Investigating a Signal of Acquired Hemophilia Associated with COVID-19 Vaccination: A Systematic Case Review.

Acquired hemophilia A (AHA), a rare but life-threatening disorder, most commonly occurs in older people and during pregnancy. During the coronavirus disease 2019 (COVID-19) vaccination campaign, an unexpected number of newly diagnosed AHA patients have been identified in clinical practice that were temporally related to COVID-19 vaccination. We present the result of a signal detection analysis aimed at exploring a possible association between COVID-19 immunization and occurrence of AHA. A disproportionality analysis on the World Health Organization (WHO) database was performed to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. Reports of AHA associated with any COVID-19 vaccine included in the WHO database were then integrated with those available on the Food and Drug Administration Vaccine Adverse Events Reporting System and those published in the medical literature. The WHO database included 146 reports of AHA. The information component (IC) was significant for the association of AHA with all COVID-19 vaccines (IC025: 1.1) and with the vaccine product BNT162b2 (IC025: 1.6). After duplicate exclusion, 96 unique cases of AHA following COVID-19 vaccines have been reviewed. Median time to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Overall, in 57% of the investigated cases, a preexisting condition predisposing to AHA was excluded. About 22% of cases occurred in subjects with age ≤65 years and there was no case associated with pregnancy. Mortality was 11%. Although we cannot exclude that the unexpected frequency of AHA diagnosis can be explained by a detection bias, the signal for COVID-19 vaccine-related AHA is robust and deserves further investigations.

Tixagevimab + cilgavimab against SARS-CoV-2: the preclinical and clinical development and real-world evidence.

INTRODUCTION: Direct-acting SARS-CoV-2 antiviral monoclonal antibodies have been an integral part of therapeutic strategies against COVID-19 pandemic. The monoclonal strategy was jeopardized by the emergence of new variants and resistant strains, making many monoclonal antibodies quickly obsolete. Nevertheless, a possible strategy consists in the use of antibody cocktails and the development of the cilgavimab + tixagevimab in combination is placed in this context. AREAS COVERED: In this review, we describe the development of the cilgavimab + tixagevimab cocktail, from pre-clinical to real-world evidence. EXPERT OPINION: The pre-clinical and clinical development of cilgavimab + tixagevimab followed a similar path to that of the antibodies developed in the earlier stages of the pandemic. Both antibodies have been developed from convalescent plasma and have been shown to be effective in clinical trials in prophylaxis and in early therapy. This cocktail has found its position in therapy especially in immunocompromised subjects for whom vaccine prevention is not feasible. The cocktail strategy, together with a more stable pandemic situation, could ensure a certain longevity to the drug against resistance, especially when compared with that of other antibodies. Recently emerged Omicron sub-lineages have demonstrated the ability to escape this cocktail's activity and so the future of this treatment could be compromised.