Limitations
NHFO, dyspneic
DISEASE
This study has several limitations. First, because of the nature of self-prone positioning, blinding patients and caregivers was not possible.Second, subgroup analyses were underpowered.Third, as for other studies [Fourth, criteria for intubation were not defined a priori and were at the discretion of wards or ICU physicians.Fifth, the small proportion of patients initially treated with nasal high-flow oxygen (NHFO) therapy (4.5%) prevented any meaningful comparison between the different types of oxygen therapy. The choice we made not to include the use of NHFO therapy into our composite primary endpoint as an initial step of ventilatory support escalation is debatable. However, during the first surge of the COVID-19 pandemic, when we designed the study, the use of NHFO was not recommended due to the risk of aerosolisation of viral particles. After the first surge, we did not make any modification to the protocol, considering NHFO therapy to represent a far lesser therapeutic escalation than the use of NIV or intubation. Since then, several RCTs showed that NHFO did not significantly reduce ventilatory support escalation compared with standard oxygen in COVID-19 patients [Sixth, the study design did not allow for an assessment of the impact of duration of prone position on outcomes because it was dependent on patient tolerance and different durations were not protocol-mandated.Seventh, the variability in time from enrolment to prone positioning could be explained by the extra workload of caregivers during the pandemic. Caregivers had less time than usual to encourage and help patients to self-prone position. It is also possible that some patients were too tired or dyspneic for prone positioning after the enrolment.Eighth, the night-time position was not recorded because of the extra workload of caregivers and could have impacted our results. The duration of prone position may have been determined by disease severity, which would bias any analysis towards worse outcomes associated with shorter prone position durations.Ninth, whether patients of both groups have lied prone at night was not recorded. However, only 10% of patients declared prone position as their preferred sleeping position, and patients of the usual care group were clearly instructed not to lie prone at night. Therefore, we think unlikely that this could have biased our results. Finally, periods of prone position applied to patients of the intervention group were relatively short, which may explain our negative main result.