Allergic Reactions to COVID-19 Vaccines: Risk Factors, Frequency, Mechanisms and Management

Abstract

Conventional vaccines have been widely studied, along with their risk of causing allergic reactions. These generally consist of mild local reactions and only rarely severe anaphylaxis. Although all the current COVID-19 vaccines marketed in Europe have been shown to be safe overall in the general population, early post-marketing evidence has shown that mRNA-based vaccines using novel platforms (i.e., lipid nanoparticles) were associated with an increased risk of severe allergic reactions as compared to conventional vaccines. In this paper we performed an updated literature review on frequency, risk factors, and underlying mechanisms of COVID-19 vaccine-related allergies by searching MEDLINE and Google Scholar databases. We also conducted a qualitative search on VigiBase and EudraVigilance databases to identify reports of "Hypersensitivity" and "Anaphylactic reaction" potentially related to COVID-19 vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Janssen Vaccine), and in EudraVigilance to estimate the reporting rates of "Anaphylactic reaction" and "Anaphylactic shock" after COVID-19 vaccination in the European population. We also summarized the scientific societies' and regulatory agencies' recommendations for prevention and management of COVID-19 vaccine-related allergic reactions, especially in those with a history of allergy. Key PointsSerious allergic reactions observed after the receipt of an mRNA vaccine are rare.Reporting rate of serious allergic reactions for viral vector COVID-19 vaccines seems to be similar to that for COVID-19 mRNA vaccines.The underlying mechanism of COVID-19 vaccinerelated allergies have not yet been fully elucidated.A risk stratification assessment for the development of allergic reactions should be conducted before the receipt of a vaccine against COVID-19.Nicoletta Luxi and Alexia Giovanazzi have contributed equally to the paper as first authors.

Does COVID-19 vaccination still have a role in maternal and perinatal outcomes during the Omicron era? A multicentre observational study

“…The role of vaccination was shown previously during previous COVID-19 waves as it improved maternal and fetal outcomes by reducing the severity of COVID-19 [8]. Vaccination has been shown to reduce the incidence of pneumonia and ARDS [8,20], which can cause lifethreatening hypoxemia and necessitate advanced resuscitation and, in some cases, cesarean delivery for fetal distress or maternal life-saving [8]. This may explain why vaccination allowed lower rates of cesarean deliveries and better maternal and fetal outcomes [8,21].…”

Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions and immunogenicity of PEG-containing Covid-19 vaccines

“…There is consensus in the literature that the incidence of HSRs and anaphylaxis caused by mRNA-LNP vaccinations is increased relative to that of traditional vaccines. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Taken the ~1.3 anaphylaxis/million out of >25 million recipients of flu vaccines, 44 as reference, the extent of increase is in the 3-400-fold range (STable 2). Nevertheless, this potentially lethal side effect is still considered as very rare, and its occurrence is further decreasing with time, as precautions are increased.…”

“…Since the mRNA-LNP vaccines include polyethylene glycol (PEG) as an excipient, allergy to PEG has been proposed as the mechanism of anaphylaxis. However, over time, it has been shown that the overwhelming majority of these reactions are not IgE-mediated classic type I allergies against PEG, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] leaving the underlying cause unclear. Among the studies addressing this puzzle, the possible role of anti-PEG antibodies (Abs) was raised, 1,17,19,20 but conclusive experimental or clinical evidence was not presented to date.…”

“…Yet, there are still life-threatening reactions and the phenomenon still represents a problem for severely allergic people. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Additionally, the specter of an allergic reaction helps fuel vaccine hesitancy.…”

Impact of COVID-19 vaccination among pregnant women requiring hospital admission: prospective observational research

“…Although the benefit-risk profile of these vaccines was proven to be largely favorable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, is still limited. The vaccines and particularly mRNA vaccines used in our population may induce additional cellular or humoral immune regulation, including T helper cell responses and germinal center responses, and form relevant memory cells, greatly improving their efficiency [14]. However, in pregnancy, there is a shift in Th1/Th2 that may trouble the immune response after infection [15] and may reduce the efficacy of vaccination [16].…”