Reply to Lapadula et al

To the Editor—We reviewed with interest the comments of Lapadula and colleagues regarding our case-control study of bamlanivimab use in high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) [1]. Their comments reinforce one of our major discussion points—the need for bamlanivimab to be administered as early as possible in the course of COVID-19. As noted, 12 (6.5%) control patients were ineligible to receive the antibody infusion due to severity of disease—either at time of presentation (4 patients) or at time of planned infusion (8 patients). Timelier initial presentation along with a streamlined referral and bamlanivimab administration process would have resulted in these patients receiving therapy. In consideration of the logistical challenges, we included these controls in our analysis. These patients represent the expected clinical trajectory of patients at high risk for decompensation to severe COVID-19 and reflect the de facto challenges clinicians face when caring for this population.

Regarding our decision to include patients who were hospitalized on initial day of presentation (ie, time 0) in our Kaplan-Meier analysis, this was done to be transparent in our real-world experience. When patients who were hospitalized on day 0 are excluded from analysis, the Kaplan-Meier curve remains statistically significant (χ ² = 10.323, P = .001). Dyspnea and hypoxia caused by severe acute respiratory syndrome coronavirus 2 typically occur within 5 to 8 days of symptom onset [2, 3]. There is a finite window in which patients develop these symptoms, and all patients were studied for 30 days from first positive test result; therefore, both cases and controls had adequate time to progress to severe disease requiring hospitalization.

We recognize the limitations of using a retrospective design. However, during a pandemic with limited therapies to prevent severe disease and hospitalization, we aimed to determine if the findings of bamlanivimab demonstrated in clinical trials were consistent with real-world experience [4, 5]. Additionally, our study design and analysis were consistent with recently described approaches [6]. Future randomized controlled trials are needed to confirm our observed benefit associated with neutralizing antibody therapy in high-risk populations.

Ultimately, we hope our experience can aid clinicians in shared decision making with their patients. Although bamlanivimab monotherapy is no longer recommended nor available via emergency use authorization, neutralizing monoclonal antibody combinations remain an encouraging option. Our study highlights the potential benefits of continuing to develop and consider use of monoclonal antibody combinations in at-risk populations during the COVID-19 pandemic.

Notes

Financial support. Research reported in this publication was supported, in part, by the National Institutes of Health’s National Center for Advancing Translational Sciences, grant number UL1TR001422. R. N. K. is supported by the National Institute of Health’s grant number T32 AI095207. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Potential conflicts of interest. V. S. reports an Eli Lilly and Company Grant paid to Northwestern University. C. A. reports Gilead Sciences Grant for Investigator Sponsored Research Project; Viiv paid honoraria for HIV and Aging lectures and development; Abivax DSMB; Atea DSMB; Viiv Advisory Board on HIV aging and telomeres. M. G. I. reports research support, paid to Northwestern University, from AiCuris, Janssen, and Shire; he is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech, Roche, Janssen, Shionogi, and Viracor Eurofins; he is also a paid member of data and safety monitoring boards from Janssen, Merck, SAB Biotherapeutics, Sequiris, Takeda, and Vitaeris (Vitaeris acquired by CSL Behrling). M. P. A. reports DKBMed paid honoraria for lectures on SARS-CoV2 and COVID; Paradigm Medical Communications LLC Paid Honoria for lectures on influenza; Abbvie DSMB for Venetoclax; DMID Protocol Number 20-0026 data and safety monitoring board for NIH influenza vaccine study, grant number U01AI152967. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.