Living with COVID- the role of antivirals 5 Apr 2022
In the UK, we now seem to be moving into a new phase of pandemic management, with the government aiming to” transition to managing COVID-19 like other respiratory illnesses”. In their recent March 2022 statement, the government attributes this evolution in approach to vaccines and treatments. They point out that while COVID-19 infections and hospitalisations have risen in recent weeks, over 55% of those in hospital that have tested positive are not there with COVID-19 as their primary diagnosis.
Vaccines have undoubtedly been the primary tool in pandemic management, helping to break the linkage between disease, hospitalisation, and death. Nevertheless, for some patients whose immune systems cannot respond fully to vaccination or who experience breakthrough infections other tools are required.
That’s where treatments like antivirals, and monoclonal antibodies come in- to help such patients better manage the disease and reduce their risk of severe outcomes. Importantly, as Professor Penny Ward pointed out in an article for The Telegraph late last year, “These drugs are vital in tackling infectious diseases: indeed, our strategy for pandemics caused by influenza includes the deployment of a range of antiviral medicines, averting the need for lockdowns.”
In the UK treatments currently available for COVID-19 include the antivirals nirmatrelvir (Paxlovid), ritonavir, remdesivir and molnupiravir, and a neutralising monoclonal antibody (nMAb) Sotrovimab. Other monoclonal antibody products include tixagevimab and cilgavimab, usually in combination.
These prophylactic treatment options are available in the UK to those who at high risk of becoming seriously ill from COVID, helping to manage the symptoms more effectively. Eligible patients include those with certain types of cancer, HIV, those who are having chemotherapy, and autoimmune or inflammatory conditions among others. 
One key benefit of such therapies is their ability at least up to this point, to retain activity against new variants and maintain robust treatment options for these affected patients. They may shorten the disease duration, reduce hospitalisations, and if used preventatively by those who have been in close contact with a positive case, might help to reduce onward transmission. 
Interestingly variants and sub-variants of COVID-19 display different and rapidly evolving response characteristics to different treatments.
On the 1st April the COVID 19 Treatment Guidelines Panel announced that for non-hospitalised patients with COVID-19, sotrovimab which had previously been a preferred treatment, for patients with the Omicron BA.2 subvariant it no longer was. Though the product had been successful in combatting the Omicron BA.1 and BA.1.1 subvariants, it had a substantially decreased activity in the their perceived successor, the BA.2 subvariant.5
In addition to the ongoing switching and addition of new medicines in our fight to wrestle control of the Covid-19 subvariants, the doses of products are being modified, generally upwards. The Omicron BA.1 and BA.1.1 subvariants have a decreased susceptibility to both tixageimab and cilgaimab, as pre-exposure prophylactics, necessitating a recommendation to increase the dose of the combination treatment from 150mg to 300mg.5
While we have come a long way since the bleak days of early 2020 in mitigating the risks of the disease, as Dame Jenny Harries points out,” the pandemic is not over and how the virus will develop over time remains uncertain.”
Notably, in parallel with the government’s ‘Living with Covid’ approach, it was also decided to merge the Government’s Therapeutics Taskforce, with the Antivirals Taskforce to “focus on securing access to the most promising treatments for COVID-19” under a single umbrella. 
Certainly, there are many more developments to come which will be needed to be kept under review to ensure that the most promising vaccines and treatments are made available to patients, while monitoring for variants of concern that might shift the dial. As Nature recently reported, pipelines are still brimming with new treatments, with 100 compounds in late phase trials including antivirals, treatments to improve disease symptoms, and of course vaccines. Commenting in the Nature article, Lawrence Tabak, Acting Director of the NIH predicted that the next few months of 2022 are likely to be very exciting in terms of clarity on how to best treat COVID-19. 
The Therapeutics Taskforce will have vital responsibility in the months and years to come, to ensure that it can acquire sufficient supplies of the right treatments, to mitigate the challenges ahead, and ensure that ‘living with COVID’ remains a reality.