Fungal infections should be part of the core outcome set for COVID-19 – Authors' reply

Abstract

We thank Paul E Verweij and Alexandre Alanio for their interest in our minimal common outcomes set for studies of COVID-19,1WHO Working Group on the Clinical Characterisation and Management of COVID-19 infectionA minimal common outcome measure set for COVID-19 clinical research.Lancet Infect Dis. 2020; 20: e192-e197Summary Full Text Full Text PDF PubMed Scopus (664) Google Scholar 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,2Hughes S Troise O Donaldson H Mughal N Moore LS Bacterial and fungal coinfection among hospitalised patients with COVID-19: a retrospective cohort study in a UK secondary care setting.Clin Microbiol Infect. 2020; (published online June 27.)https://dx.doi.org/10.1016/j.cmi.2020.06.025Summary Full Text Full Text PDF Scopus (314) Google Scholar 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. 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. Fungal infections should be part of the core outcome set for COVID-19In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium published a minimum set of common outcome measures for studies of COVID-19.1 A core outcome set is crucial in the setting of an evolving research response to the COVID-19 pandemic and will greatly facilitate pooling of data across cohort studies and clinical trials. Full-Text PDF A minimal common outcome measure set for COVID-19 clinical researchClinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. Full-Text PDF