Two Years and Counting

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It’s been over two years since the COVID-19 pandemic began. In January 2020, we witnessed the first cases of COVID-19 surface outside of China and, since then, cases have soared along with repeat infection, new strains and a plethora of efforts to research and develop combative therapeutics.

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This research effort into COVID-19 is no more obvious than in the clinical trials industry, with rapid registration of trials in this space since January 2020. These trials have taken various forms, investigating the potential of behavioural interventions, biologicals, devices, dietary supplements and drugs to name a few- but where do we stand today? As vaccines have become a lot more available and some countries have adopted a "live with COVID" approach, where does this set the precedence for future work in human trials?

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Vaccines (BioNTech / Pfizer / Moderna / Oxford / AstraZenica) have certainly proven incredibly effective at providing immunity and in dampening COVID-associated health problems, but the research focus into COVID-19 aetiology and management has taken wildly different forms.

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We've taken both direct and indirect approaches to COVID-19 management and these include therapeutic strategies covering a variety of areas. Here are some of the most popular and impactful strategies trialists have been adopting since the pandemic began.

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Behavioural Interventions

In the interest of public health, low-cost behavioural interventions have been adopted at-scale to help control the virus. Perhaps most commonly, we will all be familiar with behavioural interventions adopted by most governments such as social distancing, mask-wearing, televised educational sessions about virus biology and the finer points of personal hygiene. A number of less well-known and equally important strategies have also been tested at trial to monitor and control COVID-19 transmission and consequences of "long COVID". While these can be incredibly broad in their scope, main focal points lie in: sense rehabilitation, mindfulness, wellbeing, depression and anxiety support, promotion of physical exercise and community support.

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Biologicals

Encompassing a large number of therapeutics, trials involving biologicals have been highly popular and have the propensity to take more targeted approaches, including vaccines designed specifically to interact with the COVID-19 virus itself. We've all observed the incredible successes of vaccine therapy from pioneers in this space (BioNTech / Pfizer / Moderna / Oxford / AstraZenica), but there have been some other highlights in novel efficacious biologicals which are not vaccine-based. These have included some alternative mRNA- and miRNA-based therapies, secretome and plasma therapies and even modified bacterial and viral strains promising the delivery of anti-COVID-19 activity in vivo.

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Devices

Healthcare devices have also evolved during the past two years, too. Mask wearing, at a very basic level, has already been a rudimentary medical device. However, digital and electronic tools have taken wildly different forms in this recent pandemic. Apps and wearables have taken centre-stage here by provisioning rich information and resources to users via their smartphones, tablets or computers. Tools to encourage physical activity regimes, monitor and track symptoms and a variety of new mask and ventilator formats have arisen for efficacy testing.

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Dietary Supplements

The popularity of dietary supplements as affordable agents to potentially fight against COVID-19 has also come into focus. History has already proven to us the importance of Vitamin B12, Vitamin C and Vitamin D (in their various forms) and zinc in participating in human health and immunity, but what of other more novel innovations? We've seen a sharp rise of nutraceutical- and microbiome-centred therapeutics, particularly probiotics, take more emphasis in clinical trials research. While the links between diet, nutrition, the microbiome and immunity make for both a complicated and interesting story in their own right, we are beginning to see strong empirical evidence linking gut-derived signals and metabolites to health, disease and even brain function. The gut has become a crucial consideration in a lot of emerging disciplines and both targeting and manipulating this complex organ through diet, probiotics, antibiotics and even faecal microbial transplantation (FMT) is providing some interesting outcomes, particularly in immunological research.

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Drugs

Over-the-counter drugs already used as inflammatory-dampening agents have been explored extensively during the COVID-19 pandemic. In the rarer cases where COVID-19 impacts significantly on lung functionality and poses a serious threat to life, amelioration of inflammation is key. Glucocorticoids and other targeted anti-inflammatories have been explored extensively in this regard at trial. Reports of the benefits and wider use of drugs such as dexamethasone and colchicine in alleviating inflammatory activity in severe COVID-19 cases are becoming increasingly commonplace. Because of cross-talk between diseases which also have strong inflammatory roots, including arthritis and gout, repurposing drugs for use in COVID-19 is proving incredibly effective. The Food and Drug Administration (FDA) have permitted the use of a number of suitable drugs in extreme COVID-19 cases via emergency use authorization (EUA). EUA-authorised products include anti-inflammatories such as baricitinib and tocilizumab in addition to more targeted SARS-CoV-2 drugs sotrovimab, bamlanivimab and etesevimab. More general anti-virals (veklury and favipiravir, for example) have also shown efficacy during the pandemic through their actions against many viral groups including influenza and coronaviruses.

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Going forward?

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A rich diversity of techniques across many disciplines have been exploited in the last two years to improve our COVID-19 arsenal both directly and indirectly, but with so many potentially useful strategies arising, where does the future of COVID-19 lie at trial? Data indicate that COVID-19 trials interest has taken a dramatic plunge from its first spike in the first quarter of 2020, but while studies are still underway and being picked up by groups worldwide, there is perhaps a new focus on alternative and complementary strategies to already tried and tested drugs. Data from 2020-2021 suggest a small shift in more "lifestyle-centred" management by targeting behavioural, device and dietary supplement research in combination with biologicals, such as vaccines. But will this be sufficient to lead us out of the pandemic once and for all? or will COVID-19 (and management of it) be here for decades to come?

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