Autoimmune screening before adenovirus vector-based DNA vaccine in women may avoid underuse for all the subjects

Abstract

Dear Editor, Initially, the UK COVID-19 distribution strategy for the viral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), was to deliver a single dose to the entire population. However, March 2021 data from the Medicines and Healthcare Products Regulatory Agency (MHRA) reported 79 cases of immune thrombotic thrombocytopenia (ITT) following the administration of the vaccine: 44 cerebral venous sinus thromboses (CVST), and 35 severe vein thromboses at other sites. All 79 cases had occurred after receiving a first dose of the vaccine, and 51 of these were women aged between 18 and 79 years [1]. The number of vaccinated women with the AZD1222 vaccine was 3525 on a total of 5807 vaccinated people (60.7%). Regarding mortality, 19 of the 79 people died of which 13 were women. Eleven out of the 19 people who died were under 50 years of age, and 3 were under 30 years of age. Fourteen of these 19 cases were CVST and 5 thromboses with ITT [1, 2]. Whereas of March 31 2021, European Union countries had administered a total of 33,385,052 vaccinations, including 5,181,905 women under 50 years of age. The reported incidence of CVST with ITT was 44/5,181,905 (8.5 cases/ million) and the reported overall incidence of venous thrombotic events was 79/5,181,905 (15 cases/million people) [2]. In line with previous research reporting sex differences in vaccine responses, women exhibited a more significant immune response that might facilitate vaccine efficacy, but they also experienced more frequent and more severe adverse events (AEs) [3–5]. The interim analysis of phase 1/2/3 ongoing AZD1222 vaccine trials has reported that almost 80% of the enrolled women were aged between 18 and 55. As of 5807, there were eighty-four (1.45%) serious AEs reported, but only 2 were considered possibly related to vaccination, a transverse myelitis case and fever, but no specific sex-related AEs were reported [2]. In February 2021, the “Centers for Disease Control and Prevention” (CDC) released data on AEs pertaining to the first month of the COVID-19 vaccine rollout, reporting that women received 61% of the first vaccine doses, whereas 72% of the reported side effects occurred in women [6]. These findings suggest that this higher reactivity of the women immune system should be taken into account. The extremely rare number of cases of ITT following the administration of a single dose of the COVID-19 viral vector vaccine shares many clinical and pathogenetic aspects with another immune-mediated complication affecting a low proportion (0.3 to 4.8%) of patients with previous heparin exposure, the so-called autoimmune heparin-induced thrombocytopenia (HIT) [7, 8]. The ITTs of vaccinated patients have had a relatively high incidence of venous thrombosis in unusual sites, such as the cerebral veins. This is in line with data from an 11-yearobservational study focusing on HIT patients after highdose heparin administration. In fact, out of the 120 consecutive patients enrolled with thrombotic complications, Maria Giulia Mosconi and Francesco Caso contributed equally to this work.