Are Covid-19 treatments working? – Expert Q&A

Timely treatment for Covid-19 is front of mind for many people, in light of NZ’s mounting hospitalisation and death statistics.

Now that Aotearoa has 960 people in hospital and a steepening death curve from Covid-19, how are people being treated for the disease at present? What’s working against the Omicron variant (and what’s not) – and when are new treatments anticipated to arrive in the country?

The SMC asked experts for an update on Covid-19 treatments in New Zealand. 

Dr Colin McArthur, Intensive Care Specialist, Auckland City Hospital, comments:

What Covid-19 treatments are being used in NZ now, and how are they working out?

“Treatments with proven efficacy for COVID-19 are in two broad areas: those directed against the virus itself (antivirals) and those which modify the body’s response to the infection (immune modulators). In general, antiviral treatments need to be given early (within 5 to 7 days of symptom onset) to be of benefit, while immune-modulating treatments are only appropriate for patients who are hospitalised and need oxygen or higher levels of breathing support.

“In New Zealand, we have the intravenous antiviral drug remdesivir, which has been used for patients hospitalised within the first 7 days of illness. It is also effective at reducing the risk of hospitalisation in those at high risk, but early administration of an intravenous drug outside of hospital is difficult. Processes are being established now to provide this treatment in the community for those at the greatest risk of deterioration, as supplies are limited.

“The oral antiviral agents, Paxlovid (a combination of nirmatrelvir and ritonavir) and molnupiravir, are also of benefit to those at higher risk of hospitalisation, and are expected to be available over the next few months. These treatments need to be commenced within 5 days of symptom onset to have an effect – and so good systems for early diagnosis of COVID-19 after symptom onset, and prompt prescription and dispensing, will be important.

“Another treatment aimed at the virus are monoclonal antibodies, which help the body identify and eliminate the virus. We have supplies of Ronapreve (a combination of casirivimab and imdevimab) in New Zealand currently, but unfortunately although this is effective against earlier variants such as Delta, it is not active against Omicron.

“Some monoclonal antibodies such as sotrovimab do retain activity against Omicron, but these are understandably in high demand globally and are not yet available here. These treatments are also given by injection and their use pre-hospital where they are most effective has similar challenges to remdesivir (explained above).”

Note: Australian researchers have also found Sotrovimab may cause drug-resistant mutation. They say this treatment’s increased use requires increased surveillance to help detect potential resistance earlier.

What triggers a need for Covid-19 treatment?

“Treatment in hospital depends on a patient’s severity and rate of progression. Those with mild disease need no specific COVID treatments, but low doses of blood-thinning treatment may be commenced because COVID-19 can cause problems with blood clots. When there is evidence of lung inflammation (pneumonitis), more intense blood-thinning therapy may be used.

“Once there is a sustained need for additional oxygen, immune-modulating treatment is begun, initially steroid treatment with dexamethasone. If there is further deterioration, tocilizumab, or more recently barcitininb, is added. Both of these drugs block parts of the inflammatory response. As lung function worsens, higher flows of oxygen are provided. Additional assistance with breathing can be given with a sealed mask to provide additional support, and in some severe cases mechanical ventilation – via a tube into the lungs – may be required.”

How effective are current treatments against Omicron?

“An important caveat with specific COVID treatments is that we don’t know if the Omicron – or other variants – have an impact on their effectiveness because all were studied before Omicron came on the scene. This is a known issue for the monoclonal antibodies, many of which are less effective because they were designed to attach to the original SARS-CoV-2 spike protein. We also know that Omicron is a less severe variant and so treatments given to reduce the risk of severe disease need to be highly-targeted to those at the very highest risk to be beneficial. However, although not known for certain, it is less likely that other treatments – such as the antiviral drugs and especially the immune-modulation therapies – will lose effectiveness.”

No conflict of interest declared. 

Dr Michael Maze, Senior Lecturer, Department of Medicine, University of Otago, Christchurch, comments:

What is important to understand about COVID-19 treatment?

“COVID is a disease with two phases of illness – and these are important to understand when thinking about treatment. As more people are hospitalised due to COVID-19 it is worthwhile for everyone to understand a bit more about treatment options. The first key aspect to understand is that there are really two phases to this illness – the early stage, for around 5-7 days when we are teeming with the virus and feeling unwell. After about the first week, the body begins to win the fight against the virus and the amount of the virus in the body drops dramatically. Most people will get better at this point – except the few who don’t.

“This group enters the second phase of their illness when the body’s immune system becomes over-activated. The inflammation that this over-reaction from the immune system causes is the main reason that some people end up very sick from COVID. For those of us who are vaccinated and have few or no existing medical issues – the risk of going on to the second phase of the illness is very, very low. However for those who are unvaccinated, are very elderly, or have severe underlying medical conditions, the risk is considerably higher.

“The treatments for COVID-19 vary according to which phase of the illness we are in. If we can attack the virus early in the first phase the hope is that by limiting the amount of virus in our body (or viral load) it will limit the amount our over-exuberant immune system gets turned on. Later in the illness, attacking the virus is much less useful as the body has basically cleared it already. When we get really sick in the second week of the illness, we need treatments that try and turn off the immune system.

How does COVID-19 treatment work?

“In New Zealand we got early access to the drugs that are most useful in the second phase of illness – drugs that turn down the volume on the inflammatory immune response. These are drugs that we use for auto-immune diseases such as dexamethasone and tocilizumab. These have been shown – in the minority of patients who end up in hospital in the second phase, who are in the inflammatory phase of the illness – to speed recovery and reduce the chance of dying. Our hospitals have good access to these medications and have been using them for some time now.

“Finding drugs that work during the first phase of COVID-19, to reduce the chances of going on to the second phase, has been harder. Initial treatments – such as using plasma-containing antibodies from patients who had recovered from COVID-19 or some of the re-purposed antivirals – failed in trials. In the last year however, there have been a range of trials that have changed the landscape – the key breakthrough was working out that these drugs needed to be given early in the illness – certainly within the first 5-7 days but probably the earlier the better.

“Treatments that have been now shown to help when given early, include anti-viral medication such as nirmatrelvir (paxlovid), molnupiravir and remdesivir – which kill the virus directly and stop it replicating. Targeted antibodies that enhance the body’s immune system early in the illness and help the body take care of COVID more efficiently have also been shown to help – but these can only be given by injection, which is a lot more complicated when it comes to scaling up delivery. Both these groups of drugs have been shown to reduce the viral load and consequently the numbers of people going on to the second inflammatory phase. This leads to fewer people ending up in hospital and probably (although not proven) fewer deaths. Until now, we really haven’t had the oral drugs in New Zealand and the ones by injection have been hard to deliver in a scaled-up way. But the game is about to change with oral antiviral drugs nirmatrelvir and molnupiravir arriving in the next few months.

Oral antiviral drugs change the game

“So, when these new oral antiviral drugs arrive, we will need to think differently about COVID. For most of us, it is probably OK to take a RAT test, hunker down and just wait to get better. We don’t need treatment. But if we can get early treatment to those who are at risk of progressing to severe COVID then we can change the trajectory of the illness and prevent them dying. The key is to recognise who is most at risk of getting very unwell and then prioritise early diagnosis and delivery of treatment to these people.

“That will require a change in approach. We know RATs often take some days to turn positive, and then due to the numbers of people testing positive it can take another day or two for primary care teams to get in touch. If you are in that vulnerable group, then these days matter and delays will reduce the effectiveness of the medication. The approach we will need to take is to focus on identifying those at risk of severe illness, provide good access to PCR testing (which although slower to process can turn positive earlier in the illness than RATs), and get systems for fast delivery of antivirals.

“I think it is important that people who think that they might be at greater risk of progressing to severe COVID – those who are unvaccinated, immunosuppressed, very elderly or with underlying medical problems – are aware of how the important it will be to get early diagnosis and begin rapid action once anti-viral medication has arrived. If at-risk Kiwis are aware, then they can be pro-active about getting tested and seeking treatment.”

Conflict of interest statement: “I’m a member of the Ministry of Health’s Therapeutic technical advisory group – although my comments here are my own and unrelated to that work. Here I am speaking as an infectious diseases expert at the University of Otago.”