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A trial claiming to show efficacy with hydroxychloroquine plus azithromycin received wide coverage in the lay media.This study had important methodological flaws and its conclusions have been disputed. In addition, this combination is associated with an increased risk of QT prolongation. A controlled trial indicated that the combined viral protease inhibitor formulation of lopinavir/ritonavir is ineffective.

An uncontrolled trial of remdesivir, which has in vitro activity against SARS-CoV-2, achieved improvement in severely ill patients (oxygen saturation ≤94% or receiving oxygen support). More recently (29 April), a randomised control trial has been published from China and headline results released from a global phase 3 trial. Both included hospitalised patients with pneumonia and confirmed COVID-19. In the Chinese study, remdesivir did not significantly reduce time to clinical improvement, though there was a trend towards faster improvement in patients with a symptom duration of 10 days or less. By contrast, the ACTT study suggested that treatment with remdesivir was associated with a more rapid recovery compared with placebo (median time to recovery 11 vs 15 days,, and there was a trend towards improved mortality. More data is needed to provide a clearer picture on its benefits.

Work on vaccines is also developing quickly. In March, WHO identified two vaccines in phase 1 trials and in preclinical development. A review published on 9 April described 115 candidate vaccines, of which the development status is unknown for the projects known to be progressing, 73 were noted to be in exploratory or preclinical stages and five in phase 1 trials.

These vaccines are being developed using a diverse range of delivery platforms, including DNA and RNA, self-amplifying RNA, virus-like particle, peptide, viral vector, recombinant protein, live attenuated virus and inactivated virus. RNA and DNA delivery platforms offer rapid development of a vaccine from sequencing the virus to beginning a clinical trial. In the case of one vaccine now in trials, the interval between sequencing the virus genome and beginning the clinical trial was only 10 weeks. Others, including the Oxford Vaccine Centre's ChAdOx1nCoV-19 vaccine, for which phase 1 clinical trials are now underway in the UK, use a non-replicating viral vector such as an adenovirus.

Specialists at the Coalition for Epidemic Preparedness and Innovation have highlighted three challenges to vaccine development.There is uncertainty about which is the optimal target antigen on SARS-CoV-2. Experience with vaccines against SARS and MERS infections revealed a risk of exacerbating lung disease, therefore testing in animal models is essential. And the duration of immunity and effectiveness of single-dose vaccines is unknown. To this can be added the challenge of upscaling production to meet the urgent global demand. Given the seriousness of the challenge posed by COVID-19, there may be calls to waive some of the usual requirements for evidence of safety to accelerate access to a vaccine. For example, an experimental vaccine was used to control an outbreak of Ebola virus disease in Guinea in 2015

The idea that herd immunity might protect the population from SARS-CoV-2 has proved controversial, largely because it is a concept normally applied to immunisation programmes rather than a pandemic with a high mortality rate. For herd immunity to be effective in the UK, the proportion of the population with immunity must exceed the threshold of about Achieving that level by national exposure to the virus would be associated with an unacceptable number of deaths. However, the extent to which lockdown measures can ultimately prevent rather than delay infection is uncertain, and it is unknown how the death rate would compare with the final mortality after the pandemic has run its course.

The preferred way to build herd immunity is through vaccination. It is currently uncertain when a vaccine will be available to the general population; it is likely that frontline health workers would be the first to receive it, then high-risk individuals. How quickly production can be scaled up to meet international demand is another unknown. There has been some anxiety in the media that infection may not confer lasting protection against SARS-CoV-2. However, evidence from an animal study. suggests that reinfection will not occur, and some cases of alleged re-infection have been errors due to unreliable testing or relapse. It has also been suggested that prior infection by established coronaviruses might confer partial immunity, and that may partially explain why some people have only very mild symptoms. However, more evidence is needed.