RESUMEN
There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.
Asunto(s)
COVID-19 , Infecciones por CoronavirusRESUMEN
- ImportanceMany COVID-19 prognostic factors for disease severity have been identified and many scores have already been proposed to predict death and other outcomes. However, hospitals in developing countries often cannot measure some of the variables that have been reported as useful. - ObjectiveTo assess the sensitivity, specificity, and predictive values of the novel LOW-HARM score (Lymphopenia, Oxygen saturation, White blood cells, Hypertension, Age, Renal injury, and Myocardial injury). - DesignThe score was designed using data from already published cohorts of patients diagnosed with COVID-19. Afterwards, it was calculated it in 438 consecutive hospital admissions at twelve different institutions in ten different cities in Mexico. - SettingTwelve hospitals in ten different cities in Mexico. - ParticipantsData from 438 patients was collected. Data from 400 patients (200 deaths and 200 survivors) was included in the analysis. - ExposureAll patients had an infection with SARS-CoV-2 confirmed by PCR. - Main OutcomeThe sensitivity, specificity, and predictive values of different cut-offs of the LOW-HARM score to predict death. - ResultsMean scores at admission and their distributions were significantly lower in patients who were discharged compared to those who died during their hospitalization 10 (SD: 17) vs 70 (SD: 28). The overall AUC of the model was 95%. A cut-off > 65 points had a specificity of 98% and a positive predictive value of 96%. More than a third of the cases (36%) in the sample had a LOW-HARM score > 65 points. - Conclusions and relevanceThe LOW-HARM score measured at admission is highly specific and useful for predicting mortality. It is easy to calculate and can be updated with individual clinical progression. KEY POINTSO_ST_ABSQuestionC_ST_ABSIs it possible to predict mortality in patients diagnosed with COVID-19 using easy-to-access and easy-to-measure variables? FindingsThe LOW-HARM score (Lymphopenia, Oxygen saturation, White blood cells, Hypertension, Age, Renal injury, and Myocardial injury) is a one-hundred-point score that, when measured at admission, had an overall AUC of 95% for predicting mortality. A cut-off of [≥] 65 points had a specificity of 98% and a positive predictive value of 96%. MeaningThe LOW-HARM score measured at admission is highly specific and useful for predicting mortality in patients diagnosed with COVID-19. In our sample, more than a third of patients met the proposed cut-off.