Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo

Background The rVSV Delta G-ZEBOV-GP vaccine constitutes a valuable tool to control Ebola virus disease outbreaks. This retrospective cohort study aimed to assess the protective effect of the vaccine against death among patients with confirmed Ebola virus disease. Methods In this retrospective cohort analysis of patients with confirmed Ebola virus disease admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018, and April 27, 2020, we performed univariate and multivariate analyses to assess case fatality risk and cycle threshold for nucleoprotein according to vaccination status, Ebola virus disease-specific treatments (eg, mAb114 and REGN-EB3), and other risk factors. Findings We analysed all 2279 patients with confirmed Ebola virus disease. Of these 2279 patients, 1300 (57%) were female and 979 (43%) were male. Vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0<middle dot>0001). In adjusted analyses, vaccination significantly lowered the risk of death compared with no vaccination, with protection increasing as time elapsed from vaccination to symptom onset (vaccinated <= 2 days before onset: 27% [27/99], adjusted relative risk 0<middle dot>56 [95% CI 0<middle dot>36-0<middle dot>82, p=0<middle dot>0046]; 3-9 days before onset: 20% [28/139], 0<middle dot>44 [0<middle dot>29-0<middle dot>65, p=0<middle dot>0001]; >= 10 days before onset: 18% [12/68], 0<middle dot>40 [0<middle dot>21-0<middle dot>69; p=0<middle dot>0022]; vaccination date unknown: 33% [39/117], 0<middle dot>69 [0<middle dot>48-0<middle dot>96; p=0<middle dot>0341]; and vaccination status unknown: 52% [441/841], 0<middle dot>80 [0<middle dot>70-0<middle dot>91, p=0<middle dot>0011]). Longer time from symptom onset to admission significantly increased risk of death (49% [1117/2279], 1<middle dot>03 [1<middle dot>02-1<middle dot>05; p<0<middle dot>0001]). Cycle threshold values for nucleoprotein were significantly higher-indicating lower viraemia-among patients who were vaccinated compared with those who were not vaccinated; the highest difference was observed among those vaccinated 21 days or longer before symptom onset (median 30<middle dot>0 cycles [IQR 24<middle dot>6-33<middle dot>7]) compared with patients who were not vaccinated (21<middle dot>4 cycles [18<middle dot>4-25<middle dot>9], p<0<middle dot>0001). Interpretation To our knowledge, this is the first observational study describing the protective effect of rVSV Delta GZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission. Funding M & eacute;decins Sans Fronti & egrave;res.