Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults.

OBJECTIVES: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. METHODS: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. RESULTS: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. CONCLUSIONS: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.

Single-cell multi-omics analysis of the immune response in COVID-19.

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

[Clinical spectrum of patients with spontaneous retroperitoneal hematomas]. / Perfil clínico de los pacientes con hematomas retroperitoneales espontáneos.

INTRODUCTION AND OBJECTIVE: Spontaneous retroperitoneal hematoma (SRH) is a potentially fatal clinical entity requiring immediate recognition and intervention. MATERIAL AND METHODS: The clinical records of 18-year-old and older patients admitted to the University Hospital Marqués de Valdecilla from 2003 to 2013 were reviewed. "Spontaneous" was defined as unrelated to trauma, invasive procedures or bleeding due to aortic aneurysm rupture. RESULTS: Thirty-four patients with SRH (44% were on anticoagulant drugs). One-third of cases had chronic renal insufficiency. Abdominal pain was the most common symptom both in anticoagulated and non-anticoagulated patients (80% in anticoagulated and 89% in non-anticoagulated patients). About one half of the patients developed shock. A CT scan was the most commonly performed diagnostic test, followed by abdominal ultrasound. Most cases were managed conservatively (80%). More than half of the patients (66%) restarted anticoagulation therapy after the acute event with a mean delay of 19 days (range 2-90 days). None of them suffered a new bleeding episode. CONCLUSION: Restarting the anticoagulation treatment after hematoma resolution seems to be a safe practice. There is an increasing frequency of SRH in non-anticoagulated patients.

Perfil clínico de los pacientes con hematomas retroperitoneales espontáneos / Clinical spectrum of patients with spontaneous retroperitoneal hematomas

Introducción y objetivo: Los hematomas retroperitoneales espontáneos (HRE)son una complicación del tratamiento anticoagulante. Material y métodos: Revisión retrospectiva de los HRE en el Hospital Universitario Marqués de Valdecilla (Santander, España) desde el año 2003 al 2013. Se excluyen los traumatismos, los procedimientos invasivos o las roturas de un aneurisma aórtico. Comparamos esta serie con la descrita previamente en nuestro hospital. Resultados: Identificamos 34 HRE (64% mujeres) con una media de edad de 65 años (23-88 años). El 44% estaban anticoagulados por enfermedad cardiaca (81%). Un tercio tenía insuficiencia renal, y el 15%, cáncer. El dolor abdominal se describe en el 85%. La TC se realiza en el 82%. El 32% ingresa en UCI y solo el 20% requiere cirugía. La mortalidad relacionada fue del 21% (media de supervivencia de 5 días; 1-15 días). El 66% reinicia la anticoagulación a los 19 días (2-90 días), sin complicaciones posteriores. Se incrementan los casos no anticoagulados en un 47%. Conclusión: En los casos anticoagulados, la reintroducción del tratamiento, tras la resolución del hematoma, parece una práctica relativamente segura. Se incrementan los casos en pacientes no anticoagulados (AU)

Introduction and objective: Spontaneous retroperitoneal hematoma (SRH) is a potentially fatal clinical entity requiring immediate recognition and intervention. Material and methods: The clinical records of 18-year-old and older patients admitted to the University Hospital Marqués de Valdecilla from 2003 to 2013 were reviewed. “Spontaneous” was defined as unrelated to trauma, invasive procedures or bleeding due to aortic aneurysm rupture. Results: Thirty-four patients with SRH (44% were on anticoagulant drugs). One-third of cases had chronic renal insufficiency. Abdominal pain was the most common symptom both in anticoagulated and non-anticoagulated patients (80% in anticoagulated and 89% in non-anticoagulated patients). About one half of the patients developed shock. A CT scan was the most commonly performed diagnostic test, followed by abdominal ultrasound. Most cases were managed conservatively (80%). More than half of the patients (66%) restarted anticoagulation therapy after the acute event with a mean delay of 19 days (range 2-90 days). None of them suffered a new bleeding episode. Conclusion: Restarting the anticoagulation treatment after hematoma resolution seems to be a safe practice. There is an increasing frequency of SRH in non-anticoagulated patients (AU)