Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare disorder described after vaccination with adenoviral vector-based COVID-19 vaccines. Co-occurring thrombosis with thrombocytopenia reported after vaccination can be a proxy for identification of TTS. METHODS: Descriptive database review of all cases of co-occurring (within 42 days) thrombosis with thrombocytopenia in participants in Ad26.COV2.S clinical trials or recipients of Ad26.COV2.S in real-world clinical practice. Cases were retrieved from Janssens' clinical trial and Global Medical Safety databases. RESULTS: There were 34 cases of co-occurring thrombosis with thrombocytopenia in Ad26.COV2.S recipients (46 per 100,000 person-years) and 15 after placebo (75 per 100,000 person-years) in clinical trials. Among Ad26.COV2.S recipients, mean age at the time of the event was 63 years (range 25-85), 82 % were male, mean time-to-onset 112 days (range 8-339) post-last Ad26.COV2.S dose, 26 events occurred post-dose-1, and 7 within a 28-day risk window post-vaccination. Diagnostic certainty was evaluated using Brighton Collaboration, US Centers for Disease Control and Prevention, and European Medicines Agency Pharmacovigilance Risk Assessment Committee case definitions. One case met the highest level of diagnostic certainty for all 3 definitions. There were 355 spontaneous reports of co-occurring thrombosis with thrombocytopenia in the Global Medical Safety database, 47 % males, 85 % within 28-days after vaccination. Twenty-seven cases met the highest level of diagnostic certainty for all definitions, 21 female, 19 with cerebral venous sinus thrombosis, age-range 18-68 years. Time-to-onset was 7-14 days post-vaccination in 20 cases. There were 8 fatalities. CONCLUSION: TTS induced by Ad26.COV2.S is very rare. Most co-occurring thrombosis with thrombocytopenia does not constitute TTS.

Situación del brote de Ébola en África Occidental en el año 2014 / Status Ebola outbreak in West Africa in 2014

Resumen Desde el comienzo del brote en diciembre del 2013, y hasta el corte del 20 de septiembre de 2014, de un total de 6,185 casos probables de Ébola, se han registrado un total de 2,909 defunciones. Con una letalidad inferior al 50%, considerablemente menor a la reportada en brotes previos de la enfermedad, se cree que dichas estimaciones están sesgadas debido a la dificultad en la recolección y análisis de la información. El 23 de septiembre, la OMS presentó una revisión a dichas estimaciones, señalando una letalidad del 70%. El brote se registró originalmente en Liberia y Guinea, y posteriormente se han repostado casos en Nigeria, Sierra Leona y Senegal. Todos los casos confirmados por laboratorio han sido positivos al vírus del Ébola. La fuente inicial del brote se localizó en la aldea de Meliandou, prefectura de Guáckádou, Guinea. El caso índice fue un niño de 2 años, el cual falleció el 6 de diciembre de 2013. Su madre, hermana y abuela también fallecieron también por la enfermedad. La gente de la aldea infectada por estas víctimas iniciales transmitió el brote a aldeas aledañas. El brote se esparció inicialmente a Liberia y posteriormente a Sierra Leona. En los tres países continúa la circulación del virus. La llegada de algunos casos a Nigeria y Senegal obligó a dichos países a cerrar sus fronteras, y a poner en cuarentena a ciudadanos de los que se sospechara que estuvieran infectados. Hasta la fecha, ambos países no han presentado casos nuevos, por lo que se consideran en control. Asimismo, se han reportado casos importados de dichos países en Estados Unidos, Francia, Alemania, España, Suiza y el Reino Unido.

Abstract Since the onset of the outbreak im December 2013 and up to the September 20 cut-off, there have been 2,909 deaths in the 6,185 likely cases of Ebola. It is considered that the letality under 50%, considerably lower tan the one reported in previous outbreaks of the disease, is biased due to the dificulty to collect and analyze information. On September 23, WHO showed a review of such estimations, indicating 70% letality. The outbreak was originally reported in Liberia and Guinea. Further cases were reported in Nigeria, Sierra Leone, and Senegal. All the cases confirmed by laboratory have been EBOV positive. The initial source of the outbreak was found in the village called Meliandou in the in Guéckédou Prefecture, Guinea. The index case was a two-year-old boy, who die don December 6, 2013. His mother, sister and grandmother also died because of the disease. The people from this village transmitted the disease to people in nera-by villages. The outbreak initially spread to Liberia and then to Sierra Leone. Virus circulation continues in three countries. The transmision of some cases to Nigeria and Senegal led these countries to close their borders to the three formerly mentioned countries and quarantine suspicious individuals. So far, neither country has presented new cases; hence they are considered under control. Likewise, cases imported from those countries into the United States, France, Germany, spain, Switzerland, and the Uited Kingdom have been reported.