Assessing the potential association between SARS‐CoV‐2 RNA load in the respiratory tract and COVID‐19 mortality

The magnitude of nasopharyngeal (NP) severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) load either at hospital admission or during the course of hospitalization has been directly associated with mortality of coronavirus disease 2019 (COVID‐19) patients.1-3 Yet this assumption has been disputed.4 While that association is pathogenetically plausible, there are several issues we wish to discuss. First, the quality of NP specimens is known to be highly variable,5 so normalization of measured SARS‐CoV‐2 RNA levels to sample cellularity inferred by quantitating messenger RNA encoded from housekeeping genes provides a more precise estimation of the viral load present. Unfortunately, this is not usually done.2, 3 Our experience reported herein further underscores the existence of a wide range of cellularities across NP specimens, which may notably impact on true SARS‐CoV‐2 RNA load estimates. The current study was approved by the Research Ethics Committee of Hospital Clínico Universitario INCLIVA (March, 2020).