Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine (dNS1-RBD, Pneucolin; Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) confers long-lasting and broad protection in animal models and is, to our knowledge, the first COVID-19 mucosal vaccine to enter into human trials, but its efficacy is still unknown. We aimed to assess the safety and efficacy (but not the immunogenicity) of dNS1-RBD against COVID-19. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, adaptive design, phase 3 trial at 33 centres (private or public hospitals, clinical research centres, or Centre for Disease Control and Prevention) in four countries (Colombia, Philippines, South Africa, and Viet Nam). Men and non-pregnant women (aged ≥18 years) were eligible if they had never been infected with SARS-CoV-2, and if they did not have a SARS-CoV-2 vaccination history at screening or if they had received at least one dose of other SARS-CoV-2 vaccines 6 months or longer before enrolment. Eligible adults were randomly assigned (1:1) to receive two intranasal doses of dNS1-RBD or placebo administered 14 days apart (0·2 mL per dose; 0·1 mL per nasal cavity), with block randomisation via an interactive web-response system, stratified by centre, age group (18-59 years or ≥60 years), and SARS-CoV-2 vaccination history. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary outcomes were safety of dNS1-RBD in the safety population (ie, those who had received at least one dose of dNS1-RBD or placebo) and efficacy against symptomatic SARS-CoV-2 infection confirmed by RT-PCR occurring 15 days or longer after the second dose in the per-protocol population (ie, those who received two doses, were followed up for 15 days or longer after the second dose, and had no major protocol deviations). The success criterion was predefined as vaccine efficacy of more than 30%. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100051391) and is completed. FINDINGS: Between Dec 16, 2021, and May 31, 2022, 41 620 participants were screened for eligibility and 31 038 participants were enrolled and randomly assigned (15 517 in the vaccine group and 15 521 in the placebo group). 30 990 participants who received at least one dose (15 496 vaccine and 15 494 placebo) were included in the safety analysis. The results showed a favourable safety profile, with the most common local adverse reaction being rhinorrhoea (578 [3·7%] of 15 500 vaccine recipients and 546 [3·5%] of 15 490 placebo recipients) and the most common systemic reaction being headache (829 [5·3%] vaccine recipients and 797 [5·1%] placebo recipients). We found no differences in the incidences of adverse reactions between participants in the vaccine and placebo groups. No vaccination-related serious adverse events or deaths were observed. Among 30 290 participants who received two doses, 25 742 were included in the per-protocol efficacy analysis (12 840 vaccine and 12 902 placebo). The incidence of confirmed symptomatic SARS-CoV-2 infection caused by omicron variants regardless of immunisation history was 1·6% in the vaccine group and 2·3% in the placebo group, resulting in an overall vaccine efficacy of 28·2% (95% CI 3·4-46·6), with a median follow-up duration of 161 days. INTERPRETATION: Although this trial did not meet the predefined efficacy criteria for success, dNS1-RBD was well tolerated and protective against omicron variants, both as a primary immunisation and as a heterologous booster. FUNDING: Beijing Wantai Biological Pharmacy Enterprise, National Science and Technology Major Project, National Natural Science Foundation of China, Fujian Provincial Science and Technology Plan Project, Natural Science Foundation of Fujian Province, Xiamen Science and Technology Plan Special Project, Bill & Melinda Gates Foundation, the Ministry of Education of China, Xiamen University, and Fieldwork Funds of Xiamen University.

Reporte de cuatro casos COVID-19 hospitalizados en unidad de cuidados intensivos en una institución hospitalaria en Barranquilla, Colombia / Original article: Case-Serie of 4 COVID-19 patients hospitalized in an intensive care unit in a hospital institution in Barranquilla, Colombia

Resumen Presentar una serie de casos de COVID-19 con requerimiento de ingreso a Unidad de Cuidados Intensivos. La información fue tomada de las historias clínicas, y su evaluación y diagnóstico fue realizado mediante estudios paraclínicos en sangre, orina, PCR e imágenes diagnósticas en 4 pacientes con diferentes comorbilidades y nexo epidemiológico presente para desarrollo de la enfermedad. Los cuatro casos fueron manejados con cloroquina 300 mg vía oral, cada 12 horas, y azitromicina 1 gr vía oral, cada 24 horas, durante 5 días, sin complicaciones ni toxicidad asociada. El caso 1 desarrolló falla orgánica múltiple, incluyendo injuria renal aguda con una estancia en UCI de 4 días antes de su fallecimiento, mientras los casos 2, 3 y 4 tuvieron una evolución favorable y fueron dados de alta de UCI. Se requieren estudios multicéntricos rápidos que orienten científicamente hacia un mejor abordaje diagnóstico y manejo, en el contexto de una enfermedad con un comportamiento clínico-epidemiológico que debe estudiarse en profundidad y que probablemente cobrará muchas vidas; además, debido a la ausencia de pruebas diagnósticas rápidas, la utilización de una clasificación basada en la severidad de lesiones radiológicas llamada CO-RADS (Covid-19 Imaging Reporting and Data System) podría ser de gran importancia para instalar de manera temprana los tratamientos farmacológicos disponibles y la asistencia respiratoria mecánica precoz.

Abstract To present a COVID-19 case series with clinical admission criteria to Intensive Care Unit. Patients information was obtained from medical records, and daily clinical evaluation whereas diagnosis was carried out through paraclinical studies in blood, urine, PCR and diagnostic images in 4 patients with different comorbidities and epidemiological link for the development of COVID-19. All four cases were managed with chloroquine 300 mg orally every 12 hours and azithromycin orally every 24 hours for 5 days without complications or associated toxicity. The case 1 developed multiple organ failure, including acute kidney injury with an ICU stay of 4 days before his death, while cases 2, 3 and 4 had a favorable evolution and were discharged from the ICU. Rapid multicenter studies are required to scientifically guide a better diagnostic and management approach, in the context of a disease with a clinical-epidemiological behavior that must be studied in depth and will probably take many lives. In addition, due to the absence of sufficiently rapid tests, the use of a classification based on the severity of radiological lesions called CO-RADS (Covid-19 Imaging Reporting and Data System) could be of great importance to install available pharmacological treatments early and early mechanical respiratory support.