key: cord-0061743-hbg430ly
authors: Patel, Maulin; Dominguez, Eduardo; Sacher, Daniel; Desai, Parag; Chandar, Ashwin; Bromberg, Michael; Caricchio, Roberto; Criner, Gerard J.
title: Response
date: 2021-04-06
journal: Chest
DOI: 10.1016/j.chest.2020.11.035
sha: d39a1828d38c4dcda241f700e5c88400a8f3fc0b
doc_id: 61743
cord_uid: hbg430ly

nan

To the Editor:

We would like to thank Delgado-Lopez et al for their response to our original manuscript. 1 We agree with the sentiment echoed by the writers that, after failure of various antiinflammatory-like corticosteroids and biologic therapies (anti IL-6, anti-IL-1), etoposide has a role in selective patients who still have laboratory and clinical data suggestive of hyperinflammatory syndromes. 1,2 Although the authors have reported on eleven patients with coronavirus disease 2019 who were treated with etoposide as salvage therapy in June 2020, our initial submission was in April 2020 at which time none of the publications had reported any such cases. We are, however, very happy to see the results from the authors' case series reporting similar outcomes as ours. We, like the authors, await the result of the ongoing clinical trial NCT04356690, 3 I read with great interests on the study by Pandya et al 1 in CHEST (February 2021), in which they compared the difference between late vs early intubation of patients with coronavirus disease 2019. They found that late intubation was associated with longer length of stay in ICU and duration of mechanical ventilation than the early intubation group. Although it is plausible that the late intubation group may experience prolonged periods of hypoxia that result in pathophysiologic derangements such as hypoxemia and multiorgan dysfunction, the finding may also be attributable to the immortal time bias. 2 Immortal time bias refers to a distortion that modifies an association between an exposure and an outcome, caused when a cohort study is designed so that follow up includes a period of time in which participants in the exposed group cannot experience the outcome and are essentially "immortal."

In the present study, the time from admission to intubation is the immortal time, in which the outcome of mortality cannot occur. When the length of stay in ICU was calculated from admission, this immortal time is attributed inappropriately to the effect of intubation. As a result, the length of stay is prolonged in the late intubation group. A potential solution to the immortal time bias is to reset the time zero of follow up to the time chestjournal.org

Etoposide as salvage therapy for cytokine storm due to coronavirus disease 2019

Etoposide as salvage therapy for cytokine storm due to coronavirus disease 2019

Etoposide treatment adjunctive to immunosuppressants for critically ill COVID-19 patients

A phase II singlecenter, randomized, open-label, safety and efficacy study of etoposide in patients with COVID-19 infection. NCT04356690. ClinicalTrials.gov. National Institutes of Health