Many aspects of our behaviour and life have been turned upside down by the COVID-19 pandemic. Interestingly, this disease has also caused a significant divide in the population with a small, but very vocal, minority of anti-VAXXERs and conspiracy theorists making very loud noises about the entire way this pandemic has been managed.
Recently, two major trials have brought into question the “go to” oral antivirals against SARS-CoV2. The first trial from the University of Oxford, known as the PANORAMIC trial enrolled just under 26,000 people with COVID-19 given the oral antiviral Molnupiravir, in a placebo controlled trial. After 28 days, 103 people given Molnupiravir had died compared with 96 in the placebo group. This is clearly not statistically significant but shows no significant benefit in reducing mortality using Molnupiravir in people with COVID-19.
The second trial recently published in the Journal of the American College of Cardiology examined the role of Paxlovid, another commonly prescribed anti-viral used in the treatment of COVID-19. This was specifically looking about the potential for any interactions between Paxlovid and cardiovascular drugs. It is well known that sicker patients with comorbid illnesses such as cardiovascular disease and more likely to succumb from COVID-19 or be hospitalised. Therefore, this group of patients are typically on cardiovascular medications.
The study showed drug interactions with commonly used cardiovascular medications such as blood thinning drugs, rhythm controlling drugs, antianginals, some statin drugs and some immunosuppressive therapies used widely in people who have undergone some form of transplantation, in particular, heart transplantation.
We must then ask the question, does this mean that these previously thought to be highly effective antiviral medications should no longer be used for the acute management of COVID-19?
My response would be that the problem is more with the interpretation of the research rather than with the drugs themselves. When COVID-19 first hit the planet, the initial Wuhan strain had around a 3% mortality rate. As the virus mutated around the world, although many of the new strains became more contagious, they became less deadly.
This may have been because the virus was mutating to a less serious strain or equally may have been due to widespread infection and vaccination, the so-called hybrid immunity.
Regardless, the mortality rate quoted in the PANORAMIC trial was around 0.4%, nowhere near the initial 3% mortality rate with the Wuhan strain.
When Molnupiravir was initially studied, this was around the time of the Delta strain which had a much higher mortality rate but was less contagious. Also, in the earlier phase of this trial, Molnupiravir was administered to much sicker patients & appeared to markedly reduce death rates & hospitalisation. As the PANORAMIC trial continued until the middle of 2022, the predominant strain was Omicron which appears less sensitive to vaccination and probably from this trial, to antiviral drugs.
In Australia, it is only suggested that those people over 70 or people with significant comorbid conditions take either Molnupiravir or Paxlovid.
This brings me to the second trial suggesting significant interactions with Paxlovid and cardiovascular therapies. This is very important information and suggests strongly that Paxlovid should be avoided in people with cardiovascular disease who are on medications. If this group of patients develops SARS-CoV2, they probably should be described Molnupiravir, for the reasons stated above.
We have known from early on in the pandemic that SARS-CoV2 tends to affect the very old, the very sick with comorbid conditions or the very overweight and it is my opinion that these are the groups that need booster vaccinations and aggressive antiviral therapy. But, it may well be that in the variants of Omicron, all of these therapies are less effective.
The typical mortality rates of standard influenza are around 0.5% and also appear to occur more commonly in the above groups I have just mentioned. It is my opinion we should now view COVID-19 infections in the same light as influenza.
From all of the evidence, vaccinations and antiviral drugs have some effect but are certainly not miraculous therapies, nor do they protect everyone. Although it appears that the pandemic has now finished, it may well be that like influenza, SARS-CoV2 and its multiple strains will become an endemic virus that we will need to learn to live with. Part of living with this virus, of course, requires ongoing research into developing more effective preventative vaccines and therapies not only to treat the acute illness but also to support and help the 10% of people who appear to be developing Long Covid.