ChAdOx1 nCoV-19 vaccine for SARS-CoV-2

As a participant in the ChAdOx1 nCoV-19 vaccine trial, I was particularly excited to read the preliminary report by Pedro Folegatti and colleagues¹ and congratulate the team on their promising results.

However, glancing at the summary of adverse reactions in figure 1 of the Article,¹ I was uncomfortably surprised to discover that I had unmasked myself. I self-reported moderate feverish­ness, which was experienced by 21% (12 of 56) of the ChAdOx1 nCoV-19 paracetamol group and none of the associated control group.

Other symptoms might also provide insight to participants: the presence of malaise and myalgia were predictive of allocation to the experimental group (positive predictive value of 78% for malaise and 71% for myalgia, calculated for the combined cohort of partici­pants who received ChAdOx1 nCoV-19 vaccine with and without para­ce­ta­­mol). The positive predictive values increase if the timing or severity of symp­toms is considered. These symptoms were common in participants who received the ChAdOx1 nCoV-19 vaccine (59% [323 of 543] of participants had malaise and 59% [321 of 543] of participants had myalgia) so many participants could have at least partly unmasked themselves.

In most trials, this unmasking might have been inconsequential as few participants would analyse preliminary results in detail. However, this trial is different. Recruitment was targeted at scientifically literate health-care workers near academic centres. The article was emailed by the study team to all participants, who have substantial personal interests in the results. The charts showing side-effects are prominent and easy to interpret. I fear that I am not the only person with an inappropriate insight into my allocation.

Relaxation of prophylactic measures (eg, physical distancing) due to perceived immunity by participants who had severe side-effects could cause a false-negative trial result with substantial consequences for public health and the economy. Although there is clearly public interest in interim publication of trial data, this interest should be balanced against the risk of compromising the integrity of the trial.