Chronic spontanous urticaria following anti-covid 19 vaccine: Is there a link?

Background: Urticarial reactions following Covid-19 vaccine were rarely reported and have a short self-limited resolution. However only one case of chronic spontaneous urticaria (CSU) after mRNA vaccine was observed (1). Herein, we describe an original case series of patients who exhibited a CSU after Sars-Cov- 2 vaccination. Method(s): It was a retrospective case series of patients referred to the department of Clinical pharmacology of the University of Monastir for exploration of urticaria after Covid-19 vaccination., between January 2021 and January 2022. Result(s): Eight patients (8 F /5M) were included in this study. The median patient age was 36.5 years. None of them had a medical history of CSU. Urticaria was reported in 4 patients following mRNA vaccine (BNT162b2 and Moderna). Viral vector vaccine (Oxford/ AstraZeneca) was offended in 2 cases and inactivated virus vaccine (Sinovac, CoronaVac) was reported in 2 others cases. The mean time interval between vaccination and the onset of urticaria was 28.5 hours. The first shot of vaccine was the mostly offended dose (n = 6). Urticaria was associated with angioedema in 5 patients after Oxford/AstraZenecavaccine (n = 2) and following mRNA vaccine (n = 2). One case of urticaria was associated with angioedema and dyspnea after the CoronaVac administration. Blood tests showed polynuclear leucocytosis in 37% of patients. Positive anti-thyroperoxidase antibodies, and elevated polyclonal hypergammaglobulinemia were present in one patient 3 months after receiving BNT162b2 vaccine. Total serum IgE were high in 25% of patients following BNT162b2 and CoronaVac. All patients required antihistamines and 4 cases required intravenous betametasone. The median time to symptom resolution was 3 days but urticaria rapidly reccured throughout the entire body inspite the regular use of full dose of antihistamine. Intradermal test for the vaccine excipient as well as the offended Covid-19 vaccine was carried out in 5 patients, and were negative in all of them.Currently, all patients still has the pruritic rash daily. Conclusion(s): These cutaneous reactions seem to be particularly prolonged despite the use of symptomatic drugs, as compared with of drug induced-urticaria. Consequently, careful monitoring of urticaria over an extended period of time is needed.

Biological factors that may impair transplacental transfer of RSV antibodies: Implications for maternal immunization policy and research priorities for low- and middle-income countries.

Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infection (ALRI), including bronchiolitis and pneumonia, in infants and children worldwide. Protection against RSV is primarily antibody mediated and passively acquired RSV neutralizing antibody can protect infants from RSV ALRI. Maternal immunization is an attractive strategy for the prevention of RSV in early infancy when immune responses to active immunization may be suboptimal and most severe RSV disease and death occur. However, several biologic factors have been shown to potentially attenuate or interfere with the transfer of protective naturally acquired antibodies from mother to fetus and could therefore also reduce vaccine effectiveness through impairment of transfer of vaccine-induced antibodies. Many of these factors are prevalent in low- and middle-income countries (LMIC) which experience the greatest burden of RSV-associated mortality; more data are needed to understand these mechanisms in the context of RSV maternal immunization. This review will focus on what is currently known about biologic conditions that may impair RSV antibody transfer, including preterm delivery, low birthweight, maternal HIV infection, placental malaria, and hypergammaglobulinemia (high levels of maternal total IgG). Key data gaps and priority areas for research are highlighted and include improved understanding of the epidemiology of hypergammaglobulinemia and the mechanisms by which it may impair antibody transfer. Key considerations for ensuring optimal vaccine effectiveness in LMICs are also discussed.

Comparison of positivity to the direct coombs test in the 2 years before and after patient 1 in Italy at the UOC SIMT-CPE of ASL Rome 1

Background: The Direct Antiglobulin Test (DAT) is performed by testing the patient's red cells with poly or monospecific Anti Human Globulin (AHG) to demonstrate the in vivo link of red blood cells with antibodies and/or complement. The positive result of this test is usually due to the reaction of AHG with autoantibodies, alloantibodies (maternal or post transfusion) reactive against antigens present on the red cells, drugs that fix on the erythrocyte membrane (penicillin) or that alter it (cephalosporins), proteins often associated with hypergammaglobulinemia or I.V. infusion of immunoglobulins, complement fixation on red cells (from allo-autoAb, bacterial infections, drugs). Aims: The objective of this study is to understand if the positive result at DAT, in terms of frequency and specificity, has changed after the Covid 19 pandemic, and investigate the possible causes. Methods: We analysed the positive result of DAT performed on red cells of adult patients admitted to the wards of Asl Rome 1 and the affiliated clinics through the use of polypecific and monospecific sera (IgG, IgM, IgA, C3d, C3c) analysed using the IH 1000 System-Biorad Lab. All examinations performed was divided into two groups: those taken from 20/02/2018 to 20/02/2020 and from 21/02/2020 until 20/02/2022, representing the 2 years anniversary of the discovery of patient 1 in Italy. Results: In the first group of 101 patients who tested positive for DAT, 98% of them had positive results to IgG, while only the remaining 2% had positive results to the C3d isolated or associated with IgG. In the second group of 179 patients the positive results to IgG was 82% and the remaining 18% to C3d in isolation or in combination with IgG and C3c. We can observe how in the second group the overall positive results increased of about 80% and also the relative positive results to the C3d/C3c complement portion. It is also interesting to note that the positive results of only half of the second group (last 14 months in the period 2021-2022) are numerically about 50% higher than the previous year and 20% higher than the entire first group analysed (24 months). Summary/Conclusions: This increase in DAT positive results occurred in the second group, in particular in the last 14 months of the pandemic, could reflect the high levels of circulating immunoglobulins in the subjects analysed due to the endemic circulation of Sars Cov 2 virus and mass vaccination. These, according to our hypothesis, could have contributed to the outcome of positive results through a 'iatrogenic hypergammaglobulinemia' due to the high post vaccination titre and the immune response due to the increased circulation of the virus. It could also be assumed that the percentage of C3d detected 'Berzuini et al, Blood, 2020' is due to alterations of the complement receptors present on the surface of the red blood cells caused by the activation of the complement against the protein N of the nucleocapsid of the virus Sars Cov2 'J.E.Hendrickson and C.A.Tormey, Blood, 2020'.