With almost a year since cases of COVID-19 first began to spike, a wide variety of potential treatments have been studied across dozens of clinical trials. Results have often been contradictory or open to various interpretations, and it has proven extremely difficult to find therapies that do provide significant benefit.

Here we assess the treatment landscape for the pandemic, and examine the available data on therapies that will still be crucial as the vaccines are slowly rolled out across the population.

Remdesivir

Remdesevir was among the first treatments to show significant efficacy in patients hospitalised with COVID-19. Two randomised phase III studies originally published in May 2020 showed that the drug can shorten the time to recovery compared with placebo. As a result, the MHRA’s first positive scientific opinion for a COVID-19 therapy was issued on 26 May. However, a trial conducted by the World Health Organization (Solidarity trial) found no impact on survival with remdesivir, calling its use into question – especially given its hefty price tag.

Convalescent plasma

The UK-based RECOVERY trial recently stopped recruiting to its convalescent plasma arm, after an analysis showed it had no impact on the risk of death in hospitalised patients. However, other research has suggested there may be a role for this treatment.

One study showed that mortality differed depending on the levels of antibody titres in the infused plasma, with a lower rate of death in those with high titre levels. Another showed that high-titre plasma infused in the first three days of illness, before patients become severely ill, can reduce the likelihood of severe disease developing. This suggests the specific timing of COVID-19 therapies is an important factor in their efficacy.

IL-6 inhibitors

Tocilizumab and other IL-6 inhibitors have also been widely studied, again with conflicting results. Some small studies showed some benefit with regard to outcomes such as the need for ventilatory support, though generally with no effect on mortality. A trial conducted at seven American hospitals found no evidence of benefit on intubation or the risk of death.

The conflicting evidence has continued to accumulate into 2021. Interim results from the REMAP-CAP trial did in fact demonstrate a reduction in the risk of death for hospitalised patients with both tocilizumab and sarilumab compared with standard care, leading the DHSC to issue an interim position statement recommending their use. However, a Brazilian study found just the opposite, with no improvement over standard care with tocilizumab.

These agents are in use now in the UK, but clearly their optimal position in the treatment landscape remains hazy. The large RECOVERY trial continues to recruit patients to its tocilizumab arm.

Corticosteroids

Dexamethasone and hydrocortisone are both approved for use in patients with severe COVID-19. The RECOVERY trial found that dexamethasone reduced all-cause mortality at 28 days by 36% in patients ventilated at study entry compared with a control group. The effect was less in patients receiving oxygen without invasive ventilation, but still significant.

Other disappointing results

Other therapy possibilities have recently showed disappointing returns. One recent study found that the IL-1 receptor antagonist anakinra did not improve outcomes in patients hospitalised with mild to moderate COVID-19. Meanwhile, the PRINCIPLE trial found no improvement in time to recovery for patients over 50 when treated at home early in the disease course with azithromycin or with doxycycline. Those treatment arms are no longer recruiting.

Clearly, the search for effective therapies has been a rocky one over the course of the pandemic. But with almost 11% of the UK’s population now having received at least one dose of a vaccine, and more than 360,000 doses administered every day, there is hope that the urgent need for treatments will soon start to diminish.