The importance of antiviral drugs for COVID-19
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The numbers of people affected by COVID-19 will repeatedly fluctuate over the coming months. However, as more of the population gets vaccines that reduce the risk of developing COVID-19, the virus has fewer and fewer people to infect. Thus, mass vaccination is very important because it carries the potential of making the pandemic a thing of the past. In the years ahead, new vaccines will likely be needed and possibly regular booster shots or regular vaccinations, as is done annually with the flu vaccine.
Until the day that COVID-19 disappears, in the short and medium term it will remain an issue for at least the following reasons:
The rise of mutants
Like all viruses, SARS-CoV-2 can and does mutate—change its shape or structure. The virus does this because, from time to time, small errors occur in the production of copies of SARS-CoV-2. Some of these errors lead to the creation of defective viruses. Other errors inadvertently lead to the creation of mutations that confer an advantage to the virus.
Possible advantages to the virus conferred by mutations can include the following:
- it is more easily spread
- it has the potential to cause more severe COVID-19
- it may be able to escape from natural immunity; that is, people who have previously been infected with the virus and recovered may become infected in the future
- it may be able to escape from vaccine-induced immunity
Strains of SARS-CoV-2 that have mutated and become more troublesome in some way (as outlined above) are referred to by scientists as “variants of concern” (VOC).
Variants of concern
It is plausible that a year or two from now some VOC that can partially evade the protective effect of vaccines could become more numerous. It is therefore crucial that pharmaceutical companies develop second-generation vaccines that can provide a high degree of persistent protection from VOC currently in circulation as well as ones that are increasing in circulation.
These second-generation vaccines need to be developed, tested and manufactured quickly. Despite the challenges of large-scale vaccine manufacturing and distribution, it is possible that some second-generation vaccines could begin to be rolled out late in 2021 and early 2022.
Elements of a strategy to help reduce hospitalization
In the meantime, we need to vaccinate as many people as possible with currently available vaccines in order to reduce the risk of people becoming ill and hospitalized due to COVID-19-related complications. In addition to public health measures and currently available testing and vaccination deployment, here are three potential elements related to biomedicine that can be part of a larger strategy to help reduce hospitalizations from COVID-19:
Easier access to testing
To further reduce hospitalizations, governments need to make testing for SARS-CoV-2 more accessible, particularly in communities and sectors hit hard by COVID-19. Easier access to SARS-CoV-2 testing could help speed up the diagnosis of infected people. People who test positive could be fast-tracked to be screened by a healthcare professional about their exposure to SARS-CoV-2 and the presence of symptoms. The next step could be that they are advised of public health measures to limit the further spread of SARS-CoV-2. However, interventions are needed, particularly for people who are at high risk for developing severe COVID-19.
Stockpile treatments
A key part of a strategy to reduce hospitalizations is to consider the antiviral drugs that are highly effective in COVID-19 clinical trials and that are likely to be approved in the months ahead. Governments can create modest stockpiles of these drugs with bulk purchasing once they are approved. Depending on their performance in clinical trials and on their regulatory approval, these antiviral drugs may include molnupiravir, antibodies such as Regen-CoV and VIR-7831, interferon, and so on.
Selective deployment of treatment and biomedical prevention of SARS-CoV-2
These drugs could be prescribed by doctors who have some expertise in COVID-19, either diagnosing or caring for patients. The patients that could be fast-tracked for access to these drugs would be the ones who tested positive and who are early in the course of COVID-19 and who, in the opinion of a physician, are at high risk for developing COVID-19.
The need for treatment guidelines
Antiviral drugs for COVID-19 treatment and prevention are new, and at this time many physicians do not have experience using them. Once these drugs are approved, ministries of health could bring together a panel of physicians to help craft guidelines for the use of antiviral drugs for selected people who have been diagnosed with SARS-CoV-2 infection.
Further research
Governments could partner with the pharmaceutical industry to launch what scientists call open label clinical trials (where everyone gets an antiviral drug), so that physicians get more experience using these novel drugs. Such trials could be used to compare the effects of different antiviral drugs by randomly assigning people to different drugs. Large open label clinical trials have been used to explore the potential efficacy of repurposed antiviral drugs during the first wave of COVID-19. One such trial found the steroid dexamethasone to be highly useful.
Putting it all together
If deployed early in the course of COVID-19, these antiviral drugs would probably be very useful. In the months ahead, as more people are vaccinated, there will hopefully be less need for these drugs.
Some of the antiviral drugs being developed have activity against SARS-CoV-2 and other coronaviruses as well, at least in laboratory experiments with cells. Therefore, a modest stockpile of antiviral drugs could also be useful in this worst-case scenario: another wave of illness that occurs in the future that is driven by an entirely new coronavirus not previously encountered by humanity. Over the past 18 years humanity has been threatened by three coronaviruses:
- SARS-CoV-1 – 2002 to 2004
- MERS-CoV (Middle East Respiratory Syndrome Coronavirus) – 2012
- SARS-CoV-2 – beginning in late 2019
It is possible that we could again be faced by a coronavirus that is new and causes serious illness in some people.
Between intensified mass vaccination campaigns, continued use of public health measures to restrict the spread of SARS-CoV-2, and the selective deployment of antiviral drugs (once they have been approved), it should be possible to bring the current pandemic under control either later this year or in early 2022.
—Sean R. Hosein
Resource
REFERENCES:
- Editorial. Funders, now is the time to invest big in COVID drugs. Nature. 2021; 592:326.
- Dolgin E. The race for antiviral drugs to beat COVID—and the next pandemic. Nature. 2021;592:340-343.
- Abdool Karim SS, de Oliveira T. New SARS-CoV-2 variants—clinical, public health and vaccine implications. New England Journal of Medicine. 2021; in press.
- Tchesnokova V, Kulakesara H, Larson L, et al. Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants. bioRxiv [Preprint]. 2021.
- Mascola JR, Graham BS, Fauci AS. SARS-CoV-2 viral variants—tackling a moving target. JAMA. 2021; in press.
- McMahan K, Yu J, Mercado NB, et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature. 2021 Feb;590(7847):630-634.
- Jewell BL. Monitoring differences between the SARS-CoV-2 B.1.1.7 variant and other lineages. Lancet Public Health. 2021; in press.
- McCormick KD, Jacobs JL, Mellors JW. The emerging plasticity of SARS-CoV-2. Science. 2021 Mar 26;371(6536):1306-1308.