We thank Paul E Verweij and Alexandre Alanio for their interest in our minimal common outcomes set for studies of COVID-19,1 which we developed in collaboration with a broad group of clinical researchers. We agree with Verweij and Alanio that fungi are important nosocomial pathogens that merit evaluation in addition to bacterial and viral infections as potential complications of some interventions against COVID-19. However, the evidence that fungal coinfections are more common in patients with COVID-19 than bacterial or viral coinfections is limited. Hughes and colleagues,2 for example, identified only three fungal infections, all line-related, among 836 hospitalised patients with COVID-19.
We also wish to correct a misperception about the final outcome set, in contradistinction to the candidate measures that were considered in developing it. Our primary goal was to identify a minimal, yet comprehensive list of outcomes that, independent of the specific study question being addressed, would be reported in all trials to facilitate cross-trial comparisons. Our set includes three variables: a measure of viral presence (viral RNA by qPCR), a measure of aggregate morbidity over time (the 11-point ordinal scale), and a measure of mortality (at 60 days or hospital discharge). Secondary infections are not an element of the core set, regardless of microbiology, although clearly they will be important endpoints in some trials (eg, trials of immunomodulatory agents) and unimportant in others (eg, trials of differing modes of mechanical ventilation or sedation). The longer list of outcomes in panel 1 of our Personal View includes measures that were considered by the working group but not included in the final set.
We see the outcomes set we have proposed as a dynamic one that will change over time as more is learned about the natural history and manifestations of COVID-19. Perhaps more notably absent from the list of outcomes we considered are measures of altered coagulation, an aspect of the disease that was only dimly appreciated when we undertook our initiative.
Acknowledgments
JCM is co-chair of the WHO Working Group on Clinical Characterisation and Management of COVID-19 infection and chair of the International Forum for Acute Care Trialists. He reports travel support from the Bill & Melinda Gates Foundation, and personal fees from Asahi Kasei Pharma America. SM is co-chair of the WHO Working Group on Clinical Characterisation and Management of COVID-19 infection. JD is an employee of WHO.
References
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