And so that Liverpool COVID-19 Interaction Checker is still your first go-to, Josh?

Yes. So that's still being updated and the best place to look.

Excellent. And I think what I was alluding to is really the fact that when we're talking about a 5-day course, those interactions where a lot of the data had at the time originated from the use in HIV patients, it's not always applicable when you're talking about something that is stopped at 5 days, but it was impossible to separate it, right? So we had to use that same level of caution regardless.

Yeah.

Good to know. Now moving to molnupiravir. Is there evidence really to continue using this even in patients that can't have Paxlovid?

If you'd asked me this a year ago, I would've said no. Molnupiravir just doesn't do anything. But in fact, I don't think that's accurate. The PANORAMIC trial, the one I mentioned that was published recently for Paxlovid, they also did a huge community-based trial enrolling people, randomising people to take molnupiravir or not. It was tens of thousands of people anyway.

Right.

26,000.

Oh, wow. That's huge. That's a huge number.

Yeah, in the UK. And so they were randomised to get molnupiravir or not. They were at moderate to high risk of disease, and it had no effect at all on their hospital admission or death, same as the Paxlovid trial, but they did get better a little bit faster and their viral load dropped a little bit faster. So it was really pretty similar findings in the Paxlovid trial. And in vitro, molnupiravir does actually work as an antiviral.

Right.

So it's got a reputation for being less potent than Paxlovid, which probably isn't quite true. I think nowadays, if they have any benefit, it is small, and they're probably pretty similar in terms of their benefit. The difference is in their side effects and drug interactions and so on.

That's kudos really to molnupiravir, because potentially then if you've got any question about risk, then you don't have to be as concerned that you're not giving anything effective, is what you are saying. If it's comparable really to Paxlovid in the more recent trial data.

Yeah.

That's a good outcome really, that there is this safer alternative that has equal efficacy. Was it open label as well?

Yes, so it was also open label. So again, we don't know what to make of those symptom-based outcomes. The reason I was a bit kind of biased against molnupiravir in my own mind is that the original registrational trial for it, it was called the MOVe-OUT trial, this was 4 years ago, 5 years ago. They reported an interim analysis when they were halfway recruited, and it showed a huge benefit of molnupiravir, like 50% decrease in hospitalisation and death. And on that basis, the drug got registered, but then the trial went on to finish. And in the second half of the trial, there was absolutely zero benefit. And so, the average benefit was 20 or 30%. And it was just really misinterpreted by people that, “Oh, this drug works 30%.” But like I said, I think it's not really that much different to Paxlovid now. I'd love to see big placebo-controlled trials of these things.

Yeah, yeah, for sure.

But that's too complicated to do on a community basis.

And then, what role do the immune-modifying therapies still play in the management of COVID today? So that things like your inhaled or oral glucocorticoids and your JAK [Janus kinase] inhibitors like baricitinib and tofacitinib.

They still have a role, maybe just starting with the inhaled corticosteroids. Early on in the pandemic, there were several trials showing some benefit of inhaled corticosteroids and more recently, there have been trials showing no benefit. So they're not routinely recommended. But what I would emphasise is that anyone who has asthma or COPD [chronic obstructive pulmonary disease], if they're not already taking inhaled corticosteroids and they get COVID, they should start them. Or if they're already taking them, but at a sort of low dose, they should increase the dose temporarily because COVID, like other viruses, usually worsens asthma.

But for someone who doesn't have any indication normally for it, it's no longer recommended to start inhaled steroids if they get COVID. And then for oral or systemic steroids like dexamethasone, they're still recommended for people that have severe disease and are hypoxic. So basically, hospitalised patients who have hypoxaemia, we still generally use steroids in those patients. The caveat is, if people have normal oxygen saturations or only mildly reduced, in the RECOVERY trial that showed this was effective, it was effective for people with hypoxaemia. It reduced their mortality. But if they had normal oxygen saturation, steroids actually increased their mortality in the RECOVERY trials.

So it's important not to just give it to everyone willy-nilly. But if they're hypoxaemic, particularly if it seems that hypoxaemia is due to pneumonitis like lung involvement, which is really rare these days, then steroids are indicated. And then the other more potent immunomodulatory agents like tocilizumab and tofacitinib, they're now still kind of in guidelines, but it's really rare that we need to use them. And that's for people that have progressive pneumonitis despite an antiviral and despite steroids. They're still getting worse and worse and they've got worsening pulmonary infiltrates and hypoxia, for example, that's when we'd give those drugs. And I can only think once or twice in the last 6 months that I've been involved with a patient who's needed that.

Okay. Well, that's more than what I thought you were going to say. I thought you were going to say you haven't used it for years. There's still the odd patient that really has that slow response to those first-line care, standard of care management. Great to know. Well, that's unfortunately all the time we have today. Thank you so much for joining us, Prof Davis.

No worries.

[Music]

Prof Josh Davis reviewed an initial draft of Dr Eliza Milliken's article, Treatment of Acute COVID-19 in the Community, which is available on the Australian Prescriber website.

The views of the hosts and guests on the podcasts are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Josh was a panel chair of the National COVID-19 Evidence Task Force. He is the global co-lead of the ASCOT trial, which is a platform trial assessing various COVID therapeutics and now is expanded to all acute respiratory infections. I'm Dhineli Perera, and thanks for joining us on the Australian Prescriber Podcast.

[This interview was conducted on 28 July 2026.]