Unlocking the Value of Antiviral Drugs for COVID-19 and Beyond

13 July 2022 | Wednesday | Opinion | By Dr Paul Shea Tat Ming, Specialist in Geriatrics


As of 23 June 2022, Asia has reported over 130 million COVID-19 cases[1] and 1.2 million deaths[2] from the time the first case was detected in the region. More than 3.1 billion doses of vaccinations[3] have been administered to populations in the region but until now, mutations including the Delta and Omicron variants continue to spread across the region. It is clear that the response to COVID-19 is complex and challenging, and that a range of medicines and vaccines is needed in our continued fight against COVID-19 and future pandemics. Dr. Paul Shea Tat Ming, Specialist in Geriatric Medicine, shares his views on the current COVID-19 treatment landscape and the importance of treatment modalities in response to COVID-19 and potential large-scale pandemics.
Dr Paul Shea Tat Ming, Specialist in Geriatrics

Dr Paul Shea Tat Ming, Specialist in Geriatrics

The State of COVID-19 in Asia Pacific

Across Asia, over 130 million[1] COVID-19 cases have been reported across 39 countries from the time the first case was detected, resulting in 1.2 million[2] deaths as of 23 June 2022. Although more than 3.1 billion[3] doses of vaccinations have been administered to populations in the region in the last two years, continuous mutations, including the Delta and Omicron variants, have continuously challenged existing pharmaceutical and non-pharmaceutical interventions. The most recent fifth wave of COVID-19 in Hong Kong started in January 2022 and is the worst yet. This suggests that adequately responding to COVID-19 must include several robust approaches as vaccination alone is insufficient to curb the pandemic.

More recently, markets including Singapore and Taiwan have reported local cases with Omicron BA.4 and BA.5 variants. In early June, Singapore’s health minister warned that the city-state could expect a new Omicron wave in July or August as COVID-19 antibodies begin to wane.[4]  The emergence of new sub-variants across the region is a sign that the number of cases will inevitably increase, so early treatment is critical to prevent the disease from worsening and patients with mild and moderate COVID-19 can recover in outpatient settings.  For this reason, it is critically important that we have a range of medicines and vaccines as part of disease control which can prevent disease progression and reduce the risk of death.[5]  

COVID-19 treatment landscape and the role of antivirals

More than three years since the first case of COVID-19 was identified, it is clear that the response to COVID-19 is complex and challenging. Vaccines are undoubtedly the backbone of any pandemic response as they act as the first line of defense for the prevention of COVID-19. Were it not for vaccines, markets in Asia Pacific would not have taken a step toward endemic living with COVID-19. However, the presence of new strains with immune escape and increased transmissibility of newer subvariants such as Omicron BA.4 and BA.5 have spotlighted the need for multiple therapies across the COVID-19 treatment landscape due to a variety of patient, pathogen, and environmental factors. As the virus continues to mutate, we can expect likely episodes of breakthrough infections and surges in COVID-19 cases to occur. The presence of new strains and subvariants as well as populations who remain unvaccinated mean that antiviral therapies are necessary complements to vaccines in the continued fight against COVID-19.[6]

Not a substitute for vaccines, antiviral therapies play a significant role in the early treatment of patients with mild or moderate COVID-19 as this reduces the risk of hospitalization and death in patients. Though other therapies are available in-hospital settings under medical supervision, antivirals that can be taken orally in outpatient or home settings have become increasingly important as we enter this new phase of endemic living with COVID-19. Rather than devote intensive medical resources to patients in clinical settings, patients who are detected early with mild or moderate symptoms and are eligible for the indications can be given oral small molecule antivirals to limit disease progression and recover at home. This approach will help to reduce the strain on medical resources and the possibility of community transmission.

Additionally, drug-drug interaction (DDI) is a key consideration for physicians when prescribing treatment for patients with polypharmacy. Physicians like myself who work closely with patients living with co-morbidities regularly perform additional tasks such as checking DDI lists and adjusting doses to ensure that any new medication we add will not interact with existing medication regimes. Being able to prescribe antivirals without carrying out these additional steps will facilitate prompt treatment access for patients who need it most and urgently.

When Hong Kong experienced its fifth COVID-19 wave earlier this year, outbreaks were detected across several hundred care homes for the elderly, which overwhelmed Hong Kong’s isolation facilities and further strained the city’s overloaded healthcare system. Despite having early, privileged, and sustained access to COVID-19 vaccines, there was still a large vulnerable group that remained sub-optimally covered.[7] This included the elderly and immunocompromised, many of whom had co-morbidities such as ischaemic heart disease, diabetes mellitus, and chronic kidney disease which puts these groups at significant risk of complications.

Oral COVID-19 antivirals were introduced in Hong Kong in February this year for use in patients who did not respond well to conventional symptomatic treatment, or who met the criteria for antiviral treatment. Elderly and vulnerable patients were prioritised.[8] We found that when these patients received antivirals within the first five days of the onset of symptoms, hospitalisation and mortality rates were significantly reduced. This is an encouraging sign that these oral antivirals may be another reliable tool in the COVID-19 response, especially for at-risk groups including the unvaccinated, the elderly, and those with comorbidities, who continue to bear the brunt of this pandemic. Particularly, oral antivirals with no known DDI have made it easy for physicians to prescribe and administer treatment to patients with existing chronic medical conditions. Therefore, it is critical to call for expanding access to antivirals so that more patients can manage the disease within the five-day golden window from disease onset through faster access to the needed treatment.

A range of tools facilitate a return to care in a post-COVID world

The pandemic impacted healthcare delivery for countries around the world. It forced us to postpone non-elective procedures such as knee and hip replacement surgeries to divert resources to the pandemic response. As outpatient appointments were also cancelled, the disruption resulted in noticeable deterioration of patients with chronic diseases due to medication non-compliance and poor overall health management.[9]

Population-based rollouts of COVID-19 vaccines and the introduction of antivirals have facilitated a return to normal operations in many healthcare settings as people have better confidence in being outside of the indoor venues to resume pre-COVID-19 lives. These include the resumption of care services such as in-person routine check-ups, receiving routine care, and clinics or hospital visits. However, we are not out of the woods yet. With more projected waves ahead of us[10], it is crucial to build on the progress made with the first generation of antivirals for COVID-19. To that end, the scientific community is ramping up efforts to optimize a pan-coronavirus inhibitor[11] and advancing work on a potential next-generation antiviral[12] that targets SARS-CoV-2. Research is also going on to develop molecules aimed at different targets in case antiviral resistance emerges.

The Way Forward in a post-COVID world

As evidenced by the last three years, we need to develop a more holistic strategy to tackle large-scale outbreaks. From a scientific point of view, we must consider other modalities besides vaccines to contain any pandemic. Vaccines have been proven to prevent infection, serious illness, and death but breakthrough infections do happen and there are those who cannot mount appropriate antibody responses or remain ineligible for vaccines. As such, complementary measures are needed to treat these vulnerable populations and prevent the virus from spreading. Furthermore, preventing infections from becoming more severe by increasing the effectiveness and supply of antivirals will help reduce unnecessary burdens to health systems and the undue suffering of infected patients. Managing these measures will be key to preparing for the next pandemic.

As we look to the future and continue our fight against COVID-19, it is also crucial for the scientific community to continue investing in research and development to ensure that we have a range of tools to combat future pandemics. As a community, we have made promising progress and I am hopeful that there will be a breakthrough as long as we continue to lend our expertise in tackling existing and future pandemics.

 

Ref 

1 Asia Pacific COVID-19: Humanitarian Data Portal. (2022). Retrieved 23 June 2022, from  https://interactive.unocha.org/data/ap-covid19-portal/impact-crisis.html

2 Asia Pacific COVID-19: Humanitarian Data Portal. (2022). Retrieved 23 June 2022, from  https://interactive.unocha.org/data/ap-covid19-portal/impact-crisis.html

3 Asia Pacific COVID-19: Humanitarian Data Portal. (2022). Retrieved 23 June 2022, from  https://interactive.unocha.org/data/ap-covid19-portal/impact-crisis.html

4 Leo, L. (2022). Singapore could expect new Omicron COVID-19 wave in July or August as antibodies wane: Ong Ye Kung. Retrieved 23 June 2022, from https://www.channelnewsasia.com/singapore/new-omicron-wave-possibly-emerging-july-august-covid-19-antibodies-wane-ong-ye-kung-2729606

5 Merck and Ridgeback Announce New Data For Investigational LAGEVRIO™ (molnupiravir) From Phase 3 MOVe-OUT Study - Merck.com. (2022). Retrieved 24 June 2022, from https://www.merck.com/news/merck-and-ridgeback-announce-new-data-for-investigational-lagevrio-molnupiravir-from-phase-3-move-out-study/

6 Robinson, B., & Tai, A. (2021). Why we still need drugs for COVID-19 and can't just rely on vaccines. Retrieved 23 June 2022, from https://onlinelibrary.wiley.com/doi/10.1111/resp.14199

 

7 Burki, T. (2022). Hong Kong's fifth COVID-19 wave—the worst yet. Retrieved 21 June 2022, from https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00167-0/fulltext

8 Coronavirus: nearly 10,000 Hongkongers treated with oral antivirals. (2022). Retrieved 20 June 2022, from https://www.scmp.com/news/hong-kong/health-environment/article/3171122/coronavirus-nearly-10000-hongkongers-treated-oral

9 Teo, J. (2022). Hospitals will take months to clear backlog amid Covid-19 pandemic: Kenneth Mak. Retrieved 23 June 2022, from https://www.straitstimes.com/singapore/health/hospitals-to-take-months-to-clear-backlog-says-singapores-director-of-medical

10  Sandhu, H., Rai, A., Huda, F., Ravi, B., Basu, S., & Mammen, K. (2020). Post COVID-19 return to “new normal” in surgical care: joining the dots. International Journal Of Surgery: Global Health, 4(1), e45-e45. doi: 10.1097/gh9.0000000000000045

11 Dolgin, E. (2021). The race for antiviral drugs to beat COVID — and the next pandemic. Retrieved 15 June 2022, from https://www.nature.com/articles/d41586-021-00958-4#ref-CR2

12  Whitlock, J. (2022). https://cen.acs.org/business/next-generation-COVID-19-antivirals/100/i11. Retrieved 15 June 2022, from https://cen.acs.org/business/next-generation-COVID-19-antivirals/100/i11

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