Serum polyethylene glycol-specific IgE and IgG in patients with hypersensitivity to COVID-19 mRNA vaccines

BackgroundThe mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies.MethodsFourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls.ResultsSerum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG.ConclusionsThe results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.     

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys^® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.     

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies.MethodsWe administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization.ResultsResponses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis.ConclusionsThis study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.     

Vaccination and anaphylaxis

The incidence of anaphylactic or severe allergic reactions to vaccines is very low, less than one case per million vaccine doses. Larger studies from later years report no deaths. The cause of the reaction is usually not the immunizing antigen itself, but rather some other vaccine ingredient such as egg protein from the production process or gelatin added as a stabilizer. Most people with egg allergy can be vaccinated without any reaction. Vasovagal reactions with or without hyperventilation are common after vaccination. They can be rather dramatic and are often mistaken for anaphylactic reactions. Correct diagnosis is important in making it possible to vaccinate those who might otherwise run the risk of serious infections.     

Evaluation of patients with antiphospholipid syndrome subsequently COVID-19 vaccinations: A retrospective cohort study

The aim of this study is to evaluate development of side effects, thrombotic or obstetric complications in our antiphospholipid syndrome (APS) patient group, after vaccination against coronavirus disease 2019 (COVID-19). A cohort was formed from patients who have previously been followed up with a diagnosis of APS. The patients of the cohort were evaluated retrospectively to find out if they were vaccinated with CoronaVac and/or BNT162b2 vaccines which are being used in our country. To evaluate the side effects seen after the vaccination, the information was collected by the patients in their outpatient appointments or making a phone call. Thirty-five APS patients who had received at least 1 dose of any of the COVID-19 vaccines were included in the study. Median (min–max) number of vaccine doses per patient was 2 (1–3). Eleven patients had a booster dose after primary vaccination. Twenty patients were ever vaccinated with BNT162b2 and 18 with CoronaVac. Among BNT162b2 recipients, 9 (45.0%) and among CoronaVac recipients 15 (42.9%) reported an adverse event after a vaccine administration. The most common adverse events were myalgia and malaise after any dose of both vaccines. No vaccine-related new thrombotic events or APS flares were observed. Our results were comparable with those reported in the literature. Comprehensive large-scale studies are needed for more accurate results on the evaluation of side effects after COVID-19 vaccination in APS patients.     

Antibody Response to SARS-CoV-2 Infection and Vaccination in COVID-19-naïve and Experienced Individuals

Understanding the magnitude of responses to vaccination during the ongoing SARS-CoV-2 pandemic is essential for ultimate mitigation of the disease. Here, we describe a cohort of 102 subjects (70 COVID-19-naïve, 32 COVID-19-experienced) who received two doses of one of the mRNA vaccines (BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna)). We document that a single exposure to antigen via infection or vaccination induces a variable antibody response which is affected by age, gender, race, and co-morbidities. In response to a second antigen dose, both COVID-19-naïve and experienced subjects exhibited elevated levels of anti-spike and SARS-CoV-2 neutralizing activity; however, COVID-19-experienced individuals achieved higher antibody levels and neutralization activity as a group. The COVID-19-experienced subjects exhibited no significant increase in antibody or neutralization titer in response to the second vaccine dose (i.e., third antigen exposure). Finally, we found that COVID-19-naïve individuals who received the Moderna vaccine exhibited a more robust boost response to the second vaccine dose (p = 0.004) as compared to the response to Pfizer–BioNTech. Ongoing studies with this cohort will continue to contribute to our understanding of the range and durability of responses to SARS-CoV-2 mRNA vaccines.     

Factors associated with COVID-19 breakthrough infection among vaccinated patients with rheumatic diseases: A cohort study

ObjectiveRheumatic disease patients on certain immunomodulators are at increased risk of impaired humoral response to SARS-CoV-2 vaccines. We aimed to identify factors associated with breakthrough infection among patients with rheumatic diseases.MethodsWe identified patients with rheumatic diseases being treated with immunomodulators in a large healthcare system who received at least two doses of either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccines or one dose of the Johnson & Johnson-Janssen (J&J) vaccine. We followed patients until SARS-CoV-2 infection, death, or December 15, 2021, when the Omicron variant became dominant in our region. We estimated the association of baseline characteristics with the risk of breakthrough infection using multivariable Cox regression.ResultsWe analyzed 11,468 patients (75% female, mean age 60 years). Compared to antimalarial monotherapy, multiple immunomodulators were associated with higher risk of infection: anti-CD20 monoclonal antibodies (aHR 5.20, 95% CI: 2.85, 9.48), CTLA-4 Ig (aHR 3.52, 95% CI: 1.90, 6.51), mycophenolate (aHR 2.31, 95% CI: 1.25, 4.27), IL-6 inhibitors (aHR 2.15, 95% CI: 1.09, 4.24), JAK inhibitors (aHR 2.02, 95% CI: 1.01, 4.06), and TNF inhibitors (aHR 1.70, 95% CI: 1.09, 2.66). mRNA-1273 recipients had a lower risk of breakthrough infection compared to BNT162b2 recipients (aHR 0.66, 95% CI: 0.50, 0.86). There was no association of sex, body mass index, smoking status, race, or ethnicity with risk of breakthrough infection.ConclusionAmong patients with rheumatic diseases, multiple immunomodulators were associated with increased risk of breakthrough infection. These results highlight the need for additional mitigation strategies in this vulnerable population.     

Spike-specific humoral and cellular immune responses after COVID-19 mRNA vaccination in patients with cirrhosis: A prospective single center study

Background and AimsCOVID-19 mRNA vaccines were approved to prevent severe forms of the disease, but their immunogenicity and safety in cirrhosis is poorly known.MethodIn this prospective single-center study enrolling patients with cirrhosis undergoing COVID-19 vaccination (BNT162b2 and mRNA-1273), we assessed humoral and cellular responses vs healthy controls, the incidence of breakthrough infections and adverse events (AEs). Antibodies against spike- and nucleocapsid-protein (anti-S and anti-N) and Spike-specific T-cells responses were quantified at baseline, 21 days after the first and second doses and during follow-up.Results182 cirrhotics (85% SARS-CoV-2-naïve) and 38 controls were enrolled. After 2 doses of vaccine, anti-S titres were significantly lower in cirrhotics vs controls [1,751 (0.4–25,000) U/mL vs 4,523 (259–25,000) U/mL, p=0.012] and in SARS-CoV-2-naïve vs previously infected cirrhotics [999 (0.4–17,329) U/mL vs 7,500 (12.5–25,000) U/mL, (p<0.001)]. T-cell responses in cirrhotics were similar to controls, although with different kinetics. In SARS-CoV-2-naïve cirrhotics, HCC, Child-Pugh B/C and BNT162b2 were independent predictors of low response. Neither unexpected nor severe AEs emerged. During follow-up, 2% turned SARS-CoV-2 positive, all asymptomatic.ConclusionHumoral response to COVID-19 vaccines appeared suboptimal in patients with cirrhosis, particularly in SARS-CoV-2-naïve decompensated cirrhotics, although cellular response appeared preserved, and low breakthrough infections rate was registered.     

Impaired Humoral Response in Renal Transplant Recipients to SARS-CoV-2 Vaccination with BNT162b2 (Pfizer-BioNTech)

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. Therefore, the effect of established messenger RNA (mRNA)-based SARS-CoV-2 vaccines have to be evaluated for solid organ transplant patients (SOT) since they are known to have poor responses after vaccination. We investigated the SARS-CoV-2 immune response via SARS-CoV-2 IgG detection in 23 renal transplant recipients after two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol. The antibody response was evaluated once with an anti-SARS-CoV-2 IgG CLIA 15.8 +/− 3.0 days after the second dose. As a control, SARS-CoV-2 IgG was determined in 23 healthcare workers (HCW) and compared to the patient cohort. Only 5 of 23 (22%) renal transplant recipients were tested positive for SARS-CoV-2 IgG antibodies after the second dose of vaccine. In contrast, all 23 (100%) HCWs were tested positive for antibodies after the second dose. Thus, the humoral response of renal transplant recipients after two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech, Kronach, Germany) is impaired and significantly lower compared to healthy controls (22% vs. 100%; p = 0.0001). Individual vaccination strategies might be beneficial in these vulnerable patients.     

Global reports of myocarditis following COVID-19 vaccination: A systematic review and meta-analysis

Background and aimsRecent media reports of myocarditis after receiving COVID-19 vaccines, particularly the messenger RNA (mRNA) vaccines, are causing public concern. This review summarizes information from published case series and case reports, emphasizing patient and disease characteristics, investigation, and clinical outcomes, to provide a comprehensive picture of the condition.MethodsA systematic literature search of PubMed and Google scholar was conducted from inception to April 27, 2022. Individuals who develop myocarditis after receiving the COVID-19 vaccine, regardless of the type of vaccine and dose, were included in the study.ResultsSixty-two studies, including 218 cases, participated in the current systematic review. The median age was 29.2 years; 92.2% were male and 7.8% were female. 72.4% of patients received the Pfizer-BioNTech (BNT162b2) vaccine, 23.8% of patients received the Moderna COVID-19 Vaccine (mRNA-1273), and the rest of the 3.5% received other types of COVID-19 vaccine. Furthermore, most myocarditis cases (82.1%) occurred after the second vaccine dose, after a median time interval of 3.5 days. The most frequently reported symptoms were chest pain, myalgia/body aches and fever. Troponin levels were consistently elevated in 98.6% of patients. The admission ECG was abnormal in 88.5% of cases, and the left LVEF was lower than 50% in 21.5% of cases. Most patients (92.6%) resolved symptoms and recovered, and only three patients died.ConclusionThese findings may help public health policy to consider myocarditis in the context of the benefits of COVID-19 vaccination.     

Response to COVID-19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose

Background

Coronavirus disease 2019 (COVID-19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two-dose and additional dose of messengerRNA COVID-19 vaccine.

Methods

After measuring high-affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA-1273), time from second/third vaccination, molecular-targeted agent (anti-tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular-targeted agents), thiopurine, steroid, and 5-aminosalicylic acid.

Results

Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non-carriers of HLA-A24 associated with severe disease during COVID-19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti-TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers.

Conclusions

Our findings further support the recommendation for COVID-19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti-TNF agents and/or thiopurine or tofacitinib.     

Recommendations for administering the triple viral vaccine and antiinfluenza vaccine in patients with egg allergy

Actually, food allergy is an emerging pathology; and egg allergy is the most frequent in childhood. The recommendations for measles, mumps and rubella (MMR) and influenza vaccination are increasing each year. This implementation increases the exposure of patients with egg allergy to such vaccines. In Spain, since 2004 the only available vaccine for MMR is grown in cultures of fibroblast from chick embryos; previously, patients with egg allergy were vaccinated with an alternative vaccine cultivated in diploid human cells which is no longer commercialized. Influenza vaccines grow in chick egg and the final product contains egg proteins (large variation in egg protein content has been reported). As controversy exist, the Food Allergy Committee of Spanish Society of Clinical Immunology and Pediatric Allergy decided to report some recommendations for the safe administration of MMR and influenza vaccines in patients with egg allergy. In summary, MMR vaccine is safe for children with egg allergy, only in patients with severe anaphylactic reaction after egg ingestion is recommended the administration in his reference hospital. Influenza vaccine is contraindicated in patients with severe anaphylactic reaction after egg ingestion. The rest can receive influenza vaccine in a 2-dose protocol with a vaccine that contains no more than 1.2 mcg of egg protein for mL.     

Incidence of immediate allergic reactions to mRNA COVID-19 vaccines in adults with drug allergies and other allergic disorders

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines.To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders.We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded.Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable.Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.     

Allergies et vaccins

Atopy and the onset of an allergic reaction during vaccination sometimes result in abstention that disadvantages the patient. First, the problem of vaccinating the atopic individual is discussed with the recurrent problem of egg allergy. Only severe anaphylaxis to egg requires hospitalization for vaccines containing egg protein. Asthma exacerbation reactions or atopic dermatitis (flash phenomenon) require certain precautions before vaccination. Apart from these measures, there is no systematic vaccine contraindication for the atopic child and the French vaccination schedule can be applied to children with allergies. After reviewing the components of vaccines that have an allergic potential, we discuss the course to follow in cases of reaction to a vaccine.     

IgA Nephropathy with Gross Hematuria Following COVID-19 mRNA Vaccination

A 28-year-old woman experienced gross hematuria after the administration of the second dose of an messenger ribonucleic acid (mRNA) vaccine (BNT162b2). She was diagnosed with Immunogloblin A nephropathy (IgAN) by a renal biopsy two weeks after vaccination, which revealed a mild increase in mesangial cells and a matrix with co-depositions of galactose-deficient IgA1 and C3 in the mesangial region. The gross hematuria and proteinuria gradually improved without any medication, suggesting that immune activation by the mRNA vaccine may not elicit continuous disease progression of IgAN. Thus, further studies investigating the relationship between mRNA vaccines against COVID-19 and the progression of IgAN should be conducted.     

Incidence and Risk Factors of COVID-19 Vaccine Breakthrough Infections: A Prospective Cohort Study in Belgium

The objective of this study was to investigate the incidence and risk factors associated with COVID-19 vaccine breakthrough infections. We included all persons ≥18 years that had been fully vaccinated against COVID-19 for ≥14 days, between 1 February 2021 and 5 December 2021, in Belgium. The incidence of breakthrough infections (laboratory confirmed SARS-CoV-2-infections) was determined. Factors associated with breakthrough infections were analyzed using COX proportional hazard models. Among 8,062,600 fully vaccinated adults, we identified 373,070 breakthrough infections with an incidence of 11.2 (95%CI 11.2–11.3)/100 person years. Vaccination with Ad26.COV2.S (HR1.54, 95%CI 1.52–1.56) or ChAdOx1 (HR1.68, 95%CI 1.66–1.69) was associated with a higher risk of a breakthrough infection compared to BNT162b2, while mRNA-1273 was associated with a lower risk (HR0.68, 95%CI 0.67–0.69). A prior COVID-19-infection was protective against a breakthrough infection (HR0.23, 95%CI 0.23–0.24), as was an mRNA booster (HR0.44, 95%CI 0.43–0.45). During a breakthrough infection, those who had a prior COVID-19 infection were less likely to have COVID-19 symptoms of almost all types than naïve persons. We identified risk factors associated with breakthrough infections, such as vaccination with adenoviral-vector vaccines, which could help inform future decisions on booster vaccination strategies. A prior COVID-19 infection lowered the risk of breakthrough infections and of having symptoms, highlighting the protective effect of hybrid immunity.     

The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2

The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.

The unprecedented development of efficacious vaccines against SARS-CoV-2 has represented a triumph in the global effort to control the ongoing COVID-19 pandemic. Vaccines have been shown to provide short-term protection from major adverse health outcomes of hospitalization and death (1–4). However, protection against breakthrough infection wanes (5), and breakthroughs have been extensively documented (6, 7). In response, the Food and Drug Administration advisory committee has recommended a booster of the Pfizer-BioNTech and Moderna vaccines at least 5 mo after completion of the primary series to people ≥12 and ≥18 y of age, respectively (8). A booster dose of the Johnson & Johnson/Janssen vaccine has been authorized on a faster timescale—as early as 2 mo after the single dose to individuals 18 y of age and older (8). Nevertheless, the optimal timing of boosting remains challenging to assess. Consequently, rigorous prediction of the durability of immunity conferred by vaccination against the SARS-CoV-2 virus is essential to personal and public health decision-making, having major implications regarding policy decisions about COVID-19 vaccination around the world (9, 10).Short-term longitudinal studies of SARS-CoV-2-neutralizing antibodies in vaccinated individuals (11–13) can provide information crucial to our understanding of the durability of vaccine-mediated immunity. Peak antibody responses following vaccination versus natural responses have also been quantified (14), facilitating analytical comparison of initial immune responses. For endemic viruses, longitudinal data on reinfection can provide reinfection probabilities associated with antibody level. However, longitudinal data on SARS-CoV-2 reinfection are not available during the short term associated with pandemic spread. Nevertheless, longitudinal reinfection data for a diversity of coronaviruses have been collected (15–20). SARS-CoV-2 reinfection probabilities have been obtained from them by phylogenetic analysis, using continuous ancestral and descendent state estimation (21). These estimates, produced before reinfection was commonplace, proved accurate (predicting an 18% probability of reinfection at ∼270 d [ref. 21] that was validated by a subsequent empirical finding of 18% reinfection by 275 to 300 d after primary infection [ref. 22] and, likewise, predicting a 34% probability of reinfection at ∼450 d after primary infection [ref. 21] that was validated by a subsequent empirical finding of 34% breakthrough infection 420 to 480 d after primary vaccination [ref. 23]). Similar analyses pairing antibody response and rates of waning for each vaccine with infection probabilities can enable quantification of the durability of vaccine-mediated immunity against breakthrough infections. The aim of this study is to leverage data on antibody response to each vaccine and corresponding probabilities of infection to estimate the durability of vaccine-mediated immunity against breakthrough SARS-CoV-2 infection for four well-studied vaccines: mRNA-1273, BNT162b2, ChAdOx1, and Ad26.COV2.S.     

Successful Treatment of Immune Thrombocytopenic Purpura with Intracranial Hemorrhaging and Duodenal Bleeding Following SARS-CoV-2 Vaccination

Several vaccines have been developed for coronavirus disease 2019 - caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - in record time. A few cases of immune thrombocytopenic purpura (ITP) following SARS-CoV-2 vaccination have been reported. We herein report a 90-year-old man who received the Pfizer-BioNTech SARS-CoV-2 vaccine (BNT162b2) and developed severe thrombocytopenia with intracranial hemorrhaging and duodenal bleeding, consistent with vaccine-related ITP. He was successfully treated with intravenous immunoglobulin, prednisolone, and eltrombopag and discharged without cytopenia. Vaccine-related ITP should be suspected in patients presenting with abnormal bleeding or purpura after vaccination.     

Correction to: Immunogenicity and safety of the mRNA-based BNT162b2 vaccine in systemic autoimmune rheumatic diseases patients

Background

The COVID-19 outbreak has led to the rapid development and administration of the COVID-19 vaccines worldwide. Data about the immunogenicity and adverse effects of the vaccine on patients with systemic autoimmune rheumatic diseases (SARDs) is emerging.

Aim

To evaluate Pfizer/BioNTech (BNT162b2) mRNA-based vaccine second-dose immunogenicity and safety, and the relation between them, in patients with SARDs.

Methods

A total of one hundred forty tow adults who received two doses of the BNT162b2 vaccine were included in the study. The SARDs group included Ninety-nine patients and the control group (forty-three participants) comprised a mixture of healthy participants and patients who were seen at the rheumatology clinic for non-SARDs. Anti-SARS-CoV-2 IgG antibodies against the Spike protein were evaluated using a SARS-CoV-2 IgG immunoassay. A level of > 150 AU/mL was considered positive. An adverse effects questionnaire was given to the participants upon their first visit to the clinic after their BNT162b2 vaccination.

Results

Of the 142 participants, 116 were seropositive (81.7%) and 26 (18.3%) were seronegative. Of the seronegative participants, 96.2% were SARDs patients. The proportion of seropositivity in the SARDs patients treated with any immunosuppressant was significantly lower (69.9%) compared to the control group and SARDs patients not receiving immunosuppressants (96.8%). A significant negative correlation between seronegativity and treatment with rituximab, mycophenolate mofetil (MMF), and prednisone was found in the SARDs group (p = 0.004, 0.044, 0.007 respectively). No fever was observed following the BNT162b2 vaccine in seronegative patients, and the frequency of musculoskeletal adverse effects upon the second dose of the BNT162b2 vaccine was significantly higher in seropositive compared to seronegative patients and in the control group compared to the SARDs patients (p = 0.045, p = 0.02 respectively).

Conclusion

A decline in the immunogenicity to the second dose of BNT162b2 mRNA is seen in patients with SARDs, especially in patients treated with rituximab, MMF, and prednisone. Adverse effects of the vaccine including fever and musculoskeletal symptoms might be a signal for the acquisition of immunity in those patients.

Key Points

• BNT162b2 mRNA vaccine is less immunogenic in SARDs patients compared to the control group.

• Rituximab, prednisone, and mycophenolate mofetil significantly reduced immunogenicity to the vaccine.

• There is a correlation between immunogenicity and adverse effects of the vaccine.