COVID-19 five years later: successes and remaining challenges

When COVID-19 emerged in early 2020, the scientific community moved quickly to identify the novel pathogen and began development of a prototype vaccine using messenger RNA (mRNA) technology. Within one year, mRNA vaccines were delivered to countries and healthcare systems, and vaccines using other technologies were released soon after, helping prevent millions of deaths.1 Concurrently, researchers developed antivirals and other therapies to provide additional options for patients at higher risk of severe illness.2

Despite advances that helped reframe the COVID-19 landscape, many countries continue to feel the impact of the disease. The World Health Organization (WHO) reported an estimated 2,860 COVID-19-related deaths worldwide from 15 December 2024 to 12 January 2025.3 New variants continue to emerge and cause periodic spikes in emergency room (ER) visits and hospitalisations among the elderly and pose challenges in managing COVID-19 infection in people who are immunocompromised.4,5 Although the surges are becoming smaller, COVID-19 still poses a substantial threat.6

People who are immunocompromised – which includes the elderly and those who take immunosuppressive treatments for cancer, HIV, or after an organ transplant – are another high-risk patient population.9,10 About 6.6% of adults in the US have immunosuppression, which is more than twice as high as the previous decade (2.7%).11 A recent study found that severe COVID-19 cases accounted for about two-thirds of the $310m in hospitalisation costs for immunocompromised patients for a first COVID-19 hospitalisation in 2022.12

Racial and ethnic disparities in healthcare have long been a global problem.15,16 The pandemic exposed these gaps that contributed to comparatively higher infection rates and more severe illness and hospitalisations in certain minority groups during the height of COVID-19.17,18 Some of these groups continue to take on a disproportionate burden from the disease. A recent US survey found that Black and Hispanic people experience more bias (ie, different care as well as discrimination during care) and often lack access to adequate COVID-19 care compared to White people. In particular, individuals diagnosed with long COVID-19 were more likely to perceive bias in their care than those with COVID-19 without long COVID-19.19,20

During the pandemic, real-world evidence (RWE) complemented randomised, controlled trial (RCT) data to help identify potential COVID-19 therapies for clinical practice. While most current global guidelines recommend antivirals as effective interventions to reduce the risk of disease progression and death for hospitalised adults, some healthcare providers (HCPs) may ‘watch and wait’ for symptoms to progress before prescribing an antiviral.1 More efforts are needed to protect older and immunocompromised populations through earlier diagnosis and treatment of COVID-19.6

The endemic presents opportunities for strengthening health systems to support comprehensive, evidence-based COVID-19 care both inside and outside the hospital. The scientific and medical communities will be called on to develop new strategies to bolster the resilience of HCPs and minimise the risks of severe COVID-19 outcomes for high-risk populations. At the same time, scientists and national health systems continue to monitor for emerging COVID-19 variants that may cause severe disease or escape protection from vaccines and current treatments. In this era of rapid technological advancement, researchers will have an opportunity to leverage AI-enabled RWE to inform the quality, safety and effectiveness of therapeutic approaches for COVID-19 and other potentially dangerous viruses that may pose future threats to global health.